The significance of DNA mismatch repair genes in the diagnosis and management of periocular sebaceous cell carcinoma and Muir-Torre syndrome

Objective The aims of this study were to determine the significance of expression of DNA mismatch repair proteins in detecting systemic malignancies in a series of patients with periocular sebaceous cell carcinoma and to determine the clinical characteristics and frequency of Muir-Torre syndrome in this cohort. Design The study was a retrospective non-comparative interventional case series. Participants 31 patients with histologically proven sebaceous cell carcinoma of the eyelid participated in the study. Methods The authors made use of retrospective chart review and immunohistochemical staining of specimens. Main outcome measures The main outcome measures are as follows: location, tumour size, sites of origin, growth patterns, management, histopathological and immunohistochemical findings, metastasis, other visceral malignancies and mortality. Results The median age of presentation of the 31 patients in this study was 71 years (range 35-92 years). There was a near-equal gender distribution (M:F-14:17). The average follow-up was 72 months. Seventeen patients had tumours arising from the upper lid, 13 from the lower lid and 1 from the caruncle. Nine patients had clinical Muir-Torre syndrome. Four patients were positive for microsatellite instability complexes and four were negative. Histologically, 14 patients had a high-grade tumour, 13 were intermediate grade and 4 were low grade. Based on the in situ pattern, six patients had a bowenoid pattern, five had both bowenoid and pagetoid patterns and two had a pagetoid pattern. Eighteen patients had no in situ disease detected. Twenty-one patients were alive without disease, and two were alive with disease. Six patients had died, five from other causes and one from the disease. Conclusions Visceral malignancies are common in patients with periocular sebaceous cell carcinoma. Approximately one in eight demonstrated a heritable risk for further visceral malignancy through failure to express DNA mismatch repair proteins. Diagnosis of periocular sebaceous cell carcinoma should prompt physicians to search for other associated malignancies. Immunohistochemical characterisation of these sebaceous lesions is useful in identifying increased risk in affected patients and family members.