Mismatch Repair Deficiency in Benign and Atypical Ocular Sebaceous Neoplasms: Implications for Muir-Torre Screening and Classification.

Abstract

To assess mismatch repair (MMR) deficiency in ocular sebaceous neoplasms that are not poorly differentiated sebaceous carcinomas, and to explore the characteristics of atypical lesions based on clinicopathologic and immunophenotypic findings. A retrospective observational case series. Consecutive cases of 14 benign or atypical ocular sebaceous neoplasms diagnosed from January 2018 to June 2025. Clinical and pathological data were reviewed and compared among three groups: sebaceous adenomas (n = 6), atypical sebaceous neoplasms (n = 3), and sebaceomas (n = 5). The association with Muir-Torre syndrome (MTS) was also evaluated. Clinical and histomorphological features (including growth pattern and ulceration), immunohistochemistry (MMR protein status, epithelial membrane antigen, adipophilin, Ki-67, and p53), and Mayo MTS risk scores. All atypical sebaceous neoplasms and 67% of adenomas were MMR-deficient, most commonly concurrent MSH2/MSH6 loss, versus none in sebaceomas (P = .013). Atypical neoplasms also shared other key clinicopathologic features with adenomas, including ulceration, lobular/papillary growth, high proliferation, and strong epithelial membrane antigen expression, but differed from sebaceomas (all P <.05). Six patients had personal or family histories of visceral malignancy, and 4 had a Mayo score ≥2. Ocular sebaceous neoplasms showed a relatively high rate of MMR deficiency. Lobular/papillary sebaceous adenomas and atypical neoplasms were frequently MMR-deficient and may carry implications for MTS, whereas organoid-pattern sebaceomas were typically MMR-proficient and showed no clinical evidence of MTS. Moreover, atypical sebaceous neoplasms, which are intermediate-grade and MMR deficiency-associated, may be classified separately from sebaceomas.