Mastocytosis: the puzzling clinical spectrum and challenging diagnostic aspects of an enigmatic disease

Mastocytosis is a complex disorder characterized by the accumulation of abnormal mast cells ( MC ) in the skin, bone marrow and/or other visceral organs. The clinical manifestations result from MC ‐derived mediators and, less frequently, from destructive infiltration of MC s. Patients suffer from a variety of symptoms including pruritus, flushing and life‐threatening anaphylaxis. Whilst mastocytosis is likely to be suspected in a patient with typical skin lesions [i.e. urticaria pigmentosa (UP)], the absence of cutaneous signs does not rule out the diagnosis of this disease. Mastocytosis should be suspected in cases of recurrent, unexplained or severe insect‐induced anaphylaxis or symptoms of MC degranulation without true allergy. In rare cases, unexplained osteoporosis or unexplained haematological abnormalities can be underlying feature of mastocytosis, particularly when these conditions are associated with elevated baseline serum tryptase levels. The diagnosis is based on the World Health Organization criteria, in which the tryptase level, histopathological and immunophenotypic evaluation of MC s and molecular analysis are crucial. A somatic KIT mutation, the most common of which is D816V, is usually detectable in MC s and their progenitors. Once a diagnosis of systemic mastocytosis ( SM ) is made, it is mandatory to assess the burden of the disease, its activity, subtype and prognosis, and the appropriate therapy. Mastocytosis comprises seven different categories that range from indolent forms, such as cutaneous and indolent SM , to progressive forms, such as aggressive SM and MC leukaemia. Although prognosis is good in patients with indolent forms of the disease, patients with advanced categories have a poor prognosis.