Acute Leukemias of Ambiguous Lineage

Abstract

Acute leukemias of ambiguous lineage are defined by the World Health Organization (WHO) classification as leukemias that either lack a specific lineage association or show features of concurrent multiple lineage associations [1, 2]. Ambiguous-lineage leukemias are more rare and more diagnostically challenging than conventional acute myeloid leukemias and lymphoblastic leukemias [1–11]. Given that the cytologic features of these leukemias are generally nonspecific, the diagnosis rests upon extensive immunophenotypic analysis. Multiparametric flow cytometric immunophenotyping is the preferred method for immunophenotyping, but in some cases, immunohistochemistry may be performed and may facilitate the recognition of two distinct blast populations in tissue sections. In addition to standard immunophenotypic studies, further evaluation should include cytogenetic studies to identify cases with t(9;22)(q34.1;q11.2); BCR-ABL1 or t(v;11q23.3); KMT2A rearranged. Table 13.1 highlights the diagnostic subcategories of acute leukemias of ambiguous lineage, Table 13.2 lists the diagnostic criteria for lineage determination, and Table 13.3 compares lineage-specific and lineage-associated markers in acute leukemia. This chapter provides pathologic examples of various ambiguous-lineage leukemias and illustrates the key diagnostic challenges, considerations, and caveats in establishing these rare diagnoses (Figs. 13.1, 13.2, 13.3, 13.4, 13.5, 13.6, 13.7, 13.8, 13.9, 13.10, 13.11, 13.12, 13.13, 13.14, 13.15, 13.16, and 13.17).