Clonal Mast Cell Proliferation in Pruriginous Skin in Hypereosinophilic Syndrome

Dermatology. 2013;227(1):67-71. doi: 10.1159/000351807. Epub 2013 Aug 31.

Abstract

Background: Hypereosinophilic syndrome (HES) is defined as a high eosinophilic granulocyte count in peripheral blood and other tissues. It can be associated with clonal and non-clonal haematological neoplastic diseases.

Methods: Here we present a patient with a 27-year history of pruritus, urticarial lesions, recurrent diarrhoea, depression and a monoclonal gammopathy in the setting of HES.

Results: The patient presented with erythemas, disseminated plaques, papules and scaling. Eosinophils continuously increased from 14% in 2002 to 65% in 2011. Tryptase levels were >20 µg/l. Skin biopsies were unspecific. In the bone marrow biopsy 30% of eosinophilic differentiated precursors and 10% plasma cells were noticed. Skin and bone marrow initially not indicative for mast cell proliferation were investigated for clonal mast cell proliferation. By immunostaining, single tryptase-, CD117c- and CD25-positive mast cells were detected not only in bone marrow, but also in the skin. Molecular investigations revealed a D816V exon 17 mutation of the c-KIT gene in bone marrow and skin biopsies.

Conclusion: In this patient HES was associated with high tryptase levels with 2 underlying clonal cell populations - IgGκ-positive plasma cells and single clonal mast cells with a high percentage of eosinophils in the bone marrow with symptoms of a clonal mast cell activation syndrome. Because of 3 minor criteria the patient finally fulfilled the criteria for systemic mastocytosis (according to the WHO). Patients with high tryptase levels and symptoms of mast cell activation syndrome should be investigated for clonal mast cell disease even in the absence of increased mast cells in the skin and bone marrow.

Publication types

  • Case Reports

MeSH terms

  • Aged
  • Biopsy
  • Bone Marrow / pathology*
  • Cell Proliferation
  • Depression / etiology
  • Diarrhea / etiology
  • Erythema / etiology
  • Female
  • Humans
  • Hypereosinophilic Syndrome / blood
  • Hypereosinophilic Syndrome / complications
  • Hypereosinophilic Syndrome / pathology*
  • Interleukin-2 Receptor alpha Subunit / analysis
  • Mast Cells / chemistry
  • Mast Cells / pathology*
  • Mastocytosis, Systemic / complications
  • Mastocytosis, Systemic / pathology*
  • Mutation
  • Paraproteinemias / etiology
  • Proto-Oncogene Proteins c-kit / analysis
  • Proto-Oncogene Proteins c-kit / genetics
  • Prurigo / complications
  • Skin / pathology*
  • Tryptases / analysis
  • Tryptases / blood

Substances

  • Interleukin-2 Receptor alpha Subunit
  • Proto-Oncogene Proteins c-kit
  • Tryptases