Complete Response to Pembrolizumab in a Patient with Lynch Syndrome: A Case Report

Background: Lynch syndrome LS is a life-threatening condition caused by heterozygous mutations in mismatch repair genes (MMR). People with this syndrome are at increased risk of developing different types of cancers, such as colorectal carcinomas, endometrial cancer, and ovarian cancers.

Case Report: The present case report discusses the case of a 36-year-old non-diabetic non-alcoholic female who came to the oncology department with a known history of Lynch syndrome. The patient had a significant past medical history. In 2003, she was diagnosed with left colon cancer for which she had left hemicolectomy followed by adjuvant chemotherapy. In 2004, she developed duodenal cancer for which she had Whipple surgery. Then, she developed ovarian cancer on both sides, which was also treated by surgery and adjuvant chemotherapy. After that, she developed uterine cancer, treated by surgery and adjuvant chemotherapy. The patient had a total colectomy and she underwent two ileostomy procedures. In 2014, immunohistochemistry testing confirmed the diagnosis that she was suffering from Lynch syndrome. Additionally, cancer sequencing panel testing in 2016 and MSH testing in 2018 further confirmed the diagnosis of Lynch syndrome as only the loss of nuclear expression of the PMS2 gene was revealed. Then in 2018, she developed a peritoneal metastasis of ovarian origin. This was the first time she started Pembrolizumab immunotherapy, that was finished at the end of 2019. One intriguing fact is that all her diseases cleared up and she continues to live normal life four years after stopping immunotherapy and she is in complete remission. Also, all her tumor markers have dropped down and normalized.

Conclusion: Carrying the PMS2 germline mutation confers an extraordinarily high risk of developing LS-associated cancers. To decrease the morbidity and mortality associated with LS-related cancers, intensive clinical monitoring, pembrolizumab therapy, and preventive surgeries are strongly advised.