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In the current classification of the World Health Organization (WHO), bone marrow mastocytosis (BMM) is a provisional variant of indolent systemic mastocytosis (ISM) defined by bone marrow involvement and absence of skin lesions. However, no additional diagnostic criteria for BMM have been proposed. Within the registry dataset of the European Competence Network on Mastocytosis, we compared characteristics and outcomes of 390 patients with BMM and 1175 patients with typical ISM. BMM patients were significantly older, predominantly male, had lower tryptase and lower burden of neoplastic mast cells, and displayed a higher frequency of allergic reactions, mainly triggered by Hymenoptera, than patients with typical ISM. The estimated 10-year progression-free survival of BMM and typical ISM was 95.9% and 92.6%, respectively. In BMM patients defined by WHO-based criteria, the presence of one B-Finding and tryptase level ≥125 ng/mL were identified as risk factors for progression in multivariate analyses. BMM patients without any of these risk factors were found to have better progression-free survival (p < 0.05) and better overall survival (p < 0.05) than other ISM patients. These data support the proposal to define BMM as a separate SM variant characterized by SM criteria, absence of skin lesions, absence of B-Findings, and tryptase levels <125 ng/mL., (© 2021. The Author(s), under exclusive licence to Springer Nature Limited.)

Mastocytosis is a rare neoplasm characterized by the expansion and accumulation of mast cells in various organ systems. Systemic mastocytosis (SM) may or may not present with cutaneous lesions. To examine the frequency and clinical impact of cutaneous involvement, data on 1,510 patients with mastocytosis collected in the registry of the European Competence Network on Mastocytosis were analyzed. Cutaneous involvement was found in 1,195 of 1,510 patients (79.1%). Of these, 286 had cutaneous mastocytosis, and 721 had SM with skin involvement. Adult patients with skin involvement who did not have a bone marrow examination (n = 188) were defined as having mastocytosis in the skin. In 315 patients, SM without skin involvement was found. The percentage of cases with cutaneous involvement was higher in indolent SM (100%) and smoldering SM (87.9%) compared to aggressive SM (46.8%) or mast cell leukemia (38.5%). After a median follow-up of 5.6 years, no patient with cutaneous mastocytosis had died, but 2.6% of the patients with mastocytosis in the skin, 5.7% of the patients with SM with skin involvement, and 28.95% of the patients with SM without skin involvement had died. Overall survival was longer in patients with skin involvement (cutaneous mastocytosis and/or mastocytosis in the skin and/or SM with skin involvement) than in patients with SM without skin involvement (P < 0.0001). These data argue for a thorough examination of both the skin and bone marrow in adult patients with mastocytosis., (Copyright © 2021 The Authors. Published by Elsevier Inc. All rights reserved.)

Background: Up to 75% of patients with severe anaphylactic reactions after Hymenoptera sting are at risk of further severe reactions if re-stung. Venom immunotherapy (VIT) is highly effective in protecting individuals with ascertained Hymenoptera venom allergy (HVA) and previous severe reactions. After a 3- to 5-year VIT course, most patients remain protected after VIT discontinuation. Otherwise, a lifelong treatment should be considered in high-risk patients (eg, in mastocytosis). Several case reports evidenced that patients with mastocytosis and HVA, although protected during VIT, can re-experience severe and sometimes fatal reactions after VIT discontinuation., Objective: To evaluate whether patients who lost protection after VIT discontinuation may suffer from clonal mast cell disorders., Methods: The survey describes the characteristics of patients who received a full course of VIT for previous severe reactions and who experienced another severe reaction at re-sting after VIT discontinuation. Those with a Red Española de Mastocitosis score of 2 or more or a serum basal tryptase level of more than 25 ng/mL underwent a hematological workup (bone marrow biopsy, KIT mutation, expression of aberrant CD25) and/or skin biopsy., Results: Nineteen patients (mean age, 56.3 years; 89.5% males) were evaluated. All of them had received at least 4 years of VIT and were protected. After VIT discontinuation they were re-stung and developed, in all but 1 case, severe anaphylactic reactions (12 with loss of consciousness, in the absence of urticaria/angioedema). Eighteen patients (94.7%) had a clonal mast cell disorder, 8 of them with normal tryptase., Conclusions: Looking at this selected population, we suggest that mastocytosis should be considered in patients developing severe reactions at re-sting after VIT discontinuation and, as a speculation, patients with mastocytosis and HVA should be VIT-treated lifelong., (Copyright © 2017. Published by Elsevier Inc.)

Mastocytosis is a clonal disease characterized by proliferation and accumulation of mast cells (MC) in different tissues, preferentially skin and bone marrow, leading to a wide variety of clinical manifestations, mainly caused by the inappropriate release of MC mediators. As a consequence, patients with mastocytosis may experience symptoms due to massive MC activation and release of mediators. Anaphylaxis is the most frequent manifestation of this phenomenon. Drugs are possible triggers of anaphylaxis in patients with mastocytosis, even though the association between mastocytosis and drug anaphylaxis does not appear to be as strong as anaphylaxis after hymenoptera sting; nevertheless, MC disorders might be ruled out in cases of severe systemic reactions to drugs. Moreover, the risk of perioperative anaphylaxis in adults appears high, mainly in patients with indolent systemic mastocytosis regardless of skin involvement. Such risk is probably lower in patients who have never experienced anaphylaxis and/or have tolerated previous general anaesthesia. However, data published about drug anaphylaxis in patients with MC disorders are scanty and currently it is not possible to provide clear recommendations., (Copyright© Bentham Science Publishers; For any queries, please email at epub@benthamscience.org.)

Background: Systemic mastocytosis is a clonal mast cell (MC) disease that can lead to potentially fatal anaphylactic reactions caused by excessive MC mediator release. The prevalence of mastocytosis in patients with Hymenoptera venom allergy is high, and thus the disease should be suspected in patients with severe reactions caused by Hymenoptera stings and increased serum basal tryptase (SBT) levels., Objective: We sought to evaluate the presence of clonal MC disorders in patients seen at our mastocytosis center with Hymenoptera sting-induced anaphylaxis, documented hypotension, absence of urticaria pigmentosa, and normal SBT levels., Methods: Twenty-two patients with Hymenoptera sting-induced anaphylaxis, without skin lesions, and with tryptase levels of less than 11.4 ng/mL underwent bone marrow evaluation. Bone mineral density was assessed in those patients with ascertained mastocytosis., Results: In 16 of 22 patients, a diagnosis of indolent mastocytosis could be established, and 1 patient had a monoclonal MC activation syndrome. Patients with mastocytosis had higher SBT levels (P = .03) but only rarely had angioedema/urticaria associated with hypotension (P = .004)., Conclusions: The absence of urticaria or angioedema in severe reactions to Hymenoptera stings with hypotension might represent the most relevant factor in identifying patients with mastocytosis, regardless of their serum tryptase levels., (Copyright © 2015 American Academy of Allergy, Asthma & Immunology. Published by Elsevier Inc. All rights reserved.)

Aims: CD30 expression by bone marrow (BM) mast cells (MC) has been reported recently in systemic mastocytosis (SM) patients. The aim of this study was to investigate the potential diagnostic and prognostic value of CD30 expression in SM as assessed by multiparameter flow cytometry., Methods and Results: A total of 163 consecutive BM samples corresponding to 142 SM patients and 21 non-mastocytosis cases were studied. CD30 was positive in most SM patients (80%), but in only one non-mastocytosis case (4.8%). When combined with CD25, CD30 contributed to an improved accuracy over that of CD25 alone (98% versus 93%) mainly because most (eight of nine) of the well-differentiated SM (WDSM), who lacked CD25, were CD30(+). Similar levels of expression of CD30 were observed among all different subgroups of SM except mast cell leukaemia; among indolent SM (ISM) patients, no significant association was observed between the levels of CD30 expression and other clinical and biological features of the disease., Conclusions: The increased expression of CD30 associated with absence of CD25 contributes to the diagnosis of WDSM and its distinction from other subtypes of SM. By contrast, CD30 expression did not contribute either to prognostic stratification of ISM or to the differential diagnosis between ISM and aggressive SM cases., (© 2013 John Wiley & Sons Ltd.)

Background: Anaphylaxis after Hymenoptera stings has been reported in subjects with mastocytosis, but few data exist regarding disease prevalence in populations allergic to these insects., Objective: The incidence of clonal mast cell (MC) disorders in subjects with both systemic reactions to Hymenoptera stings and increased serum baseline tryptase (sBT) levels was assessed by using bone marrow (BM) aspirates and biopsy specimens., Methods: Subjects with a history of a systemic reaction caused by a Hymenoptera sting underwent the standard diagnostic work-up for Hymenoptera allergy, and sBT levels were measured. Subjects with an increased sBT level had BM evaluation that included histology/cytology, flow cytometry, and detection of KIT mutations., Results: Forty-four (11.6%) of 379 subjects with systemic reactions had increased sBT levels (>11.4 ng/mL), and 31 (70.5%) of these had a history of anaphylaxis. Thirty-four subjects with increased sBT levels underwent a BM analysis. Histology detected diagnostic or subdiagnostic MC infiltrates in 22 (65%) of 34 patients. Abnormal MCs were identified by means of flow cytometry and cytology in 26 (78.8%) of 33 and 20 (58.8%) of 34 subjects, respectively. A KIT mutation was detected in 17 (54.8%) of 31 subjects. The diagnosis was indolent systemic mastocytosis in 21 (61.7%) of 34 subjects and monoclonal MC activation syndrome in 9 (26.5%) of 34 subjects. All subjects with anaphylaxis had one of those 2 disorders., Conclusion: The concomitant presence of systemic reactions (especially anaphylaxis) after Hymenoptera stings and increased sBT levels strongly suggests that a BM examination is indicated for the diagnosis of clonal MC disease.