Abstract:
Blasts in acute myeloid leukemia (AML) can show differentiation toward various lineages, including monocytic, erythroid, megakaryocytic, and plasmacytoid dendritic cell lineage. The incidence and clinicopathological features of mast cell (MC) differentiation in AML is largely unknown. Among 2,167 AML cases, we identified 21 (~ 1%) cases of AML with MC differentiation (AML-MC), defined as: (1) an increased immature MC population (> 0.3%) by flow cytometry immunophenotyping (FCI); (2) cells with metachromatic granules observed on bone marrow (BM) aspirate smears; and (3) > 1% MCs shown by tryptase immunohistochemistry in biopsy specimens. The median age of these patients was 68 years. The MCs consistently had low side scatter, consistent with immature and hypogranular forms, and were positive for CD38, CD123 and CD45 (dim), partially positive for CD34 in 81%, positive for CD25 in 33% of cases, and consistently negative for CD2. Tryptase immunohistochemistry showed interstitial MCs. Conventional chromosomal analysis showed a complex karyotype in 13 (68%) cases. Recurrent translocations were identified in 5 cases, including t(9;22)(q34.1;q11.2), inv(16)(p13.1q22), and t(8;21)(q22;q22.1). Fluorescence in situ hybridization showed TP53 deletion in 9 (43%) cases. Next generation sequencing showed TP53 mutations in 11 of 21 (52%) cases analyzed. All cases were negative for KIT mutation. Patients with AML-MC had a very poor outcome, with a median OS of 9.6 months. OS was significantly associated with older age (> 65 years; p = 0.005). In conclusion, patients with AML-MC are characterized by older age, interstitial MCs, complex karyotype, TP53 alterations, and a poor prognosis.
