A clinical, morphological and molecular study of 70 patients with gastrointestinal involvement in systemic mastocytosis

Abstract

In 70 patients with KIT D816V positive systemic mastocytosis (SM) including 36 patients with advanced SM (AdvSM), we correlated the extent of reported mucosal mast cell ([m]MC) infiltration of the upper and/or lower gastrointestinal tract (UGIT, n = 63; LGIT, n = 64; both, n = 57) with symptoms and markers of MC burden/subtype. GI symptoms were reported by all patients (mean 2.1 number of symptoms). A strong mMC infiltration was identified in 24 patients (UGIT, 17/63, 27%; LGIT, 19/64, 30%). Concurrent involvement of UGIT and LGIT (n = 12) correlated with female gender (75%) and a higher symptom burden (mean 2.7) but not with MC burden or subtype. Significant differences between non-AdvSM and AdvSM were reported regarding food intolerance (54% vs. 17%), cramping (54% vs. 22%) and weight loss (0% vs. 64%). KIT D816V was identified in 54/56 (96%) available biopsies. In 46 patients, digital PCR revealed a correlation with low albumin levels (r = - 0.270, P = 0.069) and the KIT D816V VAF in peripheral blood (r = 0.317, P = 0.036) but not with the extent of mMC infiltration or markers of MC burden/subtype. Although MC mediator triggered GI symptoms have a substantial impact on the quality of life, correlation to objective disease parameters is lacking thus making its systematic assessment challenging.

Figure 1

Patient flowchart. AdvSM advanced systemic mastocytosis, ASM aggressive systemic mastocytosis, GI gastrointestinal, GREM German Registry on Disorders of Eosinophils and Mast Cells, ISM indolent systemic mastocytosis, MCL ± AHN mast cell leukemia with/without an associated hematologic neoplasm, SM systemic mastocytosis, SM-AHN systemic mastocytosis with an associated hematologic neoplasm, SSM smoldering systemic mastocytosis.

Figure 2

KIT D816V variant allele frequency performed of gastrointestinal biopsies to (A) diagnosis and (B) extent of mast cell infiltration. AdvSM advanced systemic mastocytosis, ISM indolent systemic mastocytosis, MCI mucosal mast cell infiltration, SSM smoldering systemic mastocytosis.