Mastocytosis and Mast Cells

Abstract Mastocytosis is defined by abnormal accumulation of mast cells in various sites in the body. The clinical features of this chronic, multifaceted disorder originate from mast cell infiltration leading to systemic and local effects induced by numerous pharmacological mediators. Since mastocytosis is an unusual disorder and presents a multiplicity of symptoms, it is an often overlooked consideration in a differential diagnosis that includes not only asthma, chronic diarrhoea, urticaria, syncope, peptic ulceration but also various haematological neoplasms. Diagnosis of mastocytosis can be confirmed only by the pathologist using a combined immunohistochemical and molecular approach. Recognition and subtyping of its rare, life‐threatening high‐grade disease variant (i.e. mast cell leukaemia) includes not only the investigation of tissue samples (usually bone marrow) but also the blood and bone marrow smears. Key concepts: Mastocytosis is an unusual haematopoietic disorder derived from transformed bone marrow progenitor cells. Clinically and histologically, mastocytosis presents an extremely broad spectrum of subvariants ranging from a benign, sometimes even regressive, cutaneous disease to the progressively fatal mast cell leukaemia. Mastocytosis is a histological diagnosis established by the pathologist and cannot be confirmed by clinical findings alone. Most patients with systemic mastocytosis carry the activating point mutation KITD816V in the c‐kit proto‐oncogene. The presence of KITD816V not only explains pathophysiological disease characteristics but also enables targeting therapy using the recently developed tyrosine kinase inhibitors. Although stated in the recent WHO classification book on haematopoietic neoplasms, mastocytosis should not be grouped among myeloproliferative neoplasms. Mastocytosis should be considered as a separate group of disorders among haematological neoplasms. Mastocytosis must be separated from a variety of reactive (i.e. mast cell hyperplasia) and neoplastic (i.e. basophilic leukaemia) states.