Lynch syndrome and urologic malignancies: a contemporary review

An overview of urologic malignancies in Lynch syndrome and the current state of research.

Upper tract urothelial carcinoma (UTUC) is the third most common malignancy in Lynch syndrome. Establishment and utilization of a sensitive and practical screening method for Lynch syndrome in patients presenting with UTUC is overdue. Next-generation sequencing to evaluate for microsatellite instability (MSI) and detect mutations of mismatch repair (MMR) genes may be the future of Lynch syndrome screening. Epidemiologic data and molecular characterization suggest bladder urothelial carcinoma (BUC) and prostate cancer (PCA) as unrecognized components of Lynch syndrome. Small studies suggest that Lynch syndrome may predispose individuals to adrenocortical carcinoma. Testicular cancer literature focuses on characterizing MSI and MMR gene expression as it relates to chemotherapy sensitivity; outcomes suggest a potential avenue to investigate its relationship to Lynch syndrome.

Patients with Lynch syndrome have an increased risk of urologic malignancies, including UTUC and likely BUC and PCA. BUC and PCA have a lower penetrance than UTUC for unknown reasons. Established Lynch syndrome-associated genitourinary tumors will necessitate the development of methods to diagnose Lynch syndrome in patients presenting with these malignancies, in addition to establishing screening guidelines for patients with Lynch syndrome-associated genitourinary tumors.