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Acute Leukemias of Ambiguous Lineage
Acute Leukemias of Ambiguous Lineage
Acute Leukemias of Ambiguous Lineage
Acute Leukemias of
Ambiguous Lineage
T he addition of cytochemical and immunophenotypic Group for the Immunologic Classification of Leukemia
(EGIL) for the lineage assignments in acute leukemias.
techniques to the standard morphologic evaluation of
leukemic blast cells has led to the growing recognition l Myeloid Lineage: Myeloperoxidase (cytochemistry, flow
of acute leukemias with ambiguous lineage assignment. cytometry, or immunohistochemistry). For monocytic differen-
According to the WHO classification, these leukemias fall tiation at least two of the following markers: NSE, lysozyme,
into the following categories (Figure 25.1). CD11c, CD14, and CD64.
l B-Cell Lineage: Strong CD19 expression with:
1. Acute undifferentiated leukemia (AUL) which lacks sufficient
l Strong coexpression of at least one of the following markers:
evidence (such as morphologic, cytochemical, and immuno-
phenotypic features) of lineage differentiation. CD79a, cytoplasmic CD22, and CD10, or
l Weak CD19 expression with strong coexpression of at least
2. Mixed phenotype acute leukemia:
a. Acute bilineage (or multilineage) leukemia which repre- two of the following markers: CD79a, cytoplasmic CD22,
sents an acute leukemia with more than one population of and CD10.
l T-Cell Lineage: Cytoplasmic CD3 (with an intensity approach-
blast cells. The total number of blasts from both lineages
should be ≥20% of marrow or blood cells. ing that of normal T cells) or surface CD3.
b. Acute biphenotypic (multi-phenotypic) leukemia in which
the population of leukemic cells coexpress more than one
lineage-specific marker, such as a combination of myeloid-
specific and lymphoid-specific, or B- and T-specific mol-
ecules. In rare occasions, the leukemic blasts may express Acute Undifferentiated Leukemia
a combination of myeloid-, B-cell- and T-cell-associated
markers.
Acute undifferentiated leukemia (AUL) is defined as a
The following WHO criteria for lineage assignment in leukemia with no morphologic, cytochemical, or specific
acute leukemia with ambiguous lineage have replaced immunophenotypic features of lymphoid or myeloid dif-
the scoring system which was proposed by the European ferentiation. AUL is extremely rare and probably accounts
for <1% of acute leukemias.
MORPHOLOGY
l Bone marrow is often hypercellular with increased number of
uniform, undifferentiated immature cells.
l Blasts consist of primitive undifferentiated cells with scant dark
and/or leukopenia.
FIGURE 25.1 Scheme of clonal development of acute leukemias
of undifferentiated, bilineal, and biphenotypic types.
A A
B
FIGURE 25.4 Acute bilineal leukemia. Bone marrow (A) and B
peripheral blood (B) smears show two distinct populations of FIGURE 25.5 Acute bilineal leukemia. Bone marrow (A) and
leukemic blast cells (larger and smaller). peripheral blood (B) smears show two distinct populations of
leukemic blast cells (larger and smaller).
FIGURE 25.8 Flow cytometric findings of acute biphenotypic leukemia FIGURE 25.10 Flow cytometric findings of acute biphenotypic
(myeloid/B-lymphoid). Open gate display by CD45 gating (in green) leukemia (myeloid/T-lymphoid). Open gate display by CD45 gating
reveals excess blasts (25% of the total) that are dimly positive (in blue) shows excess abnormal blasts (94% of the total) that
for CD45. The blast-enriched gate (in magenta) demonstrates are CD45 dimly positive. Density plots of the blast-enriched
abnormal blasts expressing both B- and myeloid-lineage-specific gate (in magenta) demonstrate that the blasts express T-lineage
markers. The positive B-lineage antigens include CD19 (moderate markers CD2, CD5 (partial, dim; not shown), CD7, and intracellular
to bright), CD22 (dim), and intracellular CD79a. The positive CD3. In addition, the blasts are positive for myeloid antigens
myeloid markers include CD11b (not shown), CD13 (dim), CD15 CD13, CD15 (partial), CD117 (heterogeneous), and intracellular
(partial), CD33, and intracellular myeloperoxidase (partial). myeloperoxidase (partial, heterogeneous). Positivity for
myeloperoxidase is further confirmed by immunohistochemical
studies. The blasts are also positive for CD34, HLA-DR (partial; not
shown), and intracellular TdT.
myeloid biphenotypes.
l Rarely, blasts may express B- and T-cell biphenotype, or mixed
l The Philadelphia chromosome may be a part of a complex set l Since a small proportion of T-cell leukemias can show sec-
of cytogenetic abnormalities, such as combination of t(9;22) ondary rearrangement of immunoglobulin genes, and vice
and del(7) or t(2;9;22) (Figure 25.13). versa for B-cell leukemias, care must be taken not to overcall a
l The T-precursor/myeloid biphenotypic or bilineal acute leukemias biphenotypic diagnosis based on such findings.
may be associated with t(5;18)(q31;q23) and t(3;12)(p25;q24.3). l Cyclin A1 and HOXA9 gene expression have also been
l Also, in some cases trisomy 10 has been reported in associa- reported in these lesions.
tion with acute biphenotypic leukemia (see Figure 25.11).
l Some cases of acute biphenotypic leukemia may show com-
immunohistochemistry, it is not possible by PCR to distinguish In this category the blast cells show coexpression of
whether these gene rearrangements are present in two distinct myeloid-specific and lymphoid-specific molecules, but lack
sets of malignant cells, as opposed to coexisting in the same cells. recurrent genetic abnormalities.
Differential Diagnosis 323
Additional Resources
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