Identification of Muir-Torre syndrome among patients with sebaceous tumors and keratoacanthomas: role of clinical features, microsatellite instability, and immunohistochemistry

Cancer. 2005 Mar 1;103(5):1018-25. doi: 10.1002/cncr.20873.


Background: The Muir-Torre syndrome (MTS) is an autosomal-dominant genodermatosis characterized by the presence of sebaceous gland tumors, with or without keratoacanthomas, associated with visceral malignancies. A subset of patients with MTS is considered a variant of the hereditary nonpolyposis colorectal carcinoma, which is caused by mutations in mismatch-repair genes. The objective of the current study was to evaluate whether a combined clinical, immunohistochemical, and biomolecular approach could be useful for the identification of Muir-Torre syndrome among patients with a diagnosis of sebaceous tumors and keratoacanthomas.

Methods: The authors collected sebaceous skin lesions and keratoacanthomas recorded in the files of the Pathology Department of the University of Modena during the period 1986-2000. Through interviews and examination of clinical charts, family trees were drawn for 120 patients who were affected by these skin lesions.

Results: Seven patients also were affected by gastrointestinal tumors, thus meeting the clinical criteria for the diagnosis of MTS. In the MTS families, a wide phenotypic variability was evident, both in the spectrum of visceral tumors and in the type of skin lesions. Microsatellite instability was found in five MTS patients: These patients showed concordance with immunohistochemical analysis; moreover, a constitutional mutation in the MSH2 gene was found in 1 patient. Lack of expression of MSH2/MSH6 or MLH1 proteins was evident in the skin lesions and in the associated internal malignancies of 3 patients and 2 patients with MTS, respectively.

Conclusions: The clinical, biomolecular, and immunohistochemical characterization of sebaceous skin lesions and keratoacanthomas may be used as screening for the identification of families at risk of MTS, a disease that is difficult to recognize and diagnose.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adult
  • Aged
  • Colorectal Neoplasms, Hereditary Nonpolyposis / diagnosis
  • Colorectal Neoplasms, Hereditary Nonpolyposis / genetics
  • Female
  • Genomic Instability
  • Humans
  • Immunohistochemistry
  • Keratoacanthoma / diagnosis*
  • Keratoacanthoma / genetics
  • Male
  • Microsatellite Repeats
  • Middle Aged
  • Mutation
  • Pedigree
  • Sebaceous Gland Neoplasms / diagnosis*
  • Sebaceous Gland Neoplasms / genetics
  • Skin Neoplasms / diagnosis
  • Syndrome