Identifying Lynch Syndrome in Two Families with Classical Hereditary Breast and Ovarian Cancer Syndrome Phenotype: A Case Report

Abstract

Introduction: Although the consideration of breast cancer as spectrum of Lynch syndrome has not been clearly delineated, multigene panel studies suggest that individuals with Lynch syndrome may have an increased risk for breast cancer and may present with a Hereditary Breast and Ovarian Cancer Syndrome (HBOC) phenotype. In this case report, we present two cases who presented to the genetics clinic with classical HBOC phenotype and who didn’t meet Lynch syndrome testing criteria and were later found to be negative for BRCA mutations but positive for Lynch syndrome through multigene panel testing. Case 1: A 57-years-old French-Canadian female with high grade serous ovarian cancer with intact MMR nuclear expression and family history of young onset breast cancer was referred to the genetics clinic to be evaluated for HBOC. The patient was later found to be negative for BRCA mutations but positive for a pathogenic mutation in the MSH2 gene through multigene panel. Case 2: A 59-years-old unaffected patient of Ashkenazi Jewish descent with bilateral fibrocystic breast who presented to our clinic with family history of young onset breast and gastric cancers. Through multi-gene panel, the patient was found to be negative for BRCA genes mutations but positive for a pathogenic mutation in the PMS2 gene. Discussion and Conclusion: This report draws the attention on the importance of multigene panels in identifying individuals with Lynch syndrome who present with HBOC like phenotype. In addition, it suggests that the current Lynch syndrome diagnostic criteria’s may not be sufficiently sensitive in identifying MMR mutations in HBOC like families who might miss the opportunity from being identified and benefit from risk reducing strategies, targeted therapies and reproductive options. We therefore suggest a re-consideration of the available Lynch syndrome testing criteria’s and we suggest that MMR testing to be considered in families with breast and ovarian cancer and HBOC like phenotype.