N42: Improving Triaging Of Patients With Sebaceous Neoplasia For The Identification Of Muir-Torre/Lynch Syndrome

I. M. Winship1, M. D. Walsh2, H. Jayasekara3, T. Green3, M. Clendenning3, K. Mahmood3, B. J. Pope3, D. J. Park3, A. K. Win3, K. Storey1, J. Taylor1, M. A. Jenkins3, D. D. Buchanan3

1 – Royal Melbourne Hospital. 2 – Sullivan Nicolaides Pathology. 3 -University of Melbourne.


Aim: Loss of expression of mismatch repair (MMR) proteins is frequently observed in sebaceous skin lesions, but the positive predictive value of MMR-deficiency for identifying a germline MMR gene mutation is low.  Determining which sebaceous neoplasms should be tested for MMR protein expression and of those with MMR-deficiency, which should undergo subsequent germline MMR gene mutation testing, currently presents significant clinical challenges.

Method: An audit between January 2009 and April 2014 was undertaken of a single pathology practice in Queensland, Australia of all sebaceous lesions where pathologist-initiated MMR IHC had been performed comprising 928 lesions from 882 individuals.  A subset of 125 participants provided a blood sample for germline MMR and MUTYH gene testing.  Individuals and their lesions were further characterised for differences in gender, age at diagnosis, lesion type and anatomic location, personal and family history of cancer, and stratified by MMR status.

Results: MMR-deficiency, observed in 282 of the 919 lesions included (30.7%), and was most common in sebaceous adenomas (210/282; 74.5%).  Loss of MSH2/MSH6 protein expression was the most common (187/282; 66.3%).  Characteristics of germline MMR mutation carriers will be presented.

Conclusion: Further elucidation of genotype-phenotype correlations in sebaceous neoplasia should result in improved triaging for MMR testing and clinical decision making.