LYMPH NODE REPORT TEMPLATES

The specimen is received fresh labeled with the patient's name, medical record number and "1. right cervical lymph node". It consists of one oval shaped tissue segment measuring 2.0 x 1.5 x 0.9 cm. The external surface of the specimen is pink-tan, smooth and shiny. The cut surface is pale-gray and homogenous. Two touch preps are prepared and a portion of the specimen is submitted for flow cytometry and the remainder of the specimen is entirely submitted in 1A. J. Xiao, M.D./ddr 03/06/08 16:23

1 block, 1 H&E, 2 touch preps

CPT: 88305-GC, 88161-GC x 2

JXX:DDR

MICROSCOPIC DESCRIPTION:

Histologic sections of the (R) cervical lymph node show intact capsule with follicular hyperplasia. The follicles are increased in number and size. Many secondary follicles with prominent follicular center are seen. The follicles exhibit considerable variation in size and shape. The mantle zone of the follicles is well defined. The germinal centers contain many mitoses and tingible-body macrophages. No granuloma or necrosis is seen in histologic sections.

Touch preps show mostly small lymphocytes with mature cytological features. A small number of larger lymphocytes and histiocytes are seen admixed with the small lymphocytes.

Immunophenotyping of the cervical lymph node by flow cytometry shows a T cell population (about 70% of the cells analyzed) with no aberrant loss or aberrant expression of T cell markers, a B cell population (about 30% of the cells analyzed) that is negative for CD5, CD10, no surface light-chain restriction.

++++++++++++++++++++++++++++++++++++++++

2. LYMPH NODE: DLBCL

DIAGNOSIS:

Left supraclavicular lymph nodes:

Diffuse large B-cell lymphoma

CLINICAL INFORMATION:

75 year-old female with mediastinal adenopathy and bilateral supraclavicular

adenopathy.

SPECIMEN SUBMITTED:

Received from Alliance Pathology Consultants, Pasadena, TX, for consultation:

- 6 paraffin blocks labeled "3842-FS1A, 1B, FS2A, 2B, 2C, 3"

- 7 glass slides labeled "S2003-3842-FS1A cryo, S2004-3842-1B, FS2A,

FS2A cryo, 2B, 2C, 3"

- A one-page letter from Dr. Dorothy Willis dated 05-06-04

- A two-page surgical pathology report specimen "BM:S3842-04"

ADDITIONAL TECHNIQUES (block 3842-2C):

CD3, CD10, CD20, CD30, CD45, Bcl-2, cytokeratin immunohistochemical
stains

GROSS DESCRIPTION:

See Alliance Pathology report S3842-04.

MICROSCOPIC DESCRIPTION:

Histologic sections of the left supraclavicular lymph nodes show effacement of

lymph node architecture by large cells with irregular nuclear contour,

vesicular nuclei with fine chromatin, and one to several nucleoli. Frequent

mitotic figures are seen. Necrotic foci and bands of sclerosis are also found

in sections.

IMMUNOPEROXIDASE:

Immunohistochemical stains, with adequate controls, show that the neoplastic

cells are positive for CD20, CD45, and bcl-2. These cells are negative for

CD3, CD10, and CD30. Normal T cells (positive for CD3) are scattered

throughout the sections. No epithelial components are detected with

cytokeratin.

+++++++++++++++++++++++++++++++++++++++++

3. REACTIVE LYMPH NODES (Follicular hyperplasia and sinus hyperplasia) WITH FLOW

~~~~~ DIAGNOSIS:

Lymph nodes, cervical, excisional biopsy:

- Follicular and sinus hyperplasia.

- No evidence of granuloma, necrosis or malignancy.

~~~~~ MICROSCOPIC DESCRIPTION:

Immunophenotyping of cervical lymph node biopsy by flow cytometry shows a T cell population (about 76% of the cells analyzed) with no aberrant loss or aberrant expression of T cell markers, a B cell population (about 23% of the cells analyzed) that is negative for CD5, CD10, CD56, also no surface light-chain restriction.

++++++++++++++++++++++++++++++++++++++++++++++++++++

4. REACTIVE LYMPH NODES (Follicular hyperplasia and sinus hyperplasia ) WITH IMMUNOSTAINS

Diagnosis:

Lymph node, right inguinal, biopsy:

- Benign reactive lymph node with follicular hyperplasia and sinus hyperplasia

Histologic sections of the (R) inguinal lymph node show preservation of lymph node architecture. The capsule is moderately thickened. Follicular hyperplasia and sinus hyperplasia are noted. The follicles have well-formed mantle zone. No evidence of granuloma or necrosis is seen. Vascular proliferation is moderately increased.

Immunohistochemical stains, with adequate controls, are performed on block 1A for CD3, CD10, CD20, and bcl-2. The germinal centers are positive for CD20, CD10, and negative for bcl-2. CD3 and bcl-2 are positive for lymphocytes in the interollicular areas.

+++++++++++++++++++++++++++++++++++++++++++==

5. NASOPHARYNX, CHRONIC INFLAMMATION

DIAGNOSIS:

Nasopharynx biopsy: Benign lymphocytic infiltration, no evidence of malignancy

Histologic sections of nasophrynx biopsy shows diffuse infiltration with

lymphocytes, admixed with a small number of histiocytes. The lymphocytes
have small size with mature cytological features.

Immunophenotyping of nasopharynx biopsy by flow cytometry shows a T cell

population with no aberrant loss or aberrant expression of T cell markers, a B

cell population with no abnormal profile.

Immunohistochemical stains, with adequate controls, are performed on block 1A

for bcl-6, CD3, CD20, and Ki-67. The lymphocytes are positive for CD3, with a

small number of cells positive for CD20. Ki-67 and bcl-6 show scattered

positivity.

++++++++++++++++++++++++++++++++++++++++++++++++++++++

6. LYMPH NODE: SLL

~~~~~ DIAGNOSIS:

Lymph nodes: Small lymphocytic lymphoma

Parotid gland: Normal morphology

Histologic sections of lymph nodes show effacement of lymph node architecture with diffuse infiltration of small lymphocytes. The lymphocytes have small nuclei with mature cytological features. Parafollicles (proliferation centers) are seen throughout sections.

Immunohistochemical stains, with adequate controls, are performed on block 1B for bcl-1, CD3, CD5, CD20, and CD23. The lymphocytes are positive for CD5, CD20, and CD23. They are negative for bcl-1. Scattered T cells (positive for CD3) are also seen.

Immunophenotyping of parotid lymph node by flow cytometry shows a T cell population (about 17% of the cells analyzed) with no aberrant loss or aberrant expression of T cell markers, a B cell population (about 88% of the cells analyzed) that is positive for CD5, CD19, CD20, CD22, CD23, surface kappa light chain restriction (dim signal). These B cells are negative for CD10, and CD38. These B cells have small nuclear size (based on forward-scatter signal).

++++++++++++++++++++++++++++++++++++++++++++++++++++

7. WORK-UP FOR PTLD: FAVORING BENIGN LYMPHOID AGGREGATES

DIAGNOSIS:

1. Duodenal mucosal biopsy:

- Lymphoid hyperplasia in the lamina propria (see comment).

- Negative for Epstein Barr virus by EBV-LMP immunoperoxidase stain

2. Gastric antrum mucosal biopsy:

-Hypercellular lamina propria (see comment).

3. Distal esophageal mucosal biopsy:

-No disease found.

4. Proximal esophageal mucosal biopsy:

- Submucosal lymphoid hyperplasia (see comment).

- Negative for Epstein Barr virus by EBV-LMP immunoperoxidase stain

5. Right colon:

- No disease found.

6. Transverse colon:

- Lymphoid hyperplasia in the mucosa (see comment).

7. Left colon:

- Lymphoid hyperplasia in the submucosa (see comment).

COMMENT:

The morphological findings, together with immunoperoxidase stains, favor benign lymphoid aggregates. Since transplant patients are at risk for

post-transplant lymphoproliferative disorders, thick sections from part 1 (duodenal mucosal biopsy) were sent for B and T cell gene rearrangement by PCR to rule out the presence of a monoclonal lymphocytic population. Results will be added as Addendum to this report.

CLINICAL INFORMATION: Status post OLT, diarrhea, esophagus-mildly and nodular, colon, lymphoid nodular hyperplasia.

MICROSCOPIC DESCRIPTION:

In specimen 1 from the duodenum, the lamina propria is densely packed with mononuclear cells with several dense aggregates. There is no distortion of the glandular or surface epithelium. The cellular elements are principally small lymphocytes with mature cytological features. A few plasma cells and isolated eosinophils are seen admixed with the lymphocytes.

In specimen 2 from the antrum, the surface and glandular epithelium are preserved. There is an increase cellularity in the lamina propria but with only one small area of cellular density. The cellular elements are principally small lymphocytes with a few plasma cells and a few eosinophils.

In specimen 3 from the distal esophagus, the architecture is preserved and there is no inflammation.

In specimen 4 from the proximal esophagus, the epithelium shows a mild basilar hyperplasia but no inflammation and no elongation of rete. The subepithelial area contains a large number of compactly-arranged lymphocytes with scattered eosinophils and plasma cells.

In specimen 5 from the right colon, the lamina propria is loosely cellular with only a small lymphoid nodule. The surface and glandular epithelium are intact.

In specimen 6, transverse colon, the lamina propria is densely cellular with several small lymphoid nodules. The surface and glandular epithelium are intact. There is a scattering of eosinophils and of plasma cells.

In specimen 7, left colon, the surface and glandular epithelium are intact. The lamina propria is densely cellular with several condensed nodules. The cellular elements are principally small lymphocytes, a few plasma cells, and a few eosinophils.

Immunohistochemical stains, with adequate controls, are performed on blocks 1A and 4A for Epstein Barr Virus (EBV-LMP), CD3, and CD20. A mixture of T cells (CD3-pos) and B cells (CD20-pos) is seen in the lymphoid aggregates. EBV-LMP is negative. EBER-1 in situ hybridization is pending. Results will be added as Addendum to this report.

+++++++++++++++++++++++++++++++++++++++++++++++

8. CERVICAL LN: CLASSICAL HL, MIXED CELLULARITY (SAMPLE 1)

DIAGNOSIS:

Cervical lymph node: classical Hodgkin lymphoma, mixed cellularity

MICROSCOPIC DESCRIPTION:

Histologic sections of cervical lymph node show capsule with mildly increased

thickness. Foci of small lymphocytes are seen infiltrating adjacent adipose

tissue. A small number of follicles with variable size are seen, some with

folliculolysis. The lymph node is infiltrated in an interfollicular pattern by

a moderate number of large atypical cells with prominent nucleolus, some with

binucleated form. These cells are admixed with an inflammatory background of

small lymphocytes, a few eosinophils, macrophages, and plasma cells.

Immumohistochemical stains, with adequate controls, are performed on block 1A

for bcl-2, CD3, CD10, CD15, CD20, CD45, and C30. The large atypical cells are

positive for CD15, CD30, focally positive for CD20, and negative for CD3 and

CD45 (consistent with the expected pattern for Hodgkin and Reed-Sternberg

cells). The follicles and paracortical areas show normal distribution of

bcl-2, CD3, and CD10.

Immunophenotyping of cervical lymph node by flow cytometry shows no abnormal

immunophenotypes (typically seen in flow cytometric studies for classical

Hodgkin lymphoma).

+++++++++++++++++++++++++++++++++++++++++++++++++++++++++++

9. SPLEEN, PTCL, NOS

DIAGNOSIS:

Spleen, splenectomy:

- Peripheral T cell lymphoma, unspecified

COMMENT:

Immunophenotyping of the spleen biopsy by flow cytometry shows a T cell population with no aberrant loss or aberrant expression of T cell markers, a small B cell population that is negative for CD5, CD10, no surface light-chain restriction. Note that these results are compromised by low viability of the cells analyzed (ranging from 34% to 76%).

CLINICAL INFORMATION:

Splenomegaly.

TISSUE/SOURCE DESCRIPTION:

"Spleen"

GROSS DESCRIPTION:

The specimen is received in a container without fixative, labeled with the patient's name and medical record number. It consists of a spleen weighing 2050 gm and measuring 27.0 x 20.0 x 8.5 cm. Several surgical incisions are identified on the posterior side. The hilum is unremarkable. The splenic capsule is tan-red with a 2.0 cm area of purple discoloration. The splenic parenchyma is red and homogenous. The splenic vessels are unremarkable with no thrombi present. Gross photographs are taken. A specimen was submitted in RPMI for flow cytometry Representative sections are submitted in cassettes 1A-1F. (E.Sotelo, M.D.)/bt 02/05/08 14:51

5 blocks, 5 H&E

EPS:BMT

MICROSCOPIC DESCRIPTION:

The splenic capsule is intact with normal thickness. The white pulp is markedly atrophic. The red pulp is diffusely infiltrated with lymphocytes of small-medium size and irregular nuclear outline. Many large pleomorphic cells with polylobated nuclei are seen admixed with other small-medium lymphocytes. Moderate number of mitotic figures are also seen.

Immunohistochemical stains, with adequate controls, are performed on block 1B for CD2, CD3, CD4, CD8, CD15, CD20, CD30, ALK-1 protein and factor 8 related antigen. The abnormal lymphocytes, including the large cells, are positive for CD3, CD2, and CD4. They are negative for CD20, CD8, CD15, CD30, ALK-1, and Factor 8-related antigen.

+++++++++++++++++++++++++++++++

10. CERVICAL LN: CLASSICAL HL, MIXED CELLULARITY (SAMPLE 2)

DIAGNOSIS:

Lymph node from (L) neck: classical Hodgkin lymphoma, mixed cellularity

CLINICAL INFORMATION:

Left neck mass.

TISSUE/SOURCE DESCRIPTION:

Lymph node biopsy from left neck"

FROZEN SECTION DIAGNOSIS:

LYMPH NODE, LEFT NECK, FS: ONE LYMPH NODE IDENTIFIED,
DEFER FOR PERMANENT AND FLOW CYTOMETRY. NO CARCINOMA IDENTIFIED. (BZ)

GROSS DESCRIPTION:

Received in a container without fixative, labeled the patient's name, medical

record number, "left neck lymph node", is a tan-pink, soft tissue with

attached fat measuring 0.6 x 0.5 x 0.3 cm. The specimen is bisected. A

representative portion is submitted for frozen section analysis and

resubmitted in FS1A. Representative portion was sent for flow cytometry and

the remainder of the specimen is submitted in 1B. (M. Swaby, M.D.)/bt 03/24/08

2 blocks, 2 H&E

MICROSCOPIC DESCRIPTION:

Histologic sections of the lymph node show effacement of architecture. A

moderate number of large atypical cells with prominent nucleolus, some with

binucleated form are seen throughout the sections. These cells are admixed

with an inflammatory background of small lymphocytes, a few eosinophils,

macrophages, neutrophils, and moderate number of plasma cells. No increase in

fibroconnective tissue is seen in the sections. Portions of the capsule seen

in the sections are intact and of normal thickness.

Immumohistochemical stains, with adequate controls, are performed on block 1B

for CD3, CD15, CD20, CD45, and C30. The large atypical cells are positive for

CD15, CD30, and negative for CD45, CD3, and CD20 (consistent with the
expected pattern for Hodgkin and Reed-Sternberg cells). The small lymphocytes in the

bacground are mostly T cells (CD3-positive) with a smaller number of B cells

(CD20-positive).

Immunophenotyping of the lymph node biopsy by flow cytometry shows no
abnormal immunophenotypes (typically seen in flow cytometric studies for
classical Hodgkin lymphoma).

++++++++++++++++++++++++++++++++

11. TONSILLAR MASS: BURKITT LYMPHOMA

DIAGNOSIS:

Left tonsil mass biopsy: highly-aggressivee B cell lymphoma (see comment)

COMMENT:

The immunophenotypic profile of the malignant cells (negative bcl-2, positive

bcl-6, Ki67 approaching 100%) favor Burkitt lymphoma. However, the

cytological features of the malignant cells are more pleomorphic (in nuclear

size and contour) than those seen in typical cases of Burkitt lymphoma. This

case may represent atypical Burkitt lymphoma. Further FISH testing for

t(8;14)(q24; q32), or its variants involving the light chain genes on 2p11 and

22q11, is suggested to confirm/rule out the diagnosis of atypical Burkitt

lymphoma if clinically indicated. If FISH results are negative for these

mutations, a diagnosis of diffuse large B cell lymphoma should be

considered.

MICROSCOPIC DESCRIPTION:

Histologic sections of the left tonsillar mass shows diffuse infiltration of

intermediate-large cells with irregular nuclear contour, vesicular nuclei and

one to several nucleoli. Frequent mitotic figures are seen. Numerous

macrophages with ingested apoptotic tumor cells are found throughout the

sections, imparting a "starry sky" pattern.

Immunohistochemical stains show that the neoplastic cells are positive for

CD20, bcl-6, and Ki67 (proliferation rate approaching 100%). They are negative

for pan-keratin, CD3, CD10, and bcl-2. Scattered T cells (positive for CD3)

are seen admixed with tumor cells.

+++++++++++++++++++++++++++++++++++++++++++++++++++++++++++++++

12. SKIN BX: HISTIOCYTIC SARCOMA

DIAGNOSIS:

Soft tissue, left palm, excision:

- Histiocytic sarcoma.

Tumor left hand palm.

TISSUE/SOURCE DESCRIPTION:

"Tumor left hand palm"

GROSS DESCRIPTION:

The specimen is received in formalin, labeled with the patient's name, medical record number, and "tumor left hand palm". It consists of one pale-gray fibroadipose tissue measuring 2.2 x 1.0 x 0.6 cm. The external surface is pale-yellow, rough without skin. No hemorrhage is identified. The external surface is inked and the specimen is bisected. The cut surface is pale-yellow and homogenous. Entirely submitted in 1A. (Jianguo Xiao, M.D.)/bt 03/07/08 14:51

1 block, 1 H&E

JXX:BMT

MICROSCOPIC DESCRIPTION:

The lesion is comprised of a sheets of cells with poorly defined cell borders, amphiphilic, granular cytoplasm and enlarged, pleomorphic nuclei. The cells have varying contours ranging from round to stellate. There is a variable presence of nucleoli with some cells lacking nucleoli and others having distinct nucleoli. The nuclei have frequent grooves and indentations. Some of the nuclei appear to be bilobed. The nucleus is in an eccentric position in those cells with more abundant cytoplasm. Mitotic figures are easily found. The background is variable ranging from fibrous to myxoid. A panel of immunohistochemical stains with adequate controls was performed to characterize this lesion. Stains for pan-cytokeratin and epithelial membrane antigen with negative and weakly positive in a cytoplasmic granular pattern eliminating epithelial malignancies and epithelioid sarcoma. A stain for vimentin is strongly positive in a cytoplasmic pattern and highlights the granularity of the cytoplasm. A stain for smooth muscle actin was weakly positive in rare nuclei. A stain for myogenin-D1 was weakly to moderately reactive in the cytoplasm of many cells. However, it was negative in nuclei. The patterns of both muscle muscle markers are inappropriate for the distribution of the target protein. Therefore these stains are interpreted as negative eliminating smooth muscle and skeletal muscle lesions from consideration. A stain for S-100 is negative eliminating neural lesions. A stain for beta-catenin is reactive in a membranous and cytoplasmic pattern but negative in nuclei. A stain for Ki-67 will be automatically quantitated in our laboratory and results issued in an addendum. A stain for CD45 (Leukocyte common antigen) is positive in a cytoplasmic and membranous pattern consistent with a hematolymphoid process. Stains for CD34, CD30, Alk-1 protein, and myeloperoxidase are negative in tumor cells eliminating granulocytic lesions and anaplastic large cell lymphoma from consideration. Stains for CD68 and lysozyme are strongly positive in a granular cytoplasmic pattern confirming that this is a histiocytic proliferation. A stain for CD4 is also positive consistent with a maturing histiocytic infiltrate. The negative S-100 stain eliminates a Langerhans cell histiocytosis. A stain for CD23 is negative eliminating follicular dendritic cell sarcoma.

The immunohistochemical stains referenced were performed at the University of Texas - Houston Medical School Pathology Histology Laboratory.

+++++++++++++++++++++++++++++++++++++++++++++++++++++++++++++++

13. SKIN BX: MYELOID SARCOMA

DIAGNOSIS:

(L) forearm skin biopsy:

Leukemic cell infiltrates consistent with myeloid sarcoma

CLINICAL INFORMATION:

13 year AAM, status post multiple antibiotics with two weeks history of

hemorrhagic targetoid patches with central hemorrhage. Patient was just

diagnosed with acute myeloid leukemia (AML) yesterday (3/25/08), positive

fever and edema. Differential diagnosis: Bullous erythema multiforme vs leukemia cutis vs infection

MICROSCOPIC DESCRIPTION:

Histologic section of the skin biopsy shows acantholysis, dermal infiltrations

consisting of immature cells of intermediate nuclear size, some with prominent

nucleolie. These infiltrating cells are seen admixed with a small number of

necrotic cells.

Immunohistochemical stains, with adequate controls, are performed on block 1A

for CD43, c-kit, and myeloperoxidase. The abnormal cells are positive for

myeloperoxidase and CD43. c-kit shows scattered positivity.

+++++++++++++++++++++++++++++++++++++++++++++++++++++++++

14. INGUINAL LN: DLBCL /FL (grade 3/3)

DIAGNOSIS:

- (R) inguinal lymph node: Diffuse large B-cell lymphoma (70%) and follicular lymphoma, grade 3/3 (30%), indicating transformation of follicular lymphoma to diffuse large B-cell lymphoma

- Appendix: Diffuse large B-cell lymphoma and follicular lymphoma, grade 3/3

CLINICAL INFORMATION:

Peritoneal tumors. Intussusception.

TISSUE/SOURCE DESCRIPTION:

"1. Appendix; 2. Right inguinal lymph node"

GROSS DESCRIPTION:

Specimen 1 is received in formalin, designated with the patient's name, medical record number, and "appendix". Present is a single white-tan, tubular appendix (5.5 x 0.8 cm). The proximal resection margin is filled by a silver suture line. The serosal surface has focal areas of hemorrhage but no exudate or rupture site. On sectioning, the luminal wall is very scalloped and irregular with intraluminal brown-tan semi-soft material. The tip is longitudinally sectioned. Representative sections are submitted as follows:

1A: longitudinally section tip and proximal resction margin cross section 1B: remaining longitudinally section tip and additional cross section

Specimen 2 designated with the patient's name, medical record number, and "right inguinal lymph node", is received fresh (2.5 x 1.5 x 1.0 cm). There is a small amount of adjacent adipose tissue present. On sectioning the tissue is white-tan and homogenous. A touch prep is prepared from the lymph node tissue. A small portion of the specimen is retained in RPMI fluid and sent for flow cytometric analysis and some for microbiological studies. The remaining node is entirely submitted in cassette 2A-2C. (Tracy Koen, M.D./A.Lapus, M.D.)/bt 04/23/08 10:20

5 blocks, 5 H&E

AXL:BMT

MICROSCOPIC DESCRIPTION:

Touch prep of (R) inguinal lymph node shows presence of intermediate-large cells with scant cytoplasm, vesicular nuclei and one to several nucleoli. Only rare cells with a few cytoplasmic vacuoles are seen. Moderate number of tingible-body macrophages are also seen.

Histologic sections of the (R) inguinal lymph node show effacement of the normal lymph node architecture. About 70% of the examined area shows diffuse infiltration by malignant cells with intermediate-large size, with vesicular nuclei and one to several nucleoli. Frequent mitotic figures are seen. Many macrophages with ingested apoptotic tumor cells are found throughout the sections. About 30% of the examined area shows poorly-defined neoplastic follicles of varying size. The follicles lack mantle zone and contain mostly centroblasts. An unusually high number of tingible-body macrophages are also seen in the follicles.

Immunohistochemical stains, with adequate controls, are performed on block 2A of the lymph node for bcl-2, CD3, CD10, CD20, CD43, Ki-67, and TdT.

The neoplastic cells (in the follicular area and also in the diffuse area) are positive for bcl-2, CD20, CD10; and negative for CD3, CD43, and TdT. Ki-67 shows approximately 60% proliferation rate. CD3 and CD43 show a small number of normal T cells surrounding the neoplastic follicles.

Immunophenotyping of the (R) inguinal lymph node biopsy by flow cytometry shows a T cell population (about 8% of the cells analyzed) with no aberrant loss or aberrant expression of T cell markers, a prominant B cell population (about 92% of the cells analyzed) that is positive for CD19, CD20, CD22, CD10, FMC7, surface lambda light chain restriction. These B cells are negative for CD5, and CD23. These B cells have intermediate-large nuclear size (based on forward-scatter signal).

Histologic sections of the appendix show neoplastic follicles and also diffuse infiltration by malignant cells with morphology similar to that seen in the (R) ingunal lymph node.

The morphology and immunophenotyping (by immunostains and flow cytometry) are consistent with diffuse large B-cell tranformed from follicular lymphoma (grade 3/3)

Burkitt lymphoma is ruled out with the following findings for malignant cells: (a) lack of typical cytoplasmic vacuoles in almost all cells, (b) positivity for bcl-2, (c) negativity for CD43, (d) Ki-67 not in the 90-100% range.

The referenced immunohistochemical stains were performed at the University of Texas - Houston Medical School Pathology Histology Laboratory.

+++++++++++++++++++++++++++++++++++++++++++++++++++++++++++++++

15. CERVICAL LYMPH NODE: Degeneration artifacts / NO EVIDENCE OF LYMPHOMA

Diagnosis:

Cervical lymph node:

-No evidence of malignancy or granuloma

-Special stains for acid-fast bacilli and fungi are negative

Histologic sections of the cervical lymph node show thickened capsule. The follicles are decreased in number and size. No granuloma or abnormal cellular infiltrates are seen. Focal areas with degeneration artifacts are seen in sections.

Immunophenotyping of the cervical lymph node by flow cytometry shows a T cell population (about 67% of the cells analyzed) with no aberrant loss or aberrant expression of T cell markers, a B cell population (about 32% of the cells analyzed) that is negative for CD5, CD10. The B cells show no surface light-chain restriction.

Immunohistochemical stains, with adequate controls, show a mixture of B cells (CD20-positive) and T cells (CD3-positive). Cells in the follicles are positive for CD20, CD10, and CD23.

AFB and GMS are negative for organisms.

++++++++++++++++++++++++++++++++++++++++++

16. Lumbar epidural lesion/ Left chest wall lesion: diffuse large B-cell lymphoma

DIAGNOSIS:

Lumbar epidural lesion and left chest wall lesion: diffuse large B-cell lymphoma

Microscopic Description

Histologic sections of the lumbar epidural lesion show diffuse infiltration by large lymphocytic cells with irregular nuclear contour, vesicular nuclei with fine chromatin, and one to several nucleoli. Frequent mitotic figures are seen.

Histologic section of left chest wall lesion shows overall architecture of a lymph node. The lymph node is effaced by large lymphocytic cells with features similar to those seen in lumbar epidural lesion. Touch prep shows large lymphocytic cells with similar cytological features.

Immunophenotyping of both the left chest wall lesion and the lumbar epidural lesion by flow cytometry shows a T cell population with no aberrant loss or aberrant expression of T cell markers, a B cell population that is positive for CD19, CD20, CD22, and surface kappa light-chain restriction. They are negative for CD5, CD10, and CD23. These B cells have large nuclear size (based on forward-scatter signal).

Immunohistochemical stains, with adequate controls, performed on lumbar epidural biopsy (2A) show that the neoplastic cells are positive for CD20, and bcl-6. These cells are negative for CD3, and Cyclin D1 (bcl-1). Ki67 shows proliferation rate of about 70%. Normal T cells (positive for CD3) are scattered throughout the section.

Immunohistochemical stains, with adequate controls, performed on the left chest wall biopsy (3A) for CD3 and CD20 show that the neoplastic cells are positive for CD20 and negative for CD5. A small number of small T cells (positive for CD3) are found scattered in the section.

The flow cytometric immunophenotype, morphology, and immunostain findings are consistent with diffuse large B-cell lymphoma.

+++++++++++++++++++++++++++++++++++++++++++++++++

17. RETROPERITONEAL MASS: FL, GR1

Retroperitoneal mass:

-Follicular B-cell lymphoma, grade 1 (out of 3).

Histologic section of the retroperitoneal mass biopsy shows effacement of the lymphoid tissue with poorly-defined neoplastic follicles of varying size. The follicles lack mantle zone and contain mostly centrocytes. Very few centroblasts are present in the follicles.

The provided immunohistochemical stains show that the neoplastic cells in the follicular area are positive for bcl-2, bcl-6, CD20, CD10; and negative for CD5, CD23, and cyclin-D1.

Immunophenotyping of the biopsy by flow cytometry, performed at Clinical Laboratories of Hawaii, Honolulu, HI, reportedly shows a clonal B cell population that is positive for CD19, CD20, CD10 (dim), surface kappa light chain restriction. These B cells are negative for CD5, CD38, CD22, and CD23.

The flow cytometric immunophenotype, morphology, and immunostain findings in this case are consistent with follicular B-cell lymphoma, grade 1/3.

++++++++++++++++++++++++++++++++++++++

18. LUNG and LNs: cHL, mixed cellularity

Diagnosis

1. Right lung:

Classical Hodgkin lymphoma, mixed cellularity

(bronchial margin is free of tumor)

2. Subcarinal lymph node:

Classical Hodgkin lymphoma, mixed cellularity

3. Tracheal bronchial lymph node:

Classical Hodgkin lymphoma, mixed cellularity

4. Anterior hilar lymph node:

Classical Hodgkin lymphoma, mixed cellularity

5. Subcarinal lymph node:

Classical Hodgkin lymphoma, mixed cellularity

6. Right paratracheal lymph node:

Classical Hodgkin lymphoma, mixed cellularity

7. Right vagus nerve:

No pathological changes

8. Anterior mediastinal lymph node:

Classical Hodgkin lymphoma, mixed cellularity

Special stains for acid-fast bacilli and fungi are negative for organisms

Microscopic Description

In specimen 1 from the right lung with bronchial margin, the bronchial margin is found free of tumor. Sections of the right lung biopsy show effacement of normal architecture by abnormal lymphoid tissue. A moderate number of large atypical cells with prominent nucleolus, some with binucleated form are seen throughout the sections. These cells are admixed with an inflammatory background of small lymphocytes, and a small number of neutrophils. A large number of epithelioid histiocytes in clusters are also seen in the sections. No increase in fibroconnective tissue is seen. Touch preps show a predominant small lymphocyte population admixed with a small number of large cells with prominent nucleolus. Immumohistochemical stains, with adequate controls, are performed on block 1A for CD3, CD15, CD20, CD45, and C30. The large atypical cells are positive for CD15, CD30, and negative for CD45, CD3, and CD20 (consistent with the expected pattern for Hodgkin and Reed-Sternberg cells). The small lymphocytes in the background are mostly T cells (CD3-positive) with a smaller number of B cells (CD20-positive).

In specimen 2, 3, 4, 5, 6, 8 from subcarinal lymph node, tracheal bronchial lymph node, anterior hilar lymph node, subcarinal lymph node, right paratracheal lymph node, and anterior mediastinal lymph node, respectively, the lymph nodes show effacement of normal architecture by abnormal lymphoid tissue with the same features as seen in specimen 1 from the right lung. A large number of epithelioid histiocytes in clusters are also seen in the sections. No increase in fibroconnective tissue is seen. Immunohistochemical stains, with adequate controls, are performed on block 8A for CD3, CD10, CD15, CD20, CD23, CD30, CD45, CD57, CD68, and EBER-1 ISH. The large atypical cells are positive for CD15, CD30, and negative for CD45, CD3, and CD20. The small lymphocytes in the background are mostly T cells (CD3-positive) with a smaller number of B cells (CD20-positive). CD23 shows follicular dendritic cells in a small number of residual follicles. CD68 shows a large number of histiocytes throughout the section. CD57 and CD10 are negative. EBER-1 ISH is pending, the result of which will be reported in Addendum.

AFB and GMS stains performed on block 8A show no evidence of organisms.

In specimen 7 from the right vagus nerve, no pathological changes are found.

Immunophenotyping of specimen 1 from the right lung biopsy by flow cytometry shows no abnormal immunophenotypes (typically normal results in flow cytometric studies for classical Hodgkin lymphoma).

The morphological findings, together with immunophenotypes, are most consistent with Classical Hodgkin lymphoma, mixed cellularity.

+++++++++++++++++++++++++++++++++++++++++++

19. REACTIVE LYMPH NODES (follicular hyperplasia, granuloma) WITH FLOW & STAINS

~~~~~ DIAGNOSIS:

Cervical lymph node biopsy:

- Follicular hyperplasia.

- Presence of granuloma; special stains for acid-fast bacilli and fungi are negative for organism

- No evidence of lymphoma

Histologic sections of cervical lymph node show presevation of lymph node architecture. Follicular hyperplasia is noted. The follicles have well-formed mantle zone. Several small foci of granuloma are seen (section 1A). AFB and GMS stains, performed on block 1A, are negative for organisms.

Immunophenotyping of cervical lymph node biopsy by flow cytometry shows a T cell population (about 52% of the cells analyzed) with no aberrant loss or aberrant expression of T cell markers, a high CD4/CD8 ratio (5:1); a B cell population (about 43% of the cells analyzed) that is negative for CD5, CD10, no surface light-chain restriction. These results indicate no abnormal immunophenotypes with flow cytometry.

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20. INGUINAL LYMPH NODE CORE BIOPSIES, CANNOT RULE OUT LYMPHOMA

DX:

Inguinal lymph node: predominant B cells in submitted core biopsies; B-cell lymphoma cannot be ruled out (see comment)

Comment:

The morphological findings, together with immunohistochemical results, are not diagnostic due to the lack of adequate sample for reliable evaluation. In light of the predominant B cell population in the core biopsies , an excisional biopsy is suggested to rule out B-cell lymphoma if clinically indicated.

Histologic sections of left inguinal lymph node show a predominant population of small lymphocytes. The lymphocytes have small nuclei with mature cytological features, admixed with a smaller number of larger lymphocytes. The overall architecture of the lymph node cannot be assessed due to small size of the core biopsies. Aspirate and touch prep also show a predominant population of small lymphocytes.

Immunohistochemical stains, with adequate controls, are performed on block 1 for bcl-1, bcl-2, bcl-6, CD3, CD5, CD10, CD20, and CD23. Most of the lymphocytes are positive for CD20 (B cells), a smaller number of lymphocytes are positive for CD3 and CD5 (T cells). bcl-2 is positive for most of the lymphocytes (more than that expected for T cells alone). CD23 and bcl-6 show focal positivity. Bcl-1 is negative.

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21. LYMPH NODE, FOLLICULAR/PARACORTICAL HYPERPLASIA, FLOW AND IHC

Diagnosis

Left cervical lymph nodes, posterior triangle:

- Follicular and paracortical hyperplasia.

- No evidence of granuloma, necrosis or malignancy.

Microscopic Description

Histologic sections of left cervical lymph nodes show presevation of lymph node architecture. Follicular hyperplasia and paracortical hyperplasia are noted. The follicles have well-formed mantle zone and reactive germinal center. No evidence of granuloma or necrosis is seen. A small number of large cells (immunoblasts) are found admixed with lymphocytes in the paracortical area.

Immunophenotyping of cervical lymph node biopsy by flow cytometry shows a T cell population (about 58% of the cells analyzed) with no aberrant loss or aberrant expression of T cell markers, a B cell population (about 43% of the cells analyzed) that is negative for CD5, CD10, also no surface light-chain restriction.

Immunohistochemical stains, with adequate controls, are performed on block 1A for CD3, CD15, CD20, CD30, and CD45 (leukocyte common antigen). Normal distribution of T cells and B cells are demonstrated with CD3, and CD20, respectively. Immunoblasts and granulocytes/histiocytes are postive for CD30 and CD15, respectively. Histiocytes and immunoblasts are also positive for CD45.

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22. MEDIASTINAL MASS: NON-DIAGNOSTIC DUE TO NECROSIS

- Pericardum: focal lymphocytic infiltrate with necrosis, see comment

- Mediastinal mass: lymphocytic infiltrate with necrosis, see comment

Comment

A marked degree of necrosis is found in the lymphoid infiltrate which masks the morphology and also renders immunophenotyping non-diagnostic (flow cytometry and immunohistochemical stains).

Microscopic Description

Histologic section of pericardium shows a focal lymphoid aggregate. The lymphocytes have small nuclei and are degenerated with necrotic features.

Histologic section of mediastinal mass shows diffuse distribution of small lymphocytes. They also have small nuclei and show a marked degree of necrosis.

An immunohistochemical stain, with adequate controls, is performed on blocks 1A and 2A for TdT and on block 2A for CD2, CD5, CD20, and Ki-67. Many lymphocytes are positive for CD2 and negative for CD20. Other stains (CD5, Tdt, and Ki-67) show scattered positivity with much background artifacts, most likely due to necrosis.

Immunophenotyping of mediastinal mass by flow cytometry is not diagnostic due to failure to obtain intact lymphocytes for analysis, most likely due to necrosis.

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23. SUPRACLAVICULAR LN: CLASSICAL HL, NS SYNCYTIAL VARIANT

DIAGNOSIS:

Supraclavicular lymph nodes: Nodular sclerosis classical Hodgkin lymphoma

Comment:

Due to the presence of prominent aggregates of Hodgkin and Reed-Sternberg cells, this case may also be described as syncytial variant of nodular sclerosis classical Hodgkin lymphoma.

CPT: 88305-GC, 88342-26x10, 88342-TCx10

MICROSCOPIC DESCRIPTION:

Histologic sections of the lymph nodes show effacement of architecture. A nodular pattern is seen with collagen bands surrounding the nodules. Prominent aggregates of large atypical cells with prominent nucleoli, some with binucleated / multinucleated form and lacunar form, are seen throughout the sections. These cells are admixed with an inflammatory background of small lymphocytes, macrophages, and neutrophils.

Immumohistochemical stains, with adequate controls, are performed on block 1A for CD3, CD4, CD5, CD8, CD15, CD20, C30, ALK-1, bcl-6, and Ki-67. The large atypical cells are positive for CD15, CD30 (both with a membrane-Golgi pattern), and negative for CD3, CD4, CD5, CD8, CD20, ALK-1 (consistent with the pattern for Hodgkin and Reed-Sternberg cells). The small lymphocytes in the background are mostly T cells (positive for CD3, CD5, and CD4 or CD8) with a smaller number of B cells (CD20-positive).

Immunophenotyping of the lymph node biopsy by flow cytometry shows no abnormal immunophenotypes (typically seen in flow cytometric studies for classical Hodgkin lymphoma which analyze the background lymphocytes).

++++++++++++++++++++++++++++++++++++++++++

24. Benign lymphoid aggegates

Diagnosis

- XXXX biopsies: a few small focal benign lymphoid aggregates.

Microscopic Description

Histologic sections of XXXX biopsies show a few focal lymphoid aggregates. The aggregates are small and consist of small lymphocytes with mature cytological features.

Immunohistochemical stains, with adequate controls, are performed on blocks 1A and 2A for CD2, CD3, CD5, CD10, CD20, and CD23. The lymphocytes show a mixture of T cells (positive for CD2, CD3, CD5) and B cells (positive for CD20). They are negative for CD10. Immunostain CD23 shows scattered positivities. The heterogenous mixture of T cells and B cells in the small lymphoid aggregates favors benign lymphoid cells.

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25. AORTIC WALL: SLL

Diagnosis

- Aortic wall biopsies: a few small foci of small lymphocytic lymphoma infiltrate, see comment.

Comment

The cytological features and immunophenotypic profile of the lymphoma cells in the focal infiltrates are identical to those found in previous aortic wall biopsy (surgical pathology report HS-9-103, issued 1/9/2009).

Microscopic Description

Histologic sections of aortic wall biopsies (1A and 2A) show a few focal lymphoid aggregates. The aggregates are small and consist of small lymphocytes with mature cytological features. The clot section (2B) shows fibrin clot containing erythrocytes, neutrophils and lymphocytes.

Immunohistochemical stains, with adequate controls, are performed on blocks 1A and 2A for CD2, CD3, CD5, CD10, CD20, and CD23. The lymphocytes in the lymphoid aggregates are positive for CD5, CD20, CD23, and negative for CD10. A small number of T cells (positive for CD2, CD3, CD5) are found scattered in the lymphocytic aggregates. The number of CD5-positive cells accounts for both (lymphoma) B cells and (reactive) T cells.

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26. ORBITAL MASS: FL, Gr 3

DIAGNOSIS:

- Right orbital mass: follicular lymphoma, grade 3 (out of 3)

CPT: 88307-GC, 88342-26x11, 88342-TCx11

Microscopic Description

Touch prep of orbital mass biopsy shows presence of a mixture of small lymphocytes with mature cytological features, and many intermediate-large lymphocytes with scant cytoplasm, vesicular nuclei and one to several nucleoli.

Histologic sections of the orbital mass biopsy show many poorly-defined neoplastic follicles of varying size. The follicles lack a well-defined mantle zone and contain mostly centroblasts with intermediate-large size, vesicular nuclear chromatin pattern and one to several nucleoli. Tingible-body macrophages and mitotic figures are also seen in the follicles.

Immunohistochemical stains, with adequate controls, are performed on block 1A for bcl-2, bcl-1, CD3, CD10, CD20, CD5, CD23, CD15, CD30, CD57, and Ki-67. The neoplastic cells in the follicles are positive for bcl-2, CD20, and CD10 (partial positivity). They are negative for bcl-1, CD3, and CD5. Ki-67 shows approximately 30% proliferation rate with even distribution in the follicles. CD23 shows residual follicular dendritic cells in the follicles. CD15 and CD30 show scattered positivity. CD57 is negative.

Immunophenotyping of the orbital mass biopsy by flow cytometry shows a T cell population (about 14% of the lymphocytes analyzed) with no aberrant loss or aberrant expression of T cell markers, a prominent B cell population (about 86% of the cells analyzed) that is positive for CD19, CD20, CD22, FMC7, surface kappa light chain restriction (dim), and cytoplasmic kappa light chain restriction. These B cells are negative for CD5, and CD10. The negative finding of CD10 corresponds to the small number of neoplastic cells expressing CD10 seen in immunohistochemical stains (see description above). These B cells have intermediate-large nuclear size (based on forward-scatter signal).

The morphology and immunophenotyping (by immunohistochemical stains and flow cytometry) are consistent with follicular lymphoma (grade 3 out of 3)

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27. RETROPENITONEAL LYMPH NODE: DLBCL, ANAPLASTIC VARIANT

DIAGNOSIS:

Retroperitoneal lymph node core biopsies:

Diffuse large B-cell lymphoma, anaplastic variant

CLINICAL INFORMATION:

65 year-old female with retroperitoneal lymphadenopathy.

SPECIMEN SUBMITTED:

Received from Tissue Laboratory of the Park Plaza Hosptial, Houston, TX are 32 slides labeled Pathology Park Plaza and tissue block labeled 06-03290. Also submitted is a pathology report on patient Alicia Demetriou,accession # S06-03290, and patient demographics information.

GROSS DESCRIPTION:

See Tissue Laboratory of the Park Plaza Hospital report S-06-03290.

MICROSCOPIC DESCRIPTION:

Histologic sections of the core biopsies show a diffuse lymphocytic infiltration consisting of large cells with pleomorphic nuclei. Many have one to several prominent nucleoli. Multinucleated cells are also seen. The large malignant cells are admixed with a large number of small lymphocytes with mature cytological features. Touch preps show many pleomorphic large cells, some multinucleated, admixed with small mature lymphocytes.

Immunohistochemical stains, with adequate controls, show that the neoplastic large cells are positive for CD79a, bcl-2, Pax-5, CD30 (no membrane-golgi pattern seen), Oct-2, bcl-6, MUM1, Vimentin, Ki-67 (40-50%). There is a focal area with large cells positive for CD20. The malignant cells are negative for CD15, bcl-1, CD5, CD10, CD43, CD3, CAM5.2/AE-1, BOB-1, and S-100. Aberrant loss of CD45 is also seen in the large cells.

The morphology and immunophenotypes are most consistent with diffuse large B-cell lymphoma, anaplastic variant

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28. THORACIC SPINE MASS: PLASMACYTOMA (IN MM)

DIAGNOSIS:

Thoracic mass: multiple myeloma

MICROSCOPIC DESCRIPTIONS:

Histologic sections of the thoracic mass biopsy (blocks 1A and 2A) show diffuse infiltration with plasma cells. Most of the plasma cells have small nuclei with mature cytological features. Some variation in cell size and irregular nuclear contour are noted. A small subset of plasma cells have large nuclei with prominent nucleolie. Touch preps show many plasma cells with the described cytological features.

Sections from block 3A show infiltrates of plasma cells and also foci of bone marrow. Normal bone marrow is seen together with sheets of plasma cells in some bone marrow areas.

Immunophenotyping of spinal mass biopsy by flow cytometry shows a large monoclonal plasma cell population (about 70% of the cells analyzed) that is positive for CD56, CD38, CD20 (partial expression), and cytoplasmic Lambda light-chain restriction. These plasma cells are negative for CD19.

The immunophenotype results, together with morphology findings and recent diagnosis of multiple myeloma, are consistent with multiple myeloma involvement in the thoracic spine.

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29. ORBITAL MASS: PLSMACYTOMA

Diagnosis

1. Left orbital biopsy: plasmacytoma

2. Left orbital tumor: plasmacytoma

3. Left orbital fat: plasmacytoma

Comment

The immunophenotype results, together with morphology findings, are consistent with plasmacytoma in the left orbit. Further testing and clinical correlation are suggested to rule out multiple myeloma in this patients (serum and urine protein electrophoresis and immunofixation, serum quantitative immunoglobulins, serum calcium, CBC, renal function tests, bone marrow aspirate and biopsy, imaging studies to look for lytic lesions).

Microscopic Description

Histologic sections show diffuse infiltration with plasma cells. The plasma cells have small nuclei with mature cytological features. Touch preps show many plasma cells with the described cytological features.

Sections from block 3A and 3B show large infiltrates of plasma cells and also adipose tissue.

Immunophenotyping of orbital mass biopsy by flow cytometry shows a large monoclonal plasma cell population that is positive for CD56, CD38, cytoplasmic Kappa light-chain restriction. These plasma cells are partially positive for CD20 and negative for CD19.

The immunophenotype results, together with morphology findings, are consistent with plasmacytoma in the orbit.

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30. LN: cHL, mixed cellularity with unusual diffuse CD20 pos (extensive IHCs and flow)

25 y/o female

Diagnosis

Left cervical lymph node:

Classical Hodgkin lymphoma, mixed cellularity

Comment:

The morphological findings, together with immunophenotypes, are most consistent with Classical Hodgkin lymphoma, mixed cellularity. The only unusual finding in this case is the diffuse and strong intensity pattern for CD20. Hodgkin and Reed-Sternberg cells, in cases with positivity for CD20, are often associated with a focal and dim intensity pattern. However, “grey-zone” B cell lymphoma (B-cell lymphoma, unclassifiable with features intermediate between diffuse large B cell lymphoma and classical Hodgkin lymphoma) is not under consideration since almost all the immunophenotypic markers for diffuse large B cell lymphoma are not seen in this case (see microscopic description).

Microscopic Description

Sections of the left cervical lymph node biopsy show effacement of normal architecture by abnormal lymphoid tissue. A moderate number of large atypical cells with prominent nucleolus, some with multinucleated form are seen throughout the sections. These cells are admixed with an inflammatory background of small lymphocytes and a moderate number of histiocytes. Rare plasma cells are also seen. No increase in fibroconnective tissue is seen.

Immunohistochemical stains are performed for CD15, CD30, CD20, CD79a, PAX5, CD3, CD5, CD7, CD8, CD10, CD45, CD68, Cyclin-D1, bcl-2, bcl-6, MUM-1, EMA, CD21, BOB1, OCT2, ALK-1, EBV-LMP1, and Ki67. The large atypical cells are positive for CD30 (many with membrane-Golgi pattern), CD20 (strong intensity), PAX5 (dim intensity), MUM1, OCT2, EBV-LMP1, and Ki67. They are negative for CD15, CD79a, CD45, EMA, BOB1, ALK-1, CD3, CD5, CD7, CD8, CD10, Cyclin-D1, bcl-2, bcl-6. The background lymphocytes are mostly T cells that are positive for T cell markers (CD3, CD5, and CD7). The histiocytes are positive for CD68. Residual follicles show CD21 positivity of the follicular dendritic cells. The immunohistochemical stain pattern is most consistent with the expected pattern for Hodgkin and Reed-Sternberg cells. The only unusual finding is the diffuse and strong intensity pattern for CD20. Hodgkin and Reed-Sternberg cells, if positive for CD20, are often associated with focal and dim pattern.

Immunophenotyping of lymph node biopsy by flow cytometry reportedly showed no abnormal immunophenotypes (typically seen in classical Hodgkin lymphoma and not diffuse large B cell lymphoma).

The morphological findings, together with immunophenotypes, are most consistent with Classical Hodgkin lymphoma, mixed cellularity.

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31. Submaxillary LN: atyp lymphoid tissue suspicious for cHL

Diagnosis

Submaxillary lymph node (1C, T1):

Follicular hyperplasia

Submaxillary lymph node (1A):

Paracortical hyperplasia with atypical lymphoid tissue (see comment)

Submaxillary salivary gland (1B):

No pathological changes

Breast tissue (3A-3C, T2, T3):

Gynecomastia

Comment:

The morphological findings, together with immunophenotypes, of the atypical cells in block #1A are suggestive of classical Hodgkin lymphoma. However, B-immunoblasts (positive for CD30 and CD20) seen in reactive condition, cannot be ruled out. Since the available immunohistochemical stains are inadequate for a definitive diagnosis, we would like to obtain the original specimen (block# 1A) for additional stains. Addendum to this report will be issued once additional stains are available.

Microscopic Description

Sections of the breast tissue (blocks #3A-3C, T2, T3) show terminal ducts lined by multilayered epithelium. The ducts are surrounded by periductal hyalinization and fibrosis.

Sections of submaxillary salivary gland (1B) show normal salivary glands with no pathological changes.

Sections of the submaxillary lymph node biopsy (block # 1C, T1) show follicular hyperplasia. The follicles are increased in number and size, with prominent follicular center. The follicles exhibit considerable variation in size and shape. The mantle zone of the follicles is well defined. The germinal centers contain mitoses and tingible-body macrophages. No granuloma or necrosis is seen.

Sections of the submaxillary lymph node biopsy (block # 1A) show a small number of follicles and paracortical hyperplasia. A moderate number of large atypical cells with prominent eosinophilic nucleolus, some with multinucleated form are seen throughout the sections. These cells are admixed with a background of small lymphocytes. No increase in fibroconnective tissue is seen.

Immunohistochemical stains are performed on block #1A for CD30, CD20, CD3, bcl-2, CD34, EBV-LMP1, and Ki67. The large atypical cells are positive for CD30 (many with membrane-Golgi pattern), CD20, and Ki67. They are negative for CD3, bcl-2. The background lymphocytes are mostly T cells that are positive for T cell markers (CD3 and bcl-2). The B cells in follicles are positive for CD20. EBV-LMP1 is negative.

The morphological findings, together with immunophenotypes, of the atypical cells in block #1A are suggestive of classical Hodgkin lymphoma. However, B-immunoblasts (positive for CD30 and CD20) seen in reactive condition, cannot be ruled out. In order to have a definitive diagnosis, we would like to obtain the original sample (block#1A ) for additional stains. Addendum to this report will be issued after additional stains are available.

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32. Submaxillary LN: atyp lymphoid tissue with B immunoblasts mimicking cHL

Diagnosis

Submaxillary lymph node (1C, T1):

Follicular hyperplasia

Submaxillary lymph node (1A):

Paracortical hyperplasia

Submaxillary salivary gland (1B):

No pathological changes

Breast tissue (3A-3C, T2, T3):

Gynecomastia

Microscopic Description

Sections of the breast tissue (blocks #3A-3C, T2, T3) show terminal ducts lined by multilayered epithelium. The ducts are surrounded by periductal hyalinization and fibrosis.

Sections of submaxillary salivary gland (1B) show normal salivary glands with no pathological changes.

Sections of the submaxillary lymph node biopsy (block # 1A) show a small number of follicles and paracortical hyperplasia. A small number of large cells with prominent nucleolie are found admixed with lymphocytes in the paracortical area. No increase in fibroconnective tissue is seen.

The submitted immunohistochemical stains are performed on block #1A for CD30, CD20, CD3, bcl-2, CD34, EBV-LMP1, and Ki67. The atypical large cells are positive for CD30, CD20, and Ki67. They are negative for CD3, bcl-2. The background lymphocytes are mostly T cells that are positive for T cell markers (CD3 and bcl-2). The B cells in follicles are positive for CD20. EBV-LMP1 is negative.

Additional immunohistochemical stains, with adequate controls, are performed at the University of Texas-Medical School at Houston on block 1A for CD3, CD15, CD20, CD30, CD45 (LCA), CD79a, PAX-5, and EBER-1 in-situ hybridization. The atypical large cells are positive for CD20, CD30, CD45, CD79a,and PAX5. They are negative for CD3, CD15. EBER is negative. Normal distribution of T cells (pos for CD3) and B cells (pos for CD20 and CD79a) is seen in the section.

The morphological findings, together with immunophenotypes, of the atypical cells in block #1A are consistent of B-immunoblasts, typical seen in reactive conditions with paracortical hyperplasia.

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33. ABNOMINAL MASS: FL, Gr 1

DIAGNOSIS:

1 Abdominal mass core biopsy: follicular lymphoma, grade 1 (out of 3)

2 Ascending colon polyp biopsy: hyperplasic polyp

3 Rectal polyp biopsy: hyperplasic polyp

4 Submucosal mass biopsy in the rectum: hyperplasic polyp

Microscopic Description

1. Abdominal mass (Outside case BSA-09-03057):

Histologic sections of the abdominal mass core biopsy show infiltration by small lymphocytes with mature cytological features, without prominent nucleoli. Some lymphocytes have irregular nuclear contour. No increase in mitosis is found. Due to the small size of the specimen, overall architecture of the lymphoid tissue cannot be assessed. Subsequently, follicular pattern of the lymphoid tissue, if present, cannot be observed.

Immunophenotyping of the abdominal mass biopsy by flow cytometry (by TRICOR) reportedly showed a clonal B-cell population (47% of the analyzed cells) co-expressing CD10, CD19, CD20, FMC-7 with surface kappa light-chain restriction. These B cells are negative for CD5.

Immunohistochemical stains, with adequate controls, are performed on block A1 (at University of Texas-Medical School Laboratory) for bcl-2, CD10, CD20, CD5, and bcl-1. The neoplastic cells are positive for bcl-2, CD20, and CD10. They are negative for bcl-1. Scattered positivity for CD5 is seen with reactive T cells.

The morphology and immunophenotyping (by immunohistochemical stains and flow cytometry analysis) are most consistent with follicular lymphoma (grade 1 out of 3).

2. Ascending colon polyp biopsy, rectal polyp biopsy, submucosal mass biopsy in the rectum (outside case S-ADE-2009-399):

Histologic sections show hyperplasic polyps consisting of well-formed glands and crypts lined by benign epithelial cells, many of which are goblet cells. Small foci of benign lymphocytic aggregates are seen in the lamina propria. No evidence of malignancy is seen.

++++++++++++++++++

34. Thoracic BX (T11): Bone marrow with FL, GR1

DIAGNOSIS:

Thoracic (T11) core biopsy: follicular lymphoma, grade 1 (out of 3)

COMMENTS:

The T11 core biopsy shows bone marrow tissue with trabecular bone. The marrow is diffusely infiltrated by follicular lymphoma. These findings indicate bone marrow metastasis by follicular lymphoma. Further investigation (especially with imaging) is suggested to detect the primary site of lymphoma.

MICROSCOPIC:

Histologic section of the T11 needle biopsy shows bone marrow tissue with trabecular bone. The bone marrow is diffusely infiltrated with small lymphocytes. The lymphocytes have mature cytological features, some with irregular nuclear contour.

Immunohistochemical stains, with adequate controls, are performed on block 1A for bcl-1, bcl-2, CD3, CD10, CD20, and Ki-67. Immunohistological stains show that the lymphocytes are positive for bcl-2, CD20, CD10; and negative for CD3, and bcl-1. Ki-67 shows approximately 15% proliferation rate.

Immunophenotyping of thoracic core biopsy by flow cytometry shows a T cell population (about 14% of the cells analyzed) with no aberrant loss or aberrant expression of T cell markers, a prominent B cell population (about 84% of the cells analyzed) that is positive for CD19, CD20, CD22, CD10, FMC7, and surface kappa light chain restriction. These B cells are negative for CD5, and CD23. These B cells have small nuclear size (based on forward-scatter signal).

The flow cytometric immunophenotype, morphology, and immunostain findings in this case are consistent with follicular B-cell lymphoma, grade 1 (out of 3).

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35. Left inguinal lymph node biopsy: Angioimmunoblastic T cell lymphoma

DIAGNOSIS:

Left inguinal lymph node biopsy:

Angioimmunoblastic T cell lymphoma

MICROSCOPIC DESCRIPTION:

Histologic sections of the lymph node biopsy show effacement of lymph node architecture with a polymorphous population of small to medium-sized malignant lymphocytes. The lymphocytes have abundant clear cytoplasm, most with minimal cytologic atypia. Prominent arborizing blood vessels (high endothelial venules) are also seen throughout the sections. The malignant cells are admixed with a small number of histiocytes, eosinophils, and plasma cells. Focal infiltration of lymphocytes into adjacent adipose tissue is also seen.

Immunohistochemical stains, with adequate controls, are performed on block 2D for bcl-2, CD3, CD4, CD5, CD7, CD8, CD10, CD20, and CD23. Also performed on block 2D, with adequate controls, is in-situ hybridization for EBER-1. The malignant cells are positive for CD3, CD4, CD5, CD10, and bcl-2. They are negative for CD7 (aberrant loss of a T-cell marker), and CD20. A small number of CD8-positive lymphocytes are also seen. Proliferation of follicular dendritic cells is shown with CD23.

Immunophenotyping of lymph node lymphocytes in gate #2 (small lymphocytes) by flow cytometry shows a T cell population (about 52% of the cells analyzed) with aberrant loss of CD7 (a T-cell marker), a B cell population (about 33% of the cells analyzed) that is negative for CD5, CD10, no surface light-chain restriction. Analysis of the cells in the gate #1(a smaller number of lymphocytes with intermediate size) shows a T cell population (about 56% of the cells analyzed) also with aberrant loss of CD7, a B cell population (about 20% of the cells analyzed) that is negative for CD5, CD10, no surface light-chain restriction.

The morphology and immunophenotypes are most consistent with angioimmunoblastic T cell lymphoma.

EBER-1 is pending. Result wil be reported in Addendum.

***ADDENDUM:

Left neck lymph node biopsy:

Angioimmunoblastic T cell lymphoma

Positive for EBV (see comment)

COOMENT

In-situ hybridization for EBER-1 on block 2D shows positivity in a few lymphocytes in the section. Note that EBV infection is a common finding in angioimmunoblastic T cell lymphoma.

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36. Left inguinal lymph node biopsy: cHL- mixed cellularity mimicking AITCL

DIAGNOSIS:

Left inguinal lymph node biopsy: classical Hodgkin lymphoma, mixed cellularity

MICROSCOPIC:

Histologic sections of the lymph node show effacement of architecture. A moderate number of large atypical cells with prominent nucleolus, some with multi-nucleated form are seen throughout the sections. These cells are admixed with an inflammatory background of small lymphocytes, a few eosinophils, macrophages, neutrophils, and plasma cells. No broad bands of fibrosis are seen in the sections. Portions of the capsule seen in the sections are intact and of normal thickness. Prominent proliferation of blood vessels is also seen throughout the sections.

Immunohistochemical stains, with adequate controls, are performed on block 1B for CD3, CD4, CD8, CD10, CD15, CD20, CD23, CD30, and ALK-1 protein. Also performed on block 1B, with adequate controls, is EBER-1 in-situ hybridization. The large atypical cells are positive for CD15, CD30 (both with membrane-golgi pattern), and negative for CD3, CD20, CD10, CD4, CD8, and ALK-1 (consistent with the expected pattern for Hodgkin and Reed-Sternberg cells). The small lymphocytes in the background are mostly T cells (CD3-positive, more CD4-positive cells than CD8-positive cells) with a smaller number of B cells (CD20-positive). The T cells are also negative for CD10. EBER-1 shows positivity in a small number of small lymphocytes. CD23 shows no proliferation of follicular dendritic cells.

The morphology and immunophenotypes are consistent with classical Hodgkin lymphoma, mixed cellularity. Note that angioimmunoblastic T-cell lymphoma is considered as a differential diagnosis in this case due to prominent proliferation of blood vessels but subsequently is ruled out with the given immunohistochemical stains.

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37. Omentum, partial omentectomy: Benign lymphoid tissue with primary follicles

Omentum, partial omentectomy:

- Acute fascitis and tissue necrosis.

- Benign lymphoid tissue with primary follicles (see comment)

Comment

Lymphoid tissue is seen in the omentum biopsy with ill-defined follicular pattern. The follicles are few in number, small in size and spaced apart from each other. The lymphocytes in the follicles are small with mature cytological features, admixed with follicular dendritic cells. No well-defined mantle zone is seen in the follicles. The surrounding lymphocytes are also small with mature cytological features.

An immunohistochemical stain, with adequate positive controls, is performed on block 3A for bcl-1, bcl-2, CD3, CD4, CD5, CD8, CD10, CD20, CD23, and bcl-6. The cells in the follicles are positive for CD20, and bcl-2. They are negative for CD10, CD5, bcl-1, CD3, CD4, CD8, and bcl-6. The surrounding lymphocytes are positive for bcl-2, CD5, CD3, and mixture of CD4 and CD8-positivity. Follicular dendritic cells in the follicles are postive for CD23.

The histology and immunostains are consistent with benign lymphoid tissue containing primary follicles.

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38. LN: DLBCL and FL, Gr 2

Diagnosis

- Right femoral lymph node:

Diffuse large B-cell lymphoma and follicular lymphoma, grade 2 out of 3, with focal areas of grade 3

- Left femoral lymph node:

Follicular lymphoma, grade 2 out of 3, with focal areas of grade 3

Comment

The histology suggests transformation of follicular lymphoma to diffuse large B-cell lymphoma. Dr. Khan was notified of the findings by phone on 9/18/09.

Specimen Source

1. right femoral lymph node; 2. Left femoral lymph node

Clinical Information

Clinical History: abdominal aortic aneurysm

Operative Procedure: endovascular aortic repair

Operative Findings: same

Gross Description

Specimen 1 is received in formalin in a container labeled with the patient's name, medical record number and "right femoral lymph node", and is a 3.8 x 2.5 x 1.5 cm fragment of tan-yellow fibrofatty tissue. On sectioning the cut surface reveals tan-pink surface with a few areas of yellow fatty tissue. The entire specimen is submitted in cassettes 1A-1E.

Specimen 2 is received in formalin in a container labeled with the patient's name, medical record number and "left femoral lymph node", and contains a 1.6 x 1.0 x 1.0 cm fragment of lymph node. The cut surface reveals a tan-white surface with areas of hemorrhage. The entire specimen is submitted in cassettes 2A-2B. B. Stewart, M.D./ddw 9/14/2009 13:47

7 blocks, 7 H&E

Microscopic Description

Histologic sections of the right femoral lymph node show effacement of the normal lymph node architecture with malignant cells. Both diffuse and follicular patterns are seen. In 1C, 1D, 1E, about 60% of the examined area shows diffuse infiltration by malignant cells with intermediate-large size, with vesicular nuclei and one to several nucleoli. Frequent mitotic figures are seen. About 40% of the examined area shows poorly-defined neoplastic follicles of varying size. The follicles lack mantle zone and contain mixture of centrocytes and centroblasts. In 1B, only diffuse infiltration of large malignant cells are seen. In 1A, small foci of lymphocytic infiltrates are seen.

Sections of the left femoral lymph node (2A, 2B) show only follicular pattern similar to that found in the right femorallymph node.

Immunohistochemical stains, with adequate controls, are performed on block 1D for bcl-1, bcl-2, bcl-6, CD3, CD5, CD10, CD20, CD23, and Ki-67. The neoplastic cells (in the follicular area and also in the diffuse area) are positive for bcl-2, CD20, CD10, bcl-6; and negative for CD3, CD5, and bcl-1. Ki-67shows approximately 40-50% proliferation rate. CD3 and CD5 show a small number of normal T cells surrounding the neoplastic follicles. Residual follicular dendritic cells in the follicles are positive for CD23.

The morphology and immunophenotyping are consistent with diffuse large B-cell transformed from follicular lymphoma (grade 2/3 with focal areas with grade 3)

The referenced immunohistochemical stains were performed at the University of Texas - Houston Medical School Pathology Histology Laboratory.

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39. SCALP BIOPSY: Cutaneous FL, Gr 3

DIAGNOSIS:

- Biopsy of the right scalp: follicular lymphoma, grade 3 (out of 3) with focal area of grade 2

COMMENT: the expression of bcl-6 in the malignant cells in the setting of negative staining for CD10 and bcl-2 is characteristic of cutaneous follicular lymphoma (versus nodal follicular lymphoma with metastasis to scalp tissue). Clinical correlation is suggested. Findings were notified to Dr. Sean Boutros on 10/01/2009.

Microscopic Description

Histologic sections of the right scalp biopsy show lymphoid tissue with many poorly-defined neoplastic follicles of varying size. The follicles lack a well-defined mantle zone and contain mostly centroblasts with intermediate-large size, vesicular nuclear chromatin pattern and one to several nucleoli. A few follicles with mixture of small lymphocytes and centroblasts are also seen focally. A few tingible-body macrophages and mitotic figures are also seen in the follicles. Sensory nerve is also seen embedded in the lymphoid tissue. The margins are negative for tumor cells.

Immunohistochemical stains, with adequate controls, are performed on block 1C for bcl-2, bcl-1, CD3, CD10, CD20, CD5, CD23, bcl-6, and Ki-67. The neoplastic cells in the follicles are positive for CD20, and bcl-6. They are negative for bcl-2, CD10, bcl-1, CD3, and CD5. Ki-67 shows approximately 30% proliferation rate with even distribution in the follicles. CD23 shows residual follicular dendritic cells in the follicles. Normal T cells (positive for CD5, CD3, and bcl-2) are found in areas between the follicles.

The morphology immunohistochemical stains are consistent with follicular lymphoma (grade 3 out of 3) with focal areas of grade 2

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40. Anaplastic large cell lymphoma, ALK positive

1. Soft tissue right distal radius, excisional biopsy:

- Anaplastic large cell lymphoma, ALK positive

2. Soft tissue, left axillary lesion, excisional biopsy:

- Anaplastic large cell lymphoma, ALK positive

Microscopic Description

Histologic sections of the left axillary lesion show diffuse infiltration by intermediate-large cells with irregular nuclear contour, vesicular nuclei with fine chromatin, and one to several nucleoli. Some cells have horseshoe-shaped morphology. Frequent mitotic figures are seen. A small number of histiocytes, neutrophils, small lymphocytes, and plasma cells are seen admixed with the malignant cells. Histologic sections of the right distal radius lesion show similar diffuse infiltration by intermediate-large cells admixed with a larger number of inflammatory cells. AFB and GMS stains for the right distal radius lesion show no evidence of organisms.

Immunohistochemical stains, with adequate controls, are performed on block 1A for CD3, CD4, CD30 (ki-1), ALK-1, TdT; blocks 2B and 2C for CD1a and S100 protein; and on 2B for CD3, CD4, CD8, CD20, CD30, CD68, ALK-1, TdT, and myeloperoxidase.

The malignant cells are positive for CD3, CD4, CD30, ALK-1, and negative for CD1a, S-100, CD8, CD20, CD68, TdT, and myeloperoxidase. CD30 stain shows membrane-golgi pattern and ALK-1 stain shows nuclear-cytoplasmic pattern in the malignant cells. A small number of normal cells are seen throughout the sections: small lymphocytes (positive for CD8), histiocytes (positive for CD68 and CD4), and neutrophils (positive for myeloperoxidase).

Immunophenotyping of the left axillary mass by flow cytometry shows a predominant population of lymphocytes with intermediate-large nuclear size (based on forward-scatter signal). These cells show expression of CD2, CD3, CD4, and CD7. They also show aberrant loss of CD5. CD8-positive cells account for less than 3% of the lymphocytes.

The morphological findings, together with immunophenotyping by flow cytometry and immunostains, are consistent with anaplastic large cell lymphoma, ALK positive.

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41. NECK MASS: FL, Gr1/3

1. Left posterior auricular lymph node: follicular lymphoma, grade 1 (out of 3)

2. Left neck mass: follicular lymphoma, grade 1 (out of 3)

Microscopic Description

Histologic sections of the left posterior auricular lymph node and left neck mass show many poorly-defined neoplastic follicles of varying size. The follicles lack a well-defined mantle zone and contain mostly centrocytes with small nucei size, and clumped chromatin pattern.

Immunohistochemical stains, with adequate controls, are performed on block 2A for bcl-2, CD10, and CD20. The neoplastic cells in the follicles are positive for bcl-2, CD20, and CD10.

Immunophenotyping of of the left posterior auricular lymph node and left neck mass by flow cytometry shows a T cell population (about 17% of the lymphocytes analyzed) with no aberrant loss or aberrant expression of T cell markers, a prominent B cell population (about 85% of the cells analyzed) that is positive for CD19, CD20, CD22, FMC7, surface kappa light chain restriction. These B cells have small nuclear size (based on forward-scatter signal).

The morphology and immunophenotyping (by immunohistochemical stains and flow cytometry) are consistent with follicular lymphoma (grade 1 out of 3)

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42. LYMPH NODE: HIV PATIENT, PARACORTICAL HYPERPLASIA, FLOW AND IHC

Diagnosis

Left axillary lymph nodes:

- Paracortical hyperplasia

- No evidence of granuloma or lymphoma

- Special stains for acid –fast bacilli and fungi are negative for organisms

Microscopic Description

Histologic sections of left axillary lymph node show paracortical hyperplasia. A small number of large cells (immunoblasts) are found admixed with lymphocytes in the paracortical area. Vascular proliferation is increased throughout the sections. Parts of the capsule are moderately thickened. The follicles are small in number with involuted germinal center, lacking well-formed mantle zone and showing folliculolysis. No evidence of granuloma or necrosis is seen. Special stains for acid–fast bacilli (AFB) and fungi (GMS) are negative for organisms.

Immunophenotyping of left axillary lymph node biopsy by flow cytometry shows a T cell population (about 57% of the cells analyzed) with no aberrant loss or aberrant expression of T cell markers, a B cell population (about 39% of the cells analyzed) that is negative for CD5, CD10, and no surface light-chain restriction.

Immunohistochemical stains, with adequate controls, are performed on block 1A for CD2, CD3, CD4, CD5, CD7, CD8, CD10, CD20, and CD23; and also on block 1A for EBER-1 in-situ hybridization. T cells show normal expression and distribution of CD2, CD3, CD4, CD5, CD7, and CD8. CD20 shows B cells in the follicles which show patterns of folliculolysis. CD23 shows residual follicular dendritic cells in the follicles. CD10 is negative. EBER-1 is pending (result will be reported in Addendum).

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43. TESTICULAR MASS: DLBCL, 43 y/o M, HIV

1. Right testicular mass: Diffuse large B-cell lymphoma (see comment)

Negative for Epstein Barr virus

2. Right testicle: Diffuse large B-cell lymphoma

Comment

Ki-67 shows a high proliferation rate of about 90% in lymphoma cells. Findings were discussed with Dr. Quesada on 11/11/09

Microscopic Description

Histologic sections of the testicular mass (1B-1D) show diffuse lymphocytic infiltration consisting of intermediate-large cells with pleomorphic nuclei. Many have one to several prominent nucleoli. The malignant cells are admixed with a small number of small lymphocytes with mature cytological features. Frequent mitotic figures are seen. Many macrophages with ingested apoptotic tumor cells are found throughout the sections, imparting a "starry sky" pattern. Malignant cells are found at the marked deep margin. Touch preps show many pleomorphic intermediate-large cells, admixed with a small number of mature lymphocytes. The malignant cells have basophilic cytoplasm without vacuoles.

Immunohistochemical stains, with adequate controls, are performed on block 1C for Epstein Barr virus (EBV-LMP*), bcl-1, bcl-2, CD3, CD10, CD20, CD30, ALK-1 protein, and Ki-67. The malignant cells are positive for CD10, and CD20. They are negative for bcl-1, bcl-2, CD3, CD30, and ALK-1. Ki-67 shows a proliferation rate of about 90%. EBV-LMP is negative.

Immunophenotyping by flow cytometry of the testicular biopsy in gate #2 shows a small normal lymphocytic (B cells and T cells) population. Analysis of cells in gate#1 shows a very small T cell population (less than 1% of the cells analyzed), a predominant B cell population (about 99% of the cells analyzed) that is positive for CD10, CD19, CD20, CD22, and surface lambda light-chain restriction. They are negative for CD5, and CD23. These B cells have intermediate-large nuclear

size (based on forward-scatter signal).

The morphology and immunophenotypes of the malignant cells are most consistent with diffuse large B-cell lymphoma.

Histologic sections of the right testicle (2A-2X) show normal testicular tissue with spermatic cord and epididymis except for a focal infiltration of malignant cells (in 2K) with the same cytolgical features as descibed in the testicular mass.

CPT: 88309-GC x 2, 88331-GC x 1, 88187-GC x 1, 88342-26 x 9, 88342-TC x 9

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44. SKIN BX: MYCOSIS FUNGOIDES

DIAGNOSIS:

(R) Abdomen skin biopsy: mycosis fungoides

(L) Abdomen skin biopsy: mycosis fungoides

MICROSCOPIC DESCRIPTION:

Histologic sections of the (R) abdominal skin biopsy and the (L) abdominal skin biopsy show several small epidermotropic infiltrates consisting of small atypical lymphocytes with irregular nuclear contour, and clumped nuclear chromatin. Haloed cells are seen in the basal layer of epidermis. In the dermis, several large lymphocytic aggregates are found, some surrounding the hair follicles and vessels. The cells in the aggregates have morphology similar to that of lymphocytes in the epidermis.

Immunohistochemical stains, with adequate controls, are performed on block 1A

for CD3, CD4, CD8, CD7, CD20, and CD30. The abnormal lymphocytes, in both the epidermis and dermis, are positive for CD3, CD4 and negative for CD7, CD20 and CD30. A small number of CD8-postive lymphocytes and CD20-positive lymphocytes are also seen in the dermis.

The morphology and immunophenotypes of the abnormal lymphocytes are most consistent with mycosis fungoides.

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45. RECTAL POLYPS: MANTLE CELL LYMPHOMA

Diagnosis:

Rectal polyps: mantle cell lymphoma

Histologic sections of the rectal polyps show diffuse infiltration of lamina propria with monomorphic lymphocytes. The lymphocytes have small nuclei with slightly irregular nuclear contour and mature cytological features, admixed with a small number of plasma cells. A few small clusters of lymphocytes (2-4 lymphocytes) are also seen in epithelial glands.

Immunohistochemical stains, with adequate controls, are performed on blocks 1A for CD3, CD20, bcl-1, bcl-2, CD5, CD10, and CD23. The abnormal lymphocytes are positive for CD5, CD20, bcl-2, and bcl-1. They are negative for CD3, CD10, and CD23. Scattered T-lymphocytes (positive for CD3 and CD5) are also seen in tissue sections. The morphology and immunophenotypes of the abnormal B lymphocytes are most consistent with mantle cell lymphoma.

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46. LN: DLBCL, Possible Richter Syndrome

Left supraclavicular lymph node:

Diffuse large B-cell lymphoma with Ki-67 of 50%

Histologic sections of the left supraclavicular lymph nodes (1A and 1C) show effacement of lymph node architecture by an abnormal population of large lymphocytes with irregular nuclear contour, vesicular nuclei with fine chromatin, and one to several nucleoli. Frequent mitotic figures are seen. The large lymphocytes are admixed with a subpopulation of smaller lymphocytes with mature cytological features. Increase in vascular proliferation is seen throughout the sections. No pseudo follicles are seen in sections. Histologic section from 1B shows adipose and fibroconnective tissue and small foci of small lymphocytes with mature cytological features.

Immunohistochemical stains, with adequate controls, are performed on block 1A for bcl-1, CD3, CD4, CD5, CD7, CD8, CD20, CD23, CD79a, CD138, and Ki-67. The abnormal lymphocytes are positive for CD20, CD79a, CD5, and CD23. They are negative for bcl-1 and CD138. Ki-67 shows a proliferation rate of 50%. Scattered T cells (positive for CD3, CD7, CD4 or CD8) are also seen.

The morphology and immunophenotypes are consistent with diffuse large B-cell lymphoma. Expression of CD5 and CD23 in lymphoma cells suggests the possibility of transformation of small lymphocytic lymphoma to diffuse large B-cell lymphoma.

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47. SUPRACLAVICULAR LN: cHL, NS

DIAGNOSIS:

Supraclavicular lymph node: Nodular sclerosis classical Hodgkin lymphoma

Histologic sections of the lymph node show effacement of normal architecture. A nodular pattern is seen with collagen bands surrounding the nodules. Aggregates of large atypical cells with prominent nucleoli, some with binucleated / multinucleated form and lacunar form, are seen in lymphoid tissue throughout the sections. These cells are admixed with an inflammatory background of small lymphocytes, macrophages, eosinophils, and neutrophils.

Immumohistochemical stains, with adequate controls, are performed on block
1B for CD3, CD15, CD20, C30, ALK-1, and CD45. The large atypical cells are positive for CD15, CD30 (both with a membrane-Golgi pattern), and negative for CD3, CD20, CD45, and ALK-1 (consistent with the pattern for Hodgkin and Reed-Sternberg cells). The small lymphocytes in the background are mostly T cells (positive for CD3) with a smaller number of B cells (CD20-positive).

The morphology and immunophenotypes of the abnormal cells are consistent with classical Hodgkin lymphoma, nodular sclerosis subtype.

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48. FACIAL MASS: CUTANEOUS MZL

Left facial mass, inferior to lower lid:

Marginal zone (B cell) lymphoma

MICROSCOPIC DESCRITION:

Histologic sections of the facial mass biopsy shows areas with diffuse infiltration by small lymphocytes. No epidermis is identified in the sections. The small lymphocytes have mature cytological features, some with cleaved nuclei, and some with monocytoid features.

Immunohistochemical stains, with adequate controls on block A1, shows that the lymphocytes are predominantly B cells, positive for CD20 and partially positive for bcl-2. They are negative for CD3, CD4, CD8, CD5, CD7, CD23, CD10, bcl-6 and bcl-1. A small number of T lymphocytes are shown with T cell markers (CD3, CD4 or CD8, CD5, and CD7).

The morphological and immunophenotypic findings are most consistent with marginal zone (B cell) lymphoma.

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49. SKIN BX: panniculitis-like T cell lymphoma

Skin punch biopsy, abdominal wall:

Subcutaneous panniculitis-like T cell lymphoma

Microscopic description:

Histologic sections of the abdominal wall biopsy show normal epidermis and dermis. The subcutaneous tissue is diffusely infiltrated by abnormal lymphocytes that involve that fat lobules. The lymphocytes have irregular and hyperchromatic nuclei which are intermediate-large in size. Apoptotic debris, a few plasma cells, and mitotic figures are also seen. Many lymphocytes are found rimming the adipose cells.

Immunohistochemical stains, with adequate controls on block 1A, shows that the abnormal lymphocytes are positive for CD3 and TIA. They aberrantly lose expression of CD5. They are also negative for CD10, CD56, CD20, TdT, CD30. Kappa and lambda show a small number of polyclonal B cells.

The morphological and immunophenotypic findings are most consistent subcutaneous panniculitis-like T cell lymphoma, typically positive for CD8 (the submitted immunostains do not include CD8). T-cell receptor gene rearrangement (PhenoPath, Seattle, Washington, 1/21/09) reportedly showed T cell clonality

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50. LN; BURKITT LYMPHOMA, IHC and FLOW

Left lymph node biopsy:

Burkitt lymphoma

Comment

Patient's bone marrow was also involved by Burkitt lymphoma (please refer to report HB-10-43, issued on 3/5/10). Bone marrow aspirate was sent for cytogenetics and C-MYC mutation by FISH testing.

Microscopuc description:

Histologic sections of the left lymph node show diffuse infiltration of intermediate-size cells with vesicular nuclei and one to several nucleoli. Frequent mitotic figures are seen. Numerous macrophages with ingested apoptotic tumor cells are found throughout the sections, imparting a "starry sky" pattern.

Touch preps (diff-quik) show numerous abnormal lymphocytes. These lymphocytes have intermediate nuclear size, prominent nucleoli, basophilic cytoplasm with many vacuoles.

Immunohistochemical stains, with adequate controls, are performed on block 1D for bcl-1, bcl-2, bcl-6, CD5, CD10, CD20, and Ki-67. Also performed on block 1D, with adequate control, is chromogenic in-situ hybridization for EBER-1. Immunohistochemical stains show that the neoplastic cells are positive for CD20, CD10, bcl-6, and Ki67 (proliferation rate approaching 100%). They are negative CD5, bcl-1, and bcl-2. EBER-1 is pending (the result will be reported in Addendum)

Immunophenotyping of lymph node biopsy by flow cytometry shows an abnormal B cell population (about 99% of the lymphocytes gated) that is positive for CD19, CD20, CD22, CD10, FMC7, and surface lambda light chain restriction. These B cells are negative for CD5, and CD23. These B cells are predominantly intermediate in size (based on forward-scatter signal)

The immunophenotypic results, together with morphological findings in lymph node biopsy, are consistent with Burkitt lymphoma

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51. Left groin mass, biopsy: Atypical lymphoid follicles resembling NLPHL

Left groin mass, biopsy:

Atypical lymphoid follicles, favoring reactive lymph node (see comments)

Findings were notified to Dr. Wilson on 4/21/10.

Atypical lymphoid follicles are seen in lymph node biopsy. However, no evidence of lymphoma is seen with immunophenotyping. Features of progressive transformation of germinal centers (PTGC) are seen in this biopsy, and it is recommended that this patient be followed up since there is a higher risk of development of nodular lymphocyte predominant Hodgkin lymphoma in patients with PTGC.

Intradepartmental consultation: Dr. M. Uthman

Histologic sections of the left groin mass show lymph node tissue with ill-defined large follicles admixed with a few small reactive follicles. The large follicles show predominantly small mature lymphocytes with a small number of residual cells in the germinal center (follicular dendritic cells, histiocytes, centrocytes, and centroblasts). There are also a small number of large and atypical cells in the follicles. A few follicles also show folliculolysis. Prominent arborizing blood vessels (high endothelial venules) are also seen throughout the sections.

Immunohistochemical stains, with adequate controls, are performed on block 1G for epithelial membrane antigen (EMA), bcl-1, bcl-2, CD3, CD4, CD5, CD8, CD10, CD15, CD20, CD23, CD30 (Ki-1), CD45 (LCA), and CD57 (Leu7). Also performed is EBER-1 in-situ hybridization, with adequate controls.

Proliferation of follicular dendritic cells in follicles is shown with CD23. The lymphocytes in the follicles are predominantly small and are positive for CD20, CD45; and negative for CD10, CD5, and bcl-1. T-lymphocytes are shown in the interfollicular areas and also a relatively increased number of cells in the follicles (positive for CD3, CD5, bcl-2, and CD4 or CD8). Kappa and lambda show no monoclonality. Immunostains CD20, CD15, CD30, and EMA are negative for the large and atypical cells in the follicles. CD57 show even distribution of this T-cell subset in the follicles with a few rosetting formations. In-situ hybridization for EBER-1 is negative.

Immunophenotyping of left groin mass biopsy by flow cytometry shows a T cell population (about 60% of the cells analyzed) with no aberrant loss or aberrant expression of T cell markers, a B cell population (about 41% of the cells analyzed) that is negative for CD5, CD10, CD56, no surface light-chain restriction.

The morphology and immunophenotypes are most consistent with reactive lymph node. Note that nodular lymphocyte predominant Hodgkin lymphoma was ruled out with the lack of large LP (L&H) cells in the follicles (that are expected to be positive for CD20, EMA, and surrounded by CD57-positive cells).

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52. MANDIBLE: INFLAMMATION WITH MANY POLYCLONAL PLASMA CELLS

1. Mandible, fistula tract, excision:

- Acute and chronic inflammation with many polyclonal plasma cells

- No evidence of malignancy

2. Mandible, intramedullary soft tissue, excision:

- Acute and chronic inflammation with many polyclonal plasma cells

- No evidence of malignancy

3. Mandible, anterior, resection:

- No evidence of malignancy

Histologic sections of the fistula tract mandible, intramedullary soft tissue mandible show acute and chronic inflammatory cells (lymphocytes, neutrophils, and many plasma cells). The plasma cells have small nuclei with mature cytological features. Sections of the anterior mandible show trabecular bone with suboptimal histology in the marrow area due to decalcification artifacts.

Immunohistochemical stains, with adequate controls, are performed on intramedullary soft tissue mandible (block 2FSA1) for kappa and lambda doublestain, CD38, and kappa and lambda (separate stains). The plasma cells are positive for CD38, and polyclonal pattern for Kappa and Lambda light chains. They are negative for CD56. CD138 shows focal positivity.

The immunophenotype results, together with morphology findings, are consistent with polyclonal plasma cells in the mandible.

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53. Benign lymphoid aggregates in nasopharyngeal biopsy

Diagnosis

Nasopharyngeal mass, biopsy:

Submucosal benign lymphoid aggregates.

No evidence of malignancy

Microscopic Description

Histologic section of nasopharyngeal mass biopsy show lymphocytic infiltrates in the submucosa. The lymphocytes are small with mature cytological features, admixed with a small number of histiocytes and rare plasma cells. A few reactive follicles are also seen with reactive germinal center and well-defined mantle zone. No necrosis is found in the section. The epithelial layer is intact.

Immunohistochemical stains, with adequate controls, are performed on blocks 1A for CD2, CD3, CD4, CD8, CD20, CD56, and bcl-2. The stains show normal distribution of B cells (CD20-positive) in the follicles, and T cells in the interfollicular area (positive for bcl-2, CD2, and CD3). T cells show a mixture of CD4-positive cells and CD8-positive cells. CD56 is negative for all the lymphocytes.

Immunophenotyping of nasopharyngeal mass biopsy by flow cytometry shows a T cell population (about 37% of the cells analyzed) with no aberrant loss or aberrant expression of T cell markers, a B cell population (about 61% of the cells analyzed) that is negative for CD5, CD10, and no surface light-chain restriction. All the analyzed cells are negative for CD56. All the lymphocytes have small nuclear size (based on forward-scatter signal).

The immunophenotype results, together with morphology findings, are consistent with submucosal benign lymphoid aggregates in the nasopharynx.

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54. LN: cHL-NS with residual follicles, also with flow

Diagnosis:

Supraclavicular lymph node: classical Hodgkin lymphoma, nodular sclerosis subtype

Histologic sections of the left supraclavicular lymph node show areas of thickened capsule, and effacement of normal architecture. A nodular pattern is seen with collagen bands surrounding the lymphoid nodules. Aggregates of large atypical cells with prominent nucleoli, some with binucleated / multinucleated form and lacunar form, are seen in lymphoid tissue throughout the sections. These cells are admixed with an inflammatory background of small lymphocytes, and macrophages. Rare residual follicles are also seen in the section.

Immumohistochemical stains, with adequate controls, are performed on block
1 for CD3, CD15, CD20, C30, CD45, EMA, CD57, PAX5, and bcl-2. The large atypical cells are positive for CD15 (focal), CD30 (with a membrane-Golgi pattern), CD20 (focal), and PAX5 (dim). They are negative for CD3, CD45, and EMA (consistent with the pattern for Hodgkin and Reed-Sternberg cells). The small lymphocytes in the background are mostly T cells (positive for CD3 and bcl-2) with a smaller number of B cells (CD20-positive). The rare residual follicles show positive bcl-2 stain in the mantle zone. CD57 shows only scattered positive cells with no resetting pattern.

The morphology and immunophenotypes of the abnormal cells are consistent with classical Hodgkin lymphoma, nodular sclerosis subtype. Note that imunophenotyping of lymph node biopsy by flow cytometry shows no abnormal immunophenotypes, an expected finding in classical Hodgkin lymphoma.

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55. LN: Atypical lymphoid aggregates with CD30-pos cells, cannot r/o cHL, also with flow

Diagnosis:

Left neck mass: Atypical lymphoid aggregates, see comment

Comment:

The morphology and immunophenotypes of the atypical large cells in the neck mass are suggestive of reactive immunoblasts. However, Hodgkin lymphoma cannot be completely ruled out. This case is being sent to MDA Cancer Center for consultation. Results of this consultation will be reported in Addendum.

Dr. Karni was notified of the findings on 6/29/2010

Histologic sections of the left neck mass biopsy show local areas with thickened capsule, and presence of reactive follicles. Aggregates of large atypical cells with prominent nucleoli are seen in paracortical areas throughout the sections. Rare binucleated forms of large cells are also seen. The atypical cells are admixed with background of small lymphocytes, and macrophages.

Immumohistochemical stains, with adequate controls, are performed on block
1 for CD3, CD15, CD20, C30, CD45, EMA, CD57, PAX5, and bcl-2. The large atypical cells are positive for CD30 (with a membrane-Golgi pattern), CD20, and PAX5 (dim). They are negative for CD15, CD3, and EMA. Staining for CD45 is difficult to evaluate for the large atypical cells due to the large number of surrounding CD45-positive cells.. The small lymphocytes in the background are mostly T cells (positive for CD3 and bcl-2). The reactive follicles show positive bcl-2 stain in the mantle zone, and positive CD20 stain in the follicles. CD57 shows only scattered positive cells with no resetting pattern.

Imunophenotyping of left neck biopsy by flow cytometry shows no abnormal immunophenotypes.

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56. Right neck mass: Follicular hyperplasia with progressive transformation of germinal center

Right neck mass

- Follicular hyperplasia with progressive transformation of germinal center, favoring a reactive
condition (see comment)

Comment

Dr. Maillard was notified of the findings on 6/23/2010. Due to the large size of the neck mass and recurrent presentation, this case is being referred to M.D. Anderson Cancer Center in consultation. The results of this consultation will be reported in Addendum when available.

Addendum Diagnosis

Right neck mass:

- Follicular hyperplasia with progressive transformation of germinal center

- No evidence of lymphoma (see comment)

Comment

- Consultation report done at MDA Cancer Center (L.J. Medeiros, MD; Hematopathology, MDACC, dated 6/29/2010, MDACC case S-10-040686). Diagnosis: marked reactive follicular hyperplasia and with multiple foci of progressive transformation of germinal centers; no morphological evidence of malignant lymphoma.

- On 6/29/10, Dr. Maillard was notified of this second opinion which is in line with our original diagnosis.

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57. Left axillary lymph node: Nodular sclerosis classical Hodgkin lymphoma

Comment: Dr Robinson was notified of the results on 7/16/2010

Histologic sections of the left axillary lymph node show effacement of architecture. A nodular pattern is seen with collagen bands surrounding the nodules. Prominent aggregates of large atypical cells with prominent nucleoli, some with binucleated / multinucleated form and lacunar form, are seen throughout the sections. These cells are admixed with an inflammatory background of small lymphocytes, macrophages, eosinophils and a few plasma cells.

Immunohistochemical stains, with adequate controls, are performed on block 1C for CD3, CD15 (leu M1), CD20, CD30 (Ki-1), CD45 (LCA), ALK-1 protein and PAX-5. Also performed on block 1C, with adequate controls, is EBER-1 in-situ hybridization.. The large atypical cells are positive for CD15, CD30 (both with a membrane-Golgi pattern), PAX-5 (weak stain), and negative for CD3, CD20, CD45, ALK-1 (consistent with the pattern for Hodgkin and Reed-Sternberg cells). The small lymphocytes in the background are mostly T cells (positive for CD3) with a smaller number of B cells (CD20-positive).

EBER-1 is pending. The result will be reported in Addendum.

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58. LN: Follicular lymphoid hyperplasia

DIAGNOSIS:

- Left axillary lymph nodes:

Follicular lymphoid hyperplasia

No evidence of lymphoma

- Left auricular region:

Normal skin tissue and lymphoid tissue with reactive follicles

No evidence of lymphoma

Histologic sections of the left axillary lymph nodes show intact capsule with follicular hyperplasia. The follicles are increased in number and size. The follicles exhibit with prominent follicular center with variation in size and shape. The mantle zone of the follicles is well defined. The germinal centers contain many mitoses and tingible-body macrophages. No granuloma or necrosis is seen in histologic sections. Sections of the left auricular region show normal skin tissue and a small area of lymphoid tissue with reactive follicles.

Immunohistochemical stains, with adequate controls, are performed on outside block 4B for bcl-2, bcl-6, CD3, CD10, CD20, and Ki-67. The germinal centers are positive for CD20, CD10, bcl-6, Ki-67 (70%), and negative for bcl-2. CD3 and bcl-2 are positive for T cells in the interfollicular areas.

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59. HIV-LYMPHADENOPATHY

Left neck mass (lymph nodes):

- Benign reactive lymph nodes with follicular hyperplasia and sinus hyperplasia.

- No evidence of lymphoma.

- Special stains for acid-fast bacilli and fungi are negative for organism.

- Toxoplasma is negative with immunohistochemical stain.

- Congo-red stain is negative for amyloidosis.

Histologic sections of the left neck mass (lymph nodes) from blocks 1E, 1F, 1G, 1H show preservation of lymph node architecture. The capsule is thickened in some areas. Follicular hyperplasia and sinus hyperplasia are noted. Most of the fhe follicles have well-formed mantle zone. A few follicles have more attenuated mantle zone and folliculolysis. No evidence of necrosis is seen. Vascular proliferation is moderately increased. Also seen are increase in plasma cells, focal areas with granulation tissue, small clusters of histiocytes, and foci of eosinophilic proteinaceous materials.

Histologic sections from blocks 1A, 1B, 1C, and 1D show a few follicles with loss of mantle zone. Also seen are thickened capsule, vascular proliferation, areas with granulation tissue.

Immunohistochemical stains, with adequate controls, are performed on block 1A for toxoplasma, kappa, lambda, bcl-2, bcl-6, CD3, CD4, CD8, CD10, CD20, CD56, CD79a, and CD138. Cells in the residual follicles are positive for CD20, CD10, CD79a, bcl-6, and negative for bcl-2. Mixture of T cells (CD3-pos, CD4-pos or CD8-pos) is seen in interfollicular area. A moderate number of plasma cells are seen with positivity for CD138, negativity for CD56, and polyclonal distribution of kappa and lammbda. Toxoplasma stain is negative for organism.

Immunophenotyping of lymph node biopsy by flow cytometry shows a T cell population (about 60% of the cells analyzed) with no aberrant loss or aberrant expression of T cell markers, a B cell population (about 31% of the cells analyzed) that is negative for CD5, CD10, no surface light-chain restriction. These results indicate no abnormal immunophenotypes with flow cytometry.

Congo-red stain on block 1Fshows no evidence of amyloid deposit.

AFB and GMS stains on block 1E show no evidence of organisms.

+++++++++++++++++++++++++++++++++++++++++

60. LN: DLBCL with many T cells (~TCRHR BCL)

Left groin lymph node biopsy

- Diffuse large B-cell lymphoma

- Areas with coagulative necrosis

Comment:

-Dr. Farnie, patient's attending physician, was notified of the diagnosis on 9/3/2010 at 12:30 PM

-Ki67 shows 80% positivity for the lymphoma cells

Histologic sections of the left groin lymph node show effacement of lymph node architecture by abnormal lymphoid tissue. There is diffuse infiltration by atypical lymphocytes with intermediate-large nuclei, irregular nuclear contour, vesicular nuclei with fine chromatin, and one to several nucleoli. The abnormal cells are admixed with a large number of small lymphocytes with mature cytological features and a small number of histiocytes. Frequent mitotic figures and tingible-body macrophages are seen. Several large necrotic foci are also found in sections. No normal follicles are found.

Immunohistochemical stains, with adequate controls, are performed on block 1B for bcl-1, bcl-2, bcl-6, CD3, CD4, CD5, CD8, CD10, CD15, CD20, CD23, CD30, CD45 (LCA), CD57, ALK-1 protein, EMA, and Ki-67. The abnormal lymphocytes are positive for CD45, CD20, partially postive for CD30, and bcl-6. They are negative for CD10, bcl-2, bcl-1, CD3, CD4, CD5, CD8, CD15, AlK-1, and EMA. Ki-67 is approximately positive in 80% of the abnormal lymphocytes. A large number of T cells (positive for CD3, CD5, bcl-2, CD4 or CD8) are seen admixed with the abnormal cells. CD57 and CD23 only shows scattered cells with positive stain. Also no rosetting pattern is seen with CD57 stain.

The immunostains and morphology in this case are consistent with diffuse large B cell lymphoma.

++++++

61. TESTICLE: T LYMPHOBLASTIC LYMPHOMA

Right testicle:

- T lymphoblastic lymphoma

Histologic sections of the right testicle (1C through 1N) shows diffuse infiltration with malignant lymphocytes of medium size with vesicular nuclei and one to several nucleoli. Frequent mitotic figures are seen. The malignant cells are admixed with a moderate number of tingible-body macrophages. No malignant cell infiltration is seen in 1A (spermatic cord margin), and 1B (spermatic cord).

Immunohistochemical stains, with adequate controls, are performed on block 1K for CD3, CD4, CD8, and TdT and show that the neoplastic cells are positive for CD4, CD8, TdT and negative for CD3 (the same profile as that in the original diagnostic mediastinal specimen). These results, together with morphological findings, are consistent with T lymphoblastic lymphoma involvement in the right testicle.

++++

62. Benign reactive lymph node with follicular hyperplasia and sinus hyperplasia, clusters of histiocytes

Left supraclavicular lymph node:

- Benign reactive lymph node with follicular hyperplasia and sinus hyperplasia.

- No evidence of lymphoma.

- Presence of clusters of epithelioid histiocytes.

- Special stains for acid-fast bacilli and fungi are negative for organism.

- Toxoplasma is negative with immunohistochemical stain.

Histologic sections of the left supraclavicular lymph node show preservation of lymph node architecture. The capsule is of normal thickness. Follicular hyperplasia and sinus hyperplasia are noted. The follicles have well-formed mantle zone. Also seen are small clusters of histiocytes.

Immunohistochemical stains, with adequate controls, are performed on block 1A for toxoplasma. Toxoplasma stain is negative for organism. AFB and GMS stains on block 1A also show no evidence of organisms.

Immunophenotyping of lymph node biopsy by flow cytometry shows a T cell population (about 79% of the cells analyzed) with no aberrant loss or aberrant expression of T cell markers, a B cell population (about 21% of the cells analyzed) that is negative for CD5, CD10, and no surface light-chain restriction. These results indicate no abnormal immunophenotypes with flow cytometry.

++++

63. LN: Follicular hyperplasia, flow and IHCs

Right neck mass (lymph node):

- Follicular hyperplasia.

- No evidence of granuloma, necrosis or malignancy.

Histologic sections of the right neck mass (lymph node) show presevation of lymph node architecture. Marked follicular hyperplasia is noted. The follicles have variable size and contain reactive germinal center. The germinal centers have many macrophages with tingible-bodies, imparting a "starry sky" pattern Mantle zone is attenuated in some follicles. No evidence of granuloma or necrosis is seen.

Immunophenotyping of the right neck mass biopsy by flow cytometry in gate #2 shows a T cell population (about 42% of the cells analyzed) with no aberrant loss or aberrant expression of T cell markers, a B cell population (about 58% of the cells analyzed) that shows no evidence of surface-light chain restriction. All the cells in gate #2 have small nuclear size (based on forward-scatter signal).

Immunophenotyping cells in gate #1 shows a small T cell population (about 11% of the cells analyzed) with no aberrant loss or aberrant expression of T cell markers, a B cell population (about 81% of the cells analyzed) that is shows no evidence of surface-light chain restriction. All the cells in gate #1 have intermediate-large nuclear size (based on forward-scatter signal).

Immunohistochemical stains, with adequate controls, are performed on block 1A for bcl-2, bcl-6, CD3, CD10, CD20, and Ki-67. The germinal centers are positive for CD20, CD10, bcl-6, and negative for bcl-2. CD3 and bcl-2 are positive for T lymphocytes in the inter-follicular areas. Ki-67 shows strong intensity in the germinal centers with a polarized pattern.

The morphological findings, together with immunophenotypes by flow cytometry and immunostains, are consistent with follicular hyperplasia. No evidence of lymphoma is found.

+++++++

64. Lung, wedge biopsy: Lymphmatoid granulomatosis, grade 3

Lung, left lingular, wedge biopsy:

- Lymphmatoid granulomatosis, grade 3 (see comment)

Comment

This case was reviewed after discussion in Tumor Board on 11/9/2010.

The lung wedge biopsy shows a diffuse infiltration with polymorphous lymphoid cells. They consist of predominant small lymphocytes, admixed with histiocytes and a few large aggregates of large atypical cells with predominant nucleolie. Lymphocytic vasculitis is seen in walls of vessels, along with areas of necrosis throughout the sections.

Immunohistochemical stains, with adequate controls, are performed on block 1B for bcl-1, CD3, CD4, CD5, CD8, CD10, CD20, Ki-67, and FOXp3. Also performed on block 1B, with adequate controls, is EBER-1 in-situ hybridization. The stains show that the large atypical cells are positive for CD20 and EBER-1. There are mixture of CD4-pos lymphocytes and CD8-pos lymphocytes, which are both positive for CD3. FOXp3 shows only scattered positive cells. CD10 is negative. Ki-67 and bcl-1 are pending.

The morphological findings and immunostains/ISH are most consistent with lymphomatoid granulomatosis, grade 3 (out of 3).

Notes:

- Rituximab has been shown to be an effective therapy in aggressive cases of lymphomatoid granulomatosis

- With low number of T-reg (FOXp3) seen in this case, RAPAMYCIN may be considered for immune modulation

- This case was discussed in subsequent Tumor Board on xx/xx/xx

+++++

65. VAREULA/LEFT HYPOPHARYNGEAL/RIGH PYRIFORM: Chronic inflammatory infiltration

VAREULA LESION:

-Chronic inflammatory infiltration, no evidence of malignancy

LEFT HYPOPHARYNGEAL BIOPSY:

-Chronic inflammatory infiltration, no evidence of malignancy

RIGHT PYRIFORM:

-Chronic inflammatory infiltration, no evidence of malignancy

Histologic sections of the vareula lesion, left hypopharyngeal biopsy, and right pyriform biopsy show infiltration in submucosa with lymphocytes, admixed with a small number of histiocytes. The lymphocytes have small size with mature cytological features.

Immunohistochemical stains, with adequate controls, are performed on block 1A for bcl-2, CD3, CD4, CD8, and CD20. The immunostains show a heterogenous mixture of B cells (positive for CD20), and T cells (positive for CD3, bcl-2). There are more CD4-positive T cells than CD8-positive T cells in the section. The immunostains, together with morphological findings, are consistent with chronic inflammation.

+++++

66. LEFT GROIN LYMPH NODE: DLBCL /FL (grade 3/3)

DIAGNOSIS:

- Left groin lymph node biopsy: Diffuse large B-cell lymphoma (60%) and follicular lymphoma, grade 3/3 (40%), indicating transformation of follicular lymphoma to diffuse large B-cell lymphoma

MICROSCOPIC DESCRIPTION:

Histologic sections of the left groin lymph node biopsy show effacement of the normal lymph node architecture. The lymph node capsule is thickened. About 60% of the examined area shows diffuse infiltration by malignant lymphocytes with intermediate-large size, with vesicular nuclei and one to several nucleoli. Frequent mitotic figures are seen. About 40% of the examined area shows poorly-defined neoplastic follicles of varying size. The follicles have attenuated mantle zone and contain mostly of centroblasts.

Immunohistochemical stains, with adequate controls, are performed on block 1B of the lymph node for CD20, CD10, CD5, bcl-2, Ki-67, CD3, CD4, CD8, CD30, ALK-1, and bcl-1. The neoplastic cells (in the follicular area and also in the diffuse area) are positive for bcl-2 (partial positivity), CD20, and negative for CD10, bcl-1, CD3, CD5, CD4, CD8, ALK-1. The large neoplastic cells in the diffuse area shows positivity for CD30. Ki-67 shows approximately 30-40% proliferation rate in the diffuse infiltrates. CD3, CD4, CD8 show normal T cells in the paracortical areas.

Immunophenotyping of the left groin lymph node biopsy by flow cytometry in gate #1 shows a lymphocytic population with small nuclear size (based on forward-scatter signal) and consists of normal T cells and B cells. Analysis of cells in gate #2 shows an abnormal B cell population (about 46% of the cells in gate #2) that is positive for CD19, CD20, CD22, and surface kappa light-chain restriction. They are negative for CD5, CD1. These B cells have large nuclear size (based on forward-scatter signal).

The morphology and immunophenotyping (by immunostains) are consistent with diffuse large B-cell tranformed from follicular lymphoma (grade 3/3)

+++++++++++++

67. LEFT GROIN LYMPH NODE: FL (grade 2-3/3)

DIAGNOSIS:

- Left groin lymph node biopsy: follicular lymphoma, grade 2, follicular and diffuse, with focal progression to follicular lymphoma, grade 3

MICROSCOPIC DESCRIPTION:

Histologic sections of the left groin lymph node biopsy show effacement of the normal lymph node architecture. The lymph node capsule is thickened. About 40% of the examined area shows poorly-defined neoplastic follicles of varying size. The follicles lack mantle zone and contain a heterogeneous mixture of centrocytes and centroblasts and frequent mitotic figures. The remaining area in the section show a mixture of small lymphocytes and centroblasts, also admixed with frequent mitotic figures.

Immunohistochemical stains, with adequate controls, are performed on block 1B for bcl-1, bcl-2, bcl-6, CD3, CD4, CD5, CD8, CD10, CD15 (leu-M1), CD20, Ki-1 (CD30), ALK-1 protein, and Ki-67; and on block 1C for CD20. The neoplastic cells are positive for bcl-2, CD20, bcl-6. Ki67 shows 30% proliferation index. A subpopulation of the large neoplastic cells also shows positivity for CD30. The neoplastic cells are negative for CD10, bcl-1, CD3, CD5, CD4, CD8, and ALK-1. CD3, CD5, CD4, CD8 show a significant number of normal T cells in the paracortical areas. CD15 shows scattered granulocytes.

Immunophenotyping of the left groin lymph node biopsy by flow cytometry in gate #1 shows a lymphocytic population with normal T cells and B cells. Analysis of cells in gate #2 shows an abnormal B cell population (about 46% of the cells in gate #2) that is positive for CD19, CD20, CD22, and surface kappa light-chain restriction. They are negative for CD5, CD10.

The morphology and immunophenotyping findings are consistent with follicular lymphoma, grade 2, follicular and diffuse, with focal progression to follicular lymphoma, grade 3

++++++++++++

68. Paranasal sinus, right, biopsy: Plasmacytoma

Paranasal sinus, right, biopsy:

- Plasmacytoma

Comment:

The immunophenotype results, together with morphology findings, are consistent with plasmacytoma in the sinus lesion. Further testing and clinical correlation are suggested to rule out multiple myeloma in this patients (serum and urine protein electrophoresis and immunofixation, serum quantitative immunoglobulins, serum calcium, CBC, renal function tests, bone marrow aspirate and biopsy, imaging studies to look for lytic lesions). Dr. Fakhri’s receptionist (Beverly) was notified of the diagnosis on 12/7/10 at 16:00

Microscopic:

Histologic sections show diffuse infiltration with plasma cells. The plasma cells have small nuclei with mature cytological features.

Immunohistochemical stains, with adequate controls, are performed on block 2A for kappa and lambda double stain, CD3, CD20, CD38, CD56, and CD138. The plasma cells are positive for CD138 and CD38 with a diffuse pattern. The plasma cells are negative for CD56. There is a predominant population of plasma cells with cytoplasmic kappa light chain compared to those with lambda light chain. Only rare plasma cells with lambda light chain are seen. Only a small number of B lymphocytes (positive for CD20) and T lymphocytes (positive for CD3) are seen in sections.

These immunophenotype results, together with morphology findings, are consistent with plasmacytoma in the sinus lesion.

++++++++++++

69. deleted

++++

70. CORE BX: REACTIVE LYMPH NODES WITH IMMUNOSTAINS

Diagnosis:

Bilateral axillary lymph nodes (1: Left, 2: Right), core biopsies:

- Benign reactive lymph nodes with no evidence of malignancy

Histologic sections of the left axillary lymph node core biopsy (1) and the right axillary lymph node core biopsy (2) show a few lymphoid follicles with a background of small lymphocytes admixed with a small number of plasma cells. No evidence of granuloma, necrosis, or abnormal cellular infiltrates is seen.

Immunohistochemical stains, with adequate controls, are performed on block 1A for CD3, CD5, CD20, CD10, bcl-2, CD23, Ki67, and CK Pan. The follicular cells are positive for CD20, CD10, CD23, Ki67 (partial); and negative for bcl-2. CD3, CD5, and bcl-2 are positive for lymphocytes in the interfollicular areas. CK Pan is negative.

These immunophenotype results, together with morphology findings, show no evidence of malignancy in the axillary lymph nodes.

+++++++++++++++++++

71. Left tonsil, biopsy: Diffuse large B cell lymphoma

Left tonsil, biopsy:

- Diffuse large B cell lymphoma, see comment.

- Dr Karni was notified of the diagnosis on 1/13/2011 at 17:00

- Ki67 and EBER stains are pending. The results of these will be reported in Addendum

Histologic sections of the left tonsil biopsy shows effacement of tonsil architecture by large cells with irregular nuclear contour, vesicular nuclei with fine chromatin, and one to several nucleoli. Mitotic figures and areas with necrosis are seen. A small number of small lymphocytes and histiocytes are seen admixed with the abnormal large cells.

Immunohistochemical stains, with adequate controls, are performed on block 1A for AE1/AE3, CK7, CK20, CD3, CD20, CD45 (LCA), CD79a, PAX-5, and Ki-67. Also performed on block 1A is EBER-1 insitu hybridization. The large neoplastic cells are positive for PAX-5, and CD20. These cells are negative for CD3. Stains for CD45 and CD79a are suboptimal. Normal T cells (positive for CD3) are scattered throughout the sections. Epithelial components are positive for keratin stains.

The immunostains, together with morphological findings, are consistent with diffuse large B cell lymphoma.

++++++++++++++++++++

72. Cervical LN: Reactive (paracortical hyperplasia with reactive immunoblasts)

Lymph node, cervical, biopsy:

- Paracortical hyperplasia with thickened capsule

- No evidence of lymphoma

Histologic sections of cervical lymph node biopsies show thickened capsule, and presence of a few reactive follicles. Paracortical hyperplasia is noted with scattered large atypical cells with prominent nucleoli in paracortical areas. No multinucleated forms of these large cells are seen. The atypical cells are admixed with a background of small lymphocytes, and histiocytes.

Immunohistochemical stains, with adequate controls, are performed on block 2A for CD3, CD15, CD20, CD30, Leukocyte common antigen (CD45), and PAX-5. Also performed on block 2A, with adequate controls, is EBER-1 in-situ hybridization. The large atypical cells are positive for CD45, CD30, CD20, and PAX-5. They are negative for CD15, and CD3. The small lymphocytes in the background are mostly T cells (positive for CD3). The reactive follicles show positivity for CD20 stain. CD15 is positive for granulocytes in the section. The morphology and immunophenotypes of the atypical large cells in the paracortical area are consistent with reactive immunoblasts. EBER-1 is pending, the result of which will be reported in Addendum.

Immunophenotyping of lymph node biopsy by flow cytometry shows a T cell population (about 61% of the cells analyzed) with high CD4/CD8 ratio (7:1), otherwise no aberrant loss or aberrant expression of T cell markers, a B cell population (about 38% of the cells analyzed) that is negative for CD5, CD10, no evidence of surface-light chain restriction. Please refer to flow cytometry report HF-11-17 for further details.

The morphological and immunophenotypic findings are consistent with reactive lymph node. No evidence of malignancy (including lymphoma or post-transplant lymphoproliferative disorder) is found.

+++++++

73. RIGHT NECK LNs AND TONSILS: FOLLICULAR HYPERPLASIA

1. Right neck lymph node for lymphoma study:

- Follicular lymphoid hyperplasia and sinus hyperplasia.

- No evidence of granuloma, or malignancy.

2. Right neck lymph node:

- Follicular lymphoid hyperplasia and sinus hyperplasia.

- No evidence of granuloma, or malignancy.

3. Right and left tonsils:

- Follicular lymphoid hyperplasia.

- No evidence of granuloma, or malignancy.

Histologic sections of the right neck lymph nodes (1 and 2) show preservation of lymph node architecture. The capsule is of normal thickness. Follicular hyperplasia and sinus hyperplasia are noted. The germinal centers contain moderate number of mitoses and tingible-body macrophages. The follicles have well-formed mantle zone. No evidence of granuloma or necrosis is seen

Immunophenotyping of the right neck lymph node biopsy (1) by flow cytometry (Memorial Hermann Hospital Flow Cytometry Laboratory, report HF-11-26) shows a T cell population (about 43% of the cells analyzed) with a high CD4/CD8 ratio (7:1), otherwise no aberrant loss or aberrant expression of T cell markers, a B cell population (about 57% of the cells analyzed) that is negative for CD5, CD10, also no surface light-chain restriction.

Histologic sections of the right and left tonsils (3) show marked follicular hyperplasia. The follicles have well-formed mantle zone. The germinal centers contain moderate number of mitoses and tingible-body macrophages. No evidence of granuloma or necrosis is found.

+++++++

74. THYMUS: PMLBCL

1. Fibrovascular tissue, excision:

- Fibrovascular tissue with benign lymphoid aggregates

2. Fibroadipose tissue, "mediastinal tissue", excision:

- Fibroadipose tissue with benign lymphoid aggregates

3. Lymph node, "intramammary lymph node", excision:

- Reactive lymph node with no evidence of lymphoma

4. Thymus tissue, excision:

- Primary mediastinal (thymic) large B cell lymphoma,

margins free of tumor cells.

Histologic sections of fibrovascular tissue (1) show fibrovascular tissue with benign lymphoid aggregates. Sections of fibroadipose tissue (2) show fibroadipose tissue with benign lymphoid aggregates. Sections of intramammary lymph node (3) show a reactive lymph node with a few reactive follicles and no evidence of lymphoma.

Sections of thymus tissue (4) show diffuse infiltration by intermediate-large lymphocytes with irregular nuclear contour, abundant cytoplasm, vesicular nuclei with fine chromatin, and one to several nucleoli. Mitotic figures are present in moderate number. These tumor cells are admixed with small lymphocytes with mature cytological features. Large collagen bands are seen throughout sections, along with compartmentalizing fibrosis. The margins of all sections are free of tumor cells.

Immunophenotyping of thymic biopsy by flow cytometry (Memorial Hermann Laboratory, report HF-11-38) shows a T cell population (about 64% of the cells analyzed) with no aberrant loss or aberrant expression of T cell markers, a B cell population (about 37% of the cells analyzed) that is negative for CD5, CD10, no expression of surface-light chains (neither kappa nor lambda). These B cells have intermediate-large nuclear size (based on forward-scatter signal) and are positive for CD19, CD20, CD22, and FMC7. The analyzed lymphocytes (T and B cells) are negative for TdT.

Immunohistochemical stains, with adequate controls, are performed on block 4A for pan keratin, CD3, CD20, and TdT. The large tumor cells are positive for CD20. They are negative for CD3, TdT, and pan keratin. They are admixed with small T lymphocytes (positive for CD3 and negative for TdT). Scattered thymic remmants are positive for keratin.

IThe morphological findings and immunophenotypes (flow cytometry and immunostain results) are diagnostic of primary mediastinal (thymic) large B cell lymphoma

+++++

75. ILEUM/JEJUNAL BX: FL, Gr 1/3

1. JEJUNAL MUCOSAL NODULARITY:

- Follicular B cell lymphoma, grade 1 out of 3

- Negative for Helicobacter pylori micro-organisms.

2. ILEUM MUCOSAL NODULARITY:

- Follicular B cell lymphoma, grade 1 out of 3

The lamina propria of the jejunal and ileum biopsies is found to have several dense ill-defined lymphoid follicles. The follicles lack mantle zone and contain mostly small mature lymphocytes with irregular nuclear contour (centrocytes). Very few centroblasts are present in the follicles.

Immunohistochemical stains, with adequate controls, are performed on block 1A for Helicobacter pylori, bcl-1, bcl-2, bcl-6, CD3, CD10, CD20, and CD23. The lymphocytes in the follicles are positive for CD20, CD10, bcl-6, and bcl-2. They are negative for CD3, bcl-1, and CD23. A small number of T cells (positive for CD3 and bcl-2 are scattered outside the follicles. Remnants of follicular dendritic cells (positive for CD23) are seen in focal areas. Helicobacter pylori stain is negative for organisms.

The morphological findings, together with immunohistochemical pattern, are consistent with follicular B-cell lymphoma, grade 1/3.

+++++

76. LEFT JAW MASS: No evidence of plasmacytoma

Left jaw mass, biopsy:

- Chronic inflammatory infiltrates with no evidence of malignancy

Microscopic:

Histologic sections show chronic inflammatory infiltrates that consist of many plasma cells, admixed with smaller number of small lymphocytes and histiocytes. The plasma cells have small nuclei with mature cytological features.

Immunohistochemical stains, with adequate controls, are performed on block 1A for kappa and lambda double stain, CD3, CD20, CD138, and CD56. The plasma cells are positive for CD138, and negative for CD56. They show a polyclonal pattern with mixture of kappa-positive cells and lambda-positive cells. Lymphocytes show a mixture of B cells (CD20-pos) and T cells (CD3-pos).

These immunophenotype results, together with morphology findings, show no evidence of plasmacytoma in the left jaw biopsy.

+++++

77. TONSIL: PTLD, Infectious mononucleosis-like lesion,

4 y/o F, Adenotonsillar hypertrophy s/p liver transplant (at 1 y/o)

1. Tonsil, right, tonsillectomy:

- Post-transplant lymphoproliferative disorder, Infectious mononucleosis-like lesion, see comment

2. Tonsil, left, tonsillectomy:

-Post-transplant lymphoproliferative disorder, Infectious mononucleosis-like lesion

Comment

-Early lesion types of Post-transplant lymphoproliferative disorders (PTLD), such as Infectious mononucleosis-like lesion, typically regress following a reduction in immunosuppression or sometimes spontaneously. Rarely monomorphic PTLD may follow early lesion types of PTLD

-No evidence of monomorphic PTLD is found in this case.

-Dr Nidra Rodriguez was notified of the diagnosis on 3/4/2011at 17:35

Microscopic Description

Histologic sections of the right tonsil (1) and left tonsil (2) show preservation pf the overlying epithelium.The follicles are increased in number and size. Many secondary follicles with prominent follicular center are seen. The follicles exhibit considerable variation in size and shape. The mantle zone of the follicles is well defined. The germinal centers contain mitoses and tingible-body macrophages. No granuloma or necrosis is seen in histologic sections. The interfollicular area is hyperplastic and show mature lymphocytes admixed with many plasmacytoid lymphocytes, plasma cells, also scattered immunoblasts.

Immunohistochemical stains, with adequate controls, are performed on block 2A for bcl-2, CD3, CD10, CD20, and Ki-67. Also performed on block 2A, with adequate controls, is EBER-1 in-situ hybridization. The germinal centers are positive for CD20, CD10, and negative for bcl-2. Ki-67 shows high proliferation rate in the germinal centers with a polarized pattern. CD3 and bcl-2 are positive for T lymphocytes in the interollicular areas. Scatterd immunoblasts show a mixture of mostly B cells (CD20-pos) and some T cells (CD3-pos). EBER-1 shows positive expression in many cells in the section.

Immunophenotyping of tonsil biopsy by flow cytometry shows a T cell population (about 59% of the cells analyzed) with no aberrant loss or aberrant expression of T cell markers, a B cell population (about 38% of the cells analyzed) that is negative for CD5, CD10, no surface light-chain restriction. These results show no evidence of clonal T cells or clonal B cells.

The morphological and immunophenotypic findings are most consistent with an early form of post-transplant lymphoproliferative disorder, Infectious mononucleosis -like lesion

++++++++++++++++++

78. Anaplastic large cell lymphoma, ALK positive (monomorphic variant)

Mesenteric Lymph Node:

- Anaplastic large cell lymphoma, ALK positive

Microscopic Description

Histologic sections of the mesenteric lymph node show diffuse infiltration by intermediate-large cells with round nuclear contour, vesicular nuclei with fine chromatin, and one to several nucleoli. The predominant type of cells is monomorphic with round nuclei. Rare binucleated forms are also seen. Frequent mitotic figures are noted. A small number of histiocytes, small lymphocytes, and rare plasma cells are seen admixed with the malignant cells.

Immunohistochemical stains, with adequate controls, are performed on block 1B for bcl-1, bcl-2, CD4, CD8, CD10, CD20, CD30, ALK-1 protein, and Ki-67. The malignant cells are positive for CD4, CD30, ALK-1, Ki-67 and negative for bcl-2, bcl-1, CD10, CD8, CD20. CD30 stain shows membrane-golgi pattern and ALK-1 stain shows nuclear-cytoplasmic pattern in the malignant cells. Ki-67 shows 60% proliferation rate. A small number of normal B cells (CD20-pos) are seen scattered in the sections.

Immunophenotyping of mesenteric lymph node biopsy by flow cytometry (report HF-11-63) shows a predominant abnormal population of lymphocytes with intermediate-large nuclear size (based on forward-scatter signal). These cells show expression of CD2, CD3 (cytoplasmic), and CD4. They show partial loss of CD7 and CD3 (surface), also aberrant loss of CD5. They are negative for CD8.

The morphological findings, together with immunophenotyping by flow cytometry and immunostains, are consistent with anaplastic large cell lymphoma, ALK-positive. The subtype is monomorphic variant.

+++++++

79. LN: Follicular and paracortical hyperplasia, with Flow

Diagnosis

Lymph node, excisional biopsy:

- Follicular and paracortical hyperplasia.

- No evidence of granuloma, necrosis or lymphoma.

Microscopic Description

Histologic sections of the lymph node biopsy show preservation of lymph node architecture. The capsule is slightly thickened in some areas. Follicular hyperplasia and paracortical hyperplasia are noted. The follicles have well-formed mantle zone and reactive germinal center. No evidence of granuloma or necrosis is seen. Increased in vascular proliferation is noted. A small number of large cells (immunoblasts) are found admixed with lymphocytes in the paracortical area.

Immunophenotyping of the lymph node biopsy by flow cytometry (Memorial Hermann Flow Cytometry Laboratory, report HF-11-66) shows a T cell population (about 49% of the cells analyzed) with no aberrant loss or aberrant expression of T cell markers, a B cell population (about 55% of the cells analyzed) that is negative for CD5, CD10, also no surface light-chain restriction. The analyzed cells are negative for CD16, CD56 and CD34. These results show no abnormal immunophenotypes.

+++++++

80. STOMACH: DLBCL, Pos for H. Pylori

Stomach, biopsies of gastric mass:

- Diffuse large B cell lymphoma

- Warthin-Starry silver stain is positive for Helicobacter pylori

Comment

- Ki-67 shows a high proliferation rate of about 90% in lymphoma cells.

- EBV stain (EBER-1) is pending, the result of which will be reported in Addendum

- Findings were discussed with Dr. Dupont on 3/25/2011.

Microscopic Description

Histologic sections of the gastric mass show diffuse lymphocytic infiltration in the lamina propria consisting of large cells with pleomorphic features. Many have one to several prominent nucleoli. The malignant cells are admixed with a small number of small lymphocytes with mature cytological features. Frequent mitotic figures are seen. Scattered macrophages with ingested apoptotic tumor cells are found throughout the sections. Rare lymphoepithelial lesions are observed in the glands.

Immunohistochemical stains, with adequate controls, are performed on block 1A for bcl-1, bcl-2, bcl-6, CD3, CD5, CD10, CD20, and Ki-67 and for EBER-1 in-situ hybridization. The malignant cells are positive for bcl-6, and CD20. They are negative for bcl-1, bcl-2, CD3, CD5, and CD10. Ki-67 shows a high proliferation rate of about 90%. EBER-1 is pending, the result of which will be reported in Addendum. Warthin-Starry silver stain is positive for Helicobacter pylori in glandular lumen.

The morphology and immunophenotypes of the malignant cells are most consistent with diffuse large B-cell lymphoma. Burkitt lymphoma was excluded due to the large size of the malignant lymphoma cells and also negativity for CD10.

++++

81. RIGHT LACRIMAL GLAND: FL, Gr 3

DIAGNOSIS:

-Right lacrimal gland, biopsy:

Follicular lymphoma, grade 3a; with follicular pattern

CPT: 88307-GC, 88342-26x5, 88342-TCx5

Microscopic Description

Histologic sections of the right lacrimal gland biopsy biopsy show poorly-defined neoplastic follicles of varying size. The follicles lack a well-defined mantle zone and contain mostly centroblasts with intermediate-large size, vesicular nuclear chromatin pattern and one to several nucleoli. A smaller number of centrocytes are also seen in the follicles.

Immunohistochemical stains, with adequate controls, are performed for bcl-2, bcl-6, CD10, CD20, and Ki-67. The neoplastic cells in the follicles are positive for bcl-2, CD20, bcl-6, and CD10. Ki-67 shows approximately 50% proliferation rate with even distribution in the follicles.

Immunophenotyping of the right lacrimal biopsy by flow cytometry (Texas Methodist Hospital, report MM-11-317, dated 2/28/11) shows an abnormal B cell population (about 30% of the cells analyzed) that is positive for CD19, CD20, CD10, surface kappa light chain restriction.

The morphology and immunophenotyping (by immunohistochemical stains and flow cytometry) are consistent with follicular lymphoma (grade 3a).

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82. Bone, femoral neck fracture: multiple myeloma

Bone, left femoral neck fracture, hemiarthroplasty:

- Bone disruption, hemorrhage, hematoma formation and granulation tissue, consistent
with clinical history of fracture.

- Bone marrow with markedly increased plasma cells consistent with multiple myeloma.

- See microscopic description and comment.

Comment

-This patient has had previous needle core biopsies of the right sacral mass (CA-11-396) which had shown a plasma cell dysplasia (plasmacytoma) in which the plasma cells showed Kappa light chain restriction. A bone marrow performed on 4/5/11 (HB-11-46) showed findings consistent with multiple myeloma. Similar morphological findings (sheets of plasma cells) in the current specimen indicate marrow involvement consistent with multiple myeloma.

- Many sickle-shaped erythroids are seen in this specimen. Review of medical records reveals no history of sickle cell disease. The current findings are likely to be associated withh sickle cell trait. Clinical correlation is suggested.

- Dr Quesada was notified of the diagnosis of multiple myeloma on 4/6/11

Microscopic Description

Sections of the left femoral neck show bone with focal disruption of the bony trabeculae and hematoma formation consistent with fracture site. There are also areas of granulation tissue and reactive bone consistent with fracture. The marrow space shows abundant plasma cells in addition to normal hematopoietic elements and is consistent with multiple myeloma.

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83. SCALP MASS: FL, gr 1/3

Left posterior scalp mass:

-Follicular B-cell lymphoma, grade 1 (out of 3), with a predominantly follicular pattern

Comment:

This lymphoma is present in cutaneous tissue and may represent primary cutaneous follicular center lymphoma. However, a nodal follicular lymphoma with secondary cutaneous involvement cannot be ruled out with current findings, especially with positivity of bcl-2 in the lymphoma cells (usually negative in cutaneous folliculat center lymphoma). Further investigation with examination and imaging is suggested to rule out involvement in other sites, especially lymph nodes.

- Findings were notified to Dr. Bajwa on 4/12/2011at 16:30

Microscopic:

Histologic sections of the left posterior scalp mass biopsy shows diffuse infiltration of the dermis by poorly-defined neoplastic follicles of varying size. The follicles lack mantle zone and contain mostly centrocytes. Very few centroblasts or mitotic figures are present in the follicles. No epidermal cells are seen in sections.

Immunohistochemical stains, with adequate controls, are performed on block 1G for bcl-2, bcl-6, CD10, CD20, CD3, CD23, and Ki-67. The neoplastic cells in the follicles are positive for bcl-2, CD20, bcl-6, CD23, and CD10. Ki-67 shows approximately 10-20% proliferation rate with even distribution in the follicles. CD3 shows positivity for scattered T cells outside the follicles.

Immunophenotyping the scalp mass by flow cytometry at Memorial Hermann Laboratory (report HF-11-104) reveals a predominant B cell population with CD19/CD10 co-expression and lambda light chain restriction. No coexpression of CD5/CD19 is present. These B cells are positive for CD23 and FMC7. Admixed is a minor population of T cells with no aberrant antigenic loss and a CD4:CD8 ratio of 4:1.

The morphology, flow cytometric immunophenotype, and immunostain findings in this case are consistent with follicular B-cell lymphoma, grade 1/3.

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84. Left neck mass: SLL/necrosis

Left neck mass:

- Small lymphocytic lymphoma

- Foci of necrosis

- AFB stain is negative for acid-fast microrganisms.

- GMS stain is negative for fungal microorganisms.

Histologic sections of left neck mass show lymph nodes with effacement of normal architecture with diffuse infiltration of small lymphocytes. The lymphocytes have small nuclei with mature cytological features. Parafollicles (proliferation centers) are seen throughout sections. Many large foci of necrosis are seen in lymph node sections. Sections of adjacent salivary glands show infiltration of small lymphocytes around the glands. Special stains with adequate control for AFB and GMS on block 1A, 1B, 1C and 1E are negative for acid-fast and fungal microrganisms.

Immunophenotyping of lymph node biopsy by flow cytometry shows a small T cell population (about 1% of the cells analyzed), a predominant B cell population (about 98% of the cells analyzed) that is positive for CD5, CD19, CD20, CD22, CD23, surface kappa light chain restriction (dim signal). These B cells are negative for CD10, and CD38. These B cells have small nuclear size (based on forward-scatter signal).

The immunophenotype results, together with histological findings, are consistent with small lymphocytic lymphoma.

++++

85. SKIN, RIGHT ARM: DLBCL

Diagnosis:

Skin, right arm:

-Diffuse large B cell lymphoma

Comment

- Ki-67 shows a proliferation rate of about 70% in lymphoma cells.

Microscopic Description

Histologic sections of the skin biopsy show diffuse lymphocytic infiltration in the dermis consisting of large cells with pleomorphic features. Many have one to several prominent nucleoli. The malignant cells are admixed with a small number of small lymphocytes with mature cytological features. Frequent mitotic figures are seen. Scattered macrophages with ingested apoptotic tumor cells are found throughout the sections.

Immunohistochemical stains, with adequate controls, are performed on block A1 for bcl-2, bcl-6, CD3, CD4, CD8, CD20, CD30, and Ki-67. The malignant cells are positive for bcl-6, bcl-2, and CD20. They are negative for CD3, CD4, CD8, and CD30. Ki-67 shows a proliferation rate of about 70%.

The morphology and immunophenotypes of the malignant cells are most consistent with diffuse large B-cell lymphoma.

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86. LN: DLBCL (70%), FL (30%); BM: negative for lymphoma

DIAGNOSIS:

- (R) cervical lymph node: Diffuse large B-cell lymphoma (70%) and follicular lymphoma, grade 3/3 (30%), indicating transformation of follicular lymphoma to diffuse large B-cell lymphoma

- Bone marrow biopsy: Normocellular for age with no evidence of lymphoma metastasis

MICROSCOPIC DESCRIPTION:

Histologic sections of the (R) cervical lymph node show effacement of the normal lymph node architecture. About 70% of the examined area shows diffuse infiltration by malignant cells with intermediate-large size, with vesicular nuclei and one to several nucleoli. Frequent mitotic figures are seen. About 30% of the examined area shows poorly-defined neoplastic follicles of varying size. The follicles lack mantle zone and contain mostly centroblasts, admixed with a small number of small lymphocytes.

Immunohistochemical stains, with adequate controls, are performed on block 2 of the lymph node for bcl-6, CD10, CD20, MUM-1, and Ki-67. The neoplastic cells (in the follicular area and also in the diffuse area) are positive for bcl-2, CD20, CD10. Ki-67 shows approximately 60% proliferation rate. Additionally, bcl-2 immunostain was performed on block 2 for morphoproteomic study (report CP-11-11) which shows positivity for the neoplastic cells.

The morphology and immunophenotyping (by immunostains) are consistent with diffuse large B-cell transformed from follicular lymphoma (grade 3/3)

Histologic sections of bone marrow biopsy show 30% cellularity (normocellular for age, no evidence of granuloma, fibrosis or tumor metastasis.

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87. LN: Blastic plasmacytoid dendritic cell neoplasm

Diagnosis

Peritoneal lymph node, left, laparoscopic biopsy:

- Consistent with blastic plasmacytoid dendritic cell neoplasm (see comment)

Comment

The sections show sheets of malignant cells with extensive necrosis. The malignant cells have the same cytologic features as seen in the previous cores, touch preps and pleural fluid (CA09-442, CA09-492 and CN09-461).

Immunohistochemical stains for CD45, CD20, CD2, CD4, CD56, myeloperoxidase, CD68, lysozyme, CD43, ALK-1, CD138, and EBER-1 in situ hybridization were performed on 1 B.

The malignant cells are positive for CD45, CD43, CD4, and CD56.

The malignant cells are negative for CD20, CD2, myeloperoxidase, CD68, lysozyme, ALK-1, CD138, and EBER. The neoplasm is also negative for CD79a, Pax-5, CD3, CD8, CD5, CD7, myogenin, desmin, several epithelial markers and other markers as shown in the previous core biopsies and pleural fluid (CA09-442, CA09-492, CN09-461).

The overall findings are most consistent with the above diagnosis.

The results were informed to Dr. Lovy (by phone) and Dr. Bull on 5/15/09.

Controls are appropriate.

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88. Stomach: EBV-Pos DLBCL of the elderly- Addendum Diagnosis

1. Stomach, biopsy:

- EBV-positive diffuse large B cell lymphoma of the elderly (see comment)

- Warthin-Starry silver stain is positive for Helicobacter pylori.

2. Stomach, biopsy:

- Gastric fundic and antral mucosa with chronic active gastritis.

- Warthin-Starry silver stain is positive for Helicobacter pylori.

Comment

EBER-1 (by ISH testing) on block 1A is positive for EBV. This finding is consistent with EBV-positive diffuse large B cell lymphoma of the elderly in this 76 y/o patient with gastric diffuse large B cell lymphoma. This disease entity is associtaed with an aggressive clinical course [Ref: S. Swerdlow et al, WHO Classification of Tumours of Haematopoietic and Lymphoid Tissues. International Agency for Research on Cancer, 2008, p 243-244]

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89. Thigh mass: T cell/histiocyte-rich large B cell lymphoma

Diagnosis

Right anterior thigh mass:

- T cell/histiocyte-rich large B cell lymphoma, see comment

Comment

Dr. Adam Vogel was notified of this diagnosis by Dr. E. McQuitty on 5/31/2011 at 16:30.

Microscopic Description

Histologic sections of the right anerior thigh mass biopsy show infiltration in the sections consisting of large cells with pleomorphic features. Many have one to several prominent nucleoli. Rare binucleated large cells are also seen. The malignant cells are dispersed in sections and are admixed with a large number of small lymphocytes with mature cytological features, also with a moderate number of histiocytes. The malignant cells account for less than 10% of the cells in sections. Frequent mitotic figures are seen.

Immunohistochemical stains, with adequate controls, are performed on block 1B for myogenin, and CD99; on blocks 1G for CD3, CD15, CD20, CD30, CD45, CD99, ALK-1 protein, and PAX-5. The malignant cells are positive for CD45, CD20, and PAX-5. They are negative for myogenin, CD3, CD15, CD30, CD99, and ALK-1. The surrounding small lymphocytes are positive for CD45 and CD3.

The morphology and immunophenotypes are most consistent with T cell/histiocyte-rich large B cell lymphoma.

Notes: no abnormal immunophenotypes are found with flow cytometry (Report HF-11-155). Note that the flow cytometric results are not diagnostic for T cell/histiocyte-rich large B cell lymphoma in this patient due to the small number of malignant cells (less than 10% of the cells in the sample).

Addendum Diagnosis

Right anterior thigh mass:

- T-cell/histiocyte-rich large B-cell lymphoma.

- Positive Ki-67 expression in almost all malignant large B cells, see comment.

Comment

An immunohistochemical stain, with adequate positive control, is performed on block 1G for Ki-6 An immunohistochemical stain, with adequate positive control, is performed on block 1G for Ki-67 to evaluate the proliferative rate. Almost all the malignant large B cells (approaching 100%) are positive for Ki-67.

++++

90. TONSILS: Follicular lymphoid hyperplasia

1. Left tonsil:

- Follicular lymphoid hyperplasia.

- No evidence of lymphoma.

2. Right tonsil:

- Follicular lymphoid hyperplasia.

- No evidence of lymphoma.

Histologic sections of the right and left tonsils show marked follicular hyperplasia. The follicles have well-formed mantle zone. The germinal centers contain moderate number of mitoses and tingible-body macrophages. No evidence of granuloma or necrosis is found in sections.

Tonsil biopsies were sent to Memorial Hermann Laboratory for flow cytometry immunophenotyping (report HF-11-171 for the right tonsil and report HF-11-172 for the left tonsil).

Immunophenotyping of the right tonsil biopsy by flow cytometry in the large cell area (with high forward-scatter signal) shows a small T cell population (about 8% of the cells gated), a prominent B cell population (about 92% of the cells gated) that is positive for CD19, CD20, CD22, CD10, and FMC7. They show no surface light-chain restriction. Analysis of small lymphocytes with low forward-scatter signal reveals similar marker profile as that of the large lymphocytes. These immunophenotypic results are consistent with follicular lymphocytes (centroblasts and centrocytes) in reactive follicles of the tonsil. No evidence of lymphoma is found. Immunophenotyping of the left tonsil shows essentially similar results.

++++

91. Skin, right nasal, biopsy: Extranodal NK/T –cell lymphoma

Skin, right nasal, biopsy:

- Extranodal NK/T –cell lymphoma

Histologic sections of the skin biopsy shows dermal lymphocytic infiltrates admixed with extensive crush artifacts. Focal areas with coagulative necrosis and angiodestructive infiltrates are also seen. Immunohistochemical stains, with adequate controls, are performed on block 1A for CD2, CD3, and CD56. An abnormal subpopulation of intermediate-large lymphocytes is found to be positive for CD2 and CD56. They are positive for CD3 with a cytoplasmic pattern. These abnormal lymphocytes are admixed with small mature lymphocytes that are positive for CD2, CD3, and negative for CD56.

The morphological and immunostain findings are consistent with extranodal NK/T-cell lymphoma.

Dr. Citardi was notified of this finding on 7/6/2011

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92. Lung/ mediastinal mass/ lymph node: Nodular sclerosis classical Hodgkin lymphoma

Diagnosis

1. Right upper lobe:

Nodular sclerosis classical Hodgkin lymphoma (margins are involved by lymphoma)

2. Anterior mediastinal mass:

Nodular sclerosis classical Hodgkin lymphoma (margins are involved by lymphoma)

3. Subparietal node:

Necrotic tissue

4. Inferior pulmonary node:

Nodular sclerosis classical Hodgkin lymphoma

5. Level four node:

Nodular sclerosis classical Hodgkin lymphoma with necrotic tissue

6. Anterior mediastinal tissue:

Benign thymic tissue

Histologic sections of the right upper lobe show abnormal lymphoid tissue with smaller areas of residual lung tissue. The lymphoid tissue shows a nodular pattern with collagen bands surrounding the nodules. Aggregates of large atypical cells with prominent nucleoli, some with binucleated / multinucleated form and lacunar form, are seen throughout the sections. These cells are admixed with an inflammatory background of small lymphocytes, macrophages, eosinophils, and neutrophils. Lymphoid tissue with similar morphology is also seen in: anterior mediastinal mass, inferior pulmonary node, and level four node.The subparietal node shows only necrotic tissue. The anterior mediastinal mass shows benign thymic tissue.

Immumohistochemical stains, with adequate controls, are performed on block 2C for CD3, CD15, CD20, CD30, ALK-1, CD45, and PAX-5. The large atypical cells are positive for CD15, and CD30 (both with a membrane-Golgi pattern), and PAX-5 (weak intensity); and negative for CD3, CD20, CD45, and ALK-1 (consistent with the pattern for Hodgkin and Reed-Sternberg cells). The small lymphocytes in the background are mostly T cells (positive for CD3) with a smaller number of B cells (CD20-positive).

Immumohistochemical stains, with adequate controls, are also performed on block 1E for CD15, and CD30. The large atypical cells are positive for CD15 and CD30 (both with a membrane-Golgi pattern).

The morphology and immunophenotypes of the abnormal cells are consistent with classical Hodgkin lymphoma, nodular sclerosis subtype

Note that immunophenotyping of mediastinal mass biopsy by flow cytometry (report HF-11-198) showed no abnormal immunophenotypes except for a high CD4/CD8 ratio (typically seen in classical Hodgkin lymphoma).

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93. Supraclavicular lymph node biopsy: Plasmablastic lymphoma

Right supraclavicular lymph node biopsy:

- Plasmablastic lymphoma, with Ki-67 approaching 100%

Comment

Dr. Mehta was notified of the diagnosis on 8/8/2011.

Microscopic description:

Histologic sections of the right supraclavicular lymph node show effacement of normal architecture with diffuse infiltration of large-size cells with vesicular nuclei and one to several nucleoli. Frequent mitotic figures are seen. A small number of macrophages with ingested apoptotic tumor cells and scattered eosinophils are found throughout the sections.

Touch preps (diff-quik) show numerous abnormal lymphocytes. These lymphocytes have large nuclear size, prominent nucleoli, with no cytoplasmic vacuoles.

Immunohistochemical stains, with adequate controls, are performed on block 1A for CD20, Ki-67, CD5, CD10, bcl-1, CD3, CD4, CD8, CD138, CD79a, CD56, kappa/lambda, CD43, MPO, CD30, ALK-1, pan- CK, desmin, MUM-1, S-100, CD2, CD45, and CD38, Immunohistochemical stains show that the neoplastic cells are positive for CD38, MUM-1, and Ki67 (proliferation rate approaching 100%). They are partially positive for CD138 and are negative for CD56, CD20, CD5, CD10, bcl-1, CD3, CD4, CD8, CD79a, CD43, MPO, CD30, ALK-1, pan-CK, desmin, CD2, CD45, and S-100. Double stain kappa/lambda is non-contributory.

Immunophenotyping of lymph node biopsy by flow cytometry (Memorial Hermann Hospital report HF-11-220) shows an abnormal cellular population that is positive for CD38 and CD56. They are negative for CD45 and CD19. Cytoplasmic kappa and lambda do not show a definitive restriction (K/L ratio of 2:1). These cells are predominantly large in size (based on forward-scatter signal). It was noted that CD56 was detected in the malignant cells by flow cytometry study but not by immunostain.

The immunophenotypic results, together with morphological findings in lymph node biopsy, are consistent with plasmablastic lymphoma

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94. HIV-associated lymphadenopathy

Diagnosis

Lymph node (right groin):

- Benign reactive lymph node with paracortical hyperplasia, see comment.

- No evidence of lymphoma.

Comment

- The morphological features seen in this case are typically seen in HIV-associated lymphadenopathy.

- Dr. Rios was notified of this result on 8/22/2011

Microscopic Description

Histologic sections of the right groin lymph node show partial effacement of lymph node architecture. The capsule is thickened in some areas. Paracortical hyperplasia is seen with scattered follicles that form an ill-defined nodular pattern. The follicles have variable size and are well separated. Most of the fhe follicles do not have well-formed mantle zone. A few follicles have folliculolysis. No evidence of necrosis is seen. Vascular proliferation is moderately increased. Also seen is increase in plasma cells, admixed with a small number of histiocytes.

Immunohistochemical stains, with adequate controls, are performed on block 1B for CD3, CD4, CD8, CD10, CD15 (Leu M1), CD20, CD23, CD30 (Ki-1), ALK-1 protein, and Ki-67. The cells in the follicle are positive for CD20 and CD10. The interfollicular cells are positive for CD3 and show a mixture of CD4-positive cells and CD8-positive cells. These T cells are negative for CD10. Ki-67 is less than 15%. CD23 shows positivity for follicular dendritic cells. CD15 shows scattered granulocytes and histiocytes. CD30 shows scattered activated lymphocytes. ALK-1 is negative.

The morphological features seen in this case are typically seen in HIV-associated lymphadenopathy. No evidence of lymphoma is seen.

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95. LYMPH NODE: ATYP LYMPHOID TISSUE, CANNOT RULE OUT FOLLICULAR LYMPHOMA

Diagnosis

Left cervical lymph node core biopsy:

- Atypical lymphocytic infiltrates; B-cell lymphoma cannot be ruled out (see comment)

Comment:

The morphological findings, together with immunohistochemical results, are not diagnostic due to the lack of adequate sample for reliable histological evaluation. In light of the atypical B cell population in the core biopsy, an excisional biopsy is suggested to definitively rule out B-cell lymphoma (follicular lymphoma in particular). Findings were discussed with Dr. Karni on 10/26/11.

MICRO:

Histologic sections of the left cervical lymph node core biopsy show ill-defined nodules consisting of mixture of large and small lymphocytes. The lymphocytes have small nuclei with mature cytological features, admixed with larger lymphocytes with prominent nucleolie. The overall architecture of the lymph node cannot be assessed due to small size of the core biopsy.

Immunohistochemical stains, with adequate controls, are performed on block 1A for bcl-2, bcl-6, Ki-67, CD3, CD4, CD8, CD15, CD20, and CD30. The lymphocytes in the nodules are positive for CD20, bcl-2, and bcl-6. Ki67 shows approximately 50% proliferation rate. CD15 shows positive small granulocytes. CD30 show scattered positive cells throughout the section. CD3 shows T lymphocytes (outside the nodules) which consist of a mixture of CD4-pos cells and CD8-pos cells. Immunophenotyping of core biopsy is not contributory.

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96. Lymph node: follicular hyperplasia and sinus hyperplasia

Diagnosis

Left axillary lymph node:

- Benign reactive lymph node with follicular hyperplasia and sinus hyperplasia

- No evidence of granuloma or malignancy

Histologic sections of the left axillary lymph node show preservation of lymph node architecture. The capsule is of normal thickness. Follicular hyperplasia and sinus hyperplasia are noted. Most of the follicles have well-formed mantle zone and reactive germinal center. A few follicles have attenuated mantle zone. No evidence of granuloma or necrosis is seen. Vascular proliferation is moderately increased.

Immunohistochemical stains, with adequate controls, are performed on block 1A for CD3, CD10, bcl-6, CD20, bcl-2, and Ki-67. The germinal centers are positive for CD20, CD10, bcl-6 and negative for bcl-2. Ki-67 shows strong and polarized expression in germinal centers. CD3 and bcl-2 are positive for T-lymphocytes in the interollicular areas.

The morphological and immunophenotyping findings are consistent with follicular and sinus hyperplasia.

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97. Atypical polymorphic hyperplasia (a subtype of Epstein-Barr Virus Associated
Polymorphic Lymphoproliferative Disorders Occurring in Nontransplant Setting)

Diagnosis

1. Omentum lymph node:

- Atypical lymphoid proliferation, see comment

- Special stains for acid-fast bacilli and fungi are negative for organisms

2. Mesenteric lymph node

- Atypical lymphoid proliferation, see comment

3. Left lingula

- Atypical lymphoid infiltrates, see comment

4. Left lingula

- Atypical lymphoid infiltrates, see comment

Comment

Atypical chronic inflammatory cells are seen in all specimens which consist of a predominant small T-lymphocytic population, with a significant number of plasma cells, admixed with a small number of histiocytes and B-immunoblasts. Immunophenotyping by flow cytometry and immunohistochemical stains, together with morphology, show no evidence of a monoclonal T cell or B cell population (including plasmacytic malignancy).

With the significant number of plasma cells in submitted specimens of this patient with HIV infection, lymphadenopathy, and splenomegaly, Castleman lymphadenopathy (multicentric variant) is a consideration. Another consideration is polymorphic lymphoid proliferation (less commonly seen in HIV patient). Immunohistochemical stain for HHV-8 (often positive in Castleman lymphadenopathy -multicentric variant) is pending. EBER-1 in-situ hybridization is also pending The results will be reported in Addendum.

Clinical Information

HIV and lymphadenopathy, r/o lymphoma.

Microscopic Description

Histologic sections of the omentum lymph node (#1) and mesenteric lymph node (#2) show a predominant small lymphocytic population, with a significant number of plasma cells, admixed with a small number of histiocytes. The plasma cells have mature cytological features. A small number of large cells (immunoblasts) are found admixed with small lymphocytes throughout the sections. The capsule is of normal thickness. No follicles are seen in the sections. Clusters of epitheliod histiocytes, together with necrotic cells are seen in focal areas of sections. Scattered histiocytes with phagocytosis are also seen. Special stains for acid–fast bacilli (AFB) and fungi (GMS), performed on the omentum lymph node are negative for organisms.

Histologic sections of the left lingula (#3) and the left lingula (4) show focal lymphoid infiltrates consisting of cells similar to those seen in omentum lymph node (#1) and mesenteric lymph node (#2).

Touch preps of specimens 1, 2, and 3 show a predominant small lymphocytic population, with a significant number of plasma cells, admixed with a small number of histiocytes.

Immunohistochemical stains, with adequate controls, are performed on block 2A for CD2, CD3, CD15, CD20, CD30, CD56, CD138, HHV-8, kappa, and lambda. EBER-1 in-situ hybridization is pending on block 2A. The predominant T cells show expression of CD3 and CD2. CD20 shows scattered B cells in the section, some with large size (immunoblasts). CD138 shows positive expression in plasma cells which demontrate a polyclonal distribution of cytoplasmic kappa and lambda. CD15 and CD30 show scattered positive cells (granulocytes and reactive lymphocytes, respectively). CD56 is negative. HHV-8 and EBER-1 are pending (result will be reported in Addendum).

Immunophenotyping of mesenteric lymph node biopsy by flow cytometry shows a T cell population (about 79% of the cells analyzed) with low CD4/CD8 ratio, otherwise no aberrant loss or aberrant expression of T cell markers, a B cell population (about 16% of the cells analyzed) that is negative for CD5, CD10, no surface light-chain restriction. Plasma cells show no evidence of cytoplasmic light chain restriction. These indicate no abnormal immunophenotypes with flow cytometry.

Immunophenotyping of omental lymph node biopsy by flow cytometry shows a T cell population (about 74% of the cells analyzed), and B cell population (19% of the cells analyzed). Only 8% of the cells analyzed are viable. The results from this study are non-diagnostic results due to low viability of the sample.

Immunophenotyping of left lingula of lung biopsy by flow cytometry shows a T cell population (about 87% of the cells analyzed) with low CD4/CD8 ratio, otherwise no aberrant loss or aberrant expression of T cell markers, a B cell population (about 8% of the cells analyzed) that is negative for CD5, CD10, no surface light-chain restriction. These indicate no abnormal immunophenotypes with flow cytometry.

ADDENDUM 1

Addendum Diagnosis

2. Mesenteric lymph node:

- Positive for EBV.

- Negative for HHV-8.

See comment.

Comment

Immunohistochemical stain for HHV-8 and EBER-1 in-situ hybridization, with adequate controls, are performed on block 2A. HHV-8 is negative. EBER-1 shows positivity in many cells in the section.

With negative result for HHV-8, Castleman lymphadenopathy (multicentric variant) is unlikely.

Intradepartmental consultation (with Dr. xxxx in hematopathology) yields consensus that there is no definitive evidence of lymphoma.

Extramural consultation (with Dr. xxxx) indicates the possibility of lymphomatoid granulomatosis involving the lung. Further immunostains and EBER-1 in-situ hybridization were ordered on block 3A for further investigation (to rule out lymphomatoid granulomatosis). The results of these will be reported in Addendum with interpretation.

ADDENDUM 2

Addendum Diagnosis

3. Left lingula:

- Positive for EBV.

- Negative for HHV-8.

- Atypical polymorphic hyperplasia (a subtype of Epstein-Barr Virus Associated
Polymorphic Lymphoproliferative Disorders Occurring in Nontransplant Setting),

See comment.

Comment

An immunohistochemical stain for HHV-8 and in-situ hybridization for EBER-1, with adequate controls, are performed on block 3A (UT Histology Laboratory). HHV-8 stain is negative. EBER-1 shows positive expression of many cells in the section. These results are the same as those found in the mesenteric lymph node as reported previously.

Immunohistochemical stains, with adequate controls, are also performed on block 3A for CD3, CD20, CD30, CD138, kappa, and lambda (MHH Histology Laboratory). The lymphocytic infiltrates show a mixture of small T cells (positive for CD3), small B cells (positive for CD20) and plasma cells (positive for CD138) with polyclonal pattern for kappa and lambda. A few scatterd large lymphocytes (immunoblasts) with positive CD30 are seen.

Lymphomatoid granulomatosis is unlikely in this case with paucity of large B cells in the section.

Morphological and immunophenotypes obtained are most supportive of atypical polymorphic

hyperplasia (a subtype of Epstein-Barr Virus Associated Polymorphic Lymphoproliferative Disorders Occurring in Nontransplant Setting)

Patient had been referred to MDACC for further evaluation and treatment.

REFERENCE

Jianguo Tao and Mariusz A. Wasik. Epstein-Barr Virus Associated Polymorphic

Lymphoproliferative Disorders Occurring in Nontransplant Settings. Laboratory Investigation, Vol. 81, No. 4, p. 429, 2001

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98. Lymph node: Benign lymphoid tissue with sinus hyperplasia, a few benign primary follicles

Diagnosis

Left axilla lymph node:

- Benign lymphoid tissue with sinus hyperplasia, a few benign primary follicles

- No evidence of lymphoma

Microscopic Description

Lymphoid tissue is seen in the left axillary lymph node biopsy with sinus hperplasia with a few small ill-defined follicicles. The follicles are few in number, small in size and spaced apart from each other. The lymphocytes in the follicles are small with mature cytological features, admixed with follicular dendritic cells. No well-defined mantle zone is seen in the follicles. The surrounding lymphocytes are also small with mature cytological features.

Immunohistochemical stains, with adequate positive controls, are performed on block 1A for bcl-1, bcl-2, CD3, CD5, CD10, CD20, CD23, and Ki-67. The cells in the follicles are positive for CD20, and bcl-2. They are negative for CD10, CD5, bcl-1, CD3, and Ki67. The surrounding lymphocytes are positive for bcl-2, CD5, CD3 and negative for CD10, CD23, CD20, bcl-1. Follicular dendritic cells in the follicles are postive for CD23.

The histology and immunostains are consistent with benign lymphoid tissue containing a few primary follicles.

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99. Lymph node: Diffuse large B-cell lymphoma, anaplastic variant, ABC subtype

Left inguinal lymph nodes:

- Diffuse large B-cell lymphoma, anaplastic variant with Ki67 of 80%

Comment

Dr. xxxx was notified of the diagnosis on 2/6/2012

MICROSCOPIC DESCRIPTION:

Histologic sections of the largest lymph node (1A-1B) and the bivalved lymph node (1G) show thickened capsule, follicular and sinus hyperplasia with increased vascular proliferation, also many plasma cells throughout the sections.

Histologic sections of the matted lymph node (1C-1F) show thickened capsule, increase in fibroconnective tissue, together with presence of a few small residual follicles. The most significant findings are presence of areas with diffuse infiltration of large cells with pleomorphic nuclei. Many have one to several prominent nucleoli. Multi-nucleated cells are also seen. The areas with large malignant cells are admixed with other areas with large number of small lymphocytes and plasma cells with mature cytological features. The section with the most obvious lymphoma involvement is 1C.

Immunohistochemical stains, with adequate controls, are performed on block 1C for CD20, Ki67, CD10, bcl6, MUM1, CD3, CD4, CD8, CD30, ALK1, bcl1, pan-keratin, CD138, CD15, CD79a, kappa, lambda, CD45, PAX5, and CD56. The neoplastic large cells are positive for CD45, MUM1, CD30, PAX5 (dim), and CD20 (focally). Ki67 is about 80% among the malignant cells. They are negative for pan-keratin, bcl1, CD138, CD3, CD4, CD8, CD10, ALK1, bcl6, CD15, CD56, CD79a. Kappa and lambda stains are not contributory.

The morphology and immunophenotypes are most consistent with diffuse large B-cell lymphoma, anaplastic variant.

Negative expression of CD10 and bcl-6, together with positive expression for MUM-1, are consistent with activated B-cell (ABC) subtype of diffuse large B cell lymphoma in this patient [1, 2]. The ABC group is characterized by high expression of NF-kappa B activity. This gene signature is associated with a worse prognosis using conventional chemotherapy. Proteosome inhibitors such as Bortezomib may be considered in patients who fail R-CHOP regimen [3, 4]. They have also been proved beneficial to initial treatment [5].

REFERENCES

1. Alizadeh AA et al (2000). Distinct types of DLBCL identified by gene expression profiling. Nature, 403:503-511

2. Hans CP, Weisenburger DD, Greiner TC, et al. Conﬁrmation of the molecular classiﬁcation of DLBCL by immunohistochemistry using a tissue microarray. Blood. 2004;103:275-282

3. Davis, R.E., Brown, K.D., Siebenlist, U. & Staudt, L.M. (2001) Con¬stitutive nuclear factor kappa B activity is required for survival of activated B cell-like diffuse large B cell lymphoma cells. Journal of Experimental Medicine, 194,1861–1874

4. Rosenwald A, Wright G, Chan WC, et al. The use of molecular proﬁling to predict survival after chemotherapy for diffuse large-B-cell lymphoma. N Engl J Med. 2002;346:1937-1947.

5. Leonard, J. P et al. CHOP-R plus bortezomib as initial therapy for diffuse large B-cell lymphoma (DLBCL). Journal of Clinical Oncology, 2007 ASCO Annual Meeting Proceedings Part I. Vol 25, No. 18S (June 20 Supplement), 2007: 8031

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100. Spleen: splenomegaly with red pulp congestion/ no evidence of malignancy

Spleen:

-Splenomegaly with red pulp congestion

-No evidence of malignancy

Microscopic description:

Histological sections of the spleen show normal distribution of white pulp with no expansion. The red pulp shows congestion with presence of erythroid phagocytosis by macrophages in sinusoidal lumens, supportive of immune-hemolysis in this patient with Evans syndrome.

Immunohistochemical stains, with adequate controls, are performed on black 2A for CD45, CD3, CD20, CD79a, and CD61. CD79a shows B lymphocytes mainly in the white pulp and a small number in the red pulp. CD20 is markedly decreased compared to CD79 (most likely due to previous treatment with Rituximab). CD3 shows T cells in the white pulp and a smaller number in the red pulp. CD45 shows presence of macrophages throughout the red pulp in addition to T cells and B cells described earlier. CD61 shows a significant of platelets in the red pulp. In light of patient’s platelet count of 3k, this finding is consistent with platelet sequestration by the spleen in Evans syndrome. Note that white pulp is often expanded in immune-thrombocytopenia but its absence does not rule out immune-thrombocytopenia.

No histological evidence of malignancy is seen in the spleen.

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101. Tonsils, bilateral: follicular and interfollicular hyperplasia

Tonsils, bilateral: follicular and interfollicular hyperplasia

Histologic sections of the right tonsil (1A) and left tonsil (1B) show preservation of the overlying epithelium.The follicles are increased in number and size. Many secondary follicles with prominent follicular center are seen. The follicles exhibit considerable variation in size and shape. The mantle zone of the follicles is well defined. The germinal centers contain mitoses and tingible-body macrophages. No granuloma or necrosis is seen in histologic sections. The interfollicular area is hyperplastic and show mature lymphocytes admixed with immunoblasts.

Immunohistochemical stains, with adequate controls, are performed on block 1A for CD10, CD23, CD3, bcl-6, Ki67, CD20, bcl-2, CD5, and cyclin D1. The germinal centers are positive for CD20, CD10, bcl6, CD23, and negative for bcl-2. Ki-67 shows high proliferation rate in the germinal centers and lower in the interfollicular area. CD3, CD5 and bcl-2 are positive for T lymphocytes in the interfollicular areas. Cyclin D1 is negative.

The morphological and immunophenotypic findings are consistent follicular and interfollicular hyperplasia.

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102. Lymph nodes: sinus hyperplasia with benign primary follicles

4-R lymph nodes, level 7 lymph nodes:

- Sinus hyperplasia with benign primary follicles

- Increase in polyclonal plasma cells

- No evidence of malignancy

- Special stains for acid-fast bacilli and fungi are negative

Microscopic Description

Histologic sections of the lymph nodes show moderate sinus hyperplasia. There are many small lymphoid follicles that are spaced apart from each other. The lymphocytes in the follicles are small with mature cytological features, admixed with follicular dendritic cells. No well-defined mantle zone is seen in the follicles. The surrounding lymphocytes are also small with mature cytological features. They are admixed with many plasma cells and a moderate number of histiocytes.

An immunohistochemical stain, with adequate positive controls, is performed on block 1A for bcl-1, bcl-2, CD3, CD5, CD10, CD20, CD23, CD138, kappa, lambda, Ki-67, and bcl-6. The cells in the follicles are positive for CD20, and bcl-2. They are negative for CD10, CD5, bcl-1, CD3, CD138, and bcl-6. Ki67 is absent for the lymphocytes in the follicles. The surrounding T lymphocytes are positive for bcl-2, CD5, and CD3. Follicular dendritic cells in the follicles are postive for CD23. The plasma cells are positive for CD138 with mixture of both kappa-positive cells and lambda-positive cells.

The histology and immunostains are consistent with benign lymph node containing primary follicles.

ASF and GMS stains are negative for organisms.

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103. Primary cutanous anaplastic large cell lymphoma

Diagnosis

1. Right posterior thigh lesion, biopsy:

- Cutaneous anaplastic large cell lymphoma, cannot rule out lymphomatoid

papulosis (See comment)

2. Skin tissue, right posterior side, biopsy:

- Cutaneous anaplastic large cell lymphoma, cannot rule out lymphomatoid

papulosis (See comment)

NDN 02/11/2013 Electronic Signature: Nguyen, Nghia Andy D,MD

Comment

The right posterior thigh skin biopsies show an anaplastic large T-cell lymphoma (by immunohistochemistry, see microscopic description).The differential diagnosis includes: 1) cutaneous anaplastic large cell lymphoma, 2) lymphomatoid papulosis, and 3) peripheral T-cell lymphoma, NOS. The clinical history provided states the lesion has been present for 3 years. While primary cutaneous anaplastic large cell lymphoma still remains at the top of our differential, lymphomatoid papulosis must be considered given the chronic nature of the lesion and clinical correlation is necessary to distinguish the two entities. Peripheral T-cell lymphoma, NOS remains in the differential diagnosis and may be excluded by additional studies (imaging, etc.) to rule out involvement by other sites including visceral organs.

Dr. Kamran Omidvar was notified of patient results of 02/08/13 at 11:30am.

Clinical Information

51-year-old white male with history of multiple sclerosis with limited mobility, libido reticularis, and CVA at age 45 with 8 cm erythematous to violatious indurated plaque with areas of ulceration, purulent drainage on right posterior thigh x 3 year.

Differential diagnosis: Vasculopathy with pressure ulcers/ISD versus infectious (deep fungal) atypical AFB

Microscopic Description

Histologic sections of the right posterior thigh lesion show diffuse infiltration of the dermis by intermediate-large cells with irregular nuclear contour, vesicular nuclei with fine chromatin, and one to several nucleoli. Some cells have horseshoe-shaped morphology. Frequent mitotic figures are seen. A small number of histiocytes, neutrophils, small lymphocytes, and plasma cells are seen admixed with the malignant cells. The epidermis is extensively ulcerated and necrotic with no viable epidermis remaining. AFB and PAS stains for the right posterior thigh lesion show no evidence of organisms.

Immunohistochemical stains, with adequate controls, are performed on block 2A for S100, p63, panCK, Actin, HMB45, CK 5/6, CK7, CK20, CAM5.2, CD3, CD4, CD8, CD20, CD30, CD45, ALK1, and EMA.

The malignant cells are positive for CD3, CD4, CD30 (membrane-golgi pattern), CD45, and actin (granular postitivity but non-contributory). The malignant cells are negative for ALK1, EMA, CD8, CD20, S100, p63, panCK, HMB45, CK 5/6, CK7, CK20, and CAM5.2. Small number of normal cells are seen throughout the sections: small lymphocytes (positive for CD8) and interdigitating dendritic cells (positive for S100).

The morphological findings, together with immunophenotyping by immunostains, are consistent with cutaneous anaplastic large cell lymphoma (ALK negative). Please see comment for additional differential diagnosis.

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104. PTLD, plasmacytic hyperplasia cannot be ruled out

Diagnosis

1, 2, 4, 5. Retroperitoneal lymph nodes:

-Follicular and sinus hyperplasia with significant plasmacytic hyperplasia

Microscopic Description

Histologic sections of the retroperitoneal lymph nodes (blocks 1, 2, 4, 5) show preservation of lymph node architecture. The capsule is of normal thickness. Follicular hyperplasia and sinus hyperplasia are noted. The follicles have well-formed mantle zone and reactive germinal center. No evidence of granuloma or necrosis is seen. Numerous plasma cells with mature cytological features are seen in interfollicular areas. EBER-1 in-situ hybridization performed at The University of Texas-Houston Medical School and Department of Pathology, and Histology Laboratory, with adequate controls, is performed on block 1A. EBER-1 shows no positive cells in the section. Early lesion of post-transplant lymphoproliferative disorders (PTLD), plasmacytic hyperplasia subtype, cannot be ruled out since not all cases are EBER-1-positive. Regardless, early lesion of PTLD is not considered to be of immediate clinical significance in this patient with evidence of acute renal transplant rejection at this time. A concurrent PTLD of plasmacytic hyperplasia subtype is most likely resolved by decreasing immunosupression therapy which patient now no longer needs.

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105. PAROTID GLAND: MALT LYMPHOMA

Diagnosis

Left parotidectomy, resection:

-Extranodal marginal zone lymphoma of mucosa-associated lymphoid tissue
(MALT lymphoma)

- One small reactive benign lymph node.

Microscopic Description

Histological sections (1A-1E) show diffuse distribution of abnormal lymphocytes that surround a few reactive follicles and also present as numerous lymphoepithelial lesions in salivary ducts. The lymphocytes are predominantly small cells with mature cytological features and clear cytoplasm, admixed with a few scattered transformed centroblasts. Immunohistochemical stains, with adequate controls, are performed on block 1C for CD20, CD3, CD43, CD5, bcl-2, CD10, and CD23. The abnormal lymphocytes are positive for CD20, CD43 and bcl-2. They are negative for CD3, CD5, CD10, and CD23.

The morphological findings and immunophenotypes are consistent with MALT lymphoma.

Histological sections of 1F show parts of parotid gland with lymphoma infiltrates, also a small lymph node with a few reactive follicles and no evidence of lymphoma involvement in the lymph node.

Immunophenotyping of biopsy by flow cytometry is not diagnostic (see report HF-13-95), most likely due to sampling part of normal tissue.

Addendum Diagnosis

Left parotidectomy, resection:

- Extranodal marginal zone lymphoma of mucosa-associated lymphoid tissue

(MALT lymphoma). NF-kB stain shows no increased activation of NF-kB pathway,
see comment

Comment

An immunohistochemical stain, with adequate controls, was performed on block 1C at The University of Texas-Houston Medical School and Department of Pathology, and Histology Laboratory, for p-NF-kBp65 per Dr. A. Rios' request. The malignant lymphoma cells show only weak positivity for p-NF-kB (nuclear pattern, with score of 1 out of 3).

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106. T cell/histiocyte-rich large B cell lymphoma

Diagnosis

1 and 2. Right and left inguinal lymph node biopsies:

- T cell/histiocyte-rich large B cell lymphoma, see comment

- High Ki-67 expression (in almost all malignant large B cells)

Clinical Information

11 y/o male, with Kawasaki disease.

Microscopic Description

Histologic sections of the inguinal lymph node biopsies show effacement of normal lymph node architecture with a vaguely nodular pattern of infiltration consisting of abnormal large lymphocytes with pleomorphic features. Many have one to several prominent nucleoli. No multi-nucleated large cells are seen. The malignant cells are scattered in sections and are admixed with a large number of small lymphocytes with mature cytological features, also with a moderate number of histiocytes. The malignant cells account for less than 10% of the cells in sections. Frequent mitotic figures are seen.

Immunohistochemical stains, with adequate controls, are performed on block 2A for CD3, CD4, CD8, CD57, CD15, CD30, CD45, ALK-1, CD20, PAX-5, bcl-2, Ki-67, CD10, bcl-6, CD68, CD138, and MUM1. The malignant cells are positive for CD45, CD20, PAX-5, bcl-6, CD30, MUM1, and Ki-67 (almost in all the malignant cells for Ki-67). They are negative for CD3, CD4, CD8, CD15, ALK-1, bcl-2, CD10, and CD138. Most of the surrounding small lymphocytes are T cells, positive for CD3, bcl-2, mixture of CD4-pos and CD8-pos cells. The histiocytes are positive for CD68 and CD4. CD138 shows scattered small plasma cells. CD57 shows no resetting pattern around the large lymphocytes.

The morphology and immunophenotypes are most consistent with T cell/histiocyte-rich large B cell lymphoma. The subtype of large B-cell lymphoma is most likely activated B cell (ABC)-type with negative CD10, positive bcl-6, and MUM1

Notes: Immunophenotyping of lymph node biopsy by flow cytometry (report HF-13-136) shows a T cell population (about 79% of the cells analyzed) with no aberrant loss or aberrant expression of T cell markers, a B cell population (about 25% of the cells analyzed) that is negative for CD5, CD10, no surface light-chain restriction. The lymphocyte size is small according to forward-scatter signal. Note that the flow cytometric results are not diagnostic for T cell/histiocyte-rich large B cell lymphoma in this patient due to the small number of malignant cells (less than 10% of the cells in the sample).

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107. LN: HIV, Paracortical hyperplasia

Diagnosis

Right axillary lymph nodes:

- Paracortical hyperplasia

- No evidence of lymphoma

Comment

EBV stain by EBER in-situ hybridization on block 1E is pending. The result will be reported in Addendum when available.

Clinical Information

Clinical History: 48 Y/O MALE, HIV/AIDS, PRESENTS WITH COUGH, DYSPNEA, BLE NEUROPATHY, CD4 COUNT 13, RULE OUT LYMPHOMA.

Microscopic Description

Histologic sections of right axillary lymph node biopsies show thickened capsule, increase in vascular proliferation, and presence of follicles with no well-defined mantle zone. Paracortical hyperplasia is noted with scattered large lymphocytes with prominent nucleoli, admixed with a background of small lymphocytes, histiocytes (some with cytoplasmic pigment), many mature plasma cells. No multinucleated forms of large cells are seen. No increase in eosinophils is seen. .

Immunohistochemical stains, with adequate controls, are performed on block 1D for CD10, CD4, CD8, CD3, CD20, bcl-2, bcl-6, CD23, CD138, Ki67, CD15, CD30, and ALK1. The follicles show positivity for CD20, CD10, and CD23 (CD23 for follicular dendritic cells). Folliculolysis of follicles is demonstrated with disrupted nodular staining pattern of CD10, CD20, and CD23. The large cells in paracortical area are mixture of B cells (CD20-positive) and T cells (CD3-positive). The small lymphocytes in the background are mostly T cells (positive for CD3, CD8, and bcl2). Only a small number of CD8-positive lymphocytes are seen. CD15 is positive for granulocytes in the section. Plasma cells are positive for CD138. ALK1 is negative. Ki67 shows normal distribution. CD30 and bcl6 only show scattered positive cells.

Immunophenotyping of axillary lymph node biopsy by flow cytometry (report HF-13-154) shows a T cell population (about 86% of the cells analyzed) with predominant CD8-positive lymphocytes (79%), a small B cell population (about 8% of the cells analyzed) that is negative for CD5, CD10, no surface light-chain restriction. The lymphocytes have small nuclear size according to forward-scatter signal..

The morphological and immunophenotypic findings are consistent with reactive lymph node with paracortical hyperplasia. The morphology and immunophenotypes of the large cells in the paracortical area are consistent with reactive immunoblasts. No evidence of lymphoma is found.

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108. Hemophagocytic lymphohistiocytosis

Right cervical lymph node:

- Many histiocytes showing hemophagocytosis consistent with hemophagocytic
lymphohistiocytosis, see comment

- No evidence of malignancy

Comment:

-Findings of many histiocytes with hemophagocytosis in this lymph node are supportive of hemophagocytic lymphohistiocytosis (hemophagocytosis syndrome) in this patient with the following significant information:

1. Persistent fever,

2. Marked increase in serum ferritin (39,066 ng/mL),

3. Elevated Triglycerides (393 mg/dL),

4. Elevated ALT (244 u/L), and AST (503 u/L),

5. Lymphadenopathy (cervical, axillary, and inguinal),

- Dr. Heresi was notified of the findings on 6/5/2013

-EBV stain (EBER insitu hybridization) on biopsy is pending. The result will be reported in Addendum

-Microbiology cultures for lymph node biopsy in progress, final result still pending

Microscopic Description

Histologic sections of the lymph node show intact capsule with mild increase in thickness in some areas, increase in collagen bands throughout the sections. There are many small lymphoid follicles that are spaced apart from each other. The lymphocytes in the follicles are small with mature cytological features, admixed with follicular dendritic cells. No well-defined mantle zone is seen in the follicles. The surrounding lymphocytes are also small with mature cytological features, admixed with a small number of large lymphocytes. Many histiocytes showing hemophagocytosis are seen throughout the sections.

Immunohistochemical stains, with adequate positive controls, are performed on block 1A for CD3, CD20, bcl-2, Ki67, CD15, CD30, PAX5, CD45, and CD57. The cells in the follicles are positive for CD45, CD20, PAX5, and bcl-2. They are negative for CD3, and few cells with expression of Ki67. The surrounding T lymphocytes are positive for bcl-2, CD3. CD30 is negative. CD57 shows positivity in very few lymphocytes. CD15 shows positivity in granulocytes. The histology and immunostains are consistent with benign lymph node containing primary follicles, many histiocytes with hemophagocytosis.

Immunophenotyping of axillary lymph node biopsy by flow cytometry (HF-13-205) shows a T cell population (about 77% of the cells analyzed) with no aberrant loss or aberrant expression of T cell markers, a B cell population (about 25% of the cells analyzed) that is negative for CD5, CD10, no surface light-chain restriction. The lymphocytes are small in size based on forward-scatter signal. These results indicate no abnormal immunophenotypes with flow cytometry.

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109. DLBCL with significant necrosis

Diagnosis:

Left cervical mass:

-Diffuse large B cell lymphoma with extensive necrosis, Ki-67 shows a proliferation rate of about 50%

Comments:

-Previous sample (FNA, on 5/17/13) was not diagnostic, most likely due to extensive necrosis.

-Dr. Lesslie was notified of this diagnosis through his PA, Connie Klein, on 6/10/13

Microscopic Description

Histologic sections of the left cervical mass show a lymph node with thickened capsule and adjacent normal salivary glands. The lymph node architecture is effaced by a diffuse lymphocytic infiltration with significant necrosis. Many necrotic lymphocytes are seen with pyknotic nuclei. Focal areas with more intact cells reveal lymphocytes with large nuclei and pleomorphic features. These cells have one to several prominent nucleoli.

Immunohistochemical stains, with adequate controls, are performed on block 1C for CD5, CD20, bcl1, CD23, CD10 and Ki-67. Due to necrotic tissue that masks cytological features, additional stains are done on block 1D for CD5, CD20, bcl1, Ki67, CD10, and CD3. The malignant cells are positive for CD20 and CD10. They are negative for CD3 and CD5. Ki-67 shows a proliferation rate of about 50%. CD23 shows residual follicular dendritic cells. bcl1 shows only scattered positive cells. The malignant B cells are admixed with a small number of T cells (positive for CD3 and CD5).

Immunophenotyping of biopsy by flow cytometry is non-diagnostic due to significant necrosis.

The morphology and immunophenotypes of the malignant cells are most consistent with diffuse large B-cell lymphoma (DLBCL). Positivity of CD10 in lymphoma cells is consistent with germinal-center type of DLBCL.

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110. DLBCL Ki67 ~100%, cannot r/o grayzone DLBCL/Burkitt

Diagnosis

Stomach, Biopsy:

- Diffuse large B-cell lymphoma (see comment)

- Presence of Helicobacter Pylori

Comment

Ki-67 shows a high proliferation rate approaching 100% in lymphoma cells. Biopsy sample was sent for c-Myc testing by FISH to rule out possible B-cell lymphoma, unclassifiable, with features between Diffuse large B-cell lymphoma and Burkitt lymphoma.

Microscopic Description

Histologic sections of the stomach biopsy show gastritis with ulceration. A few benign lymphoid follicles are seen. Significant areas with diffuse lymphocytic infiltration consisting of intermediate-large cells with pleomorphic nuclei are found. Many have one to several prominent nucleoli. The malignant cells are admixed with a small number of small lymphocytes with mature cytological features. Frequent mitotic figures are seen. A few macrophages with ingested apoptotic tumor cells are found in the sections. The provided immunohistochemical stain for Helicobacter Pylori is positive for organism.

Immuhistochemical stains mentioned in Alliance Health Services report were performed at reference laboratory (reportedly showing malignant cells positive for PAX5, bcl6, and negative for CD10, CD20, bcl1, bcl2, CD138). The immuno slides were not available for review, requiring stains to be performed at our institution for full evaluation.

Immunohistochemical stains, with adequate controls, are performed on block B1 for CD20, CD3, bcl2, bcl1, MUM-1, CD79a, Ki67, and bcl6. The malignant cells are positive for CD79a, bcl6. Ki67 approaches 100%. They are negative for CD20, CD3, bcl2, bcl1, and MUM1.

The morphology and immunophenotypes of the malignant cells are most consistent with diffuse large B-cell lymphoma. Expression of bcl6 and lacking of CD10, MUM1 in the lymphoma cells are consistent with germinal center (GC) subtype of diffuse large B cell lymphoma in this patient. GC subtype of DLBCL is usually found to lack constitutive NF-kB activation. This group is typically associated with better prognosis using conventional therapy

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111. Lung- Castleman’s disease

Diagnosis

1. WEDGE RESECTION OF LEFT LUNG LOWER LOB:

- Diffuse infiltrates with small lymphocytes

2. INFERIOR PULMONARY LYMPH NODE:

- Multicentric variant Castleman's disease

3. AORTICAL PULMONARY LYMPH NODE:

- Multicentric variant Castleman's disease

4. POSTERIOR HILAR L/ NODE ST.10:

- Multicentric variant Castleman's disease

5. NEEDLE BIOPSY OF LUNG MASS FOR F/S

- Diffuse infiltrates with small lymphocytes

6. LEFT LUNG MASS, F/S ON THE BRONCHIAL MARGIN AND ON THE MASS:

- Multicentric variant Castleman's disease

7. NODULES ON THE AORTA

- No abnormal lymphocytic infiltrates seen

8. ANTERIOR HILAR LYMPH NODE

- Multicentric variant Castleman's disease

9. POSTERIOR MEDIASTINAL LYMPH NODE

- Multicentric variant Castleman's disease

10. PERINEURAL INVASION

- No abnormal lymphocytic infiltrates seen

11. SUBCARINAL LYMPH NODE

- Multicentric variant Castleman's disease

12. INFERIOR PULMONARY LIGAMENT LYMPH NODE BIOPSY

- Multicentric variant Castleman's disease

NDN/NDN 08/08/2013 Electronic Signature: Nguyen, Nghia Andy D,MD

Comment

-The morphology of individual lymph node shows features of hyaline vacular variant Castleman's disease. However, due to significant involvement of multiple lymph nodes and lung tissues, Castleman's disease is best subtyped as multicentric variant in this patient.

- This case was sent for pulmonary pathology consultation (8/8/13) with Dr. P. Cagle at Texas Methodist Hospital who concurred with the diagnosis of multicentric variant Castleman's disease.

- Dr R. Brown was consulted as part of intradepartmental consultation (8/8/13). He also concurred with the diagnosis.

- The case was reviewed with Dr. Khalil on 8/8/2013

Microscopic Description

Histologic sections of blocks 2, 3, 4, 6, 8, 9, 11, 12 show lymph nodes with many abnormal follicles of varying size throughout the nodal parenchyma. They have broad mantle zone consisting of small lymphocytes arranged in a concentric (onion-ring) pattern. Many follicles have atrophic and hyalinized germinal center. Penetrating hyalinized arterioles are seen in some follicles. The interfollicular area is hypervascular with focal increase in plasma cells and eosinophils. Focal clusters of histiocytes with cytoplasmic pigment are seen in some sections. Residual lung tissues are found in a few sections with involvement of the abnormal follicles and significant increase in fibroconnective tissue. Sections of block 6 also show involvement of the abnormal follicles in the submucosa of brochial biopsy. The mass in block 6 has morphological features of an intrapulmonary lymph node.

Immunohistochemical stains, with adequate controls, are performed on block 6H for CD3, CD10, CD20, CD5, CD23, bcl-1, bcl-6, CD4, CD8, CD43, and bcl-2. The germinal centers are positive for CD20, CD10, CD23, and bcl-6. They are negative for CD3, CD5, bcl-2, CD43, CD4, CD8, CD5. The interfollicular lymphocytes are positive these T cell marker (CD3, CD5, bcl-2, CD43, CD5) with more CD4-postive cells than CD8-positive cells. Only a small number of B cells are seen in interfollicular area.

Histolgic sections of blocks 1 and 5 show diffuse lymphocytic infiltrates consisting of small lymphocytes. No abnormal follicles are seen in these sections. Sections from blocks 7 and 10 show no evidence of lymphocytic infiltrates.

The morphlogical and immunophenotypic findings show no evidence of lymphoma in the provided biopsies. The morphological findings are most consistent with Castleman's disease.

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112. Follicular B-cell lymphoma, grade 1 (out of 3) with focal area with grade 3.

1. Mass base of mesentery:

-Follicular B-cell lymphoma, grade 1 (out of 3).

2. Mesenteric mass with small bowel:

-Follicular B-cell lymphoma, grade 1 (out of 3) with focal area with grade 3.

Microscopic Description

Histologic section of the mesenteric mass shows lymphoid tissue with poorly-defined neoplastic follicles of varying size. The follicles lack mantle zone and contain mostly centrocytes. Only a small number of centroblasts are present in the follicles. Lymphocytic aggregates are seen in the surrounding adipose tissue. Sections 2A, 2B, 2K show normal small bowels with no abnormal lymphocytic infiltrtaes.

Immunohistochemical stains, with adequate controls, are performed on block 2F for CD10, CD20, bcl-6, CD3, CD5, and bcl-2. The neoplastic cells are positive for bcl-2, bcl-6, CD20, and CD10. They are negative for CD3, CD5. Positivity for CD5, CD3, bcl-2 is seen with reactive small T cells surrounding the follicles.

One particular section (2C) shows presence of follicles containing mostly centroblasts with attenuated mantle zone. Immunohistochemical stains, with adequate controls, are performed for CD10, CD20, bcl-6, CD3, and bcl-2. The cells in the follicles are positive for CD20, bcl6, CD10, bcl2 and negative for CD3.

Immunophenotyping of lymph node specimen by flow cytometry (HF-13-396) shows a T cell population (about 33% of the cells analyzed) with no aberrant loss or aberrant expression of T cell markers, a prominent B cell population (about 65% of the cells analyzed) that is positive for CD19, CD20, CD22, CD10, FMC7, surface kappa light chain restriction. These B cells are negative for CD5, and CD23.

The flow cytometric immunophenotype, morphology, and immunostain findings in this case are consistent with follicular B-cell lymphoma, grade 1/3 with focal area with grade 3.

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113. Follicular hyperplasia and progressive transformation of germinal center

Diagnosis:

Right axillary lymph nodes:

- Benign reactive lymph nodes with follicular hyperplasia and progressive transformation of germinal center

-No evidence of lymphoma

Histologic sections of the right axillary lymph nodes show ill-defined large follicles admixed with small reactive follicles. The large follicles show predominantly small mature lymphocytes with a small number of residual cells in the germinal center (follicular dendritic cells, histiocytes, centrocytes, and centroblasts). No large L&H cells are seen in the follicles. Prominent arborizing blood vessels (high endothelial venules) are also seen throughout the sections.

Immunohistochemical stains, with adequate controls, are performed on block 1A for CD20, CD3, CD10, bcl6, bcl2, bcl1, CD30, and CD15.

The lymphocytes in the reactive follicles are positive for CD20, CD10, bcl6 and negative for bcl2. The lymphocytes in the ill-defined follicles are positive for CD20 and bcl2, with scattered cells positive for bcl6 and CD10. T-lymphocytes are shown in the interfollicular areas with positivity for CD3 and bcl2. CD15 shows scattered histiocytes and granulocytes. CD30 shows scattered activated immunoblasts. Stain for bcl1 is negative.

Immunophenotyping of axillary lymph node biopsy by flow cytometry (HF-13-407) shows a T cell population (about 55% of the cells analyzed) with no aberrant loss or aberrant expression of T cell markers, a B cell population (about 39% of the cells analyzed) that is negative for CD5, CD10, and no surface light-chain restriction. The lymphocytes have small nuclear size (based on forward-scatter signal). These results indicate no abnormal immunophenotypes with flow cytometry.

The morphology and immunophenotypes are most consistent with reactive lymph nodes ( follicular hyperplasia and progressive transformation of germinal center).

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114. Lymph node: Dermatopathic lymphadenopathy

Lymph nodes, axilliary, excisional biopsy:

- Follicular and sinus hyperplasia

- Dermatopathic lymphadenopathy

- No evidence of lymphoma

MICROSCOPIC DESCRIPTION:

Histologic sections of cervical lymph nodes show presevation of lymph node architecture. Follicular hyperplasia and sinus hyperplasia are noted. The follicles have well-formed mantle zone. No evidence of granuloma or necrosis is seen. Areas of lymph node also shows expansion of paracortex with infiltration of histiocytes, some contain malin pigments

Immunophenotyping of axillary lymph node biopsy by flow cytometry (HF-4-8, Memorial Hermann report) shows a T cell population (about 60% of the cells analyzed) with no aberrant loss or aberrant expression of T cell markers, a B cell population (about 42% of the cells analyzed) that is negative for CD5, CD10, no surface light-chain restriction. These B cells have small nuclear size (based on forward-scatter signal)

These results indicate no abnormal immunophenotypes with flow cytometry.

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115. Skin biopsy: CD30-positive lyphoproliferative disorder

Skin, Left Lower Leg, Biopsy:

          - CD30-positive lyphoproliferative disorder,
             primary cutaneous anaplastic large cell lymphoma / lymphomatoid papulosis,
          - See comment

Comment

-The morphology and immunophenotype of the neoplastic cells favor a malignancy of T-cell origin with positivity for bcl2, and CD45. Given the strong CD30 positve staining with negative ALK, primary cutaneous anaplastic large cell lymphoma or lymphomatoid papulosis are the most likely diagnosis. However, the lack of multiple T-cell markers including CD2, CD3, CD4, CD5, CD7, and CD8 is not characteristic. This case most likely represents a null-phenotype T cell tumor. With EMA positivity in the tumor cells, further work-up is suggested to rule out a systemic lymphoma (anaplastic large cell lymphoma, non-primary cutaneous).

-Findings were discussed with Dr xxxx on 6/16/2014. Dr xxxx mentioned that patient first noticed the skin lesion on 3/9/14, had the lesion resected, has not been on any treatment except for the resection. Patient does not have peripheral lympdenopathy. He has scheduled patient for bone marrow and PET scan to rule out any systemic lesions.

Microscopic Description

Histologic sections of the skin show a diffuse dermal infiltrate of predominantly intermediate-sized cells with vesicular nuclei and fine nuclear chromatin. There are also many scattered large cells with irregular and hyperchromatic nuclei including some with horseshoe-shaped nuclei and others with multinucleation. Occasional mitotic figures are also seen. These neoplastic cells are admixed among a background of neutrophils, small lymphocytes, eosinophils, and occasional plasma cells.

Immunhistochemical stains demonstrate that the neoplastic cells are positive for CD45, CD30, granzyme B, perforin, bcl-2, EMA, and Ki67. They are negative for CD1a, CD2, CD3, CD4, CD5, CD7, CD8, CD10, CD20, CD34, CD56, Bcl-6, ALK-1, and EBER. TIA is equivocal due to suboptimal staining in the positive control specimen. Pancytokeratin is negative and PAS is negative for fungal elements.

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116. Right lacrimal gland, biopsy: mantle cell lymphoma

Diagnosis

Right lacrimal gland, biopsy:

-Mantle cell lymphoma, see comment

Microscopic Description

Histologic sections of the lacrimal gland biopsy show diffuse infiltration by small-intermediate monomorphous lymphocytes with a vaguely nodular growth pattern. The cells have an irregular nuclear contour with no prominant nucleolie. Hyalinized small vessels are present.

Immunohistochemical stains, with adequate controls, are performed on blck 2A. The abnormal lymphocytes arepositive for CD20 and cyclin D1. Ki-67 shows positivity in 40% of the lymphoma cells.

Immunophenotyping of lacrimal gland biopsy by flow cytometry (report HF-xxxx) shows an abnormal B cell population (about 82% of the cells analyzed) that is positive for CD5, CD19, CD20 (bright signal), CD22, FMC7, surface kappa light-chain restriction (bright signal). These B cells are negative for CD10, CD23, CD11c, CD103. These B cells have small-intermediate nuclear size (based on forward-scatter signal). These results, together with morphology in lacrimal gland biopsy and positive Cyclin-D1 stain, are most consistent with mantle cell lymphoma.

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117. Right inguinal lymph node: Marked increase in polyclonal plasma cells

Right inguinal lymph node:

- Benign reactive lymph node with paracortical hyperplasia and sinus hyperplasia

- Marked increase in polyclonal plasma cells

- No evidence of lymphoma

Microscopic Description

Histologic sections of the right inguinal lymph node show partial effacement of lymph node architecture. The capsule is thickened in some areas. Paracortical hyperplasia is seen with mostly small lymphocytes, admixed with a small number of histiocytes, and numrous plasma cells with mature cytological features. Rare small scattered follicles that form an ill-defined nodular pattern are also in sections. No evidence of necrosis is seen. Vascular proliferation is moderately increased. Immunohistochemical stains, with adequate controls, are performed on block 1C for CD20, Ki67, CD4, CD8, CD10, bcl-1, CD138, CD56, kappa, lambda, CD2, CD5, CD3, CD7, CD79a, PAX5, and MUM1. The plasma cells are positive for CD138, CD79a, MUM1 with approximately equal distribution of kappa and lambda. The cells in the follicles are positive for CD20, CD79a, PAX5, and CD10. The interfollicular T cells are positive for CD3, CD2, CD5, CD7 and show a mixture of CD4-positive cells and CD8-positive cells (many more CD8 cells than CD4 cells in this HIV patient). Ki-67 is approximately 30%. CD56 and bcl1 are negative.

The morphological and immunophenotype findings are most consistent with HIV-associated lymphadenopathy. No evidence of lymphoma is seen.

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118. Lymph node: Large B cell lymphoma with high Ki-67

Right paratracheal lymph node, excision:

-Large B cell lymphoma with high Ki-67 (80-90%), see comment

Comment

-The morphology and immunophenotypes of the malignant cells are most consistent with diffuse large B-cell lymphoma, germinal center (GC) subtype.

- Ki-67 shows a high proliferation rate, focally variable (80-90%) in lymphoma cells. Biopsy sample was sent for c-Myc, bcl6, bcl2 testing by FISH to rule out possible B-cell lymphoma, unclassifiable, with features between Diffuse large B-cell lymphoma and Burkitt lymphoma. Results will be reported in Addendum.

- Dr. Rasco's assistant (Linda Marquez) was notified of the diagnosis on 4/2/15 at 12:30 pm

Histologic sections of the right paratracheal lymph node show diffuse lymphocytic infiltration consisting of intermediate-large cells with pleomorphic nuclei. Many have one to several prominent nucleoli. The malignant cells are admixed with a modeare number of small lymphocytes with mature cytological features. Frequent mitotic figures are seen. Moderate number of macrophages with ingested apoptotic tumor cells are found in the sections.

Immunohistochemical stains, with adequate controls, are performed on block 2A for CD20, CD4, CD8, bcl-1, CD10, Bcl6, MUM1, and Ki67. The malignant cells are positive for CD20, CD10, bcl6, Ki67 variable between 80% and 90%. They are negative for CD4, CD8, bcl1, and MUM1. CD4 is positive for a moderate number of histiocytes. The morphology and immunophenotypes of the malignant cells are most consistent with diffuse large B-cell lymphoma. Expression of bcl6 and CD10 in the lymphoma cells are consistent with germinal center (GC) subtype of diffuse large B cell lymphoma in this patient. GC subtype of DLBCL is usually found to lack constitutive NF-kB activation. This group is typically associated with better prognosis using conventional therapy.

Due to the high Ki-67, biopsy sample was sent for c-Myc, bcl6, bcl2 testing by FISH to rule out possible B-cell lymphoma, unclassifiable, with features between Diffuse large B-cell lymphoma and Burkitt lymphoma.

Immunophenotyping of R paratracheal lymph node biopsy by flow cytometry (HF-15-129) in gate #2 shows a T cell population (about 40% of the cells analyzed) with no aberrant loss or aberrant expression of T cell markers, a B cell population (about 8% of the cells analyzed) that is negative for CD5, CD10, no surface light-chain restriction. Analysis of cells in gate #1 shows a predominant B cell population (about 92% of the cells analyzed) that is positive for CD10, CD19, CD20, CD22, and surface kappa light-chain restriction. They are negative for CD5, and CD23. These B cells have large nuclear size (based on forward-scatter signal). These results these results are consistent with a large B-cell lymphoma.

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119. Lung biopsy: Myeloid sarcoma

Left upper lobe lung biopsy:

- Myeloid sarcoma

- Special stains for acid-fast bacilli and fungi are negative for organism

Histologic examination of the lung core biopsies shows sheets of cells with poorly defined cell borders, many with enlarged, pleomorphic nuclei. The cells have varying and a variable presence of nucleoli with some cells lacking nucleoli and others having distinct nucleoli. Immunohistochemical stains with adequate controls were performed on block 1A for CD45, CD4, CD43, CD1a, CD68, Pan-CK, S100, TdT, MPO, CD56, CD3, Mast cell tryptase, and CD117. The malignant cells are positive for CD45, CD4, CD43; partial positive for CD68; negative for CD1a, Pan-CK, S100, TdT, MPO, CD56, CD3, Mast cell tryptase, and CD117.

AFB and GMS stains, with adequate controls, were performed on block 1A and both show no evidence of AFB or fungi.

The excisional cervical lymph node biopsy done at outside laboratory (OS-15-3289, 3/17/15) was requested for further examination and testing due to limited sample in the current lung core biopsies. Examination of the lymph node sections also shows malignant cells with similar cytological features in large clusters. Immunohistochemical stains with adequate controls were performed on block B1 for CD4, CD43, CD45, CD68, CD117, MPO, CD3, CD5, and CD8. The malignant cells are positive for CD45, CD4, CD43; partial positive for CD68; negative for CD117, MPO, CD3, CD5, and CD8.

No immunohistochemical stains from outside laboratory were available for review. However, the following stains were reportedly positive for the malignant cells in the report accompanying the biopsy: CD11c, CD33, lysozyme, CD45, and CD68.

The morphological findings, together with immunohistochemical stains, are consistent with a diagnosis of myeloid sarcoma. Histiocytic sarcoma had been considered in the differential diagnosis but was ruled out with positivity of CD43 and CD33 of the tumor cells. Carcinoma was ruled out with negative keratin stain. Note that a recent bone marrow obtained at Memorial Hermann Hospital (6/3/2015) shows no evidence of acute myeloid leukemia at this time.

Findings were discussed with Dr. Adan Rios, patient’s oncologist, on 6/5/2015.

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120. Epidural mass and thoractic mass: Myeloid sarcoma

Epidural mass and thoractic mass:

-Myeloid sarcoma

Histologic sections of the epidural mass and thoractic mass show infiltration consisting of immature cells of intermediate-large nuclear size, some with prominent nucleolie.

Immunohistochemical stains, with adequate controls, are performed on block 1A for CD45, Pan CK, S100, TTF1, CDX2, synaptophysin, chromogranin, CD56; on block 2A for CD20, Ki67, CD34, MPO, CD43, CD3, CD4, CD8, bcl-1, CD5, CD2, CD30, ALK-1, CD117, CD99, CD68, and CD7.

The abnormal cells are positive for CD45, CD4, CD43, CD68, CD117, and Ki67 (80%). They are negative for Pan CK, S100, TTF1, CDX2, synaptophysin, chromogranin, CD56, CD20, CD34, MPO, CD3, CD8, bcl-1, CD5, CD2, CD30, ALK-1, CD99, and CD7.

The morphology and immunohistochemical stains are consistent with myeloid sarcoma.

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121. LN: Granulomas, no evidence of lymphoma

Lymph node, left cervical, excision:

- Presence of granuloma

- Special stains for acid-fast bacilli, fungi, and cat-scratch are negative for organisms

- No evidence of lymphoma

Comment

Immunophenotyping of lymph node biopsy by flow cytometry (report HF-15-378) shows a T cell population (about 68% of the cells analyzed) with no aberrant loss or aberrant expression of T cell markers, a B cell population (about 34% of the cells analyzed) that is negative for CD5 and CD10 with no surface light-chain restriction. These results indicate no abnormal immunophenotypes are found with flow cytometry. Note that the flow cytometry specimen is suboptimal for evaluation due to the low viability of the sample (29%) and may not be entirely representative.

Microscopic Description

Histologic sections of cervical lymph node show a few reactive follicles with well-formed mantle zone. Several large foci of granuloma are seen with karyorrechtic debris, admixed with immunoblasts. AFB, GMS, and Warthin-Starry stains, performed on block 1A, are negative for organisms.

Immunohistochemical stains, with adequate controls, are performed on block 1A for CD20, Ki67, bcl1, CD3, CD4, CD8, CD2, CD5, CD7, CD68, bcl2, bcl6, CD10, CD15, CD30, and PAX5. Stains for CD68, CD4, and CD15 are positive for the histiocytes. Most of the lymphocytes in the section are positive for CD3, CD2, CD5, CD7, bcl2 (T cells), a smaller number of lymphocytes are positive for CD20, and PAX5 (B cells). Among T cells, there is mixture of CD4-pos cells and CD8-pos cells. Bcl-1, bcl6, CD10, and CD30 are negative. Ki67 is focally high (60%) in areas with presence of many immunoblasts.

NOTES: due to suboptimal stains for CD3, CD4, CD8, and bcl2, they are repeated at The University of Texas-Houston Medical School and Department of Pathology, and Histology Laboratory.

Immunohistochemical stains performed at The University of Texas-Houston Medical School and Department of Pathology, and Histology Laboratory, with adequate controls, are performed on block 1A for bcl-2, CD2, CD3, CD4, CD5, CD7, and CD8. Also perfomed at The University of Texas Medical School and Department of Pathology and Histology Laboratory are special stains for AFB and GMS.

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122. LN: neg for recurrent HL

Left axillary lymph node, core biopsy:

- Reactive lymph node with follicular hyperplasia.

- No evidence of recurrent Hodgkin lymphoma.

Histologic sections of the left axillary lymph node core biopsy show preservation of lymph node architecture. Follicular hyperplasia is noted. The follicles have well-formed mantle zone. No evidence of granuloma or necrosis is seen. Vascular proliferation is moderately increased. Scattered large lymphocytes are seen in interfolliculatr area, none of which show multinucleated forms.

Immunohistochemical stains, with adequate controls, are performed on block 1A for CD10, bcl6, CD5, CD3, bcl2, PAX5, CD20, CD15, CD30, Ki67, and bcl1. The germinal centers are positive for CD20, CD10, bcl6, PAX5, and negative for bcl-2. Stains CD5, CD3 and bcl-2 are positive for T lymphocytes in the interollicular areas. Bcl1 only shows only scattered positive cells. Ki67 shows high proliferation rate (90%) in reactive germinal centers and no positive multinucleated cells are seen in interfollicular area. Stains CD15 and CD30 show scatterd positivity of large lymphocytes (activated immunoblasts) in interfollicular area with no multinucleated cells indentified.

++++++++

123. LN: Langerhans cell histiocytosis

Inguinal lymph node:

-Langerhans cell histiocytosis (LCH), see comment

-Special stains for acid-fast bacilli and fungi are negative for organisms.

Comment:

-Dr. D. Brown was notified of the findings on 11/18/2016

-This case was reviewed with consensus in the University of Texas-Houston Medical School Hematopathology QA Conference on 11/18/2016

MICROSCOPIC

Histologic sections of the lymph node show follicular and sinus hyperplasia. Large areas in the sinus and paracortex are infiltrated by LCH cells, with oval nuclei, fine chromatin, and inconspicuous nucleoli. Many LCH cells are with grooved nuclei. They are admixed with a small number of eosinophils and lymphocytes, and histiocytes (some with pigments). Immunohistochemical stains, with adequate controls, are performed on block 1A for CD68, CD4, CD138, CD1a, S100, vimentin, IgG, and IgG4. The LCH cells are positive for CD1a, S100, CD68 (subset), CD4, and vimentin. Vimentin positivity is not contributory since most cells in the section are positive.

The morphology and immunohistochemical stain findings are consistent with Langerhans cell histiocytosis. Dermatopathic lympadenopathy is ruled out with diffuse staining pattern for both CD1a and S100 in the LCH cells. A small number of plasma cells are seen in the section and are positive for CD138. The ratio IgG4/IgG is approximately 20% (less than the 40% threshold for IgG4-related diseases). Special stains for acid-fast bacilli and fungi (AFB and GMS, respectively) are performed on block 1A and are negative for organisms.

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124. Pelvic mass: High-grade B cell lymphoma

High-grade B cell lymphoma with high proliferative rate (Ki67 100%), see comment

Comment

-The morphology and immunophenotypes are consistent with a high-grade large B-cell lymphoma with high proliferative rate. The list includes diffuse large B cell lymphoma with high Ki67, Burkitt lymphoma, high-grade B cell lymphoma with cMYC, bcl2 and/or bcl6 rearrangement (double-hit lymphoma or triple-hit lymphoma). Definitive subtypes require molecular testing.

-Biopsy sample was sent to Genoptix Reference Laboratory for non-Hodgkin lymphoma FISH panel to rule out the following: Burkitt lymphoma, high-grade B cell lymphoma with bcl2 and/or bcl6 rearrangement (double-hit / triple-hit lymphoma). Results will be reported in Addendum

-Findings were notified to Dr. Kawaguchi on 9/1/2016

Microscopic Description

Histologic sections of the right pelvic mass show diffuse lymphocytic infiltrate consisting of intermediate-large cells with pleomorphic features. Many cells have one to several prominent nucleoli. Many mitotic figures and tingible-body macrophages are seen. The infiltrates of malignant cells are admixed with a small number of surrounding small lymphocytes with mature cytological features. Touch preps show many pleomorphic cells, some with basophilc cytoplasm and only a subset with cytoplasmic vacuoles, admixed with small mature lymphocytes lymphocytes.

Immunophenotyping of lymph node biopsy by flow cytometry (report HF-16-438) shows an abnormal B cell population (about 99% of the lymphocytes gated) that is positive for CD19, CD20, CD22, CD10, FMC7, and surface kappa light chain restriction. These B cells are negative for CD5, and CD23. These B cells are predominantly intermediate-large in size (based on forward-scatter signal). These results are consistent with a B cell lymphoma.

Immunohistochemical stains, with adequate controls, are performed on 1A for CD20, CD10, bcl6, Ki67, bcl2, CD3 and bcl1. The neoplastic large cells are positive for CD20, CD10, bcl6, and Ki-67 (100%). They are negative for bcl2, bcl1, and CD3. Cd3 is positive for a small number of surrounding T lymphocytes. The morphology and immunophenotypes are consistent with a high-grade B-cell lymphoma with high proliferative rate. The list includes diffuse large B cell lymphoma with high Ki67, Burkitt lymphoma, high-grade B cell lymphoma with cMYC, bcl2 and/or bcl6 rearrangement (double-hit lymphoma or triple-hit lymphoma). Definitive subtypes require molecular testing. Sample was sent for FISH testing (cMYC, bcl2 and/or bcl6 rearrangement). Results will be reported in Addendum.

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125. Orbital mass: Marginal zone lymphoma

Orbital Mass:

-Marginal zone lymphoma

Histologic sections of the orbital mass biopsy show fibroadipose tissue. A focal lymphoid aggregate is seen in Part 1 (1A) and Part 3 (3A). The lymphocytes have small nuclei with mature cytological features, some with cleaved nuclei, and some with monocytoid features.

Immunohistochemical stains, with adequate controls on block 1A, shows that the lymphocytes are predominantly B cells, positive for CD20 and bcl-2. They are negative for CD3, and CD43. A small number of T lymphocytes are shown with positive T cell markers (CD3, and CD43).

Immunophenotyping of orbital mass by flow cytometry (report HF-16-296, performed at Memorial Hermann Laboratory) shows a T cell population (about 30% of the cells analyzed) with no aberrant loss or aberrant expression of T cell markers, an abnormal B cell population (about 65% of the cells analyzed) that is positive for CD19, CD20, and surface lambda light-chain restriction. These B cells are negative for CD5, CD10. These B cells have small nuclear size (based on forward-scatter signal).

The morphological and immunophenotypic findings are most consistent with marginal zone (B cell) lymphoma.

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126. Lung: Castleman's disease, mixed type (hyaline vascular and plasma cell variant)

1. Level 11 lymph node, biopsy:

- One reactive lymph node.

2. Lung, right upper lobe, lobectomy:

- Castleman's disease, mixed type (hyaline vascular and plasma cell variant).

- Please see comment.

3. Level 12 lymph node, biopsy:

- One reactive lymph node

1 and 3 - Histologic sections of level 11 lymph node and level 12 lymph node show presevation of lymph node architecture. Follicular hyperplasia and sinus hyperplasia are noted.

2 - Histologic sections of lobectomy specimen show lung tissue with many abnormal follicles of varying sizes throughout the lung parenchyma. They have broad mantle zone consisting of small lymphocytes arranged in a concentric (onion-ring) pattern. Many follicles have atrophic and hyalinized germinal center. Penetrating hyalinized arterioles are seen in some follicles. The interfollicular area is hypervascular with significant number of plasma cells.

The morphlogical findings show no evidence of lymphoma in the provided tissues. The morphological findings are most consistent with Castleman's disease, mixed type, which shows features of both hyaline-vascular variant and plasma cell variant.

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127. Vertebral body: Several small benign lymphoid follicles

Lumbar 1 vertebral body:

Several small benign lymphoid follicles.

No evidence of malignancy

Microscopic Description

Histologic section of lumbar 1 vertebral body biopsy shows bone marrow with trilineage maturation, 30% cellularity (appropriate for patient’s age). A few small lymphocytic follicles in the biopsy are seen. The lymphocytes in the follicles are small with mature cytological features.

Immunohistochemical stains, with adequate controls, are performed on blocks 1A for CD5, CD23, CD10, bcl6, bcl2, CD43, bcl1, CD3, and CD20). The cells in the follicles are mostly T cells (positive for CD5, CD3, and CD43). A small number of B cells are seen in the follicles with positivity for CD20 and some in the mantle zone with positive bcl2. The cells in the follicles are negative for bcl1, CD10, bcl6, and CD23.

The immunophenotype results, together with morphology findings, are consistent with benign lymphoid follicles in the vertebral body.

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128. Submandibular mass: High-grade B cell lymphoma

Submandibular mass core biopsy:

High-grade B cell lymphoma with high proliferative rate (Ki67 > 90%), see comment

Comment

-The morphology is most consistent with diffuse large B cell lymphoma. However, other high-grade B cell lymphoma (Burkitt lymphoma, high-grade B cell lymphoma with bcl2 and/or bcl6 rearrangement) cannot be ruled out with morphology alone in this case with the given immunophenotype

-Findings were notified to Dr. R Karni on 7/29/2016

Microscopic Description

Histologic sections of the submandibular mass show several large lymphocytic infiltrates consisting of intermediate-large cells with pleomorphic features. Many cells have one to several prominent nucleoli. Many mitotic figures are seen. The infiltrates of malignant cells are admixed with surrounding small lymphocytes with mature cytological features. Touch preps show many pleomorphic cells, some with basophilc cytoplasm and only a few with cytoplasmic vacuoles, admixed with small mature lymphocytes.

Immunohistochemical stains, with adequate controls, are performed on 1A for CD20, CD79a, Ki67, bcl2, bcl6, CD10, CD5, and bcl1. The neoplastic large cells are positive for CD20, CD79a, Ki-67 (>90%), bcl6, and CD10. The malignant cells are negative for bcl2, CD5 and bcl1. The morphology and immunophenotypes are consistent with a high-grade large B-cell lymphoma with high proliferative rate. The morphology is most consistent with diffuse large B cell lymphoma. However, other high-grade B cell lymphoma (Burkitt lymphoma, high-grade B cell lymphoma with bcl2 and/or bcl6 rearrangement) cannot be ruled out with morphology alone.

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129. Left axillary breast mass: Nodular lymphocyte predominant Hodgkin Lymphoma

Left axillary breast mass, excision:

- Nodular lymphocyte predominant Hodgkin Lymphoma

- See comment.

Comment

Histologic sections of the breast mass show effacement of normal architecture. A nodular pattern is seen. Most of the nodules are large with ill-defined borders. Most of the cells in the nodules are small lymphocytes with mature cytological features. A small number of large multilobated cells with prominent nucleoli are seen in throughout the nodules. The capsule is of normal thickness. A small number of small reactive follicles are also seen in the sections.

Immumohistochemical stains, with adequate controls, were performed on block A4 by outside laboratory. The large atypical cells are positive for CD20, PAX5, BOB1, OCT2, MUM1, and bcl6. A subset of these large cells are weakly positive for CD30. They are negative for CD3, CD15 and CD57. CD45 is equivocal in the large cells due to large number of surrounding postive cells. CD3 shows T lymphocytes forming rosettes surrounding the large cells. The CD21 highlights the follicular dendritic meshwork.

The morphology and immunophenotypes of the abnormal cells are consistent with nodular lymphocyte predominant Hodgkin Lymphoma.

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130. Left axillary lymph node: Kikuchi’s disease

Left axillary lymph node:

-Necrotizing lymphadentitis most consistent with Kikuchi’s disease

-No evidence of lymphoma

Comment

-Immunophenotyping of axillary lymph node biopsy by flow cytometry (report HF-16-285) shows a T cell population (about 30% of the cells analyzed) with no aberrant loss or aberrant expression of T cell markers, a B cell population (about 70% of the cells analyzed) that is negative for CD5, CD10, no surface light-chain restriction. These results indicate no abnormal immunophenotypes with flow cytometry.

-Special stains for acid-fast bacilli and fungi (AFB and GMS) are pending. The results will be reported in Addendum.

Microscopic Description

Histologic sections of lymph node show large foci of necrosis with abundant karyorrhectic debris and marked apoptosis. The necrotic foci are confluent and include many crescentic histiocytes (having C-shaped nuclei) admixed with a smaller number of immunoblasts. Immunohistochemical stains, with adequate controls, are performed on 1A for CD3, CD20, CD4, CD8, CD30, ALK1, bcl1 , Ki67, and CD68. The stains show a significant number of histiocytes (positive for CD68) and many CD3+/CD8+ T immunoblasts in the necrotic foci. A smaller number of CD4-postive T lymphocytes are present. CD20 shows B lymphocytes surrounding the necrotic foci. CD30, ALK1, and bcl1 are negative. Ki67 shows high positive rate (60%) in the necrotic area. Neutrophils, plasma cells, and eosinophils are absent in the necrotic foci.

The morphologic and immunophenotypic findings are most consistent with Kikuchi’s disease. Lupus lymphadenitis is considered as a differential diagnosis in this necrotizing lymphadentitis case. However, frequent findings in lupus lymphadenitis such as abundant plasma cells, follicular hyperplasia, and hematoxylin bodies, are not seen in this case.

Special stains for acid-fast bacilli and fungi (AFB and GMS) are pending. The results will be reported in Addendum.

Due to suboptimal original CD4 stain finding, additional immunostains were performed at University of Texas-Houston McGovern Medical School and Department of Pathology, and Histology Laboratory, with appropriate controls on block 1A for CD3, CD4, CD8, and CD68

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131. Left axillary lymph node: Castleman's disease, hyaline vascular variant

Left axillary lymph node:

-Castleman's disease, hyaline vascular variant

Comment

Immunophenotyping of lymph node biopsy by flow cytometry (HF-15-316) shows a T cell population (about 76% of the cells analyzed) with no aberrant loss or aberrant expression of T cell markers, a B cell population (about 23% of the cells analyzed) that is negative for CD5, CD10, CD56, no surface light-chain restriction. These results indicate no abnormal immunophenotypes with flow cytometry.

Histologic sections of the left axillary lymph node show with many abnormal follicles of varying size, most with small size, throughout the nodal parenchyma. They have broad mantle zone consisting of small lymphocytes arranged in a concentric (onion-ring) pattern. Many follicles have atrophic and hyalinized germinal center. Penetrating hyalinized arterioles are seen in some follicles. The interfollicular area is hypervascular. The morphological findings are most consistent with Castleman's disease, hyaline vacular variant.

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132. Conjunctiva: Follicular B-cell lymphoma, grade 2 (out of 3), also focal areas with grade 3/3

Right conjunctiva:

- Follicular B-cell lymphoma, grade 2 (out of 3) with a predominant follicular pattern, also focal areas with grade 3/3

Comment:

Dr. Stella Kim was notified of the diagnosis on 2/15/2017

Microscopic Description

Histologic sections of the R conjunctiva mass shows lymphoid tissue with poorly-defined neoplastic follicles of varying size. The follicles lack mantle zone and contain a heterogeneous mixture of centrocytes and centroblasts and a few mitotic figures. Focal areas of the sections show follicles with mostly centroblasts.

Immunophenotyping of the R conjunctiva specimen by flow cytometry (HF-17-73, Memorial Hermann Laboratory) shows a predominant B cell population (about 73% of the lymphocytes) that is positive for CD19, CD20, CD22, CD10, and surface kappa light chain restriction.

Immunohistochemical stains, with adequate controls, are performed on block 1A for CD10, CD20, bcl-6, Ki67 and bcl-2. The neoplastic cells in the follicles are positive for bcl-2, bcl-6, CD20, and CD10. Positivity for bcl-2 is also seen with reactive small T cells surrounding the follicles. Ki67 shows proliferation rate in the follicles varying from 20% to 50%.

The flow cytometric immunophenotypes, morphology, and immunostain findings in this case are consistent with follicular B-cell lymphoma, grade 2 (out of 3) with a predominant follicular pattern, also focal areas with grade 3/3

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133. Thyroid: polyclonal plasma cells

Thyroid, right:

-Acute and chronic inflammatory cells including small foci of polyclonal plasma cells

-Focal areas with necrosis

-Special stains for acid-fast bacilli and fungi are negative for organisms

-No evidence of malignancy

Histologic sections of the right thyroid biopsy show significant infiltration of acute inflammatory cells (neutrophils) with areas of necrosis. Two small foci of plasma cells are seen in the section. Imunostains, with adequate controls, are performed on A1 for CD3, CD20, CD138, kappa, lambda, CD2, CD43, bcl2, and CD79a. The plasma cells are positive for CD138, and CD79a and consist of a mixture of kappa-positive cells and lambda-positive cells (polyclonal plasma cells). Scattered T cells are positive for CD3 and CD43. The following stains are negative: CD21, bcl2, and CD20. Stains from outside laboratory are reviewed with the following findings:

-AFB and GMS stains: negative for organisms

-Immunohistochemical stains for Keratin, TTF-1: negative

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134. Right axillary lymph node biopsy: PTCL with HLH

Right axillary lymph node biopsy:

-Peripheral T cell lymphoma, NOS

-Hemophagocytic lymphohistiocytosis

-See comment

Bone marrow aspirate and biopsy:

-Hypercellular for age with increased megakaryopoiesis

-No evidence of hemophagocytosis

-Involvement of T cell lymphoma

-See comment

Comment

-The morphologic findings of hemophagocytosis in lymph node, together with other clinical data (fever, bicytopenia, elevated triglyceride, elevated ferritin at 40,000, and hypofibrinogenemia) are consistent with hemophagocytic lymphohistiocytosis (HLH)

-Morphologic and immunophenotypic findings are consistent with peripheral T cell lymphoma, NOS with mature cytology (T-zone lymphoma). The patient’s HLH is likely associated with systemic T cell lymphoma which involves the axillary lymph node, bone marrow, and presumably mediastinum.

-Immunohistochemical stain for ALK-1 on block 2A is pending. The result will be reported in Addendum

-Dr. Rios and Dr. Rowe were notified of the findings on 6/15/2017

Microscopic Description

Right axillary lymph node:

Histologic sections of the right axillary lymph node show sinus hyperplasia, significant hemophagocytosis, and diffuse infiltration by small lymphocytes with mature cytological features. There are a few primary follicles scattered in the sections. There are also many large lymphocytes (immunoblasts) in aggregates throughout the section.

Immunohistochemical stains, with adequate controls, are performed on block 2A for bcl2, bcl6, CD2, CD3, CD4, CD7, CD8, CD10, CD15, CD20, CD30, CD45, CD57, cyclin D1, Ki67, and PAX5. Stains are also performed on block 1E for bcl2, bcl6, CD3, CD4, CD7, CD8, CD10, CD20, cyclin D1, Ki67, and PAX5. The malignant T cells are positive for CD2, CD3, with aberrant loss of CD4, CD8, CD7, CD45, and bcl2. They are also negative for bcl6, CD10, CD15, CD20, CD30, cyclin D1, and PAX5. They have a proliferation of 30% (Ki67 expression). The primary follicular cells are positive for CD20, PAX5, and bcl2. The immunoblasts are positive for CD45, CD30, CD2, CD3, CD7, Ki67; and negative for PAX5. The immunoblasts show a mixture of CD4-pos cells and CD8-pos cells. Stains for bcl6, cyclin D1, CD57, CD15 and CD10 show only scattered positivity.

The morphological findings, together with immunophenotyping by immunostains, are consistent with peripheral T cell lymphoma, NOS with mature cytology (T-zone lymphoma).

Bone marrow aspirate and biopsy:

CBC results show: RBC 3.19, Hgb 8.4, Hct 24.3, MCV 76.1, MCH 26.4, MCHC 34.7, Platelets 37 K, WBC 5.5.

Examination of blood smear shows hypochromic microcytic anemia, mild polychromasia; normal number of leukocytes with a few reactive lymphocytes, and thrombocytopenia.

Bone marrow aspirate, touch preps and clot section show adequate granulopoiesis, increased megakaryopoiesis, and decreased erythropoiesis. Iron stores are adequate. No evidence of hemophagocytois is identified.

Bone marrow biopsy (decalcified) shows a cellularity of 60%. No evidence of hemophagocytosis, granuloma, fibrosis, or abnormal lymphoid infiltrates is seen.

Immunophenotyping of aspirate by flow cytometry (report KF-17-538) shows a small T cell subset (52% of T cells or 5% of all bone marrow cells) with abnormal profile (positive for CD2, CD3, with aberrant loss of CD4, CD8, and CD7). Note that this profile is identical to that of the malignant T cells in the right axillary lymph node. The malignant T cells in bone marrow are very small in number (5%), with mature cytologic features, rendering them not detectable with morphologic examination.

+++++++

135. Right orbital mass: Diffuse large B cell lymphoma

1.Right orbital mass, fresh:

-Flow cytometry pending

2. Right orbital mass, permanent:

-Diffuse large B cell lymphoma, activated B cell subtype with high Ki67 (80%), see comment

Microscopic Description

Histologic sections of the right orbital mass show diffuse lymphocytic infiltration consisting of intermediate-large cells with pleomorphic nuclei. Many have one to several prominent nucleoli. The malignant cells are admixed with a small number of small lymphocytes with mature cytological features, also with a few mitotic figures. Many macrophages with ingested apoptotic tumor cells are found throughout the sections.

Immunohistochemical stains, with adequate controls, are performed on block 2A for CD20, Ki67, MUM1, CD5, bcl1 (cyclin D1), bcl2, bcl6, CD10, TdT, CD4, CD8, and CD3 The malignant cells are positive for CD20, MUM1, bcl2, bcl6. They are negative for CD5, bcl1, CD10, TdT, CD4, CD8, and CD3. Ki-67 shows a proliferation rate up to 80% focally. Scattered small T cells are positive for CD3 and show a mixture with more CD8-pos cells than CD4-pos cells.

Immunophenotyping of the orbital mass by flow cytometry (report HF-17-334, Memorial Hermann Laboratory) show … These B cells have intermediate-large nuclear size (based on forward-scatter signal).

The morphology and immunophenotypes of the malignant cells are most consistent with diffuse large B-cell lymphoma, activated B cell subtype.

++++++++

136. Conjunctiva: Plasma cell dyscrasia

1. Conjunctival biopsy:

-Plasma cell dyscrasia

2. Adjacent to specimen 1

-Plasma cell dyscrasia

Comment

-The immunophenotypic results, together with morphology findings, are consistent with plasma cell dyscrasia in conjunctiva biopsy. A definitive diagnosis is limited by the small size of the core biopsy that shows small infiltrate with plasma cells. Differential diagnosis includes plasmacytoma, plasma cell myeloma, and other B cell lymphoproliferative disorders. Further testing and clinical correlation are suggested to rule out plasma cell myeloma in this patients (serum and urine protein electrophoresis and immunofixation, serum quantitative immunoglobulins, serum calcium, CBC, renal function tests, bone marrow aspirate and biopsy, imaging studies to look for lytic lesions).

-Dr S Kim was notified of the results on 7/31/17.

-This case was presented in the hematopathology QA conference on 7/31/2017 with consensus.

Microscopic Description

Histologic sections of the conjunctiva biopsy show area with diffuse plasma cell infiltration. The plasma cells have small nuclei with mature cytological features. A small number of lymphocytes are seen in two small foci.

Immunophenotyping of conjunctival biopsy by flow cytometry (report HF-17-351, Memorial Hermann Laboratory) shows a T cell population with no aberrant loss or aberrant expression of T cell markers, a B cell population that is negative for CD5, CD10, also no surface light-chain restriction. Plasma cells (gated with CD38) show cytoplasmic lambda light chain restriction. The plasma cells are negative for CD19 and CD56. These results indicate presence of monoclonal plasma cells in conjunctival biopsy.

Immunohistochemical stains,….. The lymphocytes show a mixture of B cells (pos for CD20, PAX5, and CD79a) and T cells (pos for CD3, CD5, and CD43) in the 2 small foci. The plasma cell infiltrate shows positivity for CD138, CD79a, bcl2, and cytoplasmic lambda light-chain restriction. They are negative for CD20, CD43, kappa, and PAX5. The following stains are negative in the section: CD10, cyclinD1, and bcl6.

The immunophenotype results, together with morphology findings, are consistent with plasma cell dyscrasia, i.e. a monoclonal plasma cell population with cytoplasmic lambda light-chain restriction.

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137. Colon: High-grade B cell lymphoma with high proliferative rate (Ki67 > 90%)

1. Colon, "cecal mass", biopsy:

High-grade B cell lymphoma with high proliferative rate (Ki67 > 90%), see comment

Comment

-Histologic sections of the cecal mass show several large lymphocytic infiltrates consisting of intermediate-large cells with pleomorphic features. Many cells have one to several prominent nucleoli. Many mitotic figures and tingible-body macrophages are seen. The infiltrates of malignant cells are admixed with surrounding small lymphocytes with mature cytological features.

Immunohistochemical stains, with adequate controls, are performed on 1A for CD20, Ki67, bcl2, bcl6, CD10, AE1/AE3, MUM1, CD3, and bcl1. The neoplastic large cells are positive for CD20, Ki-67 (>90%), bcl6, and MUM1. The malignant cells are negative for CD10, bcl2, CD3, AE1/AE3, and bcl1. The morphology and immunophenotypes are most consistent with a high-grade large B-cell lymphoma with high proliferative rate. The following are in the differential diagnosis: diffuse large B cell lymphoma (DLBCL), Burkitt lymphoma, high-grade B cell lymphoma with cMYC, and bcl2 and/or bcl6 rearrangement.

-Biopsy sample was sent to Genoptix Reference Laboratory for non-Hodgkin lymphoma FISH panel to rule out the following: DLBCL, Burkitt lymphoma, high-grade B cell lymphoma with cMYC and bcl2 and/or bcl6 rearrangement (double-hit / triple-hit lymphoma). Results will be reported in Addendum

-Findings were notified to Dr. Ruckshanda on 3/7/2018

++++++

138. Peristoma lesion: High-grade B cell lymphoma

- Peristoma lesion:

High-grade B cell lymphoma with high proliferation rate (Ki67 at 100%), see comment

Comment

-The morphology and immunophenotypes are consistent with a high-grade large B-cell lymphoma with high proliferation rate. The most likely diagnosis is Burkitt lymphoma. However the following cannot be completely ruled out: diffuse large B cell lymphoma with high Ki67, high-grade B cell lymphoma with cMYC, bcl2 and/or bcl6 rearrangement (double-hit lymphoma or triple-hit lymphoma). Definitive subtypes require molecular testing.

-Biopsy unstained slides were sent to Genoptix Reference Laboratory for non-Hodgkin lymphoma FISH panel to rule out the following: Burkitt lymphoma, high-grade B cell lymphoma with bcl2 and/or bcl6 rearrangement (double-hit / triple-hit lymphoma). Results will be reported in Addendum

-Findings were notified to Dr. Bailey on 3/5/2018

Microscopic Description

Histologic sections of the peristoma show diffuse lymphocytic infiltrate consisting of intermediate-large cells with pleomorphic features. Many cells have one to several prominent nucleoli. Many mitotic figures and tingible-body macrophages are seen. The infiltrates of malignant cells are admixed with a small number of surrounding small lymphocytes with mature cytological features.

Immunohistochemical stains, with adequate controls, are performed on 1A for CD20, CD10, bcl6, Ki67, bcl2, CD3, CD79a, CD23, CD30, and MUM1. The neoplastic large cells are positive for CD20, CD79a, CD10, bcl6, and Ki-67 (100%). They are negative for bcl2, CD23, CD30, MUM1, and CD3. CD3 is positive for a small number scattered T lymphocytes. The morphology and immunophenotypes are consistent with a high-grade B-cell lymphoma with high proliferative rate. The list includes diffuse large B cell lymphoma with high Ki67, Burkitt lymphoma, high-grade B cell lymphoma with cMYC, bcl2 and/or bcl6 rearrangement (double-hit lymphoma or triple-hit lymphoma). Definitive subtypes require molecular testing. Sample was sent for FISH testing (cMYC, bcl2 and/or bcl6 rearrangement). Results will be reported in Addendum.

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139. Buccal mucosa biopsy: Crush Artifacts, CD20 with artifacts

Buccal mucosa, right cheek, biopsy:

- Chronic lymphocytic infiltrates, see comment

Comments:

Microscopic examination is limited by small size of sample with extensive crush artifacts. Even though no obvious evidence of lymphoma is seen in the biopsy, submission of additional sample with larger size is suggested if clinically indicated.

Histologic examination of buccal mucosa biopsy shows lymphocytic infiltrates with extensive crush artifacts. Only very small foci with intact lymphocytes are seen. The lymphocytes have small nuclei with mature cytology. The epithelial layer is intact. Immunoperoxidase staining, with appropriately stained controls, was performed on sections of block 1A for AE1/AE3, BCL-1, BCL-2, BCL-6, CD3, CD10, CD20, CD43, CD45, CD79a, Ki-67, and PAX-5. The epithelial cells are positive for AE1/AE3. The lymphocytes are positive for CD45. The lymphocytic infiltrates show a mixture of B lymphocytes (positive for CD79a, CD20, PAX5, and bcl6) and T lymphocytes (positive for CD3, CD43, and bcl2). The B lymphocytes are negative for CD43, bcl2, CD10, and bcl1. Ki67 shows a low proliferation rate at 10%.

The morphologic and immunophenotypic findings are most supportive of chronic lymphocytic infiltrates. However, examination is limited by small size of sample with extensive crush artifacts.

++++

140. Lymph node: Follicular lymphoid hyperplasia, with flow cytometry and immunostains

DIAGNOSIS:

Lymph nodes:

-Follicular lymphoid hyperplasia

-No evidence of lymphoma

Histologic sections of the xxx lymph nodes show intact capsule with follicular hyperplasia. The follicles are increased in number and size. The follicles exhibit with prominent follicular center with variation in size and shape. Due to artifacts with suboptimal fixation, the mantle zone of some follicles is not well defined. The germinal centers contain several mitoses and tingible-body macrophages. No granuloma or necrosis is seen in histologic sections.

Immunohistochemical stains, with adequate controls, are performed on block 1D for bcl-2, bcl-6, CD3, CD4, CD8, CD20, CD23, and Ki67. The germinal centers are positive for CD20, bcl-6, Ki-67 (90% with polarized pattern), and negative for bcl-2. CD23 is positive for follicular dendritic cells in the follicles. CD3 and bcl-2 are positive for T cells in the interfollicular areas. T lymphocytes show a mixture of CD4-positive cells and CD8-positive cells. Bcl2 also highlights well-defined mantle zones.

The morphological findings, together with immunohistochemical findings, are consistent with follicular hyperplasia. No evidence of lymphoma is found.

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141. Right abdomen shave biopsy: Hematolymphoid tumor, favoring myeloid sarcoma

Diagnosis

Right abdomen, shave biopsy:

-Hematolymphoid tumor, favoring myeloid sarcoma, see comment

Comment

-The tumor cells are positive for CD45, CD43, bcl2, Ki67 (70%), and negative for all B cell markers, all other T cell markers and other myeloid markers. This pattern rules out T cell lymphoma, B cell lymphoma and favors myeloid sarcoma, even though other typical markers for myeloid sarcoma (CD117, MPO, CD34, CD99) are negative.

-Dr Kanaan was notified of the findings on 4/1/2019

Microscopic Description

Since only the block was sent and the H&E slides and immunohistochemical stains were not released by outside laboratory, H&E slides and a few selected IHC stains are ordered.

Histologic section of the skin biopsy shows dermal infiltrations consisting of immature cells of intermediate nuclear size, some with prominent nucleolie. These infiltrating cells are seen admixed with moderate number of mitotic figures and a small number of lymphoctyes.

Immunohistochemical stains, with adequate controls, are performed on block 1A for CD45, CD43, bcl2, Ki67, MPO, CD117, CD34, CD56, CD99. The malignant cells are positive for CD45, CD43, bcl2, and Ki67 (70%). They are negative for MPO, CD117, CD34, CD56, CD99. These results reproduce those in the report by outside laboratory. Outside lab also reported negative expression of tumor cells with CD30, CD20, PAX5, CD79a, TdT, CD68, CD5, CD10, CyclinD1, bcl6, MUM1, CD3, CD2, CD4, CD8, CD7, Lysozyme, CD1a.

In summary, the tumor cells are postive for CD45, CD43, bcl2, Ki67 (70%), and negative for all B cell markers, other T cell markers and myeloid markers. This pattern rules out T cell lymphoma, B cell lymphoma and favors myeloid sarcoma, even though other typical markers for myeloid sarcoma (CD117, MPO, CD34, CD99) are negative.

++++++++++++++++

142. Right neck mass: Necrotizing granulomas

Diagnosis

A. Right Neck Mass, excision:

- Follicular hyperplasia, no evidence of lymphoma

- Many large foci of necrotizing granulomas, see comment

NDN/PSY 06/14/2019 Electronic Signature: Nguyen, Nghia Andy D MD

Comment

GMS, AFB, and Warthin-starry stains are pending (to rule out fungi, acid-fast bacilli and cat-scratch).

Microscopic Description

Microscopic examination of blocks 1A-1B reveals reactive lymph nodes with follicular hyperplasia; several primary follicles are seen in the section; no evidence of lymphoma is found. Blocks 1C-1D reveal many large foci of necrotizing granulomas with multinucleated giant cells.

Addendum Diagnosis

Right neck mass, excision:

- Negative for acid-fast bacilli and fungi with AFB and GMS stains

- Noncontributory for cat-scratch with Warthin Starry stain.

- See comment.

NDN 06/18/2019 Electronic Signature: Nguyen, Nghia Andy D MD

Comment

-Special stains AFB and GMS are performed at Memorial Hermann Histology Laboratory on block 1C

-A special stain for Warthin Starry is performed on block 1C at University of Texas-Houston McGovern Medical School and Department of Pathology, and Histology Laboratory

-Warthin Starry stain was sent to Clinical Mircrobiology for consultation (Dr A Wanger). The finding was deemed non-diagnostic. Serology testing for Cat-scratch is suggested for further workup if clinically indicated

+++++++++++

143. Left inguinal lymph node: Reactive follicles and primary follicles

Diagnosis

1. Left inguinal lymph node:

-A few reactive follicles with several primary follicles

-No evidence of lymphoma

2. Additional inguinal tissue:

-Adipose tissue

Comment

Immunophenotyping of L inguinal lymph node biopsy by flow cytometry (report HF-19-360) shows a T cell population (about 60% of the cells analyzed) with no aberrant loss or aberrant expression of T cell markers, a B cell population (about 38% of the cells analyzed) that is negative for CD5, CD10, no surface light-chain restriction. The lymphocytes have small nuclear size (based on forward-scatter signal). These results indicate no abnormal immunophenotypes with flow cytometry.

Microscopic Description

Histologic sections of lymph node (1A) show a few reactive follicles with well-defined mantle zone, and several small primary follicles. The follicles are few in number, small in size and spaced apart from each other. The lymphocytes in the primary follicles are small with mature cytological features. No well-defined mantle zone is seen in the primary follicles. The reactive follicles have mixture of centroblasts and centrocytes, surrounded by well-defined mantle zone.

An immunohistochemical stain, with adequate positive controls, is performed on block 1A for CD3, CD79a, bcl2, bcl6, CD10, Ki67, and bcl1. The cells in the primary follicles are positive for CD79a, bcl-2, and are negative for CD10, bcl6, with low Ki67 (<10%). The cells in reactive follicles are positive for CD79a, CD10, bcl6, Ki67 (80% with polarized pattern), and are negative for bcl2. The surrounding T lymphocytes are positive for CD3. Stain for bcl1 is negative.

The histology and immunostains are consistent with benign lymph node containing primary and reactive follicles.

Histologic sections of additional inguinal tissue (2A) show only adipose tissue.

++++++++++++++++++++++

144. R tongue base: Diffuse variant of follicular B cell lymphoma

R tongue base:

-A low grade B-cell lymphoma,
most consistent with diffuse variant of follicular B cell lymphoma (grade 1 out of 3)

Comment

-Dr Ron Karni was notified of the results on 10/17/2019

Microscopic Description

-Histologic sections of R tongue base shows diffuse infiltration with small lymphocytes. A few small reactive follicles are also seen in the section.

-Immunohistochemical stains, with adequate controls, are performed on 1B for CD79a, CD20, CD10, bcl6, bcl2, Ki67, CD3, bcl1, and CD5. The stains show an abnormal B cell population of small nuclei with diffuse pattern that is positive for CD79a, CD20 (weak), CD10, bcl6. Ki67 shows a low proliferation at 10%. They are negative for CD5, bcl2, bcl1. The abnormal B cells are admixed with small T lymphocytes in the background that are positive for CD3, CD5, bcl2. The small reactive follicles are positive for CD20, CD79a, CD10, bcl6, and negative for bcl2. Ki67 is high (90% with polarized pattern) in these reactive follicles.

-Immunophenotyping of tongue base mass by flow cytometry (report HF-19-497) shows a T cell population (about 53% of the cells analyzed) with no aberrant loss or aberrant expression of T cell markers, a prominent B cell population (about 45% of the cells analyzed) that is positive for CD19, CD20, CD22, CD10, FMC7, CD23 (subset), surface lambda light chain restriction. These B cells are negative for CD5. These B cells small nuclear size (based on forward-scatter signal). These results are consistent with a CD10-positive B-cell lymphoma

-The morphology/pattern of the abnormal B lymphocytes, together with their immunophenotypes by immunohistochemical stains and flow cytometry (positive for CD79a, CD20, CD10, bcl6, CD23; negative for bcl2), are most supportive of diffuse variant of follicular B cell lymphoma (grade 1 out of 3)

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145. R upper abdomen nodule and R hip nodule: Subcutaneous nodular panniculitis with granuloma

Diagnosis:

1. R upper abdomen nodule:

- Subcutaneous nodular panniculitis with granuloma

- No evidence of lymphoma

-Special stains for acid-fast bacilli and fungi are negative for organisms

2. R hip nodule:

- Subcutaneous nodular panniculitis with granuloma

- No evidence of lymphoma

Microscopic description:

Histologic sections of the R abdomen nodule and the R hip nodule show subcutaneous nodules separated by collagen bands. The nodules contain many adipose cells with a background of diffuse infiltration with lymphocytes, admixed with many histiocytes forming foci of granuloma and multinucleated giant cells. The lymphocytes have small size with mature cytological features. No hemophagocytosis is noted.

Immunohistochemical stains, with adequate controls, are performed on block 1A for CD3, CD79a, Ki67, CD68, Mast cell tryptase, CD45, CD20, PAX5, CD30, CD15, MUM1, CD2, CD4, CD8, CD5, CD7, and CD56. The stains show normal diffuse distribution of CD45, large number of small lymphocytes including mixture of CD4-positive cells and CD8-positive cells (normal distribution of CD2, CD3, CD5, CD7), many histiocytes with positive CD68 and CD4, only scattered cells positive for CD79a, CD20, PAX5, CD15, CD30, and MUM1. Mast cell tryptase and CD56 are negative. Rimming of adipose cells by CD8-positive cells is not observed. Ki67 is approximately at 20%. The morphologic and immunophenotypic findings are consistent with subcutaneous nodular panniculitis. No evidence of lymphoma is seen.

Special stains for AFB and GMS, with adequate controls, are also performed on block 1A. They are negative for organisms.

Immunophenotyping of R hip nodule by flow cytometry (Memorial Hermann Laboratory, report HF-20-35) was not diagnostic due to low viability of sample (44%)

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146. Mediastinal mass: Large B cell lymphoma pending NHL FISH

Diagnosis

Mediastinal mass, CT-guided FNA biopsy:

- Aggressive B-cell lymphoma

(see comment)

JOT/DJD 03/27/2020 Electronic Signature: Thomas-Ogunniyi, Jaiyeola Olayemi M

Comment

Sections show diffuse sheets of intermediate to large-sized atypical lymphoid cells with necrosis. The cells are strongly positive with CD45, negative with AE1/AE3, CAM5.2, synaptophysin and chromogranin.

Immunostaining performed: The atypical lymphoma cells stain positive with CD20, CD79a, PAX5, CD10 with KI-67 proliferative index ranging between 80-90% and CD30 positive cells. CD3 and CD5 stain residual T-cell lymphocytes; TDT, cyclin D1 are negative. CD117 shows non-specific nuclear reactivity. Overall morphology and available immunostains are consistent with aggressive B-cell lymphoma with differential diagnosis including mediastinal diffuse large B-cell lymphoma and Burkitt's type lymphoma. Additional immunostains (c-myc, bcl-2, bcl-6, CD34, CD15) and EBER are pending and will be reported as addendum. Molecular non-Hodgkin lymphoma FISH panel has been ordered from reference lab and results will follow. This case is reviewed in consultation with Dr. Lei Chen and is referred to Hematopathology for further work-up.

Addendum Diagnosis

Final Diagnosis

Mediastinal mass, CT-guided FNA biopsy:

- Large B-cell lymphoma with high Ki67 proliferative index (80-90%)

- Pending NHL FISH panel and EBER in situ hybridization

- See comment.

NDN/BM 03/31/2020 Electronic Signature: Nguyen, Nghia Andy D MD

Comment

Additional immunostains are performed on block 1B with appropriate controls as mentioned in the original report for further classification. The tumor cells are positive for BCL2, BCL6, MUM1, C-MYC (focally, with >40% positivity), and CD23 (subset). They are negative for SALL4, OCT4, PLAP, CD15, and CD34.

The morphology and immunophenotypes are most consistent with a large B cell lymphoma with high proliferation rate. The differential diagnosis include: diffuse large B cell lymphoma (GC subtype with positive CD10), double-hit lymphoma, and triple-hit lymphoma.

NHL FISH panel is pending (to rule out double-hit lymphoma, and triple-hit lymphoma), and will be reported in an addendum.

In situ hybridization for EBV (EBER1) is pending on sections of block 1A at Histology Laboratory of The University of Texas-Houston McGovern Medical School and Department of Pathology and the result will be issued in an addendum.

++++++++++++++++

147. Gastric mass: Mucosa-associated lymphoid tissue (MALT) lymphoma

Diagnosis

Gastric mass biopsy (ML20-01025-A1):

-Mucosa-associated lymphoid tissue (MALT) lymphoma, see comment

-Negative for Helicobacter pylori

Dr. A Rios was notified of the lymphoma diagnosis on 5/14/2020.

Microscopic Description

Histologic sections of the gastric mass biopsy (ML20-01025-A1) show gastric mucosa with diffuse submucosal lymphocytic infiltrates. A few scattered lymphoepithelial lesions are seen in the glands. The lymphocytes have small nuclei with mature cytological features. Immunohistochemical stains from outside laboratory, with adequate controls, show that the lymphocytes are predominantly B cells with expression of CD20, CD43. Ki67 is low at 15% (except for a small reactive germinal center with high Ki67). The B cells are negative for CD3, bcl2, CD138, cyclinD1, bcl6 (except for a small reactive germinal center), and CD5. A smaller number of T lymphocytes are seen with expression of CD3, CD5, bcl2, and CD43. Kappa and lambda ISH are not contributory. No Helicobacter is identified with special stain.

Additional test results from outside laboratory (Neogenomic reports, dated 3/10/20, 3/16/20, 3/19/20, and 3/22/20) show that the gastric mass biopsy is positive for B cell gene rearrangement (immunoglobulin heavy chain), and negative for t(11:14), t(14;18), bcl6 rearrangement, and MYD88 mutation. MALT1 rearrangement is positive for a 5’ MALT1 deletion suggestive of marginal zone lymphoma.

The overall findings of morphology, immunophenotypes by immunohistochemical stains and molecular test results, are consistent with mucosa-associated lymphoid tissue (MALT) lymphoma in the gastric mass biopsy.

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148. Left neck mass: Large B cell lymphoma with a high proliferative index

Diagnosis

Left neck mass, core biopsy:

- Large B cell lymphoma with a high proliferative index (Ki67=90%)

- See comment

NDN/RKC 06/04/2020 Electronic Signature: Nguyen, Nghia Andy D MD

Comment

Histologic sections of the left neck mass show effacement of lymph node architecture by large cells with irregular nuclear contour, vesicular nuclei with fine chromatin, and one to several nucleoli. Frequent mitotic figures and frequent tingible body macrophages are seen. Necrotic foci and bands of sclerosis are not found.

Immunophenotyping of the left neck mass by flow cytometry (report HF-20-281) shows a B cell population (about 92% of the lymphocytes analyzed) that is positive for CD5, CD19, CD20, CD22, FMC7, and surface Lambda light-chain restriction. They also show aberrant expression of CD8. They are negative for CD2, CD3, CD4, CD7, CD10, and CD23. These B cells have large nuclear size (based on forward-scatter signal).

Immunohistochemical stains, with adequate controls, on 1A show that the neoplastic cells are positive for CD20, CD79a, PAX5, CD5, Bcl2, MUM1, C-Myc (50%). Ki-67 proliferative index (Ki67) is approximately 90%. These cells are negative for CD10, Bcl-6, Cyclin D1, TdT, CD15, and CD30. Normal small T cells (positive for CD3 and CD5) are scattered throughout the sections.

The immunophenotyping and the morphological features are most consistent with large B cell lymphoma with a high proliferative index. The differential diagnosis include: high grade B cell lymphoma (double hit/triple hit lymphoma) and diffuse large B cell lymphoma (ABC subtype). The positive expression of cMyc and bcl2 by immunostains support double-expresser lymphoma. FISH panel for high-grade NHL is pending to rule out double-hit/triple-hit lymphoma and will be reported in addendum. Note that mantle cell lymphoma (pleomorphic variant) was ruled out with negative cyclinD1. Burkitt lymphoma was ruled out with: large cell morphology, positive bcl2, and negative bcl6.

CD8 by flow cytometry was found to be positive in the lymphoma cells. Since this is an unusual expression in B cell lymphoma, immunohistochemical stain for CD8 is pending on biopsy to rule out aberrant expression vs. technical artifact.

Dr A Rios was notified of the diagnosis on 6/4/20

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149. Lymph node: Follicular hyperplasia, with IHCs and Flow

1 Porta hepatis lymph node core biopsy

- Mild follicular hyperplasia.

- No evidence of lymphoma.

Histologic sections of the porta hepatis lymph node core biopsy shows normal lymph node architecture. A background of small/mature lymphocytes is seen with foci of sinus and a few small reactive follicles. The follicles have small size and contain reactive germinal center. The germinal centers have a mixture of small lymphocytes and centroblasts. Mantle zone is attenuated in some follicles. No evidence of granuloma or necrosis is seen.

Immunophenotyping of portal hepatis lymph node biopsy by flow cytometry (report HF-20-280) shows a T cell population (about 72% of the cells analyzed) with no aberrant loss or aberrant expression of T cell markers, a B cell population (about 26% of the cells analyzed) that is negative for CD5, CD10, no surface light-chain restriction. The lymphocytes have small nuclear size (based on forward-scatter signal).

Immunohistochemical stains, with adequate controls, are performed on block 1A. They show normal background T cells that are positive for CD3, CD5. The follicular cells are positive for CD10, bcl6,CD20, CD79a, PAX5, high Ki67 and negative for bcl2. MUM1 is positive for a subset of B cells. Stains for CD15, CD30, cMyc, cyclinD1, and TdT are negative. Kappa and lambda show polyclonal population

The morphological findings, together with immunophenotypes by flow cytometry and immunostains, are consistent with benign lymphoid tissue. No evidence of lymphoma is found.

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150. HIV-associated lymphadenopathy

Diagnosis

Left level 3 lymph node:

-Reactive follicular hyperplasia

-No evidence of lymphoma

Comment

Histologic sections of the lymph node show partial effacement of lymph node architecture. Follicles forming an ill-defined nodular pattern are seen throughout the sections. The follicles have variable sizes from small with involuted germinal center and concentric mantle cells to very large ones and are well separated. Most of the follicles do not have well-formed mantle zone. A few follicles have folliculolysis. No evidence of necrosis is seen. Vascular proliferation is markedly increased with hyalinization.

Immunohistochemical stains, with adequate controls, are performed on block 1B for CD20, CD79a, PAX5, CD10, bcl6, Ki67, bcl2, MUM1, CD3, CD30, CD15, PAX5, CD45. The cells in the follicle are positive for CD20, CD79a, PAX5, bcl6, Ki67, and CD10. They are negative for bcl2. MUM1 is positive for a subset of B cells. Stains for CD15 and CD30 show scattered positive cells. CD45 shows diffuse positivity in the sections. CD3 and bcl2 are positive for many T cells in the sections.

Immunophenotyping of lymph node biopsy by flow cytometry (report HF-20-276) shows a T cell population (about 99% of the cells analyzed) with no aberrant loss or aberrant expression of T cell markers, a B cell population (about 2% of the cells analyzed) that is negative for CD5, CD10, no surface light-chain restriction. These results indicate no abnormal immunophenotypes with flow cytometry.

The morphological features seen in this case are typically seen in HIV-associated lymphadenopathy. No evidence of lymphoma is seen.

Addendum Diagnosis

Left level 3 lymph node:

- Negative for HHV8 by immunohistochemical stains

- Presence of many polyclonal plasma cells in paracortical area

- No evidence of HHV8-associated lymphoproliferative disorder

NDN/NDN 06/08/2020 Electronic Signature: Nguyen, Nghia Andy D MD

Comment

Immunohistochemical stains, with adequate controls, are performed on lymph node for HHV8, CD138, kappa, lambda. This is to rule out HHV8-associated lymphoproliferative disorder. HHV8 is negative. CD138 shows many plasma cells in paracortical area with polyclonal pattern for kappa and lambda.

No change in original diagnosis was made with this addendum.

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151. Pleural fluid, cell block: T lymphoblastic lymphoma, with IHCs and flow

Addendum Diagnosis

HEMATOPATHOLOGY REPORT

Pleural fluid:

- T lymphoblastic lymphoma, see comment

Comment

Histologic section of the pleural fluid (cell block1A) shows diffuse distribution of malignant lymphocytes of small-medium size with vesicular nuclei and one to several nucleoli. A few mitotic figures are seen. The malignant cells are admixed with a moderate number of tingible-body macrophages.

Immunohistochemical stains, with adequate controls, are performed on block 1A for CD1a, TdT, CD4, CD8, CD3, Ki67, CD99, CD34, CD30, and ALK1. The neoplastic cells are positive for CD1a, TdT, CD4, CD8, CD3, Ki67 (80% proliferation rate) and negative for CD99, CD34, CD30, and ALK1. These results, together with morphological findings, are consistent with T lymphoblastic lymphoma involvement in the pleural fluid in this 20 y/o patient presenting with chest pain, CT at OSH showing anterior mediastinal mass.

Immunophenotyping by flow cytometry (report HF-20-399) is also supportive of this diagnosis.

Drs Jani and Rios were notified of the diagnosis on 7/31/2020

Non Clinical Documentation

CPT 88342, 88341 x8, 88360

Some of the immunohistochemical tests in this panel were developed and their performance characteristics determined by Memorial Hermann Southwest Hospital Laboratory. They have not been cleared or approved by the U. S. Food and Drug Administration. The FDA has determined that such clearance or approval is not necessary. These tests are used for clinical purposes. They should not be regarded as investigational or for research. This laboratory is regulated under the Clinical Laboratory Improvement Amendments of the 1988 (CLIA) as qualified to perform high complexity clinical testing.

+++

152. Neck soft tissue: EBV-associated lymphadenopathy

Diagnosis

1. Soft tissue, "neck", debridement:

- Lymph node with atypical lymphoid infiltration

- Fibromuscular tissue with necrosis, granulation tissue formation

- Pending FISH and EBER testing

- See comment

2. Left submandibular gland, excision:

- Submandibular gland with capsular acute and chronic inflammation, granulation tissue formation

NDN/DJD 08/21/2020 Electronic Signature: Nguyen, Nghia Andy D MD

Comment

Per note, the patient is a 53 year old male with no known PMH presented with necrotizing fascitis on neck, dental abscess.

One lymph node is identified from the specimen #1 (soft tissue, neck debridement). Histologic sections from the neck lymph node show preserved architecture with follicular hyperplasia. The capsule is thickened focally. The follicles have broad mantle zone consisting of small lymphocytes arranged in a concentric (onion-ring) pattern. Several follicles have atrophic and hyalinized germinal center. Penetrating hyalinized arterioles are seen in some follicles. Many small primary follicles are also seen in the section. The interfollicular area is hypervascular with increase in plasma cells and areas of necrosis.

In the center of the lymph node are patches of atypical diffuse infiltration of large cells with eccentric nuclei and one or more prominent nucleoli. A few mitosis and apoptotic bodies are also seen.

Specimen #2 shows submandibular gland with capsular acute and chronic inflammation, with granulation tissue formation.

Immunohistochemical stains with appropriate controls were performed on block 1E for CD3, CD10, CD20, CD45, CD56, CD79a, CD138, PAX5, BCL-2, BCL-6, MUM1, C-MYC, Cyclin D1, Kappa, Lambda, HHV-8 and Ki-67. The large cells are positive for CD45, CD20, CD79a, MUM1. Proliferative index with Ki-67 approaches 80% focally. These cells are negative for CD3, CD10, PAX5, CD56, CD138, Cyclin D1, BCL-2, BCL-6, HHV-8 and C-MYC. CD138 highlights small plasma cells, which are polyclonal by kappa and lambda immunostains.

Based on the morphology and immunophenotyping, current differential diagnosis includes Castleman disease, infectious mononucleosis (EBV), and lymphoproliferative disorders. The following tests are pending: CD15, CD30 immunohistochemical stains, EBER ISH, and High-grade NHL FISH panel. The results and definitive diagnosis will be reported in addendum.

Tumor Summary

N/A

Specimen Source

1. Neck debridement

2. Left submandibular gland

Clinical Information

Clinical History: Necrotizing fascitis of neck

Operative Procedure: Irrigation and debridement of neck

Operative Findings: See operative notes

Gross Description

The specimen is received in 2 parts:

1. The specimen is received in formalin labeled with the patient's name, MRN, and "neck debridement." It consists of an 8.6 x 4.6 x 2.1 cm aggregate of tan-brown, irregular, lobulated, necrotic soft tissue. Sectioning reveals a 2.8 x 1.6 x 1.4 cm pink-white possible lymph node with focal brown discoloration. Remainder of the specimen is comprised of tan-brown and brown-gray, focally necrotic muscle. Representative sections are submitted as follows:

1A-1J-possible lymph node, entirely submitted

1K-1L-focally necrotic soft tissue

2. The specimen is received in formalin labeled with the patient's name, MRN, and " left submandibular gland." It consists of a 23 g, unoriented, partially necrotic salivary gland with attached shaggy, hemorrhagic soft tissue. The overall specimen measures 5.0 x 3.6 x 2.3 cm. The salivary gland measures 4.2 x 3.1 x 2.1 cm. The outer surfaces are inked black and the specimen is serially sectioned to reveal tan-white, lobulated, unremarkable cut surfaces of salivary glands. No distinct masses are identified. Representative sections are submitted in cassettes 2A-2C.

DJD 08/17/2020

Addendum Diagnosis

1. Soft tissue, "neck", debridement:

- Positive for EBV by in-situ hybridization (EBER1).

- FISH Panel results:
negative for BCL6 rearrangement, MYC rearrangement, MYC amplification, BCL2 rearrangement

- EBV-associated lymphadenopathy; no evidence of lymphoma is found,

See comment

NDN/ML 09/01/2020 Electronic Signature: Nguyen, Nghia Andy D MD

Comment

Immunohistochemical stains with appropriate controls were performed on block 1E for CD15, CD30. Immunoblasts and granulocytes/histiocytes are positive for CD30 and CD15, respectively.

EBER (EBV encoded RNA by in situ hybridization), with adequate control, is performed on sections of 1E at the University of Texas McGovern Medical School and Department of Pathology and Histology Laboratory. EBER shows scattered positive cells in the section.

FISH Panel for high grade B cell lymphoma (Neogenomic report, dated 8/31/20) is negative for bcl6, Myc, bcl2

The overall findings are most consistent with EBV-associated lymphadenopathy. No evidence of lymphoma is found.

This case was reviewed in hematopathology QA meeting on 9/1/2020 (with Drs Chen and Wahed) with consensus

Reference: Abner Louissaint Jr et al. Infectious mononucleosis mimicking lymphoma: distinguishing morphological and immunophenotypic features Modern Pathology (2012) 25, 1149–1159

+++

153. A low-grade B cell lymphoma, most suggestive of follicular lymphoma, grade 1

Diagnosis:

Parotid, right (fine needle aspiration):

- A low-grade B cell lymphoma, most suggestive of follicular lymphoma, grade 1 (out of 3),

see comment

Comment:

Dr. R. Karni, and Dr. A. Rios were notified of the diagnosis on 2/3/2021

Microscopic description:

-Histologic sections of the R parotid aspirate smear and cell block show diffuse distribution of small lymphocytes with mature cytology. A smaller subset of large lymphocytes are admixed with the small lymphocytes.

-Immunophenotyping of parotid aspirate flow cytometry (report HF-21-63, Memorial Hermann Laboratory) shows a predominant B cell population that is positive for CD19, CD20, CD10, CD38, CD23, with kappa light-chain restriction (both surface and cytoplasmic). They are negative for CD5, and CD34. Most of these B cells have small nuclear size with a smaller subset of large size (based on forward-scatter signal). These results are most consistent with a CD10-positive B cell lymphoma.

-Immunohistochemical stains, with adequate controls, are performed on block 1A for Ki67, bcl2, bcl6, and cyclin D1. The abnormal cells are positive for bcl2, and bcl6. They are negative for cyclin D1. Ki67 shows a low proliferation rate at 20%.

-The morphology and immmunophenotypes of the abnormal lymphocytes are most consistent with a low-grade B cell lymphoma, most suggestive of follicular lymphoma, grade 1 (out of 3). However, due to lack of biopsy to assess the full histologic architecture (only aspirate and cell block are available for examination), a definitive diagnosis of follicular lymphoma cannot be obtained.

+++++

154. Mediastinum: Primary mediastinal large B cell lymphoma

Diagnosis

Mediastinum mass, presternal biopsy:

-Primary mediastinal large B cell lymphoma, see comment

Comment

-Histologic sections of the mediastimal mass show diffuse lymphocytic infiltration consisting of intermediate-large cells with pleomorphic nuclei. They are surrounded by compartmental fibrosis. Many large lymphocytes have clear-cell morphology (with nuclear halo) and have one to several prominent nucleoli. The malignant cells are admixed with a smaller number of small lymphocytes with mature cytological features.

-Touch prep from aspirate (CA-21-700) shows many large lymphocytes with prominent nucleoli.

-Immunohistochemical stains, with adequate controls, are performed on block 1B for CD3, CD20, CD79a, CD15, CD30, PAX5, Ki67. The malignant cells are positive for CD20, CD79a, CD30, PAX5. They are negative for CD3, CD15. Ki67 is variable and up to 80% in focal areas. A small number of benign small T lymphocytes (positive for CD3) are also seen in the section. The morphology and immunophenotypes of the malignant cells are most consistent with primary mediastinal (thymic) large B cell lymphoma.

-Immunophenotyping of the mediastinal mass by flow cytometry (HF-21-190) is not diagnostic. The analysis shows mostly T cell (88% of lymphocytes) and a smaller number of polyclonal B cell (11% of lymphocytes). The lymphocytes are small, indicating that they are not the malignant lymphoma cells from the sample (suboptimal sample, likely due to fibrosis).

- Dr A Rios was notified of the diagnosis on 3/30/21

-Biopsy sample was sent for high-grade B cell lymphoma FISH panel. Results will be reported in Addendum.

- The following immunohistochemical stains are pending: MUM1, AE1/AE3 (pan-keratin), bcl2, bcl6, CD23, cMyc. Results will be reported in Addendum.

+++++++

155. Colon: A non-hematopoietic tumor with high proliferation rate (Ki67 at 70%)

Diagnosis

Colon, hemicolectomy, preliminary report pending completion of further study:

- High-grade aggressive malignancy, most suggestive of hematopoietic origin, pericolonic

tissues, with transmural invasion of colon

- Extensive vascular invasion

- Extensive necrosis

- One mesenteric lymph node, positive for tumor (1/1)

- Colon margins positive for tumor in pericolonic tissues

(See comment)

RJH/JCH 03/31/2021 Electronic Signature: Hausner, Richard Jeffrey MD

Comment

The patient is a 72-year-old female with a history of abdominal pain.

The sections demonstrate high-grade aggressive malignancy with extensive necrosis in the pericolonic tissues. There is transmural invasion of the colon with focal erosion of the mucosa. One mesenteric lymph node is positive for tumor. The margins of the resection contain tumor in the pericolonic tissues.

The malignancy has features most suggestive of hematopoietic origin. The section of hematopathology are consultants in our studies. The studies are in progress and the results with a final diagnosis will be reported in an addendum.

Addendum Diagnosis

Hematopathology Consult:

- A non-hematopoietic tumor with high proliferation rate (Ki67 at 70%),

see comment

Comment:

Initial examination of morphologic features in the abnormal cellular infiltrates suggests a hematopoietic tumor. However, subsequent investigation with negative results of numerous immunohistochemical stains for hematopoietic tumors rules out such impression. The following hematopoietic tumors were effectively ruled out: mature B cell lymphomas, ALK-positive large B-cell lymphoma, B and T lymphoblastic lymphoma, peripheral T cell lymphoma-NOS, extranodal NK/T-cell lymphoma, enteropathy-associated T-cell lymphoma, monomorphic epitheliotropic intestinal T-cell lymphoma, myeloid sarcoma, mast cell sarcoma, blastic plasmacytoid dendritic cell neoplasm, histiocytic sarcoma, classical Hodgkin lymphoma, anaplastic large T cell lymphoma, interdigitating dendritic cell sarcoma, blastic plasmacytic dendritic tumor, and Langherhans cell sarcoma.

An undifferentiated tumor cannot be ruled out given negative results for an extensive list of other immunohistochemical stains performed in this case (except for Ki67).

Comment

Immunohistochemical studies:

CD2: Negative in tumor cells (block 1C)

CD3: Negative (block 1D)

CD4: Negative(block 1C)

CD5: Negative in tumor cells (block 1D)

CD7: Negative(block 1C)

CD 8: Negative(block 1C)

CD20: Negative (block 1D)

CD30: Negative (block 1D)

ALK 1: Negative (block 1D)

CD 43: Negative (block 1C)

CD45: Negative (block 1C)

CD56: Negative (block 1C)

CD79a: Negative (block 1C)

CD117: Negative (block 1C)

CD138: Negative (block 1C)

CDX2: Negative (block 1C)

CAM 5.2: Negative (block 1C)

CK 5/6: Negative (block 1C)

CK 7: Negative (block 1C)

CK 20: Negative (block 1C)

Sox 10: Negative (block 1C)

HMB 45: Negative (block 1C)

Pan melanoma: Negative (block 1C)

S100: Negative (block 1C)

Calretinin: Negative (block 1C)

D2–40: Negative (block 1C)

PAX 5: Negative (block 1C)

PAX 8: Negative (block 1C)

WT 1: Negative (block 1C)

MUM 1: Negative (block 1C)

P40: Negative (block 1C)

Myeloperoxidase: Negative (block 1C)

TTF-1: Negative (block 1C)

Napsin: Negative (block 1C)

GATA 3: Negative (block 1C)

Ki-67: 70% expression (block 1C)

Non Clinical Documentation

88342

88341x29

88360

+++

156. Skin: mycosis fungoides

Diagnosis

Skin, punch biopsy, right lower abdomen:

- Mycosis fungoides

NDN/HMR 09/22/2022 Electronic Signature: Nguyen, Nghia Andy D MD

Comment

- The morphology and immunophenotypes are most consistent with mycosis fungoides in this skin biopsy.

- Findings were notified to Dr xxx on 9/22/22

Tumor Summary

Specimen: skin

Procedure: punch biopsy

Tumor site: R lower abdomen

Histologic type: mycosis fungoides

Immunophenotyping:_

Immunohistochemistry: Performed,

Flow cytometry: _

Not performed

Specimen Source

1. Skin, Punch biopsy, right lower abdomen

Clinical Information

Clinical History: 42-year-old Hispanic male with history of eczema coming in with 2-month history of erythematous annular scaly plaques, vegetative plaques and nodules with ulceration on the trunk and extremities

Operative Procedure: Punch biopsy

Operative Findings: Differential diagnosis of cutaneous T-cell lymphoma, granulomatosis with polyangiitis, atypical mycobacterial infection, fungal infection, psoriasis, Crohn's, sarcoidosis

Gross Description

_The case is received in 1 part labeled: xxx

1. Received in formalin, labeled with the patient's name, MRN, "skin, punch biopsy, right lower abdomen" and consists of a single skin punch biopsy measuring 0.3 x 0.3 cm excised to a depth of 0.4 cm. The specimen has a tan-brown, moderately granular epidermis. The resection margin is inked blue and the specimen is bisected and submitted entirely in cassette 1A.

HR 09/15/2022 07:18

Microscopic Description

Histologic sections show diffuse lymphocytic infiltrates in dermis. The abnormal lymphocytes have small to medium size, with indented nuclei, admixed with a smaller number of larger cells and occasional eosinophils seen. Only a small area with epidermis is seen in the section. No obvious lymphocytic infiltrate is seen in the observed epidermis.

Immunohistochemical stains, with adequate controls, are performed on 1A for

CD79a, PAX5, Ki67, CD3, CD30, ALK1, CD4, CD8, CD5, CD7, CD56, CD68, CD1a, S100, CD23, MPO, CD43, mast cell tryptase. The lymphocytic infiltrate is positive for CD3, CD43, CD4 with proliferation rate of 50% (Ki67). They are negative for CD8 and show aberrant partial loss of expression for CD5 and CD7. Stain CD68 shows a small number of histiocytes.

The following stains are negative for the infiltrate: CD79a, PAX5, CD30, ALK1, CD56, CD1a, S100, CD23, MPO, mast cell tryptase.

The morphology and immunophenotypes are most consistent with mycosis fungoides in this skin biopsy.

Non Clinical Documentation

CPT: 88305, 88360, 88432, 88431x16

Specimen examined at Memorial Hermann Texas Medical Center.

Final diagnosis rendered at Memorial Hermann Texas Medical Center.

6411 Fannin St. Houston, TX 77030

Teaching Physician Statement

"I have personally reviewed the resident's preliminary interpretation and all specimen preparations and have personally issued this report".

++++++

157. Lymph node: Aggressive B cell Lymphoma, pending FISH for MYC (gain/loss) and rearrangements of MYC, bcl2, bcl6, bcl1

Diagnosis

Lymph node, left neck, biopsy:

- Aggressive B cell lymphoma with high proliferation rate (Ki67 at 90%), see comment

NDN/HLF 09/09/2022 Electronic Signature: Nguyen, Nghia Andy D MD

Comment

- The morphology and immunophenotypes are consistent with an aggressive large B-cell lymphoma with high proliferation rate (90%). Differential diagnoses include Burkitt lymphoma, diffuse large B cell lymphoma (DLBCL) with high Ki67, DLBCL/high-grade B cell lymphoma with cMYC and bcl2 rearrangement, high-grade B cell lymphoma with MYC (gain/loss). Additional immunostains for further classification are pending and will be posted in an addendum.

- Molecular non-Hodgkin lymphoma FISH panel has been ordered for further classification and results will follow in an addendum.

- Dr xxx was notified of the results on 9/9/2022

Tumor Summary

Specimen: Lymph node

Procedure: Biopsy

Tumor site: Left neck

Histologic type: Aggressive B cell lymphoma

Immunophenotyping:_

Immunohistochemistry: Performed

Flow cytometry: Not performed

Specimen Source

1. Left neck lymph node

Clinical Information

Clinical History: Metastatic disease, large left-sided chest mass

Operative Procedure: Left neck lymph node biopsy

Operative Findings: See operative report

Gross Description

The case is received in 1 part labeled: xxx

1. The specimen is received in formalin labeled with the patients name, MRN, and "left neck lymph node." It consists of multiple tan-pink ventricle tissue cores which measure 1.0 x 0.3 x 0.2 cm in aggregate and are submitted in toto in cassette 1A.

HLF 09/02/2022 15:41

Microscopic Description

Sections show diffuse sheets of intermediate to large-sized atypical lymphoid cells with pleomorphic nuclei of which many have one to two prominent nucleoli. The atypical lymphoid cells are admixed with scattered tingible body macrophages and mitotic figures.

Immunohistochemical stains, with adequate controls, were performed on block 1A for AE1/AE3, CAM5.2, CD45, CD3, CD5, CD20, PAX5, CD10, MUM1, CD30, bcl2, bcl6, c-myc, cyclin D1, and Ki-67

The atypical lymphoma cells stain positive with CD45, CD20, PAX5, MUM1 with KI-67 proliferative index up to 90%. A subset are CD30 positive. The atypical lymphoma cells are negative for CD10. CD3 stains residual T-cell lymphocytes. AE1/AE3 and CAM5.2 are negative. Overall the morphology and immunostains are consistent with an aggressive B cell lymphoma.

Immunostains for bcl2, bcl6, cyclin D1, CD5 and c-myc are pending and will be posted in an addendum.

Non Clinical Documentation

88307-gc, 88342-gc, 88341-gc x 13, 88360-gc

Teaching Physician Statement

"I have personally reviewed the resident's preliminary interpretation and all specimen preparations and have personally issued this report."

Addendum Diagnosis

Lymph node, left neck, biopsy:

- Aggressive B cell lymphoma, positive for bcl2 (strong intensity), c-myc (40%),

cyclin D1 (subset), bcl6, and negative for CD5,

see comment

NDN/NDN 09/12/2022 Electronic Signature: Nguyen, Nghia Andy D MD

Comment

- Immunohistochemical stains, with adequate controls, are performed on block 1A for bcl2, bcl6, cyclin D1, CD5 and c-myc. The malignant lymphoma cells are positive for bcl2 (strong intensity), c-myc (40%), cyclin D1 (subset), bcl6, and negative for CD5.

- Additional unstained slides are sent to Neogenomics Lab for FISH testing (myc, bcl2, bcl6, bcl1 re-arrangements).

+++

Addendum

FISH

-bcl6 rearrangement: DETECTED

-MYC(gain/loss), bcl2 rearrangements, t(8; 14), t(11;14): not detected

Final DX:

-DLBCL, ABC subtype, Ki67 90% (with bcl6 rearrangement)

+++++++++++++++++++++++++

158. Thigh mass: DLBCL, pending FISH for rearrangements of MYC, bcl2, bcl6

Diagnosis

Right thigh mass, excision:

- Diffuse large B-cell lymphoma (DLBCL), activated B cell subtype

with high proliferation (Ki67 of 80%)

(see comment)

NDN/HLF 09/09/2022 Electronic Signature: Nguyen, Nghia Andy D MD

Comment

Sections show diffuse sheets of large-sized atypical lymphoid cells with prominent nucleoli. Immunohistochemical stains, with adequate controls, are performed on 1A for CD10, bcl6, MUM1, bcl2, CD5, cyclinD1. The cells are positive for bcl6 (subset), MUM1, bcl2, negative for cyclinD1, CD10, and CD5.

Note that the same lesion reported in IS-22-xxx (8/30/22) was positive for CD20 and PAX5.

Overall morphology and available immunostains are consistent with DLBCL, activated B cell subtype. Molecular non-Hodgkin lymphoma FISH panel has been ordered from reference lab to rule out DLBCL/High grade B cell lymphoma with MYC/bcl2 re-arrangement

- Findings were notified to Dr xxx on 9/9/2022

Tumor Summary

Specimen: Right thigh mass

Procedure: Excision Of Soft Tissue Tumor

Tumor site: Right thigh

Histologic type: DLBCL

Immunophenotyping:_

Immunohistochemistry: Performed,

Flow cytometry: _

Not performed

Specimen Source

[Right Thigh]

Clinical Information

Clinical History: [Right Thigh Soft Tissue Malignant Tumor]

Operative Procedure: [Right Thigh - Excision Of Soft Tissue Tumor]

Operative Findings: [Refer To Histopathology Request Form]

Gross Description

The case is received in 1 part labeled: xxx

1. The specimen is received in formalin labeled with the patients name, MRN, and "right thigh." It consists of a 262 g aggregate of tan-pink to white, fleshy soft tissue and skin which measures 14.5 x 11.2 x 4.0 cm. The lenticular piece of skin that measures 8.0 x 2.5 cm and displays a 3.0 x 0.5 cm scar and a 2.5 x 2.0 x 0.8 cm nodule. A portion of skin is attached to the largest fragment of soft tissue which is inked blue. The specimen is serially sectioned to reveal a tan-white fleshy mass (12.3 x 7.5 x 3.2 cm) which underlines the nodule. Underlying the scar is a 3.5 x 1.5 x 1.0 cm hematoma. The mass is at the margin. The mass displays approximately 15% hemorrhage and 5% necrosis. Representative sections are submitted as follows: (Processed at UT)

1A-1H: Mass from largest fragment of soft tissue with overlying skin

1I-1J: Mass from additional aggregate of soft tissue

HLF09/02/2022 15:36

Microscopic Description

A microscopic examination has been performed and the findings are incorporated in the diagnosis above. The positive and negative controls for all histochemical and immunohistochemical stains, if performed for this case, have been reviewed and, unless otherwise noted, have been found to be appropriate.

Immunostaining was also performed at UT-PATH histology lab with appropriate controls on block 1A: BCL-2, BCL6, CD5, CD10, cyclin d1, Ki-67, MUM1

Non Clinical Documentation

88309-26, 88342-26 GC x 1, 88341-26 GC x 5, 88360-26 GC x 1 (UT-PATH)

Addendum Diagnosis

Right thigh mass, excision:

- B cell lymphoma is negative for cMyc with immunohistochemical stain,

see comment

NDN/NDN 09/13/2022 Electronic Signature: Nguyen, Nghia Andy D MD

Comment

The finding in this addendum does not change the diagnosis in original report

Non Clinical Documentation

CPT 88341

+++

Addendum

FISH

-bcl6 rearrangement: DETECTED

-MYC (gain/loss), bcl2 rearrangements, t(8; 14): not detected

Final DX:

-DLBCL, ABC subtype, Ki67 80% (with bcl6 rearrangement)

++++++++++++++++++++++++++++++++++++++++++

159. Brain: DLBCL, pending FISH for rearrangements of MYC, bcl2, bcl6

Diagnosis

1, 2. Brain, right temporoparietal, biopsy:

- Diffuse large B cell lymphoma, activated B cell subtype, with 90% proliferation rate,

see comment.

Biomarker blocks: 1A, 2A

NDN/ETR 09/22/2022 Electronic Signature: Nguyen, Nghia Andy D MD

Comment

- The morphology, immunophenotypes by immunohistochemical stains and flow cytometry (HF-22-xxx) are most consistent with diffuse large B cell lymphoma (DLBCL), activated B cell subtype. Additional samples were sent for FISH panel to rule out DLBCL/high grade B cell lymphoma with cMYC, bcl2 rearrangement.

- Dr xxx was notified of the diagnosis on 9/22/2022

Specimen Source

1. Right brain biopsy

2. Right brain biopsy

Clinical Information

Clinical history: 67 yo with persistent right sided headache for 2 weeks and unsteady gait found to have a right parietal enhancing lesion and a smaller left frontal lesion.

Operative procedure: Right stereotactic biopsy possible craniotomy

Operative findings: Brain tumor

Intraoperative Consultation

1FSA: Right brain biopsy: Favor lymphoma.

Results reported to Dr xxx on 09/19/2022 at 4:20 PM.

Gross Description

The case is received in 2 parts, labeled: xxx

1. The specimen is received fresh for intraoperative consultation, labeled with the patient's name, MRN, and "right brain biopsy" and consists of 3 tan-white soft tissue fragments (aggregating to 0.7 x 0.2 x 0.1 cm). A single touch prep was made and the specimen is submitted in toto for frozen section, resubmitted in 1FSA.

2. The specimen is received in formalin, labeled with the patient's name, MRN, "right brain biopsy", and consists of multiple tan-pink, focally hemorrhagic soft tissue fragments (aggregating to 1.7 x 1.0 x 0.3 cm). A portion of the specimen is sent for flow cytometry. The remaining soft tissue is wrapped in blue tissue paper and submitted in toto in 2A.

MV 09/19/2022 17:08

Microscopic Description

Histologic sections of the brain mass show diffuse infiltration by intermediate-large lymphocytes with irregular nuclear contour, vesicular nuclei with fine chromatin, and one to several nucleoli. They are admixed with a few mitotic figures and tingible-body macrophages. There is significant necrosis in the background.

Immunohistochemical stains, with adequate controls, are performed on block 2A for CD79a, CD3, CD5, bcl-2, CD10, bcl-6, MUM-1, c-myc, cyclin D1, and Ki-67. The abnormal cells are positive for CD79a, bc6, MUM1, bcl2, cMyc (50%). Ki-67 shows 90% proliferation rate. The abnormal cells are negative for CD10, CD3, CD5, cyclin D1.

Immunophenotyping by flow cytometry (HF22-xxx) shows a predominant B cell population (86% of lymphocytes) that are positive for CD19, CD20, with surface kappa light-chain restriction.

The morphology, immunostains, and flow cytometry are most consistent with diffuse large B cell lymphoma, activated B cell subtype. Additional samples were sent for FISH panel to rule out DLBCL/high grade B cell lymphoma with cMYC, bcl2 rearrangement.

Non Clinical Documentation

88307-GC x 2, 88331-GC, 88342-GC, 88341-GC x8, 88360

Teaching Physician Statement

"I have personally reviewed the resident's preliminary interpretation and all specimen preparations and have personally issued this report."

++++++