Medullary carcinoma of the duodenum treated with pembrolizumab: a case report

Medullary carcinoma (MC) is a recognized histologic subtype of colorectal cancer characterized by poor glandular differentiation and intraepithelial lymphocytic infiltrate. However, MC originating from the small intestine is exceedingly rare, with only nine cases described in the literature. Based on previous cases, surgical resection is currently the mainstay of treatment for those with localized disease. We report the first case of a patient who presented with unresectable microsatellite instability-high (MSI-H) MC of the duodenum and was instead treated with pembrolizumab.

A 50-year-old man with history of adenocarcinoma of the proximal descending colon status post hemicolectomy and adjuvant treatment with chemotherapy and family history of Lynch syndrome presented with abdominal pain for two weeks. Computed tomography (CT) abdomen/pelvis revealed a 10.7 cm by 4.3 cm mass in the mid-portion of the duodenum abutting against the pancreatic head. Esophagogastroduodenoscopy (EGD) demonstrated circumferential, partially obstructing, intrinsic stenosis of the duodenum with ampullary involvement and likely invasion into the pancreatic head and common bile duct. Endoscopic biopsy of the primary tumor revealed poorly differentiated MC. Immunohistochemical staining showed loss of MLH1 and PMS2 expression. Staging with CT chest showed no evidence of disease. Positron emission tomography (PET) scan redemonstrated circumferential duodenal wall thickening and hypermetabolic activity with standardized uptake value (SUV) max of 26.4, as well as PET-avid epigastric, retroperitoneal, and periaortic lymphadenopathy suggestive of metastasis. He was started on pembrolizumab and found to have stable disease on repeat imaging along with significant improvement in symptoms and performance status.

Due to the rarity of the tumor, there is no standardized approach to treatment. All patients in previously published cases underwent surgical resection. However, our patient was deemed a poor surgical candidate. Given his previous history of colon cancer and treatment with platinum-based therapy, he qualified for pembrolizumab as first line therapy for his MSI-H tumor. To our knowledge, this is the first report of MC of the duodenum as well as the first MC to be treated with pembrolizumab in the first line setting. In order to corroborate the use of immune checkpoint inhibitors as a treatment option for MC of the colon or small intestine, the aggregation of existing and future case data in this unique patient group is certainly warranted.