Mismatch repair protein deficiency in sebaceous neoplasms and its associations: a two-centre retrospective analysis in Iran

Background Sebaceous neoplasms in Muir–Torre syndrome (MTS), a subtype of Lynch syndrome, tend to occur before visceral malignancies. MTS is associated with defects in mismatch repair (MMR) proteins, such as MLH1 and MSH2. Early screening for MMR deficiencies in sebaceous neoplasms has been proposed to aid in identifying MTS. Objectives To determine, using immunohistochemistry (IHC), the prevalence of MMR defects in sebaceous neoplasms in an Iranian cohort. Methods Samples of sebaceous tumours from tissue registries at two hospitals, collected between March 2014 and March 2019, were analysed using IHC for MLH1 and MSH2. Data analyses were performed using SPSS software version 21. Results Twenty-five sebaceous neoplasms from 23 individuals were studied. Overall, 12 (48%) samples showed abnormal IHC results. Specifically, six (24%) samples had MSH2 deficiency, three (12%) exhibited MLH1 deficiency and another three (12%) were deficient in both. Two patients each had two sebaceous neoplasms; in one patient, both tumours showed MSH2 deficiency, while in the other, both tumours exhibited loss of expression for both MMR proteins. Neither tumour type nor patient sex was linked to MMR deficiency. However, tumours outside the head and neck region were significantly associated with MSH2 deficiency. Additionally, younger patients had a higher prevalence of MSH2 deficiency. Conclusions Multiple sebaceous tumours, tumours presenting at a younger age and tumours located outside the head and neck area could be the most important predictors of IHC abnormalities. After validation by larger future studies, these predictors should be considered for targeted MTS screening strategies.