Mastocytosis is defined by abnormal accumulations of mast cells in various tissue sites. The clinical features of this multifaceted disorder originate from mast cell infiltration leading to local and systemic effects induced by numerous pharmacological mediators. As 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 chronic diarrhoea, urticaria, syncope and peptic ulceration but also various haematological neoplasms. Diagnosis of mastocytosis can be confirmed only by the pathologist who should use a combined immunohistochemical and molecular approach. Recognition and subtyping of its rare, life‐threatening high‐grade disease variants including aggressive systemic mastocytosis and mast cell leukaemia is based on the thorough investigation of tissue samples (usually bone marrow) but also smear preparations of blood and bone marrow.
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
KIT
‐D816V.
The presence of
KIT
‐D816V enables targeting therapy using some of the recently developed tyrosine kinase inhibitors.
Although stated in the recent WHO classification system on haematopoietic neoplasms, mastocytosis should not be grouped among myeloproliferative neoplasms.
Mastocytosis rather should be considered as a distinct group of disorders among haematological tumours/neoplasms.
Mastocytosis must be separated from a variety of reactive (mast cell activation syndrome) and neoplastic (basophilic and myelomastocytic leukaemias) disease states.
In more than 80% of patients with advanced systemic mastocytosis (aggressive and leukaemic SM and SM‐AHNMD) mutations other than KIT‐D816V are detected.