WHOLE-SLIDE-IMAGING (WSI) CASE LIST FOR TELEPATHOLOGY

Hematopathology cases at the Cancer Center, Ho Chi Minh City, Vietnam

Last Revision on: 11/15/2024

 

Uyen Ly, MD; Quang Nguyen, MD; Dang Nguyen, MD; Tu Thai, MD; Binh Le, MD; Duong Gion, MD;

Alexander Banerjee, MD; Brenda Mai, MD; Amer Wahed, MD; Andy Nguyen, MD

 

 

Case 5_1: 42 y/o female with Plasma Cell Myeloma

Case 5_2: 50 y/o female with Thalassemia

Case 5_3: 20 y/o female with acute myeloid leukemia/myeloid sarcoma

Case 6_1: 56 y/o male with plasmablastic lymphoma

Case 7_1: 35 y/o male with negative bone marrow, history of NK/T cell lymphoma, nasal type

Case 7_2: 52 y/o male with lymphoplasmacytic lymphoma vs marginal zone lymphoma

Case 7_3: 65 y/o male with polymorphous adenocarcinoma (hard palate)

Case 8_4: 60 y/o male with marginal zone lymphoma (neck lymph node, bone marrow)

Case 8_5: 32 y/o female with interdigitating dendritic cell sarcoma

Case 9_1: 60 y/o male with T cell rich B cell lymphoma

Case 10_2: 53 y/o female with plasmablastic lymphoma

Case 10_3: 70 y/o male with follicular B cell lymphoma (grade 1)

Case 10_4: 65 y/o female with T lymphoblastic lymphoma

Case 10_5: 53 y/o female with Nodular Lymphocyte Predominant Hodgkin Lymphoma (NLPHL)

Case 11_1: 71 y/o male with CML in blast crisis

Case 11_2: 27 y/o male with CML, chronic phase

Case 12_1: 1 y/o female with ALCL, ALK pos

Case 12_2: 73 y/o male with AML

Case 12_3: 55 y/o male with possible HLH

Case 13_1: 68 y/o male with follicular B cell lymphoma (grade 3)

Case 13_2: 49 y/o male with follicular B cell lymphoma (grade 3)

Case 13_3: 50 y/o male with interdigitating dendritic cell sarcoma

Case 13_4: 30 y/o male with myeloid sarcoma

Case 14_1: 39 y/o female with possible HLH

Case 14_2: 42 y/o female with peripheral T cell lymphoma, NOS

Case 15_1: 24 y/o male with classical Hodgkin lymphoma

Case 15_2: 61 y/o female with ALCL, ALK-neg, monomorphic variant

Case 15_3: 58 y/o male with CD5-positive DLBCL

Case 15_4: 55 y/o male with splenic marginal zone lymphoma (SMZL)

Case 16_1: 46 y/o female with angioimmunoblastic T cell lymphoma (AITCL)

Case 16_2: 27 y/o male with reactive plasma cells in rectal biopsy

Case 16_3: 60 y/o male with CD30-pos lymphoproliferative disorder

Case 16_4: 21 y/o female with undifferentiated carcinoma/sarcoma

Case 16B_5: 26 y/o female with follicular B cell lymphoma, Gr 3

Case 16B_6: 76 y/o female with reactive follicular hyperplasia

Case 17_4: Adult female with plasmablastic lymphoma

Case 17_5: 37 y/o female with normal bone marrow, no evidence of leukemia

Case 17_6: 58 y/o male with reactive lymphoid tissue

Case 18_1: 40 y/o male with T lymphoblastic lymphoma

Case 18_2: 67 y/o female with follicular B cell lymphoma, with some response to chemotherapy

Case 19_1: 4 y/o male with ALK-pos histiocytosis

Case 19_3: 31 y/o male with PTCL, NOS

Case 19_4: 64 y/o male with PTCL, NOS versus ALCL (monomorphic variant)

Case 19_6: 54 y/o male with likely undifferentiated acute leukemia

Case 20_1: 60 y/o male with primary cutaneous CD30-positive lymphoproliferative disorder

Case 20_2: 43 y/o female with anaplastic large  cell lymphoma, ALK-negative

Case 20_3: 50 y/o male with CLL/SLL

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

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

CONFERENCE 5 (March 2023)

CASE 1:

42 y/o female, diagnosed at outside hospital with plasmacytoma. Bone marrow was done on admission. Serum kappa/lambda were normal.

 

BM Bx, BM Asp:

https://pathpresenter.net/public/presentation/display?token=0d836d51

 

Findings:

-Bone marrow biopsy shows sheets of plasma cells, positive for CD138 and CyclinD1 (20% of plasma cells); negative for CD79a (aberrant loss), CD3. Stain for CD56 is not diagnostic (with negative stain for positive control)

-With diffuse infiltrate of plasma cells in bone marrow, the final diagnosis if plasma cell myeloma (instead of plasmacytoma)

-It is unknown why serum kappa/lambda is normal (unless it is a case of non-secretory myeloma)

-Optional IHCs for further testing: kappa, lambda, CD117, CD56 (repeated)

Diagnosis: plasma cell myeloma

++++++

CASE 2:

50 y/o female with abdominal pain, weight loss, diagnosed with Thalassemia at outside hospital and treated at local hospital.

Imaging showed enlarged neck lymph node, axillary lymph node, splenomegaly.

CBC: WBC 21.9 K/uL, Neu 5.2 K/uL, Lym 16.5 K/uL, Mono 0.2 K/uL, no blast. Hb 8.8g/dL, Platelet: 276k/uL

 

BM Bx, BM Asp:

https://pathpresenter.net/public/presentation/display?token=f593c4fe

 

Findings:

-Biopsy: hypercellular (60%), adequate megakaryocytes, increased orthochromic normoblasts

-Aspirate: numerous erythroids

Diagnosis: Thalassemia (BM)

Note that lymphoma in LN (neck, axilla) cannot be ruled out

++++++

CASE 3:

20 y/o female, with neck lymph node biopsy and bone marrow

CBC: WBC 191 K/uL, Neu 2.2 K/uL, Lym 181 K/uL, Mono 6.9 K/uL, blast 5%. Hgb 3g/dL, Platelets 47K/uL

 

Neck lymph node, BM Bx:

https://pathpresenter.net/public/presentation/display?token=1f823a0e

 

Findings:

LN bx, BM bx: diffuse/numerous large blasts, many mitosis & tingible-body macrophages

(+) CD117 in BM bx (neg in LN bx?), Ki67 (90%)

(-) TdT, CD34 (ctl suboptimal), CD1a (ctl suboptimal), CD79a, CD4, CD3, CD20

Diagnosis: AML with myeloid sarcoma in LN

Note: neg CD117 in LN bx may be artifact, note that part of BM bx is also false-negative, may perform CD43 on LN bx to confirm AML/myeloid sarcoma

+++++

CONFERENCE 6 (April 2023)

CASE 1:

56 y/o male, with lower-jaw mass; blood test showed elevated lambda

 

Lower-jaw biopsy:  

https://pathpresenter.net/public/presentation/display?token=cf6bcc16

 

Bone marrow:

https://pathpresenter.net/public/presentation/display?token=e0d476ea

 

https://pathpresenter.net/public/presentation/display?token=f6daed86

 

Findings:

-Lower-jaw mass shows diffuse infiltration with plasma cells having large nuclei, prominent nucleoli (note that there is a floater with carcinoma in upper left section)

(+) CD138, MUM1, Ki67 (low at 10-20%?)

(-) CD3, CD20, CD45, Pan-keratin

Diagnosis: Plasmablastic lymphoma

-BM: normal distribution of all cell lineages (normal stains for CD3, CD20, CD79a, CD138, CD56,cyclinD1)

++++

CONFERENCE 7 (June 2023)

CASE 1:

35 y/o male, diagnosed at outside hospital in 2021 with oropharyngeal NK/T cell lymphoma, nasal type

 

BM on admission: (23HT1872)

https://pathpresenter.net/public/presentation/display?token=3d317206

 

BM Bx unremarkable, no infiltrates (Aspirate 1: unremarkable, Aspirate 2: out of focus)

(+) CD45, CD3 (scattered)

(-) CD56, CD2, CD20

Diagnosis: negative for NK/T lymphoma in BM

 

Follow-up:

Patient’s Hgb kept dropping in 2 recent months; also tested positive for EBV, and sinus infection

 

Another BM was performed

 

https://pathpresenter.net/public/presentation/display?token=5eb66dae

Findings:

-EBV positive

-BM BX cellularity is still low (20-30%) in a 35 y/o male

-BX and Asp show no obvious lymphocytic infiltrates

Diagnosis: BX/asp did not change from 1st to 2nd BM. Pancytopenia (with hypocellular BM) is likely secondary to other etiologies besides lymphoma

Suggestion: CD56 for BX to definitely exclude NK/T cell lymphoma

++++++++

CASE 2:

52 y/o male, with parotid gland mass for 4 months. Parotid gland biopsy was diagnosed at outside hospital as plasmacytoid B-cell lymphoma, vs. plasmacytoma. Patient was admitted. Imaging showed multiple lesions in neck (bilateral), lung, nose, abdominal lymph node, bones

 

BM Bx, Immunology blood test: (23GT8344)

https://pathpresenter.net/public/presentation/display?token=41e65c5a

 

Findings:

-SPE with gamma spike, IgG-Lambda monoclonal gammopathy, elevated Beta2-Microglobulin

-BM Bx: many lymphs, many erythroids, a few plasma cells

-Aspirate: many lymphocytes including some plasmacytoid lymphs, a few plasma cells

Differential DX: lymphoplasmacytic lymphoma vs marginal zone lymphoma

Sggestion: CD79a, CD138. MYD88 may be useful if available

 

Follow up:

More IHCs done:

https://pathpresenter.net/public/presentation/display?token=a6771211

 

Findings:

-CD20 neg may be due to Rituximab

-CD79a neg (?)

-CD138 scattered pos

Differential DX: lymphoplasmacytic lymphoma vs marginal zone lymphoma, unknown reason for neg CD79a

+++++

CASE 3:

65 y/o male, with hard palate tumor

 

Bx, IHC of hard palate tumor: (23HT1570)

 https://pathpresenter.net/public/presentation/display?token=33eb836a

 

Findings:

Morphology: glandular formation, favors carcinoma

(+) CD138

(-) CD45, CD20

Diff DX: carcinoma vs plasma cell neoplasm

Suggested: Pan-K, kappa, lambda, CD56, CD117

 

Consultation with ENT Pathologist at UT (Dr Saluja):

-Based on the IHC this tumor is more compatible with polymorphous adenocarcinoma initially known as polymorphous low grade adenocarcinoma (PLGA). The other differential is myoepithelial carcinoma as these tumor can have some immunostains overlap with polymorphous adenocarcinoma based on different lab protocols.  

-These tumor may be managed as low to intermediate grade salivary tumors.

++++++

CONFERENCE 8 (July 2023)

CASE 4:

60 y/o male, with neck mass slowly growing over a year. Patient had acute hematologic malignancy 22 years ago per verbal information. Patient now has 5cm neck mass, pancytopenia. Imaging showed lesions in nasopharynx, parotid glands, neck lymph nodes, abdominal lymph nodes, splenomegaly

 

BM Bx & Asp, core Bx of neck LN, Bx of Nasopharynx:

ruhttps://pathpresenter.net/public/presentation/display?token=c49cafbb

 

Findings:

-Morphology: diffuse distribution in aspirate, BM Bx (lower part with better resolution), nasopharynx Bx of small-intermediate lymphocytes; no mitosis. Malignant cells are mixed with orthochromic normoblasts in BM Bx

-Pos EBV by PCR

-CBC: pancytopenia

-IHCs: N/A

-Diff DX:

  (a) lymphoma/leukemia (B, T, NK)-> suggest IHCs for CD3, CD79a, CD56, TdT, Ki67; also EBER

  (b) unknown previous Hx of acute heme tumor 22 years ago?

 

Follow-up:

More IHCs on LN (updated): 

https://pathpresenter.net/public/presentation/display?token=f301ac97

 

Findings:

Mostly small lymphocytes, monocytoid lymphocytes

Pos for CD20, CD79a more than for CD3, CD5

Pos (subset) bcl6

Neg CD10, CD23, cyclinD1, CD56, TdT

Ki67 20%

 

->ruled out: SLL, FL, MCL

Diagnosis: Marginal Zone Lymphoma

 

More IHCs on BM (updated):

https://pathpresenter.net/public/presentation/display?token=349004cc

All neg (?)

Ki67 50% (proliferative BM)

++++++

CASE 5:

 

32 y/o female; in Jan 2023 had skin lesions throughout body, also bone lesions. Patient had biopsy of abdominal skin lesion, diagnosed as generalized eruptive histocytosis at outside hospital with the following IHC findings: LCA neg, CD3 neg, CD20 neg, CD1a neg, CD117 neg, S100 neg, CD68 pos, Ki67 30%. Patient underwent chemotherapy (6 cycles of CHOP), now presents with lesions in arms

 

Bx, IHCs of arms

https://pathpresenter.net/public/presentation/display?token=76292248

 

Findings:

Sheets of spindled cells with a whorled pattern

(+) CD56, S100, CD4, CD68

(-) CD1a, CD117, CD8, PanCK, TdT, CD20, CD34, SOX10, CD30, ALK, CD21, CD45, CD3

Diagnosis: Interdigitating dendritic cell sarcoma

 

Other Diff DX that were excluded:

(a) Blastic plasmacytoid dendritic cell neoplasm (CD4, CD56)-> not c/w morphology

(b) Histiocytic sarcoma-> not c/w morphology

+++++

CONFERENCE 9 (July 2023)

CASE 1:

60 y/o male, with swelling inguinal lymph node, further examination showed widespread lymphadenopathy

 

LN Bx, IHC of right superficial inguinal LN: 

https://pathpresenter.net/public/presentation/display?token=b0af61e9

 

Findings:

Numerous nodules, containing mostly small lymphocytes w scattered large cells, scattered mitosis

Diff DX at low-power microscopy: NLPHL, TCR LBCL, FL

IHCs: CD3, CD5 >>CD20

(+) in residual follicle: PAX5, CD10, bcl2, CD23

(-) bcl6, CD15, cMYC (blurred), cyclinD1, MUM1, TdT

CD30 (equivocal)

(+) Ki67 (60%, among large cells)         

Diagnosis: T cell rich B cell lymphoma (TCR BCL)

++++

CONFERENCE 10 (August 2023)

CASE 2:

53 y/o female, a year prior was diagnosed nasal tumor, underwent radiation therapy. The nasal mass currently remains at the same size.

 

Nasal mass:

https://pathpresenter.net/public/presentation/display?token=a5baa309

 

Findings:

Nasal mass having subset of large cells with prominent nucleoli, a few mitosis

(+) CD138, CD79a, MUM1,

(-) EMA

Diagnosis: Plasmablastic lymphoma

Suggestion: need to check EBV, and HIV status

+++++

CASE 3:

70 y/o male, 5 years ago diagnosed with DLBCL, underwent 6 cycles of chemotherapy, with complete remission. Now patient presents with 27 mm chest wall lesion, abdominal lymphadenopathy, bilateral inguinal lymphadenopathy, increased HBV viral load.

 

L Chest wall lesion, IHC:

https://pathpresenter.net/public/presentation/display?token=77332c91

 

Findings:

-Follicles of lymphocytes (more small lymphocytes)

(+) CD20,CD79a, PAX5, CD10, bcl6

(-) CD3,CD5,CD23 (CD23 seen in residual dendritic cells),CD15, CD30, bcl2 (?, blurred)

Ki67 low, spread-out (<20%)

Diagnosis: Follicular B cell lymphoma (grade 1)

Suggestion: repeat bcl2 for quality assurance

++++

CASE 4:  

65 y/o female, with past history of leukemia (2012), non-Hodgkin lymphoma (2020), s/p therapy. Now (Aug 2023) patient presented with enlarged neck lymph node (bilateral, 5-6 cm), axillary/abdominal/inguinal lymphadenopathy, enlarged tonsils, and mild splenomegaly. Lab results showed anemia and thrombocytopenia, decreased albumin, elevated LDH,

 

Neck lymph node biopsy:

https://pathpresenter.net/public/presentation/display?token=35575e9b

 

Findings:

Neck mass shows vague nodules containing lymphocytes of intermediate size, many tingible-body macrophages, moderate mitosis

Diff DX: T or B lymphoblastic lymphoma, follicular B cell lymphoma, Burkit lymphoma, AITCL (low in list)

(+) CD3, CD5, CD4, CD8, ki67 (80%)

(-) CD20, CD79a, MUM1 (pos in residual follicles), PAX5, CD10, bcl6. CD15, CD30, ALK1, bcl2, TdT (?), CD138 (pos in plasma cells),  
        cMYC, cyclinD1

Diagnosis: T lymphoblastic lymphoma (BM likely involved with low platelet count)

Suggestion: CD1a to r/o PTCL, NOS

+++++

CASE 5:

53 y/o female, with lymphadenopathy (bilateral neck, bilateral axillary, R inguinal). Lab results show elevated LDH, normal CBC.

 

L neck lymph node biopsy (4 cm):

https://pathpresenter.net/public/presentation/display?token=7b89b57f

 

Findings:

Neck mass shows large cells with large nucleoli (no multinucleated cells) in background of small lymphocytes in vague nodules, rare mitosis

Diff DX:TCR Large BCL, NLPHL, HL (low in diff DX)

(+) CD20, Ki67, CD45

(-) CD15, PAX5 (large cells not dim), CD10, bcl6, ALK1, CD21, CD23

CD3 forms rosettes around large B cells

Background (small cells, more B cells than T cells): pos for CD3, CD5, (neg CD2?), CD7, CD4, CD8, CD20, PAX5, residual dendritic cell (CD21, CD23).

CD30 not useful (?, too dark or too light, need to titrate CD30)

Diagnosis: Nodular Lymphocyte Predominant Hodgkin Lymphoma (NLPHL)

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

CONFERENCE 11 (August 2023)

CASE 1:

71 y/o male, with CML, undergoing treatment, widespread lymphadenopathy (neck, axillary, abdominal, inguinal), elevated beta2 gammaglobulin, leukocytosis, normal LDH

 

BM Bx and Asp:

https://pathpresenter.net/public/presentation/display?token=2a73283f

 

Findings:

CBC (no PBS available): leukocytosis (elevated lymphs by manual differential), anemia, normal platelet count

BM Asp (slide 6 is better than 1): predominant immature cells

BM Bx: 40%, focal areas with high cellularity and monomorphic

Diagnosis: blast crisis (myeloid vs lymphoid) with Hx of CML, difficult to differentiate

Suggest IHCs on BX:

-To r/o AML: MPO, CD117

-To r/o ALL: TdT, CD79a, CD3, CD4, CD8

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

CASE 2:

27 y/o male, diagnosed with CML, positive BCR::ABL1 seven years ago (2016), treated with Imatinib 100mg x 4 tabs/day, stopped taking med in Jan 2023. Now (Aug 2023) WBC is elevated; unknown treatment

 

BM Bx and Asp:

https://pathpresenter.net/public/presentation/display?token=83b004a9

 

Findings:

BM Bx: hypercellular (~100%), heterogenous myeloid cells, high M/E ratio, many dwarf megs

BM Asp: findings similar to those in BX

CBC: normal Hgb, Plt, elevated WBCs with predominant neutrophils (WBC progressively decreased, likely with TX)

Diagnosis: CML in chronic phase

+++++

CONFERENCE 12 (October 2023)

CASE 1:

1 y/o female, neck lymphadenopathy (2.5 cm), splenomegaly (11 cm), elevated LDH (1531 U/L), WBC 1,3 x109/L

 

Spleen biopsy:

https://pathpresenter.net/public/presentation/display?token=04b65589

 

Findings:

Pleomorphic cells, no predominant multinucleated cells

(+) CD30, ALK, CD3 (likely cytoplasmic), Ki67

(-) CD20

Diagnosis: ALCL, ALK pos (Not many horse-shoe cells->monomorphic variant)

Notes: the following lymphomas were ruled out:

cHL: r/o with no HRS cells, CD3 pos

DLBCL: r/o with CD20 neg

PTCL-CD30 pos: r/o with ALK pos

ALK pos-LBCL: r/o with CD30 pos

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

CASE 2:

73 y/o male, with thrombocytopenia, leukocytosis

 

BM Bx and Asp:

https://pathpresenter.net/public/presentation/display?token=db2818ba

 

Findings:

BM Asp/Bx are hypercellular, monotonous population (intermediate-large nuclear size)

(+) CD43, MPO

(-) CD3, CD20, PAX5

Diagnosis: acute myeloid leukemia (AML)

Suggestion: testing for t(8;21), t(15;17), FLT3, NPM1, CEBPA

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

CASE 3:

55 y/o male, with history of gastric cancer, spinal metastasis, currently with leukocytosis

 

BM Bx and Asp:

https://pathpresenter.net/public/presentation/display?token=d3238d80

 

Findings:

BM Asp/Bx: trilineage hematopoiesis, including a subset with large nuclear size (histiocytes), BX hypercellular (70%) with hemophagocytosis,

BM cells appear normal (no associated lymphoma/leukemia, no pathologic lesion)

Diagnosis: cannot r/o HLH

Suggestion: Check CBC, ferritin, Triglycedride, Fibrinogen, (sCD25), EBV (serology or EBER), IHC for CD68

In order to get a more definitive diagnosis of HLH, at least 5 of the following 8 criteria need to be met:

1.                   Fever (peak temperature of > 38.5° C for > 7 days)

2.                   Splenomegaly (spleen palpable > 3 cm below costal margin)

3.                   Cytopenia involving 2 cell lines (hemoglobin < 9 g/dL [90 g/L], absolute neutrophil count < 100/mcL [0.10 × 109/L], platelets < 100,000/mcL [100 × 109/L])

4.                   Hypertriglyceridemia (fasting triglycerides > 177 mg/dL [2.0 mmol/L] or hypofibrinogenemia (fibrinogen < 150 mg/dL [1.5 g/L]

5.                   Hemophagocytosis (in samples of bone marrow, spleen, or lymph nodes) already seen here in this case

6.                   Low or absent natural killer cell activity

7.                   Serum ferritin > 500 ng/mL (> 1123.5 pmol/Lng/mL)

8.                   Elevated soluble interleukin-2 (CD25) levels (>2400 U/mL or very high for age)

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

CONFERENCE 13 (December 2023)

CASE 1:

68 y/o male, enlarged axillary lymph node

 

Axillary lymph node:

https://pathpresenter.net/public/presentation/display?token=277c16dc

 

Findings:

Back-to-back follicles with >50% large centroblasts

(+) bcl6, CD20, Ki67 (60-70%, evenly-distributed), CD30, cMYC (scatterd), MUM1 (scattered)

(-) CD10, ALK, CD15, bcl2, CD5, cyclinD1, CD3, CD23,

CD21 pos for follicular dendritic cells

Diagnosis: FL, high-grade (3/3)

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

CASE 2:

49 y/o male, bilateral neck lymphadenopathy

 

Neck lymph node:

https://pathpresenter.net/public/presentation/display?token=4b5d32ec

 

Findings:

Back-to-back follicles with >50% large centrocytes

(+) bcl6 (?->repeat), CD20, Ki67 (60%, evenly-distributed),

(-) CD10, bcl2, CD5, cyclinD1, CD3, cMYC, MUM1,

CD21 pos for follicular dendritic cells

Diagnosis: FL, high-grade (3/3)

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

CASE 3:

50 y/o male, with tumor on nasal skin for 5 months, also a skin lesion 7x6 mm

 

Skin biopsy:

https://pathpresenter.net/public/presentation/display?token=67ef2ed5

 

Findings:

Diffuse dermal infiltrate with large-pleomorphic cells, many with spindle-ovoid shape

(+) CD4, S100, CD68, Ki67 (20%), vimentin

(-) CD34, CD21, CD1a, CK5/6, HMB45, CD56, Melan A, p63, CD45

 

Diff DX:

-Langerhan cell sarcoma (LC): r/o with neg CD1a

-Follicular dendritic cell sarcoma (FDC): r/o with neg CD21, pos CD68

-Blastic plamacytoid dendritic cell tumor (PDC):  less likely with pos S100; neg CD56

-Histiocytic sarcoma (H): r/o with neg CD45, pos S100

-Interdigitating dendritic cell sarcoma (IDC): favored with pos S100, vimentin, neg CD1a, neg CD45, neg CD21, neg Cytokeratin, neg CD34, Ki67 at 20%; also Dx of exclusion

Diagnosis: Interdigitating dendritic cell sarcoma

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

CASE 4:

30 y/o male, bilateral neck lymphadenopathy. A previous lymph node biopsy showed tumor cells positive for CD45, Vimentin (+/-), Ki67 (40%); negative for panCK, CD3, CD20, CD79a, CD138

 

Repeated neck lymph node biopsy:

https://pathpresenter.net/public/presentation/display?token=390548d0

 

Findings:

Largest fragment: diffuse infiltrate with large pleomorphic cells, with mitosis (smaller fragment with small T cells)

(+) bcl2,CD43, MPO, Ki67 approach 60%

(-) CD3, CD20, CD2, CD10, CD5, CD7, bcl6, MUM1, TdT, CD117, cMYC, cyclinD1

Ruled out carcinoma, T/B lymphoma, plasma cell neoplasm

Diagnosis: myeloid sarcoma;

Suggestion: need to perform BM to r/o AML

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

CONFERENCE 14 (January 2024)

CASE 1:

39 y/o female, diagnosed with HLH at outside hospital, now admitted and had another BM

 

BM Bx, Asp:

https://pathpresenter.net/public/presentation/display?token=d9291847

 

Findings:

BM aspirate shows a moderate number of histiocytes with phagocytosis.

Biopsy also shows suggested evidence of phagocytosis

Diagnosis: likely HLH

Notes:

In order to get a more definitive diagnosis of HLH, at least 5 of the following criteria need to be met:

9.                   Fever (peak temperature of > 38.5° C for > 7 days)

10.                Splenomegaly (spleen palpable > 3 cm below costal margin)

11.                Cytopenia involving 2 cell lines (hemoglobin < 9 g/dL [90 g/L], absolute neutrophil count < 100/mcL [0.10 × 109/L], platelets < 100,000/mcL [100 × 109/L])

12.                Hypertriglyceridemia (fasting triglycerides > 177 mg/dL [2.0 mmol/L] or hypofibrinogenemia (fibrinogen < 150 mg/dL [1.5 g/L]

13.                Hemophagocytosis (in samples of bone marrow, spleen, or lymph nodes) already seen here in this case

14.                Low or absent natural killer cell activity

15.                Serum ferritin > 500 ng/mL (> 1123.5 pmol/Lng/mL)

16.                Elevated soluble interleukin-2 (CD25) levels (>2400 U/mL or very high for age)

-Criterion 7 is the most important one, the ferritin level in HLH is usually much higher than the minimum threshold cited here (500). I real cases of HLH, ferritin is typically in the thousand’s range

-Criteria 6 and 8 are difficult to meet due to lack of available tests

-Since HLH is often associated with EBV infection, auto immune disease, and lymphoma (esp. T cell lymphoma). It is recommended that workup for these conditions is pursued

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

CASE 2:

42 y/o female, diagnosed with classical Hodgkin lymphoma at outside hospital, presented with pancytopenia in 2 weeks with unknown etiology

 

BM Bx:

https://pathpresenter.net/public/presentation/display?token=68a8373c

 

Findings:

Diffuse infiltrate of large lymphoma cells; only rare multinucleated cells

(+) CD45,CD3

(-) CD30, PAX5,CD20,CD15

Classical Hodgkin Lymphoma is unlikely with given morphology and IHCs

Diagnosis: Peripheral T cell lymphoma, NOS (not anaplastic large T cell lymphoma)

Suggestion: IHCs for CD4, CD8, CD7, CD5

Pancytopenia likely due to BM infiltrate by lymphoma cells

++++

CONFERENCE 15 (January 2024)

CASE 1:

24 y/o male, enlarged clavicular lymph node (bilateral)

 

L clavicular lymph node (15 mm):

https://pathpresenter.net/public/presentation/display?token=0812fe2e

 

Findings:

Large cells (HRS, mummified cells?) with many small lymphocytes in background

(+)CD30 (blurry?), Ki67

(-)CD4, CD20,PanCK, CD3, CD2, CD43,ALK

[PAX5: suboptimal (neg for CD20-pos cells)]

Diagnosis: Likely cHL,

Note: difficult to subtype with core BX

Suggestion: repeat CD30, PAX5; also perform CD45, CD15

 

Follow-up:

IHCs for CD30, PAX-5, CD15, CD45

https://pathpresenter.net/public/presentation/display?token=0812fe2e

CD15: difficult to interp (strong nuclear stain), neg CD45

Diagnosis: cHL

+++++++++

CASE 2:

61 y/o female

 

L neck lymph node biopsy (2 cm):

https://pathpresenter.net/public/presentation/display?token=bf9376f6

 

Findings:

Many large pleomorphic cells, no RS cells, no horse-shoe cells; increased mitosis

(+) CD30,KI67

(-) CD45,CD3,CD2,CD15, CD20, PAX5

Diagnosis: possible ALCL, monomorphic variant

Suggestion: to perform ALK1, CD4, CD8

 

Follow-up:

(+) CD4

(-) CD8, ALK

Diagnosis: ALCL, ALK-neg, monomorphic variant

(usually ALK-neg in adult, CD4-pos, CD30-strongly pos, CD45-neg, CD3 neg)

++++++++

CASE 3:

58 y/o male

 

R axillary lymph node biopsy (3 cm):

https://pathpresenter.net/public/presentation/display?token=2947747e

 

Findings:

Large pleomorphic lymphocytes

(+) CD5,CD20, PAX5, Ki67 (60%)

(-) CD3 (?), bcl2 (suboptimal),CD10, bcl6, ALK, CD30, PanCK, cyclinD1

CD4 and CD8 show polyclonal distribution

Diagnosis: CD5-pos DLBCL

+++++++

CASE 4:

55 y/o male, spleen tumor

 

Spleen biopsy:

https://pathpresenter.net/public/presentation/display?token=9334ce45

 

Findings:

Diffuse lymphoid infiltrate, HRS-like cells, background of small lymphocytes, collagen bands

(+) CD20, PAX5, CD45, Ki67 (low at 10%)

(-) CD15, CD3, CD30, ALK, EMA, CD138, AFB, PAS, silver, CD1a, CD23, CD21, S100

CD4, CD8: mixed, polyclonal

CD68: histiocytes in spleen

Many CD3 pos cells (T lymphocytes)

 

Differential DX’s that were excluded:

(a) cHL: not c/w IHC pattern

(b) T cell lymphoma including ALCL

(c) ALK-pos histiocytosis

(d) Follicular dendritic sarcoma: neg CD21, CD23

(e) Indeterminate dendritic cell tumour: neg CD1a, S100

(f) Reactive histiocytosis, with background of inflammatory T cells and B cells: not c/w presentation,

     neg AFB, PAS (AFB, fungal also less likely without granuloma, necrosis)

Diagnosis: splenic marginal zone lymphoma (SMZL), typically having no peripheral lymphadenopathy

(MZ lymphoma cells with clear cytoplasm, scattered large cells are part of this lymphoma)

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

CONFERENCE 16 (February 2024)

CASE 1: 24HT462

46 y/o female, enlarged clavicular lymph node in the last 6 months. Patients had biopsies done 4 times in 6 months without definitive diagnosis. Ultrasound showed R clavicular lymph node (3 cm), also many enlarged neck lymph nodes and pelvic lymph nodes, suspicious for lymphoma.

 

Clavicular lymph nodes (procedures done in 3rd and 4th times)

https://pathpresenter.net/public/presentation/display?token=39fc2047

 

Findings:

Thickened capsule, increased vessels. diffuse distribution of small-intermediate lymphocytes

(+) CD45, mixture of B cells (PAX5, CD20), and T cells (CD3) with T >> B

(-) CD15, CD30, EMA

Diff DX: Angioimmunoblastic T cell lymphoma (AITCL) vs reactive lymphoid tissue

Suggestion: bcl6, CD10, Ki67, EBER, CD21

 

Follow-up:

Additional stains:

(+) bcl6 (subset), Ki67 (high), CD4 (appears predominant even though CD8 is not done)

(-) CD10, CD21

Diagnosis: Angioimmunoblastic T cell lymphoma (AITCL)

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

CASE 2: 24HT461

27 y/o male, clinical information is included in link below

 

Rectal biopsy with ulceration, and BM:

https://pathpresenter.net/public/presentation/display?token=677ad884

 

Findings:

BM Bx: normal trilineage maturation

Normal distribution of CD3, CD79a, CD38, CD138

K/L: polyclonal

 

Rectal Bx: large cluster of plasma cells

(+) CD79a, CD38, CD138

(-) CD3

K/L: polyclonal

Diagnosis:

BM Bx: normal

Rectal Bx: focal cluster of reactive polyclonal plasma cells

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

CASE 3: 24GT2515 và 23HT4957

60 y/o male, a year ago was diagnosed with primary cutaneous ALCL (stage IV, with lesions in axillary /inguinal lymph nodes, skin lesions throughout body), s/p CHOEP 5 cycles, now with leukocytosis, monocyte > 3,000.

A BM is performed

 

Skin lesion (a year ago, in 2023):

https://pathpresenter.net/public/presentation/display?token=819e957f

 

Findings:

Diffuse pleomorphic lymphoma cells, increased mitosis

(+) CD3, CD4, CD30

(-) CD2? (suboptimal control), CD5, CD7, CD8, ALK, cyclinD1, bcl2, MUM1

Diagnosis: refractory CD30-pos lymphoproliferative disorder (including CD30-pos T cell lymphoma, and primary cutaneous ALCL)

 

BM Bx, Asp with CBC (2024):

https://pathpresenter.net/public/presentation/display?token=18409d9a

Diagnosis: normocellular with normal trilineage maturation

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

CASE 4: 24HT187

21 y/o female, with multiple bone lesions

 

BM Bx, Asp at multiple locations with MRI, CT:

https://pathpresenter.net/public/presentation/display?token=fe4437d6

 

Findings:

Diffuse, pleomorphic cells

(+) CD138, Vimentin, Ki67 (20%)

(-) CD10 (pos in basement membrane), SATB2, S100, CD99,CD45, CD1a, CD3, CD56, CD38, MUM1, K, L,

    BCL2, SALL, OCT4, CK, CK7, EMA, Desmin,  Myogenin, MyoD1, WT1, CD34,

    CD31, ERG, Synaptophysin, Chromogranin A, CD68, CD79a, SOX-10, MelanA, HMB45,

    CD68 (pos in a few pos histiocytes, with lots of background staining)

Diagnosis: Undifferentiated carcinoma/sarcoma (not lymphoma or plasma cell neoplasm)

Note: surgery as the main treatment modality

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

CONFERENCE 16B (February/March 2024)

CASE 5:

26 y/o female, enlarged neck lymph node in the last 2 months, found to have widespread lymphadenopathy, lesion in spleen

 

R neck lymph node (2 cm):

https://pathpresenter.net/public/presentation/display?token=dd9f9b96

 

Findings:

Follicular infiltrates (back-to-back), intermediate & immature lymphocytes, containing tangible-body macrophages, and mitosis

(+) CD20, bcl6, CD10, Ki67 (no polarization),

(-) bcl2

T cells (CD3) are polytypic, mixture of CD4, CD8 pos cells, outside follicles

CD21, CD23 are pos for dendritic cells in follicles

PD1 is pos for TFH cells in follicles

Diagnosis: Follicular Lymphoma, predominantly Gr 3/3 (high grade) with neg bcl2

++++++

CASE 6:

76 y/o female, imaging of R axillary lymph node suggests malignancy, that of neck/abdominal/inguinal lymph nodes suggests inflammation,

Normal size of liver/spleen, normal LDH

 

R axillary lymph node:

https://pathpresenter.net/public/presentation/display?token=cce631fe

 

Findings:

Scattered follicles, some with increased centroblasts (labeled, reactive); mantle zone not well delineated (likely due to core bx)

(+),CD45, CD20, Ki67 (high in reactive follicles)

(-) panCK,  CD3, bcl2, CD163

CD138 pos for plasma cells, increased in focal areas

 

Also a few small primary follicles (pos for CD20 and bcl2)

Diagnosis: most likely reactive follicular hyperplasia and a few small primary follicles, contained within core bx

Suggestion: cannot completely r/o a low-grade B cell lymphoma with plasmacytic differentiation (MZL); need to perform excisional BX for better LN architecture

Note that imaging with PET/CT may yield false-pos results

+++++

CONFERENCE 17 (April 2024)

CASE 4: 24HT1925

Adult female patient, 1 month history of jaw tumor. CT scan shows wide-spread lesion in R jaw, suggestive of malignancy

 

Jaw biopsy:

https://dpa-dapa.com/public/presentation/display?token=932154a2

 

Findings:

Diffuse immature lymphoid cells, some with plasmacytoid features, scattered mitosis

(+) CD38, CD79a, L>>K, CD138 (focal, less than expected)

(-) bcl2,CD23, CD3, cyclinD1, CD20

Diagnosis: likely plasmablastic lymphoma

Suggestion: Ki67, MUM1; also EBER

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

CASE 5: 24GT7409

37 y/o female, normal CBC, clinically suspected of myeloid leukemia

 

BM Bx, Asp:

https://pathpresenter.net/public/presentation/display?token=6096b504

 

Findings:

Bx: normocellular 60%, trilineage maturation

Asp (Giemsa) : trilineage maturation

Diagnosis: aspirate, Bx, CBC normal: unlikely to be associated with leukemia.

Suggestion: to completely r/o myeloid leukemia, suggest IHC on bx: MPO, CD34, E Cadherin, CD3, CD20 (to see if overall distribution is normal)

+++

CASE 6: 24HT2555

58 y/o male, admitted with L lower jaw tumor (2 month duration, 32x39 mm, imaging is suggestive of salivary gland tumor, favor pleomorphic adenoma, but cannot r/o lymphoma).

WBC 13,4k ; Neutrophil 9,2k; LDH: 332, beta2 microglobulin: 2747. Patient was discharged but was readmitted 2 weeks later due to mediastinal syndrome

 

L lower jaw biopsy:

https://pathpresenter.net/public/presentation/display?token=c9e48782

 

Findings:

-Core Bx shows vague small follicles (reactive, with no clear mantle zone).

-Interfollicular: Distribution of small lymphocytes with scattered large cells, no obvious HRS cells, no increase in mitosis; No evidence of adenoma.

-Reactive follicles

(+) CD20 [can not zoom down],CD21, CD23; Ki67 (polarized), bcl6 (weak), CD10 (weak)

(-) bcl2, CyclinD1, Myc

 

The interfollicular small lymphocytes:

(+) CD3, CD5,  bcl2

(-) CD20, CyclinD1, Myc

Diagnosis: reactive lymphoid tissue;

Note: cannot find correlation with mediastinal syndrome

+++++

CONFERENCE 18 (April 2024)

CASE 1: DM24.213

40 y/o male, with large tumor in anterior mediastinum

 

Anterior mediastinum mass biopsy:

https://pathpresenter.net/public/presentation/display?token=22e620be

 

Findings:

Diffuse distribution of immature large cells, admixed with mitosis and eosinophils. Also increase in vascular structure.

(+) CD3, CD5 (subset), CD7, TdT (subset), Ki67 (60%)

(-) Pan-CK, CD19, CD79a, CD20, CD2 (aberrant loss), CD30, CD15, MPO

Diagnosis: T lymphoblastic lymphoma

Suggestion: optional IHCs for CD1a, CD4, CD8

++++++

CASE 2:

67 y/o female, previously diagnosed with follicular lymphoma Gr 3, now with enlarged L inguinal lymph node

 

L inguinal lymph node biopsy:

https://pathpresenter.net/public/presentation/display?token=dbd8bc97

 

Findings:

Follicles, back-to-back, mostly centrocytes in follicles

(+) CD20, CD10, bcl6

(-) CD3, CD5, bcl2, cyclinD1, Ki67 (low ~10%, no polarized pattern)

 

CD21, CD23: follicular dendritic cells

Diagnosis: follicular B cell lymphoma,

Note: Grade 3 (by history); patient responded to treatment and the number of centroblasts decreased, now resembles a lower-grade follicular lymphoma under microscopic examination.

Patient is not yet in remission

+++

CONFERENCE 19 (May 2024)

CASE 1:

4 y/o male, admitted with adhesion of multiple neck lymph nodes. Imaging with ultrasound and CT shows widespread lymphadenopathy (bilateral cervical - supraclavicular - mediastinal - lung hilar lymph node; right axillary - abdominal lymph node), 34 mmm in largest dimension. Lab results: LDH: 315 U/L, beta2 microglobulin: 1913 ug/L (normal). Patient was diagnosed with peripheral T cell Lymphoma NOS at outside hospital. Patient was admitted with WBC: 29.9k,  Neu: 21.9k,   Lym: 4.8k,    RBC: 5.35,  Hgb: 108 g/L;   MCHC: 308, Plt: 260. Patient was treated with chemotherapy for peripheral T cell Lymphoma NOS with decreased size of neck/axillary lymph nodes. WBC: 5.4k,   Neu: 4.2k,   RBC: 3.76,   Hgb: 83 g/L,   MCHC: 306,   Plt: 314. No blasts in PBS.

 

Cervical lymph node biopsy at outside hospital:

https://pathpresenter.net/public/presentation/display?token=287193ae

 

Findings:

Cervical lymph node shows diffuse infiltrate with histiocytic cells, no obvious mitotic figures, histiocytes lacking high-grade atypia, admixed with small lymphocytes, background with scattered small residual follicles

(+) CD45, CD4, ALK1 (subset, not strong), CD68, Ki67 (low, <10%)

(-) CD3, CD79a, CD2, CD5, CD7, CD8, CD10, bcl6, CD21, CD23, CD30, CD1a, S100

 

Diagnosis: ALK-Pos Histiocytosis

Notes: seen in young patient, systemic involvement, effective treatment with ALK Inhibitor (such as lorlatinib);

ALK gene translocation, most commonly with exon 24 of KIF5B fused to exon 20 of ALK

 

Excluding other DX’s:

-T cell lymphoma, NOS is unlikely due to lack of many T cell markers;

-T lymphoblastic lymphoma is unlikely due to low Ki67, neg CD1a, also lack of many T cell markers

-Langherhan cell histiocytosis is unlikely with neg CD1a, S100, no increased eosinophils in section

 

A concern for ALK stain: should be cytoplasmic/membrane; the stain in this case appears nuclear?

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

CASE 3:

31 y/o male, with ulcer in duodenum having ragged edge, measuring 2/3 of duodenal circumference. Imaging shows many enlarged abdominal lymph nodes and enlarged lymph nodes in liver. Patient is doing poorly (clinically)

 

Duodenal biopsy

https://pathpresenter.net/public/presentation/display?token=bdaff103

 

Findings:

Duodenum biopsy shows diffuse lymphocyte infiltrate in submucosa, small-intermediate lymphocytes, a few lymphoepithelial lesions

(+) CD3, CD5, CD4, CD7 (subset, partial loss), bcl6

(-) CD20, CD8, CD30, bcl2, CD10, CD56, CyclinD1, CD23, PanK

Low Ki67 (<10%)

Diagnosis: PTCL- NOS

Note: indolent T cell lymphoma of GI tract is less likely due to significant clinical symptoms in this young patient

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

CASE 4:

64 y/o male, with splenic tumor (30 cm), no other lymphadenopathy seen, CBC: WBC 23.6K (Neu: 14K, Lym: 8K), RBC: 3.9K, HGB: 102, PLT: 422K.

 

Splenic biopsy:

https://pathpresenter.net/public/presentation/display?token=c257cfde

 

Findings:

Spleen biopsy shows expansion of white pulp, intermediate-large lymphs, scattered eosinophils, scattered mitotic figures

(+) CD4, CD43, CD3 (subset)

(-) CD8, CD20, CD34, CD61, ECadherin, MPO, CD117

[CD8 outlines splenic sinus]

 

Diagnosis: PTCL- NOS versus ALCL (monomorphic variant)

Suggested IHCs: CD30, ALK1

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

CASE 6:

54 y/o male, bilateral neck lymphadenopathy. BM aspirate shows 44% blasts. CBC with many blasts

 

L neck lymph node:

https://pathpresenter.net/public/presentation/display?token=3cf62e95

 

Findings:

Diffuse & monotonous infiltrate of pleomorphic cells, intermediate nuclear size, scatter mitotic figures

(+) CD7, CD43, Ki67 (60%), TdT

(-) CD3, CD20, CD2, CD5, CD4, CD8, CD117 (subset), CD34 (?), MPO

 

BM Bx, Asp:

https://pathpresenter.net/public/presentation/display?token=59ca21e1

 

Findings:

Monotonous infiltrate of pleomorphic cells, intermediate nuclear size

 

Flow cytometry:

(+) CD7, CD34, CD56, CD38, CD200

(-) CD2, CD3, CD4, CD8, CD5, TCR-gamma/delta, CD13, CD117 (partial), CD33 (partial), HLA-DR, CD15, CD19, CD10, CD20, K, L, CD11b, CD16, CD14, CD64

 

Acute leukemia, unlikely AML, B-ALL, T-ALL, blastic plasmacytoid dendritic neoplasm

Diagnosis: likely undifferentiated acute leukemia

Note:

Cannot r/o AML-M7

Suggested IHC for CD41 or CD61

+++++++

CONFERENCE 20 (June 2024)

CASE 1:

60 y/o male, skin ulceration in L inguinal area. Ultrasound shows skin lesion of 47x7 mm with no increase in vasculature, with ulceration, involving surrounding adipose tissue. Many surrounding lymph nodes are seen, thickened capsule (6 mm), umbilical lymph node with size 10-16 mm

 

Skin biopsy in inguinal area:

https://pathpresenter.net/public/presentation/display?token=f7711e32

 

Findings:

Dermal infiltrates of large cells, including multinucleated forms, a few mitosis, admixed with small lymphocytes, histiocytes, a few eosinophils; also areas with ulceration

(+) CD3, CD2 (suboptimal), CD4, CD30 (strong), TIA, Granzyme B (partial), Ki67 (70%)

(-) CD20, PAX5, CD5, CD7, CD8, ALK1, CD56, EMA

Diagnosis: Primary cutaneous CD30-positive lymphoproliferative disorder (including lymphomatoid papulosis, primary cutaneous anaplastic large cell lymphoma)

+++++

CASE 2:

43 y/o female, enlarged lymph nodes throughout body

 

L neck lymph node:

https://dpa-dapa.com/public/presentation/display?token=266de3b9

 

Findings:

Diffuse infiltrate of large cells including multinucleated forms, a few mitosis, admixed with small lymphocytes, and histiocytes

(+) CD30 (strong), CD3 (likely cytoplasmic), CD5, Ki67 (approaching 60-70%), CD45 (only subset positive only), CD2, CD4, PD1, bcl2

(-) EMA (only subset pos, dim), CD20, ALK (a bit out of focus), CD7 (aberrant loss), CD21, CD23, CD79a, EBV (a bit out of focus), CD10, bcl6, MUM1, cyclinD1, cMyc

 

CD68: pos for histiocytes

PAX5, Oct2: pos for small B lymphocytes

CD15: out of focus

Diagnosis: Anaplastic large  cell lymphoma, ALK-negative

+++++

CASE 3:

50 y/o male, enlarged neck lymph node, CBC: WBC 211k, Lymphocyte 192K, Prolymphocyte 7%. BM Aspirate shows 40% lymphocyte. 

 

Lymph node biopsy:

https://pathpresenter.net/public/presentation/display?token=0d9657cf

 

Findings:

Scattered HRS-like cells, background of small lymphocytes

HRS-like cells:

(+) CD30

(-) CD3, CD15, CD68

PAX5 out of focus

CD45: difficult to interpret (too crowded)

The HRS-like cells may be activated lymphocytes or true HRS cells

Suggestion: rescan PAX5 (to r/o cHL)

 

Small lymphocytes: include some CD3-pos cells

Suggestion: IHCs for: CD20, CD5, CD23 to r/o CLL/SLL

 

DX to consider:

-CLL/SLL (most likely)

-CLL/SLL together with cHL

 

BM Bx, Asp

https://pathpresenter.net/public/presentation/display?token=9ab80383

Findings:

Large aggregates with small lymphocytes

(+)CD5, CD20, CD79a, PAX5, CD23, bcl2

(-) CD15, CD30, CD10, bcl6, TdT, MPO, CD117

 

Flow cytometry:

(+) CD5, CD19, CD20, CD79a, CD200, lambda

(-) CD10, CD34, CD38, CD3, CD7, CD4, CD8, kappa, CD2, CD56, TdT

Diagnosis: CLL/SLL

+++++