Systemic Mastocytosis and Other Entities Involving Mast Cells: A Practical Review and Update

SIMPLE SUMMARY: In this article, we outline recent updates in systemic mastocytosis (SM) classification, including the bone marrow mastocytosis subtype; and discuss the mast cell leukemia subtype (acute or chronic), the rare variant of SM known as well-differentiated SM (morphologic variant), and other diseases involving mast cells (i.e., myelomastocytic leukemia and mast cell activation syndrome) that may be diagnostically challenging. We also provide a concise clinical update of new adjusted risk stratification models and overview new treatments that were approved for advanced SM (midostaurin, avapritinib). ABSTRACT: Evidence in the recent literature suggests that the presentation spectrum of mast cell neoplasms is broad. In this article, we elaborate on recent data pertaining to minor diagnostic criteria of systemic mastocytosis (SM), including sensitive testing methods for detection of activating mutations in the KIT gene or its variants, and adjusted serum tryptase levels in cases with hereditary α-tryptasemia. We also summarize entities that require differential diagnosis, such as the recently reclassified SM subtype named bone marrow mastocytosis, mast cell leukemia (an SM subtype that can be acute or chronic); the rare morphological variant of all SM subtypes known as well-differentiated systemic mastocytosis; the extremely rare myelomastocytic leukemia and its differentiating features from mast cell leukemia; and mast cell activation syndrome. In addition, we provide a concise clinical update of the latest adjusted risk stratification model incorporating genomic data to define prognosis in SM and new treatments that were approved for advanced SM (midostaurin, avapritinib).