1. Clinico-pathological predictors of mismatch repair deficiency in sebaceous neoplasia: A large case series from a single Australian private pathology service.
- Author
-
Walsh MD, Jayasekara H, Huang A, Winship IM, and Buchanan DD
- Subjects
- Adenoma genetics, Adenoma metabolism, Adolescent, Adult, Aged, Aged, 80 and over, Australia, Biomarkers, Tumor metabolism, Carcinoma genetics, Carcinoma metabolism, DNA-Binding Proteins genetics, DNA-Binding Proteins metabolism, Female, Humans, Immunohistochemistry, Male, Middle Aged, Mismatch Repair Endonuclease PMS2 genetics, Mismatch Repair Endonuclease PMS2 metabolism, MutL Protein Homolog 1 genetics, MutL Protein Homolog 1 metabolism, MutS Homolog 2 Protein genetics, MutS Homolog 2 Protein metabolism, Sebaceous Gland Neoplasms genetics, Young Adult, DNA Mismatch Repair, Sebaceous Gland Neoplasms metabolism
- Abstract
Background/objectives: Loss of expression of mismatch repair (MMR) proteins is frequently observed in sebaceous skin lesions and can be a herald for Lynch syndrome. The aim of this study was to identify clinico-pathological predictors of MMR deficiency in sebaceous neoplasia that could aid dermatologists and pathologists in determining which sebaceous lesions should undergo MMR immunohistochemistry (IHC)., Methods: An audit of sebaceous skin lesions (excluding hyperplasia) where pathologist-initiated MMR IHC was performed between January 2009 to December 2016 was undertaken from a single pathology practice identifying 928 lesions from 882 individuals. Lesions were further analysed for differences in gender, age at diagnosis, lesion type and anatomic location, stratified by MMR status., Results: The 882 individuals (67.7% male) had a mean (SD) age of diagnosis of 68.4 ± 13.3 years. Nearly two-thirds of the lesions were sebaceous adenomas, with 82.6% of all lesions occurring on the head and neck. MMR deficiency, observed in 282 of the 919 lesions (30.7%), was most common in sebaceous adenomas (210/282; 74.5%). MMR-deficient lesions occurred predominantly on the trunk or limbs (64.7%), compared with 23.2% in head or neck (P < 0.001). Loss of MSH2 and MSH6 protein expression was most frequent pattern of loss (187/281; 66.5%). The highest AUC for discriminating MMR-deficient sebaceous lesions from MMR-proficient lesions was observed for the ROC curve based on subgroups defined by type and anatomic location of the sebaceous lesion (AUC = 0.68)., Conclusion: The best combination of measured clinico-pathological features achieved only modest positive predictive values, sensitivity and specificity for identifying MMR-deficient sebaceous skin lesions., (© 2018 The Australasian College of Dermatologists.)
- Published
- 2019
- Full Text
- View/download PDF