Mastocytose

WHO 2022

Mastocytosis comprises rare heterogeneous neoplasms characterized by an accumulation of abnormal mast cells in various organs or tissues, typically driven by constitutive activation of the KIT receptor. The pathology of mastocytosis is complex, and clinical features span a broad spectrum that may be modulated by the presence of comorbidities. Significant comorbidities include IgEdependent allergies, vitamin D deficiency, and psychiatric, psychological or mental problems. The classification continues

to recognize three disease types: systemic mastocytosis (SM),

cutaneous mastocytosis (CM) and mast cell sarcoma (MCS).

A somatic point mutation in the KIT gene at codon 816 is detected in >90% of patients with SM. Other rare activating KIT alterations include mutations in the extracellular (e.g., deletion of codon 419 on exon 8 or A502_Y503dup in exon 9), transmembrane (e.g., NM_000222:KIT p.F522C), or juxtamembrane (e.g., NM_000222:KIT p.V560G) domains, detected in <1% of advanced SM cases but enriched in cases of indolent SM.

Most patients with advanced SM and NM_000222:KIT p.D816V have additional somatic mutations involving most frequently TET2, SRSF2, ASXL1, RUNX1, and JAK2. An associated haematologic (usually myeloid)

neoplasm may be detected in these patients.

Diagnostic criteria for SM have been modified. Namely, expression of CD30 and the presence of any KIT mutation causing ligand-independent activation have been accepted as minor diagnostic criteria. Basal serum tryptase level >20 ng/ml, which should be adjusted in case of hereditary alpha-tryptasaemia, is a minor SM criterion. In addition, bone marrow mastocytosis is now a separate subtype of SM characterized by absence of skin lesions and B-findings and a basal serum tryptase below 125 ng/

ml. Classical B-findings (‘burden of disease’) and C-findings (‘cytoreduction-requiring’) have undergone minor refinements. Most notably, NM_000222:KIT p.D816V mutation with VAF ≥ 10% in bone marrow cells or peripheral blood leukocytes qualifies as a B-finding.

The classification recognizes well-differentiated systemic mastocytosis

(WDSM) as a morphologic pattern that can occur in any SM subtype, characterized by round and well-granulated mast cells usually heavily infiltrating the bone marrow. In most patients with WDSM, KIT codon 816 mutation is not detected, and neoplastic mast cells are usually negative for CD25 and CD2 but positive for CD30.