Chapter 5: Precursor B and T Cell
Neoplasms
Precursor B lymphoblastic leukemia
(B-ALL)/ lymphoma (B-LBL)
· Definition: a neoplasm of lymphoblasts committed to the B-cell lineage.
o B-LBL: lymphoma mass, without or minimal blood and BM involvement
o B-ALL: lymphoblastic leukemia, extensive BM and blood involvement (>25% BM cells)
·
Epidemiology
o B-ALL: 75% of cases in children under 6 years old
o B-LBL: 10% of lymphoblastic lymphoma, 75% of cases in patients under 18 years old
· Clinical features:
o B-ALL:
WBC decreased, normal or markedly elevated
Anemia, thrombocytopenia,
and/or neutropenia
Lymphadenopathy,
hepatosplenomegaly
Bone pain, arthralgias
o B-LBL: skin, bone, soft tissue, and lymph node
· Sites of involvement:
o B-ALL: blood and BM, all cases
o B-LBL: skin, bone, soft tissue, and lymph node, rare in mediastinal mass
· Morphology:
o Lymphoblasts vary from small blasts (with scant cytoplasm, condensed chromatin, indistinct nucleoli) to large blasts (with moderate cytoplasm, dispersed chromatin, multiple and prominent nucleoli)
o Mitosis less numerous than in T-ALL
o A small number of cases (10%) are associated with coarse azurophilic granules in lymphoblasts, some of them associated with t(9;22)(q34; q11.2)
· Cytochemistry:
o MPO, SBB: negative
o PAS : nuclear is partially encircled by a rim of PAS reactivity
· Immunophenotype:
o TdT and HLA-DR +
o CD19, CD79a, CD10, CD24 (Note that t(4;11)(q21;q23) cases are typically negative for CD10 and CD24)
o Variably positive for CD20 and CD22
o CD45 may be negative
o Cytoplasmic Mu chain (cyt-mu) in pre-B ALL
· Genetics:
o
t(9;22)(q34;q11.2)
§
associated with BCR/ABL
§
3-4% of cases
§
in most
childhood cases associated with a 190 kd BCR/ABL fusion tyrosin kinase
§
unfavorable
prognosis
o
t(4;11)(q21;q23)
§
associated with AF4/MLL
§
2-3% of cases
§
unfavorable
prognosis
o
t(1;19)(q23;p13.3)
§
associated
with PBX/E2A
§
6% of
cases (25% of pre-B ALL)
§
unfavorable prognosis
o
t(12;21)(p13;q22)
§
associated
with TEL/AML1
§
16-29%
of cases
§
favorable
prognosis
o
Hyperdiploidy
(>50)
§
20-25% of
cases
§
favorable
prognosis
o
Hypodiploidy
(<50)
§
5% of
cases
§
unfavorable
prognosis
· Differential diagnosis:
o T-ALL and AML(M0)
§ Resolved with immunophenotyping
o Hematogones (normal B precursors)
§ Mimic blasts morphologically
§ Positive for TdT, CD34, CD10, pan B markers (with continuum of expression)
§ In very young patients or in older patients with neuroblastoma, post-chemo, iron deficiency, ITP
o Burkitt lymphoma
o Blastoid variant of mantle cell lymphoma (positive for bcl-1, negative for TdT)
· Prognosis:
o B-ALL:
§ Good prognosis in the pediatric group, 80% of patients cured
§ Poorer prognosis in adult group with more unfavorable genetic results
o B-LBL: median survival of 60 months
Precursor T lymphoblastic leukemia (T-ALL)/ lymphoma
(T-LBL)
· Definition: a neoplasm of lymphoblasts committed to the T-cell lineage.
o T-LBL: lymphoma: mass, without or minimal blood and BM involvement
o T-ALL: lymphoblast leukemia, extensive BM and blood involvement (>25% BM cells)
·
Epidemiology
o T-ALL: 15% of childhood ALL, 25% of adult ALL
o T-LBL: 85-90% of lymphoblastic lymphoma, more common in adolescents and males
· Clinical features:
o T-ALL: high WBC, large mediastinal mass (or other tissue mass), rapid growth, pleural fluid
o T-LBL: large mediastinal mass with rapid growth, pleural effusion is common
· Sites of involvement:
o T-ALL: blood and BM, all cases
o T-LBL: mediastinal mass: 50%, others: LN, skin, liver, spleen, Waldeyer’s ring, CNS, gonads
· Morphology:
o Similar to B-ALL/LBL
o Higher mitotic figures
o A small number of cases are associated with eosinophilia and myeloid hyperplasia:
§ some of them associated with t(8;13)(p11.2;q11-22)
§ some of them develop into myeloid malignancy (MDS, AML, or myeloid sarcoma)
· Cytochemistry:
o Acid phosphatase (90% of cases): focal, paranuclear
o PAS : nuclear is partially encircled by a rim of PAS reactivity
· Immunophenotype:
o TdT
o CD3 is the only linage specific marker
o CD4, CD8: double – or +
o Variable positivity: CD1a, C2, CD3( considered lineage specific), CD5, CD7, (CD4 and CD8 frequently coexpressed), CD10, CD79a, CD13, CD33, CD117 (rare)
· Genetics:
o TCR: may have rearrangement, but this is not lineage specific
o TCR loci (1/3 of T-ALL):
§
14q11.2(alpha, delta)
§
7q35(beta)
§
7p(14-15)(gamma)
o
Genes:
§
MYC(8q24.1)
§
TAL1(1p32)
§
RBTN1(LMO1)(11p15)
§
RBTN2(LMO2)(11p13)
§ HOX11(10q24)
§ LCK(1p34.3-35)
o TAL
locus is dysregulated by microscopic
o
· Differential diagnosis:
o B-ALL and AML(M0)
§ Resolved with immunophenotyping
o Hematogones (normal B precursors)
§ Mimic blasts morphologically
§ Positive for TdT, CD34, CD10, pan B markers (with continuum of expression)
§ In very young patients or in older patients with neuroblastoma, post-chemo, iron deficiency, ITP
o Burkitt lymphoma
o Blastoid variant of mantle cell lymphoma (positive for bcl-1, negative for TdT)
· Prognosis: survival comparable to B-ALL with current treatment