A Multidisciplinary Diagnostic Approach Reveals a Higher Prevalence of Indolent Systemic Mastocytosis: 15-Years’ Experience of the GISM Network

SIMPLE SUMMARY: The approach of the Interdisciplinary Group for Study of Mastocytosis (GISM) of Verona, based on a regional network of clinical specialists and expert pathologists, with the availability of sensitive molecular and flow-cytometry diagnostic techniques, allowed the discovery of a higher-than-expected number of patients with systemic mastocytosis (SM), demonstrating a prevalence of 17.2/100,000 adult inhabitants. During a 15-year period of activity, we documented a remarkable increase in diagnosis of indolent SM, which constitute over 90% of our SM series, mainly represented by the bone marrow mastocytosis subvariant (54.8%). A timely diagnosis of SM has a great practical importance, since allows discovering and treating underdiagnosed osteoporosis, especially in males, a condition which is frequently complicated with fragility fractures, also in young patients, with disabling consequences. Moreover, diagnosis of mastocytosis in patients with Hymenoptera venom allergy allows continuing lifelong venom immunotherapy in order to prevent further severe, sometimes fatal, allergic reactions. ABSTRACT: Systemic mastocytosis (SM) and other adult clonal mast cell disorders (CMD) are often underestimated, and their epidemiology data are scarce. We aimed at evaluating the impact of the activity of the Interdisciplinary Group for Study of Mastocytosis (GISM) of Verona on the prevalence and incidence of CMD. We examined the data of 502 adult patients diagnosed with CMD and residing in the Veneto Region, consecutively referred to GISM between 2006 and 2020. SM was diagnosed in 431 cases, while 71 patients had cutaneous mastocytosis or other CMD. Indolent SM represented the most frequent SM variant (91.0%), mainly with the characteristics of bone marrow mastocytosis (54.8%). The prevalence of SM in the adult population of the Veneto region and of the Verona province was 10.2 and 17.2/100,000 inhabitants, respectively. The mean incidence of new SM cases in Verona was 1.09/100,000 inhabitants/year. Hymenoptera venom allergy was the main reason (50%) leading to the CMD diagnosis. Osteoporosis, often complicated by fragility fractures, was present in 35% of cases, even in young patients, especially males. Our data show a higher prevalence and incidence of SM than previously reported, confirming that reference centers with multidisciplinary approach are essential for the recognition and early diagnosis of CMD.