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Leukemia - Acute

Other ALL

T cell acute lymphoblastic leukemia / lymphoma


Reviewer: Daniela Mihova, M.D. (see Reviewers page)
Revised: 20 March 2013, last major update September 2012
Copyright: (c) 2001-2013, PathologyOutlines.com, Inc.

General
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● Neoplasm of T lineage lymphoblasts which may form lymphomatous masses, involve blood and bone marrow (Stanford University)
● Also called pre T cell acute lymphocytic leukemia / lymphoma (preT ALL), T lymphoblastic leukemia / lymphoma (T LBL)
● See also Lymphoma and plasma cell neoplasms chapter
● Teens and young men (older than B ALL)
● Most cases begin after birth (Blood 2007;110:3036)
● T ALL versus T LBL: T ALL has more immature phenotype, CD47 expression, no 11q23 rearrangement (Pediatr Blood Cancer 2006;47:130), different gene expression profile and may derive from T cell progenitor of bone marrow; T LBL is derived from thymocytes (Leuk Lymphoma 2007;48:1745)
● T ALL constitutes 15% of childhood and 20-25% of adult ALL cases
● T LBL constitutes 85-95% of LBL, usually presents as mediastinal mass with no / minimal marrow involvement
● CNS involvement if untreated
● T LBL frequently presents with mass in anterior mediastinum, rapid growth, respiratory emergency, pleural effusion
● Younger (age 16-60 years) patients compared to older (61+ years) patients have more hepatosplenomegaly, present with mediastinal mass and lymphadenopathy; myeloid antigens and lineage inappropriate gene rearrangements are less common (Am J Clin Pathol 2002;117:252)
Diagnosis: T ALL if lymphoblasts are 25% or more of marrow cells; T LBL otherwise

Prognostic features
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Good prognostic factors: HOX11 overexpression in adults (Am J Clin Pathol 2007;127:528)
Poor prognostic factors: expression of CFLAR, NOTCH2 and BTG3 genes (Br J Haematol 2007;137:319), 3+ methylated genes (J Clin Oncol 2005;23:7043), residual disease after treatment (even if minimal)
● Pediatric patients with T ALL: TLX1(HOX11)+ was associated with favorable outcome, and TAL1+ and LYL1+ were associated with unfavorable outcome (Atlas of Genetics and Cytogenetics)
● Higher risk than B ALL due to presence of high risk features, but T ALL without high risk clinical features has survival comparable to B ALL

Treatment
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● Chemotherapy cures 60%
● Patients have earlier relapse, induction failure and isolated CNS relapse compared to preB ALL

Micro description
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● Similar to B cell disease; scant cytoplasm, delicate chromatin, indistinct nucleoli, convoluted nuclear membrane and grooves
● Frequent mitotic figures; starry sky pattern produced by interspersed benign macrophages
● Usually features of FAB L1 or L2; pattern in marrow is usually interstitial
● Lymph nodes: complete architectural effacement or partial involvement with paracortical infiltrate with germinal center sparing
● Thymus: replacement of normal parenchyma
● Occasionally eosinophilia and myeloid hyperplasia with variable t(8;13)(p11.2;q11-22) involving FGFR1 gene; some develop myeloid malignancy (MDS, AML, or myeloid sarcoma)

Micro images
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Blood smear shows atypical T cells


Blood smear shows markedly elevated leukocyte count with variable lymphoblast size and chromatin density

L2 type (blood smears):

Large leukemic blasts; also small cells with minimal cytoplasm, markedly hyperchromatic nuclei and prominent nuclear convolution, suggestive of T cell ALL

Bone marrow biopsy:

Sheets of lymphoblasts with variable size and moderate nuclear irregularity, also mitotic figures

Lymph node:

Axillary lymph node biopsy (figures a-c)

Stains:

Focal paranuclear acid phosphatase staining

Positive stains
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● CD1a, CD2 (78%), CD3 (cytoplasmic, not surface in 100%), CD5 (100%), CD7 (100%), TdT (73%)
● CD4 and CD8 both positive in 22%
● Variable CD10 (47%), CD13 (6%), CD16, CD33 (12%), CD56 (Haematologica 2009;94:160), CD57, CD79+ (40-60%, Am J Clin Pathol 2000;113:823), CD117 (12%, Exp Mol Pathol 2006;81:162)
● CD117 associated with activating mutations of FLT3, CD4 (10%) and CD8 (< 10%)

Negative stains
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● CD19, CD20; double negative CD4 / CD8 (40%)
Note: ALL with aberrant myeloid antigen expression is correct name, not biphenotypic leukemia

Molecular description
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● Different cytogenetic abnormalities than B ALL (Atlas of Genetics and Cytogenetics), often are cryptic and identified only by FISH or PCR
● t(1;14)(p32;q11) involving SCL (TAL1) and T cell receptor delta / alpha in 15-30%
● t(10;14)(q24;q11) involving HOX11 (TLX1) and T cell receptor delta / alpha in 7%
● Activating mutations of NOTCH1 in 50% (Science 2004;306:269)
● CDKN2A (INK4A) deletions in up to 80% (Blood 1995;85:2321)
● TCR: may have rearrangement, but is not lineage specific
● TCR loci (1/3 of T ALL):
     ● 14q11.2 (alpha, delta)
     ● 7q35 (beta)
     ● 7p(14-15) (gamma)

Genes:
● MYC (8q24.1)
● TAL1 (1p32)
● RBTN1 (LMO1) (11p15)
● RBTN2 (LMO2) (11p13)
● HOX11 (TLX1) (10q24)
● HOX11L2 (TLX3) (5q35)
● LYL1 (19p13)
● LCK (1p34.3-35)

Molecular images
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Chart of rearrangements involving T cell receptor genes


FISH: t(5;14)(q35;q32)

Differential diagnosis
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Burkitt leukemia: B cell phenotype
Granulocytic sarcoma: positive for myeloid markers
Mantle cell lymphoma-blastoid: B cell phenotype
Thymoma see Am J Clin Pathol 2004;121:268

End of Leukemia - Acute > Other ALL > T cell acute lymphoblastic leukemia (T ALL)


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