Mastocytosis is a rare, heterogeneous myeloid neoplasm characterized by clonal proliferation and abnormal accumulation of mast cells. It is classified into cutaneous mastocytosis (CM), systemic mastocytosis (SM), mast cell sarcoma (MCS), and extracutaneous mastocytoma. SM comprises indolent and smouldering variants as well as advanced forms, including aggressive SM and mast cell leukemia.

Clinical manifestations range from asymptomatic disease to life-threatening presentations with cytopenia, malabsorption, hepatosplenomegaly, lymphadenopathy, ascites, or osteolytic bone lesions. Mediator-related symptoms such as flushing, diarrhea, and anaphylaxis are common. The KIT D816V gain-of-function mutation represents the central pathogenic driver, leading to ligand-independent KIT activation and uncontrolled mast cell proliferation.

Diagnosis relies on WHO and ICC criteria, integrating histopathology, immunophenotyping, and KIT mutation analysis. Management depends on disease subtype: non-advanced forms are treated symptomatically with antihistamines, mast cell stabilizers, and trigger avoidance, while advanced SM requires cytoreductive agents and KIT inhibitors. Midostaurin and avapritinib, potent inhibitors of KIT D816V, have demonstrated significant improvements in mediator-related symptoms, overall survival, and quality of life, whereas imatinib is ineffective in D816V-positive patients but may benefit other KIT genotypes (e.g., K509I, V560G, F522C). Emerging inhibitors such as bezuclastinib and elenestinib show promising efficacy. Allogeneic hematopoietic stem cell transplantation remains the only curative option for aggressive SM.

In summary, mastocytosis is a clinically heterogeneous disease in which early-stage treatment focuses on symptom control and anaphylaxis prevention, whereas advanced disease benefits from targeted therapy that has markedly improved prognosis.