Identifying Lynch syndrome in patients with endometrial carcinoma: shortcomings of morphologic and clinical schemas.
It has been suggested that reflex testing for Lynch syndrome (LS) using mismatch repair immunohistochemistry and/or microsatellite instability analysis in newly diagnosed colorectal carcinoma (CRC) patients is an emerging standard of care in the United States. The risk of gynecologic malignancy in women with LS approaches and even exceeds that of CRC. Furthermore, gynecologic malignancies are often the sentinel cancers in these patients. There is significant variation in practice, but some groups have similarly recommended deployment of reflex testing strategies in patients presenting with endometrial cancer (EC). The College of American Pathologists has stated that pathologists should recognize the histologic and clinical features that should prompt at least a recommendation for mismatch repair testing. Morphologic and clinical schemas in EC to identify microsatellite unstable/LS tumors are less refined than the colon-centric schemas (Amsterdam, Bethesda, and MsPath). Studies of LS EC are few and interpretation is limited by recruitment strategies and the myriad of definitions and study designs used. Although serous cell type is used to triage ovarian cancer patients for BRCA screening, cell type correlation in LS is less certain but seems to involve a spectrum of cell types. We review the morphologic and clinical features/schemas in LS EC and highlight limitations of restrictive aged-based screening strategies, uncertainty in current clinical schemas and equivocal results of morphologic studies of LS EC. With uncertainty of histologic and clinical schemas, and following developments in CRC, reflex testing of all/vast majority of newly diagnosed EC for LS should be considered.
Department of Laboratory Medicine, University of Toronto, ON, Canada. blaise.clarke@uhn.on.ca
Blaise A
BA
Clarke
Kumarasen
K
Cooper
D000328:Adult; D000368:Aged; D003123:Colorectal Neoplasms, Hereditary Nonpolyposis / Q000175:diagnosis* / Q000235:genetics / Q000473:pathology*; D053843:DNA Mismatch Repair; D016889:Endometrial Neoplasms / Q000235:genetics / Q000473:pathology*; D005260:Female; D005820:Genetic Testing; D006801:Humans; D053842:Microsatellite Instability; D008875:Middle Aged