Myelomastocytic leukemia: histopathological features, diagnostic criteria and differential diagnosis

Myelomastocytic leukemia (MML) is an extremely rare myeloid overlap-neoplasm that belongs to the group of tryptase-positive (T+) myeloid neoplasms. Main differential diagnoses include aggressive systemic mastocytosis (ASM), in particular ASM in transformation; mast cell leukemia; T+ acute myeloid leukemia (T+ AML); acute basophilic leukemia and chronic basophilic leukemia. MML exhibits both proliferative and dysplastic features and is characterized by prominent differentiation into the mast cell lineage in an advanced myeloid neoplasm, usually primary or secondary AML. While the histological key feature of MML is a diffuse increase in neoplastic cells expressing mast cell-related antigens like tryptase and CD117 (KIT), the most important cytomorphological finding in bone marrow (BM) and peripheral blood (PB) is the metachromatically granulated blast cell (= metachromatic blast). In contrast to systemic mastocytosis (SM), MML neither shows activating point mutations at codon 816 of KIT nor the aberrant expression of CD25 by mast cells is seen. MML can only be diagnosed when tryptase-staining is performed on BM biopsy specimens, PB and BM smears are investigated for presence of metachromatic blasts and other T+ leukemias have been excluded.