Clinical, immunophenotypic, and molecular characteristics of well-differentiated systemic mastocytosis

J Allergy Clin Immunol. 2016 Jan;137(1):168-178.e1. doi: 10.1016/j.jaci.2015.05.008. Epub 2015 Jun 19.


Background: Well-differentiated systemic mastocytosis (WDSM) is a rare variant of systemic mastocytosis (SM) characterized by bone marrow (BM) infiltration by mature-appearing mast cells (MCs) often lacking exon 17 KIT mutations. Because of its rarity, the clinical and biological features of WDSM remain poorly defined.

Objective: We sought to determine the clinical, biological, and molecular features of a cohort of 33 patients with mastocytosis in the skin in association with BM infiltration by well-differentiated MCs and to establish potential diagnostic criteria for WDSM.

Methods: Thirty-three patients with mastocytosis in the skin plus BM aggregates of round, fully granulated MCs lacking strong CD25 and CD2 expression in association with clonal MC features were studied.

Results: Our cohort of patients showed female predominance (female/male ratio, 4:1) and childhood onset of the disease (91%) with frequent familial aggregation (39%). Skin involvement was heterogeneous, including maculopapular (82%), nodular (6%), and diffuse cutaneous (12%) mastocytosis. KIT mutations were detected in only 10 (30%) of 33 patients, including the KIT D816V (n = 5), K509I (n = 3), N819Y (n = 1), and I817V (n = 1) mutations. BM MCs displayed a unique immunophenotypic pattern consisting of increased light scatter features, overexpression of cytoplasmic carboxypeptidase, and aberrant expression of CD30, together with absent (79%) or low (21%) positivity for CD25, CD2, or both. Despite only 9 (27%) of 33 patients fulfilling the World Health Organization criteria for SM, our findings allowed us to establish the systemic nature of the disease, which fit with the definition of WDSM.

Conclusions: WDSM represents a rare clinically and molecularly heterogeneous variant of SM that requires unique diagnostic criteria to avoid a misdiagnosis of cutaneous mastocytosis per current World Health Organization criteria.

Keywords: KIT; Mast cell; imatinib; mastocytosis; well differentiated.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adolescent
  • Adult
  • Aged
  • Child
  • Child, Preschool
  • Female
  • Humans
  • Immunophenotyping
  • Male
  • Mast Cells / immunology
  • Mast Cells / pathology
  • Mastocytosis, Cutaneous / diagnosis*
  • Mastocytosis, Cutaneous / genetics
  • Mastocytosis, Cutaneous / immunology
  • Mastocytosis, Cutaneous / pathology
  • Mastocytosis, Systemic / diagnosis*
  • Mastocytosis, Systemic / genetics
  • Mastocytosis, Systemic / immunology
  • Mastocytosis, Systemic / pathology
  • Middle Aged
  • Mutation
  • Proto-Oncogene Proteins c-kit / genetics
  • Skin / pathology
  • Young Adult


  • Proto-Oncogene Proteins c-kit