Lymph nodes & spleen, nonlymphoma
Lymph node & spleen-nonlymphoid neoplasms
Acute lymphoblastic leukemia / lymphoma

Topic Completed: 1 November 2013

Minor changes: 21 December 2020

Copyright: 2003-2021,, Inc.

PubMed Search: Acute lymphocytic leukemia[TI] pathology full text[sb]

See also: Acute leukemia chapter

Patricia Tsang, M.D., M.B.A.
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Cite this page: Tsang, P. Acute lymphoblastic leukemia / lymphoma . website. Accessed January 17th, 2021.
Definition / general
  • Also called acute lymphoblastic leukemia (ALL)
  • May have widespread lymphadenopathy and hepatosplenomegaly at diagnosis
  • Nodal biopsies may be initial diagnostic procedure, although marrow involvement is usually present if tumor in node
  • May present as leukemia, lymphoma or both
    • Defined as leukemia if > 25% lymphoblasts in bone marrow or blood
    • Defined as lymphoma if mass lesion present in mediastinum or elsewhere and < 25% lymphoblasts in marrow and peripheral blood
  • Two subtypes based on lymphoid lineage
    • B lymphoblastic leukemia / lymphoma (B ALL)
    • T lymphoblastic leukemia / lymphoma (T ALL)
  • Subtypes differ in prognosis, clinical presentation and treatment
Cell of origin
  • Precursor B cells at various stages of maturation in bone marrow
  • Precursor T cells arising in bone marrow and undergoing differentiation in the thymus (thymic T cells)
  • Incidence of ALL is 35 - 40 per million per year in United States
  • Higher incidence in Caucasians and Hispanics than African Americans and Asians
  • In children, B ALL constitutes 85% and T ALL 15% of ALL
  • In adults, B ALL constitutes 75% and T ALL 25% of ALL
  • B ALL most common in young children (< 5 years) but also seen in adults (median age in adults 39 years)
  • T ALL more common in adolescents than in younger children
  • In T ALL, male:female = 2.2:1
  • Most cases are idiopathic and probably multifactorial
  • Specific risk factors seen in a minority of patients:
    • Prenatal exposure to Xrays
    • Postnatal exposure to high doses of radiation (e.g. therapeutic radiation was previously used for tinea capitis and thymus enlargement)
    • Genetic conditions such as Down syndrome, neurofibromatosis and ataxia telangiectasia
    • Inherited genetic polymorphisms
Clinical features
  • B ALL:
    • Thrombocytopenia, anemia or neutropenia due to bone marrow failure is most common presentation
    • Lymphadenopathy and hepatosplenomegaly are common
    • Central nervous system involvement is common, while anterior mediastinal mass is usually absent
  • T ALL:
    • Anterior mediastinal mass and high leukocyte count are typical
    • Thymic enlargement and pleural effusion can compromise respiration
    • Lymphadenopathy and hepatosplenomegaly are common
Prognostic factors
  • Significantly better survival in children (about 94% cure rate) than in adults (about 40% cure rate)
  • Strongest predictors of survival are age at diagnosis and genetic abnormalities (detailed above)
  • Unfavorable: infants < one year old, adults, CNS disease and high WBC count of > 50,000 at diagnosis
Case reports
Microscopic (histologic) description
  • Proliferation of small to medium sized primitive cells
  • In marrow or other tissue masses, effacement of architecture by round blue cells raises the differential diagnoses of ALL versus neuroblastoma, Ewing sarcoma and others
  • French-American-British classification historically described 3 morphologic variants:
    • L1 blasts:
      • Small with indistinct nucleoli and high nuclear:cytoplasmic ratio
    • L2 blasts:
      • Larger with prominent nucleoli and more abundant cytoplasm, resembling myeloblasts
    • L3 blasts:
      • Deeply basophilic cytoplasm and prominent cytoplasmic vacuoles, indistinguishable from Burkitt lymphoma cells
Microscopic (histologic) images

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ALL with L3 morphology

B ALL: atypical cells scattered singly

B ALL: rosettes with atypical cells

B ALL: myeloperoxidase negative

  • Flow cytometry more informative than immunohistochemistry, although either one may be diagnostic
  • B ALL are typically TdT+, CD34+, CD19+, cytoplasmic 22+, CD79a+, HLA-DR+, CD10+ and PAX5+
  • Surface immunoglobulin is usually absent
  • Myeloperoxidase should not be expressed
  • Myeloid associated antigens, CD13, CD33 and CD117, may be coexpressed without it being biphenotypic
  • Stage of B lymphoblast differentiation has antigenic correlates:
    • Early precursor B ALL (pro-B ALL): CD19+, cytoplasmic CD79a+, cytoplasmic CD22+, nuclear TdT
    • Common ALL: CD10 (CALLA)+
    • Late pre-B ALL: CD20+, cytoplasmic heavy chain
  • T ALL are typically TdT+, CD34+, CD99+ and CD1a+; only cytoplasmic CD3 expression is considered lineage specific
  • T ALL is often double positive for CD4 and CD8; other T cell associated antigens are variably expressed, including CD2, CD5 and CD7
Flow cytometry images

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B ALL with CD10+ blasts

Molecular / cytogenetics description
  • Most B ALL show clonal IgH@ (immunoglobulin heavy locus) gene rearrangement; simultaneous T cell receptor (TCR) gene rearrangement present in up to 70%
  • Recurrent genetic abnormalities in B ALL often have prognostic significance:
    • t(12;21) TEL-AML: very favorable prognosis; most common rearrangement in childhood B ALL (25%), with cures of > 90%
    • Hyperdiploidy: favorable prognosis; trisomies 4, 10 and 17 have the best prognosis
    • t(9;22) BCR-ABL1 (Philadelphia chromosome): very poor prognosis; incidence increases with age, 3% of childhood cases and 25% of adult cases
    • t(v;11q23) MLL gene rearrangement: poor prognosis
    • Hypodiploidy: poor prognosis
    • t(5;14) IL3-IGH: uncertain prognostic significance; reactive eosinophilia is characteristic

  • Most T ALL harbor T cell receptor gene rearrangement; simultaneous IGH@ gene rearrangement present in about 20%
  • In T ALL, recurrent cytogenetic abnormalities can also be seen:
    • TCR loci at 14q11.2, 7p35 and 7p14-15, with various partner genes
    • Del (9p) with loss of tumor suppressor gene CDKN2A occurs in at least 30%
    • NOTCH1 gene mutations can lead to shorter survival in adult T ALL
Differential diagnosis
  • Burkitt lymphoma, a high grade B cell lymphoma, has L3 cytomorphology
    • Unlike B ALL, its phenotype is mature without CD34 or TdT expression
  • Hematogones, maturing B cell precursors in bone marrow, can be confused with B ALL, especially in minimal residual disease
  • Thymoma with normal thymic T cells exhibiting CD4+ CD8+ immature T cell phenotype, resembling T ALL in mediastinal mass
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