SG12 Unmasking of Muir–Torre syndrome following tacrolimus-based immunosuppression

Abstract

Lynch syndrome is an autosomal dominant cancer predisposition syndrome caused by pathogenic variants in mismatch repair genes. Its cutaneous variant, Muir–Torre syndrome (MTS), is characterized by sebaceous neoplasms and may provide an important diagnostic clue. Immunosuppression has been proposed as a factor unmasking latent disease. We report a 52-year-old man with a history of childhood Escherichia coli-associated haemolytic uraemic syndrome resulting in chronic renal impairment and subsequent renal transplantation. Following transplantation, he was commenced on a tacrolimus-based immunosuppressive regimen. Within 2 years of commencing immunosuppression, he developed multiple slowly progressive, flesh-coloured papules and nodules involving the face and scalp. Several lesions were excised, with histological examination confirming sebaceous tumours. Immunohistochemistry demonstrated loss of MSH2 and MSH6 protein expression. Subsequent germline genetic testing identified a disease-causing splice-site variant in MSH2 (c.212–1G>A), establishing a diagnosis of Lynch syndrome with cutaneous involvement (MTS). Further evaluation identified a tubular adenoma with low-grade dysplasia on colonoscopy following a positive faecal immunochemical test. The patient also developed a moderately differentiated cutaneous squamous cell carcinoma of the face, treated surgically. Family history revealed multiple maternal relatives with Lynch syndrome-associated malignancies. Calcineurin inhibitors such as tacrolimus impair immuno­surveillance and have been implicated in the development of sebaceous neoplasms in individuals with mismatch repair deficiency. Nine similar cases of immunosuppression unmasking MTS have been reported, including one closely resembling ours. In that report, eruptive sebaceous tumours developed following tacrolimus exposure in a transplant recipient, leading to diagnosis of MTS. These observations support the concept that tacrolimus-­based immunosuppression may unmask latent Lynch syndrome rather than serve as a direct oncogenic trigger. This case underscores the importance of recognizing sebaceous neoplasms as cutaneous markers of Lynch syndrome, particularly in immunosuppressed patients. Early dermatological recognition enables timely genetic diagnosis, targeted cancer surveillance and optimization of long-term patient care.