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 mastocytosisMastocytosis Rare disease caused by the buildup of mast cells. Cutaneous mastocytosis primarily affects the skin and is more common in children, while systemic mastocytosis affects internal organs and is more common in adults..”
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.
Read more about SM testing and diagnosis
Furthermore, the ICC proposed a more detailed subclassification of SM. The new subclassification recognized bone marrow mastocytosisBone marrow mastocytosis A subtype of indolent SM that occurs when the excess mast cells accumulate in the bone marrow, but not the skin or other organs. (BMM) as a distinct SM subtype, excluded lymphoid neoplasms from the definition of SM with associated hematologic neoplasm (SM-AHN) and enabled mast cell leukemiaMast cell leukemia The most severe subtype of SM, caused by the rapid buildup of immature mast cells in the bone marrow and blood. Mast cell leukemia accounts for less than 5% of SM cases and has a poor prognosis. (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 tryptaseTryptase A protein enzyme that is primarily produced by mast cells and stored in small pockets within the cells, known as granules. High levels of tryptase are a key indicator of SM. 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.
