Systemic mastocytosis for the practicing clinician: overview, diagnostic features, prognostication and antiproliferative treatment in the era of targeted therapy

Systemic mastocytosis is a malignant neoplasm classically driven by the KIT D816V mutation. Due to the range of clinical outcomes in these patients, the diagnosis and subclassification of the disease is complex but critical to understanding management, prognosis and therapeutic approaches. In those with non-advanced systemic mastocytosis, treatment decisions are tailored towards symptom improvement, whereas in advanced disease antiproliferative agents become more critical as outcomes resemble that of other myeloid neoplasms. With the advent of novel targeted therapies, the use of these agents have begun to expand their use in both non-advanced and advanced disease. This review will highlight the pathophysiology of systemic mastocytosis and offer a simplified approach to the clinical evaluation and diagnostic criteria to stratify patients by subtype. Further, management approaches in non-advanced, symptomatic disease and those with advanced disease in the era of targeted therapies are reviewed in detail.