Leukemia - Acute - Ambiguous Lineage

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Leukemia - Acute

Other ALL

Ambiguous Lineage

Reviewer: Daniela Mihova, M.D. (see Reviewers page)
Revised: 28 September 2012, last major update September 2012
Copyright: (c) 2001-2012, PathologyOutlines.com, Inc.

General
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● 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
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● <4% of all acute leukemias, more frequent in adults

Etiology
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● Unknown

Clinical features
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● Related to bone marrow failure: fatigue, infections, bleeding

Morphology
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● 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
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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
● Dual population of blasts, each with distinct lineage: positive for myeloid, lymphoid or B and T-cell markers (Leukemia 2007;21:2264)
● May evolve into biphenotypic acute leukemia (Atlas of Genetics and Cytogenetics)

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 (non specific) 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
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● 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 karyotypes

Cell of origin
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● Multipotent progenitor stem cell

Prognosis
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● Unfavorable, particularly in adults
● t(4;11) or Ph particularly unfavorable

Treatment
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● Usually aggressive chemotherapy or bone marrow transplant

Case reports
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● 5 year old boy with t(9;17)(p11;q11) (Leuk Lymphoma 1997;25:179)
● 20 year old woman with myeloid, B cell and NK phenotype (Arch Pathol Lab Med 2003;127:E93)
● 80 year old man with blasts coexpressing CD79a and myeloid markers (Arch Pathol Lab Med 2003;127:356)
● Due to transformation of essential thrombocythemia (Am J Hematol 2006;81:624)

Micro images
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Blood smears:

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+

Blasts have minimal cytoplasm, fine chromatin with 1+ prominent nucleoli

Bone marrow smears:

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

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

Myeloid features include Auer rod (fig 1A-asterisk) and myeloperoxidase staining (fig 1B)

Flow cytometry images
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Biphenotypic acute leukemia with CD19 and myeloperoxidase coexpression (figure B)

Electron microscopy images
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Monocytoid blast has folded nucleus and scattered small electron dense granules

Molecular / genetics description
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● Many cases have IgH and TCR rearrangements or deletions

Differential diagnosis
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● For biphenotypic acute leukemia
● Myeloid antigen positive ALL
● Lymphoid antigen positive AML
● For undifferentiated acute leukemia
● Minimally differentiated AML
● Unusual precursor-B-cell or T-cell ALL

End of Leukemia - Acute > Other ALL > Ambiguous Lineage

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