Microsatellite Instability did not Confer Protection Towards Anastomotic Recurrence of Colorectal Cancer

Abstract

The role of microsatellite instability (MSI) in protecting against recurrence after colorectal resection is controversial. This case report adds to the evidence that MSI does not confer protection towards anastomotic recurrence of colorectal cancer, questioning the potential of using MSI status to identify patients that could be treated by surgery alone. A 58-year-old woman with poorly differentiated pT4aN0 adenocarcinoma requiring a right hemicolectomy 3 months prior presented with 1 day of hematochezia. Immunohistochemical stains for mismatch repair showed loss of MLH1 and PMS2, with retention of MSH2/MSH6, suggestive of Lynch syndrome. On presentation, the patient's hemoglobin was 6.3 g/dl from a baseline of 9g/dl 3 weeks prior. She underwent a colonoscopy that revealed a prolapsed ulcerated ileocecal end-to-side anastomosis with spontaneous oozing (Figure 1). Biopsy of the ulcerated mucosa revealed recurrent adenocarcinoma. Repeated resection with pathology revealed a pT2, N1b high-grade medullary carcinoma with involvement of 2 regional lymph nodes. She was started on adjuvant Nivolumab. Colonoscopy 3 months after the second resection revealed no recurrence on pathology. A recent study demonstrated that 21% of malignant recurrences occur at the anastomotic site, and several case reports have shown repeated anastomotic recurrences. Malignant anastomotic recurrences may result from positive distal margins, metachronous carcinogenesis, or implantation of exfoliated tumor cells during surgery. In this case, the latter was most likely given the negative margins on resection and a short interval to recurrence. The association of MSI and enhanced survival and protection against recurrence after resection remains widely debated. While some meta-analyses have showed evidence of a strong association, a recent study published in 2017 demonstrated no association between MSI and recurrence. Our case report supports the latter finding. Few studies are available to analyze the role of MSI in metastatic diseases as fewer than 5% of patients have MSI-associated metastatic colorectal cancer. In conclusion, our case report adds to the accumulating evidence that MSI likely does not offer protection against recurrence after resection.Figure: Interval colonoscopy on presentation with hematochezia: prolapsed end-to-side anastomosis was prolapsed with active oozing and friability.