New Insights into the Pathogenesis of Mastocytosis: Emerging Concepts in Diagnosis and Therapy

Mastocytosis is a heterogeneous group of neoplasms defined by a numerical increase and accumulation of clonal mast cells (MCs) in various organ systems. The disease may present as cutaneous mastocytosis or systemic mastocytosis (SM). On the basis of histopathological and molecular features, clinical variables, and organ involvement, SM is divided into indolent SM, smoldering SM, SM with an associated hematologic neoplasm, aggressive SM, and MC leukemia. Each variant is defined by unique diagnostic criteria and a unique spectrum of clinical presentations. A key driver of MC expansion and disease evolution is the oncogenic machinery triggered by mutant forms of KIT. The genetic background, additional somatic mutations, and comorbidities also contribute to the course and prognosis. Patients with SM may also suffer from mediator-related symptoms or even an MC activation syndrome. This article provides an update of concepts on the genetics, etiology, and pathology of mastocytosis, with emphasis on diagnostic criteria and new treatment concepts.

Automated summary

Mastocytosis is a group of heterogeneous neoplasms characterized by an increase and accumulation of clonal mast cells in various organ systems. It can present as cutaneous mastocytosis or systemic mastocytosis, and the latter is further divided into different variants based on histopathological and molecular features, clinical variables, and organ involvement. The oncogenic machinery triggered by mutant forms of KIT plays a key role in MC expansion and disease progression, and genetic background, somatic mutations, and comorbidities also contribute to the course and prognosis. This article provides an update on the genetics, etiology, and pathology of mastocytosis, focusing on diagnostic criteria and new treatment concepts.