SG02 Screening and genetic testing pathways for sebaceous tumours to identify Muir–Torre syndrome

Abstract

Muir–Torre syndrome (MTS) is a variant of Lynch syndrome caused by germline mutations in mismatch repair (MMR) genes (MLH1, MSH2, MSH6 and PMS2). Sebaceous tumours occur in up to 9% of patients with Lynch syndrome, yet national MMR and germline testing rates are low. In 2024 the Lynch Syndrome UK Sebaceous Carcinoma Workshop Group recommended reflex MMR testing in sebaceous carcinomas. Our centre has implemented reflex testing for all sebaceous tumours since 2018, but this has not previously been formally evaluated. We assessed adherence to reflex MMR testing in sebaceous tumours at a regional NHS trust to identify potential missed cases of MTS. A retrospective review of histopathology reports (January 2019 to March 2025) containing ‘sebaceous tumour’, ‘adenoma’, ‘sebaceoma’ or ‘carcinoma’ was conducted. Case-note data recorded included demographics, clinical and histological diagnoses, MMR immunohistochemistry, germline testing and cancer history. Seventy-five patients with 104 sebaceous lesions were identified; their median age was 75 years. Fifteen patients had a history of immunosuppression. Most lesions occurred on the head and neck (80%) and were histologically sebaceous adenoma (47%), sebaceoma (27%) or carcinoma (26%). Clinical diagnosis was accurate in 33 of 118 differentials. MMR immunohistochemistry was performed in 70% of tumours (73 of 104), of which 49% showed loss of at least one MMR protein. Of 33 patients with abnormal immunohistochemistry, 45% underwent germline testing, yielding two new diagnoses of MTS. Most cases without further testing had documented reasons, with five lacking explanation. Two of 33 cases with missing tests had cancer histories consistent with Lynch syndrome. This retrospective case series shows high reflex MMR testing uptake (85%) for sebaceous carcinomas, surpassing national trends. Gaps in immunohistochemistry and germline testing remain, highlighting the need for more robust onward referral pathways. Identification of two new cases of MTS highlights the importance of heightened clinician awareness and reflex testing and validates the benefits of comprehensive screening.