How I diagnose systemic mastocytosis

Abstract Objectives Systemic mastocytosis (SM) is a neoplasm of mast cells (MCs) characterized by their proliferation in extracutaneous organs. Systemic mastocytosis includes several entities with different clinical courses and prognoses. The rarity of this disease and the diversity of clinical and morphologic presentation make the diagnosis of SM very challenging. The aim of this review is to share our approach to the diagnosis of SM. Methods We present 4 cases that highlight the spectrum of clinical and laboratory features of SM and outline the diagnostic process with an emphasis on morphology. Results Pathology and laboratory medicine play a key role in investigation of SM, as correct diagnosis requires integration of morphologic, molecular, and serologic findings. In addition to awareness of microscopic findings in SM, a pathologist must keep abreast with an expanding menu of ancillary studies, particularly molecular testing. Conclusions Systemic mastocytosis is a challenging diagnosis that requires not only a demonstration of a clonal proliferation of MCs but also a correct subclassification based on the recently updated criteria.