Isolated bone marrow mastocytosis: an underestimated subvariant of indolent systemic mastocytosis

Systemic mastocytosis (SM) is a heterogeneous disorder characterized by the proliferation and accumulation of atypical mast cells (MC) in tissues, principally in the bone marrow (BM) and skin. The diagnosis of SM requires the presence of multifocal dense MC infiltrates in one or multiple extra-cutaneous organs, mostly BM (major criterion), plus at least one of the following minor criteria: (i) abnormal morphology of extra-cutaneous MC (spindle-shaped cells); (ii) increased serum tryptase level (>20 ng/ml); (iii) abnormal expression of CD2 and/or CD25 on bone marrow MC; (iv) detection of a KIT mutation at codon 816 in extra-cutaneous organs. Diagnosis of SM can also be made in the presence of at least 3 minor criteria. Diagnosis of SM in absence of the typical skin involvement presents a challenge for clinicians. We report the characteristics of 97 consecutive ISM patients, diagnosed or revised according to the 2008 WHO classification, from January 2005 to December 2009 at the Multidisciplinary Outpatient Clinic for Mastocytosis in Verona, Italy, among 145 patients referred from a regional network of Allergists and Dermatologists, following the appearance of classical skin lesions, or in case of unexplained/recurrent anaphylaxis or severe allergic reactions to hymenoptera sting with persistent raised tryptase. Isolated BMM was diagnosed in 46/84 patients (54.7%) referred for unexplained/recurrent anaphylaxis or severe allergic reactions to hymenoptera sting without skin lesions. Other 13 patients fulfilled less than three minor criteria but displayed MC clonality markers and were considered as having Monoclonal MC activation syndrome. BMM patients were predominantly males and had a lower BM MC burden, as evaluated by flow-cytometry, serum tryptase level and incidence of mediator-related symptoms other than anaphylaxis, than ISMs+ cases. In our opinion, the incidence of ISM limited to BM has been frequently underestimated. Although it is a rare condition, a close collaboration between different specialists could improve the possibility of detecting this disease. We believe that early recognition of BMM is fundamental to reduce potential life-threatening events or severe skeletal complications. Moreover, patients with systemic reactions to HV should be considered for lifelong venom immunotherapy.