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Brooke-Spiegler syndrome represents an autosomal dominant disease characterized by the occurrence of multiple cylindromas, trichoepitheliomas and (sporadically) spiroadenomas. Patients with Brooke-Spiegler syndrome are also at risk of developing tumors of the major and minor salivary glands. Patients with Brooke-Spiegler syndrome have various mutations in the CYLD gene, a tumor-suppressor gene located on chromosome 16q. To date, 68 unique CYLD mutations have been identified. We describe two families with Brooke-Spiegler syndrome, one with familial cylindromatosis and one with multiple familial trichoepithelioma, which showed wide inter-family phenotypic variability. Analysis of germline mutations of the CYLD and PTCH genes was performed using peripheral blood. In addition, formalin-fixed paraffin-embedded tumor samples were analyzed for PTCH somatic mutations and cylindroma cell cultures were obtained directly from patients for further growth and analysis. Clinically, the major features of Brooke-Spiegler syndrome include the presence of heterogeneous skin tumors and wide inter- and intra-familial phenotypic variability. Histopathologically, both cylindromas and trichoepitheliomas were found in affected individuals. Mutations or loss of heterozygosity was not found in CYLD and PTCH genes. In CYLD and PTCH mutation-negative patients, other genes may be affected and further studies are needed to clarify whether these patients may be affected by de novo germline mutations., (Copyright © 2011 John Wiley & Sons A/S.)

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., (2005 American Cancer Society.)

Background: Reports on the frequency of multiple carcinomas of the colon and rectum have varied from 3-4% to more than 10% of all tumors of the large bowel., Methods: We reviewed the files of a specialized colorectal cancer registry with the following objectives: a) to determine the frequency of multiple tumors (synchronous or metachronous) in the general population; b) to compare these values with those observed in patients with hereditary nonpolyposis colorectal carcinoma (HNPCC); and c) to evaluate the clinical outcome of patients with multiple tumors and the role of other clinical parameters in the development of these neoplasms., Results: From 1984 to 1992, 53 patients with multiple tumors (of 1298 registered patients, 4%) had large bowel carcinoma; 33 (2.5%) were synchronous and 20 (1.5%) metachronous. The total number of multiple colorectal carcinomas was 95, which was 7% of all registered colorectal carcinomas (1337 carcinomas in 1298 patients). Multiple tumors occurred significantly more often in patients with HNPCC than in those with sporadic carcinomas (P < 0.001); this increased prevalence was more marked for metachronous lesions, which occurred almost 4 times more often in patients with HNPCC (5.8% vs. 1.3%; P < 0.001). The average interval of time between the first and the second malignancy was 8.7 years; there was no significant difference between hereditary and sporadic tumors. Patients with synchronous tumors did not show appreciable differences in survival when compared with individuals who had single neoplasms. In contrast, a poor clinical outcome was observed in patients with metachronous tumors after the development of the second carcinoma. Finally, polypoid adenomas of the large bowel were found significantly more often in patients with multiple primary tumors than in those with a single tumor., Conclusions: These results emphasize the importance of preoperative pancolonoscopy for the identification of possible synchronous tumors (both benign and malignant) and long-lasting endoscopic follow-up for the detection of recurrent or metachronous lesions. The conclusions are even more pertinent for patients with HNPCC, whose risk of metachronous tumors is significantly higher than that of patients with sporadic carcinoma.