A Case of Microsatellite Instability-High Colon Cancer in a Young Woman With Familial Adenomatous Polyposis

Two major molecular pathways of colorectal carcinogenesis, chromosomal instability (CIN) and microsatellite instability (MSI), are considered to be mutually exclusive. Distinguishing CIN from MSI-high tumors has considerable therapeutic implications, because patients with MSI-high tumors can derive considerable benefit from immune checkpoint inhibitors, and tumors that evolved through the CIN pathway do not respond to these agents. Familial adenomatous polyposis (FAP) is a genetic syndrome that is defined by a mutation in the APC gene and is thought to lead to carcinogenesis through the CIN pathway. Here, we report a case of a young woman with FAP who was treated for medulloblastoma as a child and developed advanced MSI-high colon cancer as a young adult. Her response to second-line immunotherapy enabled resection of her colon cancer, and she is free of disease .10 months after surgery. This case highlights the potential for overlap between the CIN and MSI carcinogenic pathways and associated therapeutic implications.

Automated summary

The two major molecular pathways of colorectal carcinogenesis, CIN and MSI, are considered to be mutually exclusive with distinct therapeutic implications. However, this report highlights a case of a young woman with FAP who demonstrated overlapping characteristics of CIN and MSI pathways and benefited from immunotherapy for her advanced colon cancer.