Background: Muir-Torre syndrome (MTS) is an autosomal dominant disorder characterized by the concurrent or sequential development of at least 1 sebaceous gland tumor or keratoacanthoma and 1 or more internal malignancies. It is actually considered as a variant of hereditary nonpolyposis colorectal cancer (HNPCC) as both MTS and HNPCC are more often associated with germline mutations in the DNA mismatch repair (MMR) gene. Objective and Methods: We report the case of MTS diagnosed after the occurrence of a solitary subungual keratoacanthoma (SKA) in a man with a well-known family history of HNPCC and who is carrying a constitutional 1–7 deletion in the MSH2 MMR gene. Results: The link between the germline mutation and the skin tumor was reinforced by immunohistochemical staining. MSH2 immunoreactivity was decreased in SKA tumoral cells when compared to normal adjacent epidermis and to 5 cases of sporadic KA used as controls. Conclusion: This observation indicates that a solitary SKA may be the first clinical manifestation of MTS and brings up the relevance for regular dermatological screening for MTS-associated skin lesions among gene carriers (and symptomatic individuals) for HNPCC syndrome.

Keywords:
Solitary subungual keratoacanthoma, Hereditary nonpolyposis colorectal cancer, Muir-Torre syndrome, MSH2 immunostaining
1.
Lynch HT, Lynch JF, Lynch PM, Attard T: Hereditary colorectal cancer syndromes: molecular genetics, genetic counseling, diagnosis and management. Fam Cancer 2008;7:27–39.
2.
Ponti G, Ponz de Leon M: Muir-Torre syndrome. Lancet Oncol 2005;6:980–987.
3.
Lynch HT, Fusaro RM, Lynch PM: Sebaceous skin lesions as clues to hereditary non-polyposis colorectal cancer. J Invest Dermatol 2006;126:2158–2159.
4.
Ponti G, Losi L, Pedroni M, Lucci-Cordisco E, Di Gregorio C, Pellacani G, et al: Value of MLH1 and MSH2 mutations in the appearance of Muir-Torre syndrome phenotype in HNPCC patients presenting sebaceous gland tumors or keratoacanthomas. J Invest Dermatol 2006;126:2302–2307.
5.
Piñol V, Castells A, Andreu M, Castellví-Bel S, Alenda C, Llor X, et al, Gastrointestinal Oncology Group of the Spanish Gastroenterological Association: Accuracy of revised Bethesda guidelines, microsatellite instability, and immunohistochemistry for the identification of patients with hereditary nonpolyposis colorectal cancer. JAMA 2005;293:1986–1994.
6.
Akhtar S, Oza KK, Khan SA, Wright J: Muir-Torre syndrome: case report of a patient with concurrent jejunal and ureteral cancer and a review of the literature. J Am Acad Dermatol 1999;41:681–686.
7.
Ponti G, Losi L, Di Gregorio C, Roncucci L, Pedroni M, Scarselli A, et al: Identification of Muir-Torre syndrome among patients with sebaceous tumors and keratoacanthomas: role of clinical features, microsatellite instability, and immunohistochemistry. Cancer 2005;103:1018–1025.
8.
Mathiak M, Rütten A, Mangold E, Fischer HP, Ruzicka T, Friedl W, 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 2002;26:338–343.
9.
Sinha A, Marsh R, Langtry J: Spontaneous regression of subungual keratoacanthoma with reossification of underlying distal lytic phalynx. Clin Exp Dermatol 2005;30:20–22.
10.
Scarani P, Ghigi G, Bertarelli C, Eusebi V: Subungual keratoacanthoma: a variant of verrucous squamous cell carcinoma of the skin. Appl Pathol 1983;1:339–342.
11.
Baran R, Goettmann S: Distal digital keratoacanthoma: a report of 12 cases and a review of the literature. Br J Dermatol 1998;139:512–515.
12.
Keeney GL, Banks PM, Linscheid RL: Subungual keratoacanthoma: report of a case and review of the literature. Arch Dermatol 1988;124:1074–1076.
13.
Machin P, Catasus L, Pons C, Muñoz J, Conde-Zurita JM, Balmaña J, et al: Microsatellite instability and immunostaining for MSH-2 and MLH-1 in cutaneous and internal tumors from patients with the Muir-Torre syndrome. J Cutan Pathol 2002;29:415–420.
14.
Tischkowitz M, Gologan A, Srolovitz H, Khanna M, Foulkes WD: Muir-Torre syndrome and MSH2 mutations: the importance of dermatological awareness. Br J Cancer 2006;95:243–244.
15.
Thiffault I, Hamel N, Pal T, McVety S, Marcus VA, Farber D, et al: Germline truncating mutations in both MSH2 and BRCA2 in a single kindred. Br J Cancer 2004;90:483–491.
16.
South CD, Hampel H, Comeras I, Westman JA, Frankel WL, de la Chapelle A: The frequency of Muir-Torre syndrome among Lynch syndrome families. J Natl Cancer Inst 2008;100:277–281.
© 2009 S. Karger AG, Basel
2009
Copyright / Drug Dosage / Disclaimer
Copyright: All rights reserved. No part of this publication may be translated into other languages, reproduced or utilized in any form or by any means, electronic or mechanical, including photocopying, recording, microcopying, or by any information storage and retrieval system, without permission in writing from the publisher.
Drug Dosage: The authors and the publisher have exerted every effort to ensure that drug selection and dosage set forth in this text are in accord with current recommendations and practice at the time of publication. However, in view of ongoing research, changes in government regulations, and the constant flow of information relating to drug therapy and drug reactions, the reader is urged to check the package insert for each drug for any changes in indications and dosage and for added warnings and precautions. This is particularly important when the recommended agent is a new and/or infrequently employed drug.
Disclaimer: The statements, opinions and data contained in this publication are solely those of the individual authors and contributors and not of the publishers and the editor(s). The appearance of advertisements or/and product references in the publication is not a warranty, endorsement, or approval of the products or services advertised or of their effectiveness, quality or safety. The publisher and the editor(s) disclaim responsibility for any injury to persons or property resulting from any ideas, methods, instructions or products referred to in the content or advertisements.
You do not currently have access to this content.