Lymphoma and plasma cell neoplasms
T / NK cell disorders
T lymphoblastic leukemia / lymphoma

Author: Dragos Luca, M.D. (see Authors page)

Revised: 23 March 2017, last major update August 2011

Copyright: (c) 2002-2017, PathologyOutlines.com, Inc.

PubMed Search: "T lymphoblastic" AND leukemia/lymphoma [title]

Cite this page: T lymphoblastic leukemia / lymphoma. PathologyOutlines.com website. http://pathologyoutlines.com/topic/lymphomanonBpreT.html. Accessed November 19th, 2017.
Definition / general
Terminology
  • T-LBL (lymphoblastic lymphoma): mass lesion with no or minimal peripheral blood involvement
  • T-ALL (acute lymphoblastic leukemia): extensive bone marrow or peripheral blood involvement
  • Defined as T-ALL if > 25% lymphoblasts in marrow (in cases presenting with mass lesions and lymphoblasts in bone marrow)
  • No definitive agreement on the minimal blast percentage required to diagnose ALL (in contrast to AML); however, diagnosis of ALL should be avoided if < 20% blasts
Epidemiology
  • Teens and young men; 40% of childhood lymphomas and 15% of acute lymphoblastic leukemias
  • T-ALL represents 25% of adult ALL
  • T-LBL represents 85 - 90% of all LBLs
  • More common in whites than African Americans or Asians
  • Males more often affected (M:F among whites is 2.4:1)
  • In elderly ( > 60 years of age), patients usually present as T-ALL, uncommonly with a mediastinal mass
Sites
  • T-ALL: bone marrow in all cases; aleukemic presentations uncommon (in contrast to B-ALL)
  • T-LBL: frequent mediastinal (thymic) involvement, also lymph node or extranodal sites (skin, tonsils, liver, spleen, CNS, testis)
Etiology
  • Report of T-ALL in monozygotic twins with same TCR gene rearrangement suggests in utero origin of earliest genetic lesions (Blood 1997;89:281)
Clinical features
  • T-LBL usually presents as anterior mediastinal (thymic) mass with supradiaphragmatic lymphadenopathy and variable splenic, hepatic and bone marrow involvement (with leukemic phase); CNS involvement if untreated
  • T-ALL cases often present with mediastinal mass in young adult males, with early blood and diffuse marrow involvement, high leukocyte count
  • For a given leukocyte count and tumor burden, T-ALL often shows relative sparing of normal hematopoiesis compared with B-ALL
  • In T-LBL rapid growth with respiratory impairment and pleural effusion is common
  • Ataxia-telangiectasia is associated with an increased risk of T-ALL
Case reports
Prognosis and treatment
  • Aggressive disease, with 5 year survival of 26% but chemotherapy cures 60%
  • Considered higher risk than B-ALL in childhood (higher risk of induction failure, early relapse and isolated CNS relapse)
  • White count does not appear to be an adverse prognostic factor (in contrast to B-ALL)
  • Minimal residual disease after therapy is a strong adverse prognostic indicator
  • Prognosis for T-LBL depends on age, stage and LDH level
  • Rare cases of indolent T lymphoblastic proliferations (upper aerodigestive tract, multiple local recurrences, no systemic dissemination) are morphologically and immunophenotypically indistinguishable from T-LBL but no clonal TCR gene rearrangements
Postulated normal counterpart
  • T cell progenitor (T-ALL) or thymic lymphocyte (T-LBL)
Microscopic (histologic) description
  • T-ALL (similar to B-ALL): diffuse infiltrate of immature small / intermediate cells with scant cytoplasm, delicate chromatin, convoluted nuclear membrane, indistinct nucleoli; frequent mitotic figures, may have cytoplasmic vacuoles
  • T-LBL: complete architectural effacement, starry sky pattern produced by interspersed benign macrophages; often extensive pericapsular and soft tissue infiltrates; occasional multinodular pattern of T-LBL may mimic follicular lymphoma; may also see larger blasts with finely dispersed chromatin, conspicuous nucleoli and round, irregular or convoluted nuclei
  • Bone marrow: varies from scattered blasts to diffuse involvement; prominent mitotic activity (reportedly higher than B-ALL)
Microscopic (histologic) images

Images hosted on other servers:

Lymphoblastic lymphoma

Various images


Coexisting Langerhans cell histiocytosis

Immunohistochemistry
Positive stains
  • CD3 , CD99, TdT
  • Also CD7, variable expression of other T cell markers (CD1a, CD2, CD4, CD5, CD8), CD34, CD10 (63%, Arch Pathol Lab Med 2000;124:704), many tumors coexpress CD4+ and CD8+
  • Occasional CD16, CD56, CD57 (NK markers)
  • CD52 (virtually all), also CD38 and CD71 in a substantial subset
  • CD7 and cytoplasmic CD3 are most often expressed but only the latter is considered lineage specific
  • TAL1 nuclear staining in 29 - 48% of cases (not necessarily correlated with TAL1 gene alterations)
  • May also express CD79a (10%), CD13 or CD33 (19 - 32%), CD117 (occasionally, associated with FLT3 mutations)
  • The presence of myeloid markers does not exclude the diagnosis of T-ALL / LBL, nor does it indicate mixed phenotype T / myeloid leukemia (WHO)

Stages of intrathymic differentiation according to immunophenotype:
  • Pro-T: cCD3+, CD7+, CD2-, CD1a-, CD34+/-, double negative CD4 / CD8
  • Pre-T: cCD3+, CD7+, CD2+, CD1a-, CD34+/-, double negative CD4 / CD8
  • Cortical T: cCD3+, CD7+, CD2+, CD1a+, CD34-, double positive CD4 / CD8
  • Medullary T: cCD3+, CD7+, CD2+, CD1a-, CD34-, surface CD3+, either CD4+ or CD8+
Negative stains
Electron microscopy description
  • Lymphoblasts are of medium size, with smooth surfaces and no cytoplasmic processes
  • Irregularly shaped nuclei with frequent fissures and convolutions, evenly dispersed chromatin with peripheral condensation, dense nucleoli adjacent to the nuclear membrane
  • Scarce cytoplasm with few mitochondria, strands of endoplasmic reticulum, free ribosomes and perinuclear filaments and microtubules
  • Cells with filament bundles are common in blood but rare in lymph nodes
Molecular / cytogenetics description
  • Almost always clonal TCR gene rearrangements
  • Simultaneous IGH@ gene rearrangements in 20% of cases
  • Abnormal karyotypes in 50 - 70% of cases, most commonly involving 14q11.2 (α/δ TCR loci), 7q35 (β) and 7p14-15 (γ)
  • t(1;14)(p32;q11): SCL (TAL1) and T cell receptor delta / alpha (15 - 30%)
  • t(10;14)(q24;q11): HOX11 (TLX1) and T cell receptor delta / alpha (7% of childhood and 30% of adult cases)
  • HOX11L2 (TLX3)(5q35): 20% of childhood and 10 - 15% of adult cases
  • Other genes involved: MYC (8q24.1), RBTN1 (LMO1) (11p15), RBTN2 (LMO2) (11p13), LYL1 (19p13), LCK (1p34.3-35)
  • Other translocations: PICALM-MLLT10 [CALM-AF10; t(10;11)(p13;q14)] - 10%, MLL (8%) - most often with ENL (19p13)
  • Deletions: del(9p) - loss of CDKN2A (~30%)
  • NOTCH1 mutations (50%) - shorter survival in adult but not pediatric patients
  • Gene expression profiling of childhood T-ALL showed four major molecular types associated with distinct stages of arrested T cell maturation and correlated with cytogenetic abnormalities
  • T-LBL + eosinophilia + myeloid hyperplasia = 8p11.2 (FGFR1) cytogenetic abnormality
Differential diagnosis
  • Burkitt lymphoma, granulocytic sarcoma, lymphoblastoid mantle cell lymphoma, CML blast crisis (Hum Pathol 2002;33:770)
Additional references