Refined diagnostic criteria for bone marrow mastocytosis: a proposal of the European competence network on mastocytosis

Abstract

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.

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

“…The frequency of ISM assessed in such a “real life” setting with a multidisciplinary approach appears to be the highest reported to date, close to 90%. Moreover, in more than half of the cases ISM had the characteristics of BMM, confirming the underestimation of this provisional WHO variant [ 7 , 8 ]. The number of new diagnoses of BMM in our series progressively increased in the last 15 years in accordance with the greater diffusion of knowledge among specialists about the association of BMM with heterogeneous clinical scenarios, particularly severe unexplained osteoporosis, and severe allergic reactions especially after Hymenoptera sting.…”

“…Mastocytosis is a rare disease, but it is also underestimated. In fact, ISM diagnosis, above all in the provisional WHO subvariant without skin lesion (bone marrow mastocytosis–BMM), may easily be missed as symptoms can be subtle or absent, together with the lack of awareness of this disease [ 7 , 8 ].…”

Tryptase Regulates the Epigenetic Modification of Core Histones in Mast Cell Leukemia Cells

“…Tryptase is one of the established biomarkers for mastocytosis, with an increase in tryptase levels being one out several criteria for diagnosing a patient with mastocytosis ( 30 ). Tryptase is also a well-established biomarker for anaphylaxis, in which a dramatic increase in serum tryptase levels can be attained ( 31 ).…”

Systemic Mastocytosis and Other Entities Involving Mast Cells: A Practical Review and Update

“…According to Valent et al [ 8 ] and the 2022 WHO classification [ 6 ], BMM was reclassified as a discrete SM subtype (in the 2017 WHO classification, it was considered as a special type of ISM [ 5 ]) with bone marrow involvement, absence of skin lesions, B-finding(s), dense SM infiltrates in an extramedullary organ, basal serum tryptase < 125 ng/mL, no signs/criteria of MCL, and an AHN [ 34 , 46 , 47 , 48 , 49 ]. BMM is associated with osteoporosis and severe anaphylaxis [ 34 , 46 , 47 , 48 , 49 ]. Patients with BMM and low disease burden (defined as absence of B-findings and a tryptase level < 125 ng/mL) have a superior prognosis to patients with typical ISM or SSM [ 49 ]; thus, the importance to accurately diagnose this entity.…”

“…BMM is associated with osteoporosis and severe anaphylaxis [ 34 , 46 , 47 , 48 , 49 ]. Patients with BMM and low disease burden (defined as absence of B-findings and a tryptase level < 125 ng/mL) have a superior prognosis to patients with typical ISM or SSM [ 49 ]; thus, the importance to accurately diagnose this entity. Of note, in the absence of skin lesions, if B-findings are present and/or serum tryptase is over 125 ng/mL, the disease would be considered ISM and not BMM [ 8 ].…”