Authors of a recent article in the Journal of Allergy and Clinical Immunology propose an argument to unify systemic mastocytosis (SM) diagnostic criteria of the 2001 World Health Organization (WHO) with the revised criteria of the 2021 International Consensus Classification Group (ICC).
“In this article, we provide a proposal to harmonize the EU/US, WHO, and ICC classifications and the related diagnostic criteria into a single unifying classification,” the authors said. “These harmonizing criteria and the resulting classification should facilitate comparisons among clinical studies and the conduct of multicenter trials in patients with mastocytosis.”
Key differences between ICC and WHO diagnostic criteria
The ICC SM diagnostic criteria published in 2021 represented the first significant change in SM diagnostic criteria in two decades.
Fundamental changes included a broader understanding of B and C findings, specifying the presence of KIT D816V or other activating KIT mutations as a minor diagnostic criterion and establishing that the presence of one major criterion is sufficient to make a diagnosis in the absence of minor criteria.
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Furthermore, the ICC proposed a more detailed subclassification of SM. The new subclassification recognized bone marrow mastocytosis (BMM) as a distinct SM subtype, excluded lymphoid neoplasms from the definition of SM with associated hematologic neoplasm (SM-AHN) and enabled mast cell leukemia (MCL) diagnosis from a core biopsy.
Unlike the WHO diagnostic criteria, ICC criteria were more focused on genetic mutations and the morphology of the cells, reflecting the advances in understanding of the pathophysiology of the disease in the last decades.
Harmonization proposal
The authors proposed to unify WHO and ICC criteria in order to obtain consistent diagnoses and comparable results in research studies.
The proposal included accepting BMM and smoldering systemic mastocytosis (SSM) as two separate variants. The latter is defined by at least two B findings and a worse prognosis.
Regarding the differences in the application of diagnostic criteria, the authors considered that minor criteria could still be necessary for diagnosis, particularly in cases where basophilic leukemia mimics SM. Additionally, the consensus suggested including the presence of any KIT mutation as diagnostic criteria. Basal serum tryptase levels should not be used as a minor diagnostic criterion in cases with concomitant associated myeloid neoplasm.
Although weight loss remained a supportive feature for diagnosis, it was removed as a C finding. The authors proposed that bone lesions and enlarged lymph nodes should fulfill specific requirements to be considered C findings.