BI09 Microsatellite instability and loss of mismatch repair proteins in nonmelanoma skin cancer and treatment-resistant phenotypically distinct precancerous lesions in Muir–Torre/Lynch syndrome: a multicentre retrospective study

Abstract DNA mismatch repair (MMR) gene mutations resulting in microsatellite instability (MSI) are associated the pathogenesis of Muir–Torre syndrome (MTS), a variant Lynch (LS). It is characteristically defined by association at least one sebaceous skin neoplasm and/or keratoacanthoma and visceral malignancy. The presence cutaneous lesions plays vital role early detection preventive cancer screening disease; however, nonmelanoma cancers (NMSCs) their precursors seldom reported. We conducted retrospective multicentre study between 2011 2022 adults with confirmed genetic diagnosis MTS/LS across two specialist institutions presenting phenotypically distinct treatment-resistant precancerous NMSC loss MMR expressions consistent germline which currently not recognized diagnostic features. Median age onset precancerous/NMSC eight individuals was 57.5 years, an equal sex distribution. Lesions occurred mostly on face (n = 14), followed forearms 8), dorsum hands 9), legs 4) chest 1). Our histologically immunohistochemically examined MSI 20 NMSCs. Loss expression were found actinic keratoses (AK) 6/7), disseminated superficial porokeratosis (DSAP; n 1/2), squamous cell carcinoma 4/5) basal 4/4). Additionally, we sebaceomas atypia 2/2). In 17 lesions, mutations. also discovered that all identified had normal adjacent no expression. observations suggest MSI, abnormality, play critical development other than neoplasms this disease. To date, criteria for do include precursors, these have rarely been note clinically presentation widespread erythematous scaly resembling AK/DSAP, resistant to multiple treatments, additional recognizable clinical feature patient subgroup. This important cancer-prone immunohistochemistry testing genes should be encouraged. can powerful investigative tool as AK/DSAP easily identifiable, numerous readily accessible analysis; therefore, detecting may aid promptly. best managed multidisciplinary team close surveillance malignancies, highlighting importance routine monitoring nonsebaceous cancers.