1. ¹Department of Internal Medicine, Division of Dermatology, University of Modena and Reggio Emilia, Modena, Italy
2. ²Department of Pathology, University of Modena and Reggio Emilia, Modena, Italy
3. ³Department of Internal Medicine, Division of Internal Medicine, University of Modena and Reggio Emilia, Modena, Italy
4. ⁴Department of Clinical Pathophysiology, Section of Medical Genetics, University of Florence, Firenze, Italy
5. ⁵Division of Pathology, Carpi General Hospital, Carpi, Modena, Italy

Correspondence: Dr Giovanni Ponti, Department of Internal Medicine, Division of Dermatology, University of Modena and Reggio Emilia, Via del Pozzo 71, Policlinico, Modena 41100, Italy. E-mail: ponti.giovanni@unimo.it

Received 12 April 2006; Revised 16 May 2006; Accepted 22 May 2006; Published online 6 July 2006.

Abstract

Hereditary non-polyposis colorectal cancer (HNPCC) is an autosomal-dominant disorder characterized by predisposition to colorectal cancer and extracolonic malignancies, frequent multiple primary tumors in the same patient, and early age of cancer onset. A main clinical variant of Lynch syndrome, Muir–Torre syndrome (MTS) is characterized by the association between one or more visceral malignancies, with at least one sebaceous skin tumor or keratoacanthoma. In our study, we have screened a cohort of 538 HNPCC patients, related to 57 HNPCC families, to detect sebaceous skin tumors and keratoacanthomas and the role of mismatch repair (MMR) genes, MLH1, MSH2, and MSH6, in their pathogenesis. Among the 57 HNPCC families, we have identified four MTS families and one suspected MTS family, in which sebaceous carcinoma was found in one HNPCC mutation carrier subject who did not show visceral malignancy. In four of these families, linked to two MLH1 mutations and to two MSH2 mutations, biomolecular characterization showed concordance among immunohistochemistry analysis and gene mutations. The evidences of our investigations show that MLH1 and MSH2 gene mutations have an equivalent etiopathological role both for Lynch syndrome and for MTS; hence, we propose a broadened clinical criteria for definition of Lynch syndrome that will include sebaceous adenoma, carcinoma, and keratoacanthoma.