1651 Colon, Urothelial and Sebaceous Malignancy All in One: A Rare Presentation of Muir-Torre Syndrome

Abstract

INTRODUCTION: Muir-Torre syndrome (MTS) is a rare autosomal-dominant condition and phenotypic variant of Lynch syndrome caused by mutations in DNA mismatch repair genes MSH2, MSH6, and MLH1. Clinical diagnostic criteria include the presence of at least one sebaceous gland neoplasm and one visceral malignancy, often colonic or genitourinary. Compared to Lynch syndrome, the prevalence of MTS is likely underreported. We present a unique case of a patient with incidental findings of multiple visceral malignancies associated with skin cancer. CASE DESCRIPTION/METHODS: A 57-year-old Caucasian man presented for surveillance colonoscopy. His family history was significant for father with colon cancer at age 50, lung, and renal cancer. The patient was diagnosed with sebaceous adenocarcinoma, invasive squamous cell, and basal cell carcinomas requiring excisional surgery at age 46. Screening colonoscopy at that time was normal, with repeat after 7 years noting diminutive sigmoid tubular adenomas that were resected. Current colonoscopy revealed 14 colon polyps, multiple with high grade dysplasia, and an invasive sigmoid adenocarcinoma. Staging CT A/P was negative for metastatic disease. CEA was normal. The patient opted for left hemicolectomy instead of total proctocolectomy. Tumor pathology revealed moderately differentiated adenocarcinoma with negative margins (pT4N0M0). Colon cancer genetic testing showed lack of expression of MSH2/MSH6 and germline MSH2 mutation, confirming the diagnosis of MTS. A month later he developed hematuria and acute kidney injury that culminated in a new diagnosis of invasive high-grade urothelial carcinoma. Neoadjuvant chemotherapy was started with plan for cystectomy. DISCUSSION: MTS is a rare condition that warrants early recognition, regular follow-up and observation for new malignancies. Our case highlights the importance of awareness and the need for early, universal screening in high-risk individuals. MTS patients should undergo screening colonoscopy at ages 20–25 with surveillance every year thereafter to offer mortality benefit. If colon cancer is diagnosed, total rather than partial colectomy is preferred due to a high metachronous cancer rate of 25%. Patients and relatives should be counseled on increased risk of future malignancies. Reconstruction of family history may allow for the identification and selection of patients in whom to proceed with clinical, molecular, and immunohistochemical analysis. Clinicians must therefore be cognizant of this disease and its enduring effects.