Mastocytosis: recent advances in defining the disease

Abstract

Mastocytosis is a rare disease characterized by a primary pathological increase in mast cells in different tissues, which may present in a variety of clinical patterns. Major advances have been made in recent years in the understanding of the pathogenesis of mastocytosis. This review is aimed at familiarizing dermatologists with these recent findings, and at exploring their possible implications for the diagnosis and treatment of the condition. The heterogeneous clinical presentation of mastocytosis is detailed with respect to the type of skin lesions, age at onset, family history, organ systems involved, associated haematological disorders and prognosis. Recent genetic findings also indicate different pathogenetic forms of mastocytosis, as adult patients and those with associated haematological diseases usually express activating mutations of the stem cell factor receptor c-kit, whereas most cases of childhood-onset and familial mastocytosis seem to lack these mutations. Despite the presence of c-kit mutations, patients with cutaneous lesions generally have a good prognosis, even when there is involvement of other organs. Some patients, particularly those with childhood-onset disease, experience spontaneous remission, mostly by puberty. c-kit mutations do not explain the initial cause of mastocytosis, and their prognostic significance is as yet unclarified, as is the pathogenesis in patients without the mutations. Furthermore, these novel findings have as yet not resulted in a more effective treatment of the cause of the disease, so that counselling, prevention of exposure to mast cell secretory stimuli, and symptomatic treatment remain the mainstays of current patient management.

Systemic mastocytosis involving the gastrointestinal tract: clinicopathologic and molecular study of five cases

“…2,[5][6][7][8][9][10][11]13,14,[16][17][18][21][22][23]26,30,31 Malabsorption, which occurred in two patients in our series is well described in systemic mastocytosis, 2,5,7,9,10,16,23,30,31 occurring in 5-30% of patients. 30,32 While all patients in our series were women, the literature indicates an equal sex distribution for systemic mastocytosis in general 33 and for those cases with direct gastrointestinal involvement. [5][6][7][8][9][10][11]13,[16][17][18][19][21][22][23]31 Endoscopically and grossly, the most frequent and distinctive finding in our series was that of mucosal nodularity (present in four of five patients).…”

Expression of Bcl-2 and Bcl-xL in Cutaneous and Bone Marrow Lesions of Mastocytosis

“…Out of the 32 patients, 12 adults and 6 children had maculopapular cutaneous mastocytosis (urticaria pigmentosa), 7 children had solitary mastocytomas, and 7 children had multiple mastocytomas. 4,5 Lesional mast cell counts of skin biopsies were 6.58 Ϯ 1.75 mast cells/mm 2 In addition, small snap-frozen pieces of 9 mastocytosis biopsies (2 biopsies that had also been used for immunohistochemical staining and 7 additional biopsies of different patients with mastocytosis) from 3 adult patients with maculopapular mastocytosis and 6 pediatric patients with maculopapular mastocytosis or mastocytomas as well as frozen tissue of 6 healthy controls were used for RNA isolation.…”

KIT mutation in mast cells and other bone marrow hematopoietic cell lineages in systemic mast cell disorders: a prospective study of the Spanish Network on Mastocytosis (REMA) in a series of 113 patients

“…However, attempts to demonstrate the presence of KIT mutation in purified CD34 ϩ hematopoietic precursor cells have failed so far. 25 The pathogenetic relevance of the different KIT mutations in MCDs is still not fully understood; however, their identification has become of major prognostic significance 26 due to the availability of protein kinase inhibitors such as imatinib (STI571, Gleevec; Novartis, Basel, Switzerland). These new targeted drugs have proven to be of limited efficacy in patients with MCD carrying the D816V-activating KIT mutation, while they are effective in cases displaying other KIT mutations (eg V560G, 27,28 F522C, 15 K509I, 17 and del419 18 ).…”