Genetics of Skin Cancer (PDQ®): Genetics - Health Professional Information [NCI] - Rare Skin Cancer Syndromes
While the commonly noted sebaceous hyperplasia has not been associated with MTS, any sebaceous lesion with atypical or difficult to classify histologic features should prompt further exploration of the patient's family and personal medical history. Consideration should be given to referring patients with sebaceous neoplasms to medical geneticists or gastroenterologists to evaluate further for Lynch syndrome. While the diagnosis of visceral malignancy precedes that of cutaneous sebaceous neoplasms in the majority of patients, 22% of patients develop cutaneous sebaceous neoplasms first, offering an opportunity for visceral malignancy screening. Current diagnosis of MTS is based upon clinical criteria but may be supported by immunohistochemical staining for MSH2, MLH1, and MSH6 as a screening mechanism prior to molecular genetic analysis.[12,14,15,16,18] Genetic counseling and testing for the patient and family members, with appropriate visceral malignancy screening regimens, should be pursued.
Level of evidence: 3
- Bowen S, Gill M, Lee DA, et al.: Mutations in the CYLD gene in Brooke-Spiegler syndrome, familial cylindromatosis, and multiple familial trichoepithelioma: lack of genotype-phenotype correlation. J Invest Dermatol 124 (5): 919-20, 2005.
- Burrows NP, Jones RR, Smith NP: The clinicopathological features of familial cylindromas and trichoepitheliomas (Brooke-Spiegler syndrome): a report of two families. Clin Exp Dermatol 17 (5): 332-6, 1992.
- Rajan N, Langtry JA, Ashworth A, et al.: Tumor mapping in 2 large multigenerational families with CYLD mutations: implications for disease management and tumor induction. Arch Dermatol 145 (11): 1277-84, 2009.
- Young AL, Kellermayer R, Szigeti R, et al.: CYLD mutations underlie Brooke-Spiegler, familial cylindromatosis, and multiple familial trichoepithelioma syndromes. Clin Genet 70 (3): 246-9, 2006.
- Welch JP, Wells RS, Kerr CB: Ancell-Spiegler cylindromas (turban tumours) and Brooke-Fordyce Trichoepitheliomas: evidence for a single genetic entity. J Med Genet 5 (1): 29-35, 1968.
- Saggar S, Chernoff KA, Lodha S, et al.: CYLD mutations in familial skin appendage tumours. J Med Genet 45 (5): 298-302, 2008.
- Harada H, Hashimoto K, Ko MS: The gene for multiple familial trichoepithelioma maps to chromosome 9p21. J Invest Dermatol 107 (1): 41-3, 1996.
- Rajan N, Trainer AH, Burn J, et al.: Familial cylindromatosis and brooke-spiegler syndrome: a review of current therapeutic approaches and the surgical challenges posed by two affected families. Dermatol Surg 35 (5): 845-52, 2009.
- Schwartz RA, Torre DP: The Muir-Torre syndrome: a 25-year retrospect. J Am Acad Dermatol 33 (1): 90-104, 1995.
- Cohen PR, Kohn SR, Kurzrock R: Association of sebaceous gland tumors and internal malignancy: the Muir-Torre syndrome. Am J Med 90 (5): 606-13, 1991.
- Cerosaletti KM, Lange E, Stringham HM, et al.: Fine localization of the Nijmegen breakage syndrome gene to 8q21: evidence for a common founder haplotype. Am J Hum Genet 63 (1): 125-34, 1998.
- Mangold E, Pagenstecher C, Leister M, et al.: A genotype-phenotype correlation in HNPCC: strong predominance of msh2 mutations in 41 patients with Muir-Torre syndrome. J Med Genet 41 (7): 567-72, 2004.
- Mathiak M, Rütten A, Mangold E, et al.: Loss of DNA mismatch repair proteins in skin tumors from patients with Muir-Torre syndrome and MSH2 or MLH1 germline mutations: establishment of immunohistochemical analysis as a screening test. Am J Surg Pathol 26 (3): 338-43, 2002.
- Mangold E, Rahner N, Friedrichs N, et al.: MSH6 mutation in Muir-Torre syndrome: could this be a rare finding? Br J Dermatol 156 (1): 158-62, 2007.
- Arnold A, Payne S, Fisher S, et al.: An individual with Muir-Torre syndrome found to have a pathogenic MSH6 gene mutation. Fam Cancer 6 (3): 317-21, 2007.
- Murphy HR, Armstrong R, Cairns D, et al.: Muir-Torre Syndrome: expanding the genotype and phenotype--a further family with a MSH6 mutation. Fam Cancer 7 (3): 255-7, 2008.
- Akhtar S, Oza KK, Khan SA, et al.: Muir-Torre syndrome: case report of a patient with concurrent jejunal and ureteral cancer and a review of the literature. J Am Acad Dermatol 41 (5 Pt 1): 681-6, 1999.
- Entius MM, Keller JJ, Drillenburg P, et al.: Microsatellite instability and expression of hMLH-1 and hMSH-2 in sebaceous gland carcinomas as markers for Muir-Torre syndrome. Clin Cancer Res 6 (5): 1784-9, 2000.