Mast Cell Clonal Disorders: Classification, Diagnosis and Management

Mast cell clonal disorders are characterized by the clonal proliferation of pathological mast cells as a result of somatic mutations in the KIT gene, most commonly the D816V mutation. Accumulation and degranulation of these cells causes a wide variety of symptoms. Mast cell clonal disorders can be divided into mastocytosis and monoclonal mast cell activation syndrome, depending of the level of clonality. The severity of mastocytosis varies from an indolent variant with a good prognosis, to an aggressive condition with short life expectancy. Diagnosis is based on demonstration of clonality and accumulation in the skin and in extracutaneous tissues. Treatment is highly individualized, and is based on the severity of the condition. Treatment of patients with indolent systemic mastocytosis is aimed at reducing symptoms, using histamine H1 and H2 receptor antagonists as a starting point. In addition, associated conditions such as osteoporosis must be treated. Treatment of advanced systemic mastocytosis is aimed at reducing mast cell load through cytoreductive therapy. The choice of such therapy depends on the KIT mutational status. Though currently there is no curative treatment available, promising new therapies such as midostaurin are emerging that have demonstrated success in reducing symptoms and improving quality of life.