Table of Contents
Definition / general | Diagnosis | Prognostic factors | Treatment | Microscopic (histologic) description | Microscopic (histologic) images | Positive stains | Negative stains | Molecular / cytogenetics description | Molecular / cytogenetics images | Differential diagnosisCite this page: Mihova D. T lymphoblastic lymphoma / leukemia. PathologyOutlines.com website. https://www.pathologyoutlines.com/topic/leukemiaTall.html. Accessed June 8th, 2023.
Definition / general
- Neoplasm of T lineage lymphoblasts which may form lymphomatous masses, involve blood and bone marrow (Stanford School of Medicine: Precursor T Lymphoblastic Leukemia / Lymphoma [Accessed 13 April 2018])
- Also called pre T cell acute lymphocytic leukemia / lymphoma (preT ALL), T lymphoblastic leukemia / lymphoma (T LBL)
- 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 factors
- 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: T-lineage acute lymphoblastic leukemia (T-ALL) [Accessed 13 April 2018])
- 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
- Chemotherapy cures 60%
- Patients have earlier relapse, induction failure and isolated CNS relapse compared to preB ALL
Microscopic (histologic) description
- 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)
Microscopic (histologic) images
AFIP images
Markedly elevated leukocyte count
L2 type (blood smears)
Bone marrow biopsy
Focal paranuclear acid phosphatase staining
Positive stains
- 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, CD79a+ (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
Molecular / cytogenetics description
- Different cytogenetic abnormalities than B ALL (Atlas of Genetics and Cytogenetics: T-lineage acute lymphoblastic leukemia (T-ALL) [Accessed 13 April 2018]), 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 / cytogenetics images
Images hosted on other servers:
Rearrangements involving T cell receptor genes
FISH:
t(5;14)(q35;q32)
Differential diagnosis
- Burkitt leukemia:
- B cell phenotype
- Granulocytic sarcoma:
- Positive for myeloid markers
- Mantle cell lymphoma-blastoid:
- B cell phenotype
- Thymoma (Am J Clin Pathol 2004;121:268)
