A Meta-Analysis of the Prevalence of Mismatch Repair Germline Mutations in Patients With Sebaceous Neoplasms: Are We Missing an Opportunity for Lynch Syndrome Detection?

Sebaceous neoplasms are rare skin tumours linked with Lynch syndrome (LS), particularly the Muir-Torre syndrome (MTS) variant. They present an opportunity for early LS detection due to their association with mismatch repair (MMR) gene pathogenic variants. This study aims to provide an accurate estimate of LS prevalence among patients with sebaceous adenomas and carcinomas. We performed a systematic review and meta-analysis of studies published between 2005 and 2024. Eligible studies utilised germline testing for MMR mutations. The studies were stratified by diagnostic approach and analysed using proportional meta-analysis to determine LS prevalence. Subgroup analyses were conducted by population characteristics and diagnostic criteria. Lynch Syndrome prevalence among patients with sebaceous neoplasms varied across the 9 studies that met eligibility criteria, ranging from 0.8% to 29.0%. LS among patients with sebaceous carcinomas was 6.6% (95% CI: 3.6%-9.5%). Population-based studies had a higher LS identification rate (10.6%), while multi-centre and single-centre studies reported lower rates. Studies using a history suggestive of MTS or MMR-deficient tumours as criteria showed the highest LS prevalence. Male patients had higher sebaceous neoplasms prevalence, with LS-positive cases presenting at a younger age than typical sporadic cases. Our findings highlight the potential for LS detection in patients with sebaceous neoplasms, particularly those with MMR deficiency or a suggestive MTS history. Increased testing in this group could facilitate early LS detection, improving outcomes through screening and preventive strategies. Universal MMR testing for sebaceous tumours warrants consideration as a strategy to capture at-risk LS patients.