Abstract 4854: DNA mismatch repair deficiency in sebaceous skin tumors: a large case series from a single pathology practice.
Authors: Walsh Michael D. , Edwards Rhonda J. , Whitehead Kevin J. , Gattas Michael R. , Buchanan Daniel D. 
Published: August 2014

Abstract
Muir Torre syndrome is characterized by the presence of sebaceous skin tumours and/or multiple keratoacanthomas, as well as a personal or family history of internal malignancies. It is now recognized that many of these families are a phenotypic variant of Lynch syndrome in which there is an inherited genetic defect in one of the DNA mismatch repair (MMR) genes (MLH1, MSH2, MSH6 or PMS2), and that mutation carriers may be identified through testing sebaceous skin tumours for loss of protein expression. In many cases, however, loss of MMR expression in skin tumours may be sporadic in nature, and further study is required to determine whether clinicopathological features or other tumor molecular changes can refine the process of triaging patients for expensive genetic testing for Lynch syndrome. The aim of this retrospective study was to assess the results of reflex immunohistochemical screening of sebaceous skin tumours in order to identify associations between clinicopathological features of these tumours including subtypes, tumor location, and specific protein(s) showing loss of expression.An audit of sebaceous tumours tested by Immunohistochemistry (IHC) for MMR expression identified 428 individuals (149 females, 279 males) with one or more lesions tested between January 2009 and April 2012, at Sullivan Nicolaides Pathology. Patients’ ages ranged from 17 to 100 years. A total of 450 skin lesions were examined: 232 sebaceous adenomas, 66 sebaceous carcinomas, 82 sebaceomas, 27 sebaceous hyperplasias, 12 sebaceous tumours NOS, as well as 14 squamous cell and 13 basal cell carcinomas with sebaceous differentiation, and 4 keratoacanthomas. Excluding unclassified sebaceous tumours, MMR deficiency was detected in a total of 129/438 (29%) lesions. Of the MMR deficient tumours 97 showed loss of MSH2 and MSH6 (75%), with MLH1/PMS2 loss observed in 21 (16%) cases, solitary MSH6 loss in 10 (8%), and PMS2 loss alone in one (1%). No statistical association was found between MMR deficiency and gender (81/279 (29%) males; 37/149 (25%) females), or patient age (68 yr MMR deficient vs. 65 yr MMR normal). The majority of tumours were located on the head and neck (366/447: 82%), while 52 (12%) were on the trunk and 19 (4%) on the limbs. While most MMR deficient tumours were located on the head and neck (84/366; 23%), MMR loss of expression was more commonly observed in lesions on the trunk (36/62; 58%) and limbs (9/19; 47%), and MLH1/PMS2 and MSH6 only losses were proportionally more common in non-head and neck sites. MMR loss was most commonly observed in sebaceous adenomas (84/232: 36%) and sebaceomas (22/82: 27%), and less frequently in other sebaceous lesions. We have identified MMR deficiency in a significant number of sebaceous skin lesions, yet it remains unclear from the current data what proportion of these patients have a germline mutation in an MMR gene and thus have Muir Torre (Lynch) syndrome.
Citation Format: Michael D. Walsh, Rhonda J. Edwards, Kevin J. Whitehead, Michael R. Gattas, Daniel D. Buchanan. DNA mismatch repair deficiency in sebaceous skin tumors: a large case series from a single pathology practice. [abstract]. In: Proceedings of the 104th Annual Meeting of the American Association for Cancer Research; 2013 Apr 6-10; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2013;73(8 Suppl):Abstract nr 4854. doi:10.1158/1538-7445.AM2013-4854