Discordant immunohistochemistry in an unusual MLH1 gene variant in a case of Lynch syndrome

Highlights • Screening for Lynch syndrome mostly is done by IHC or MSI testing. • They are sensitive, specific and also mostly concordant with each other as well as genetic testing. • Discordance between screening and genetic testing, although rare is not unknown. • In such cases, we must proceed with germline DNA testing by Next Generation Sequencing.
Immunohistochemistry for mismatch repair proteins and microsatellite instability testing are recommended screening methods for Lynch syndrome. They have a good sensitivity and specificity, allowing for directed genetic testing and diagnosis. We report a case of Lynch syndrome with retained MMR protein expression who later showed an MLH1 gene variant on genetic testing (Next Generation Sequencing) requested because of the clinical presentation of metachronous colonic and endometrial carcinoma. This report makes the case for strong clinical suspicion and directed genetic testing despite initial screen negative results.