Bone marrow neoplastic
Bone marrow - plasma cell and lymphoid neoplasms
Acute leukemia of ambiguous lineage
Ambiguous lineage NOS


Topic Completed: 1 September 2012

Minor changes: 18 September 2020

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PubMed Search: Acute leukemias of ambiguous lineage [title]


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Cite this page: Mihova D. Ambiguous lineage NOS. PathologyOutlines.com website. http://www.pathologyoutlines.com/topic/leukemiaambiguouslin.html. Accessed October 28th, 2020.
Definition / general
  • Acute leukemias in which the morphologic, cytochemical and immuno-phenotypic features of the blasts:
    • Lack sufficient evidence to classify as myeloid or lymphoid origin
    • Or, have morphologic and / or immunophenotypic characteristics of both myeloid and lymphoid cells
    • Or, have both B and T lineages (acute bilineal leukemia and acute biphenotypic leukemia)

    Acute leukemias of ambiguous lineage include the following:
    • Acute undifferentiated acute leukemia
    • Mixed phenotype acute leukemia with t(9;22)(q34;q112.); BCR-ABL1
    • Mixed phenotype acute leukemia with t(v;11q23); MLL rearranged
    • Mixed phenotype acute leukemia, B/myeloid, NOS
    • Mixed phenotype acute leukemia, T/myeloid, NOS
    • Mixed phenotype acute leukemia, NOS rare types
    • Other acute leukemias of ambiguous lineage
Epidemiology
  • < 4% of all acute leukemias, more frequent in adults
Etiology
  • Unknown
Clinical features
  • Related to bone marrow failure: fatigue, infections, bleeding
Morphology
  • Acute undifferentiated leukemia
    • Leukemic cells lack any differentiating features
  • Acute biphenotypic and acute bilineal leukemias
    • May present as one subtype of AML with features of ALL (B, T or B and T)
Immunophenotype
Undifferentiated acute leukemia:
  • Leukemias lack specific lineage markers
  • cCD79a, cCD22, CD3 and MPO
  • Generally don’t express more than one lineage associated marker
  • Often express HLA-DR, CD34, CD38, may express TdT and CD7

Bilineal acute leukemia
Biphenotypic acute leukemia
  • Blasts co-express myeloid and T or B lineage markers
  • Or, concurrent B and T lineage markers
  • Rarely co-express markers for myeloid, T and B lineages

  • Co-expression of one or two cross-lineage (nonspecific) markers is not sufficient for biphenotypic leukemia; e.g. myeloid antigen positive ALL or Lymphoid antigen positive AML
  • Lineage switch after therapeutic intervention
    • Possible expansion of pre-existing minor population of blasts of different lineage following therapeutic suppression of the major population
    • Possible lineage instability
Genetics
  • High degree of cytogenetic abnormalities
  • 1/3 of cases have Ph chromosome
  • t(4;11)(q21;q23) or 11q23, typically have CD10(–) precursor B lymphoid component
  • T/myeloid biphenotypic or bilineal leukemia can have complex karyotype
Cell of origin
  • Multipotent progenitor stem cell
Prognostic factors
  • Unfavorable, particularly in adults
  • t(4;11) or Ph particularly unfavorable
Treatment
  • Usually aggressive chemotherapy or bone marrow transplant
Case reports
Microscopic (histologic) images

Blood smears:
Missing Image

Child with t(4;11)(q21;q23) - small blasts are early B cell precursors that are CD10 negative,
large cells are monocyte precursors that are alpha naphthyl butyrate esterase+



Bone marrow smears:
Missing Image

2 week old girl with t(4;11)(q21;q23)
- lymphoblasts and monoblasts

Missing Image

2 week old girl with t(4;11)(q21;q23) - Large
cells are monoblasts and promonocytes,
small cells are lymphoblasts with minimal
cytoplasm and coarse chromatin

Electron microscopy images
Missing Image

Monocytoid blast has folded nucleus and scattered small electron dense granules

Molecular / cytogenetics description
  • Many cases have IgH and TCR rearrangements or deletions
Differential diagnosis
  • For biphenotypic acute leukemia
    • Myeloid antigen positive ALL
    • Lymphoid antigen positive AML
  • For undifferentiated acute leukemia
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