Family with MSH2 mutation presenting with keratoacanthoma and precancerous skin lesions

J Dermatol. 2015 Nov;42(11):1087-90. doi: 10.1111/1346-8138.12949. Epub 2015 Jun 16.

Abstract

Muir-Torre syndrome (MTS) is a familial cancer syndrome characterized by a predisposition to keratoacanthoma (KA) and sebaceous tumors. Although MTS and hereditary non-polyposis colorectal cancer (HNPCC) share the same genetic alterations in mismatch repair (MMR) genes, the other skin lesions in MTS or HNPCC have been only rarely reported. We report a family with an MSH2 mutation c.1126_1127delTT (p.Leu376Thrfs*12). A 46-year-old male proband developed KA with sebaceous differentiation, colon cancer and gastric cancer, and fulfilled the diagnostic criteria for MTS. His 80-year-old mother, diagnosed with HNPCC, presented with multiple gastrointestinal tract cancers, Bowen's disease and actinic keratosis. Immunostaining revealed attenuated MSH2 protein expression in KA, as well as in Bowen's disease and actinic keratosis lesions. These findings suggest that MMR gene abnormality is also critical in the development of benign or malignant cutaneous tumors such as actinic keratosis and Bowen's disease in MTS/HNPCC patients.

Keywords: MLH1; MSH6; Muir-Torre syndrome; hereditary non-polyposis colorectal cancer; mismatch repair genes.

Publication types

  • Case Reports
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Aged, 80 and over
  • Bowen's Disease / genetics
  • Bowen's Disease / pathology
  • Female
  • Humans
  • Keratoacanthoma / genetics*
  • Keratoacanthoma / pathology
  • Keratosis, Actinic / genetics
  • Keratosis, Actinic / pathology
  • Male
  • Middle Aged
  • Muir-Torre Syndrome / genetics
  • Muir-Torre Syndrome / pathology
  • MutS Homolog 2 Protein / genetics*
  • Mutation
  • Pedigree
  • Precancerous Conditions / genetics
  • Precancerous Conditions / pathology
  • Skin Neoplasms / genetics*
  • Skin Neoplasms / pathology

Substances

  • MSH2 protein, human
  • MutS Homolog 2 Protein