Mastocytosis: Pathophysiology, Clinical Manifestations, and Current Therapeutic Approaches – A Narrative Review

Abstract

Background. Mastocytosis is a heterogeneous group of clonal mast cell disorders characterized by abnormal mast cell accumulation and activation in the skin, bone marrow, and other organs. Recent advances in molecular diagnostics and targeted therapies have significantly improved understanding of disease biology and management.

Aim. This review aims to summarize current knowledge regarding the classification, pathophysiology, clinical manifestations, diagnosis, treatment, and prognosis of mastocytosis.

Material and methods. A narrative review was performed by searching PubMed, Google Scholar, Scopus, and Medline for English-language articles. Precedence was given to current literature, clinical research, and international recommendations. Search terms included mastocytosis, systemic mastocytosis (SM), cutaneous mastocytosis (CM), mast cell, and KIT mutation.

Results. Mastocytosis is classified into cutaneous mastocytosis, systemic mastocytosis, and mast cell sarcoma. Disease pathogenesis is primarily associated with activating KIT mutations, particularly KIT D816V, together with additional somatic mutations and microenvironmental factors contributing to disease heterogeneity and progression. Clinical manifestations result from mast cell mediator release and tissue infiltration. Diagnosis requires integration of clinical, histopathological, immunophenotypic, and molecular findings. Treatment strategies range from anti-mediator therapy in indolent disease to KIT-targeted therapies, including midostaurin and avapritinib, in advanced systemic mastocytosis.

Conclusions. Mastocytosis remains a clinically diverse disorder requiring multidisciplinary diagnostic and therapeutic approaches. Advances in molecular characterization and targeted treatment have improved prognostic assessment and expanded therapeutic options, particularly in advanced disease.