Unique case of primary squamous cell carcinoma of ampulla of Vater with microsatellite instability and response to pembrolizumab immunotherapy

Abstract Primary squamous cell carcinoma of the ampulla of Vater is a very rare entity and there are only 11 reported cases to date. We describe a case of primary SCC of the ampulla of Vater with microsatellite instability (MSI) and response to pembrolizumab immunotherapy. To the best of our knowledge, this is the first reported case of SCC of the ampulla of Vater with MSI. Our patient is a 40-year-old male who presented with direct bilirubinemia (total bilirubin: 10.7, direct bilirubin: 7.1) and was noted to have a pancreatic head mass that measured 6.6 x 5.5 x 5.5 cm. The patient underwent a pylorus-preserving pancreatoduodenectomy with lymph node dissection. Pathology showed 5.5 x 3.5 x 3.5 cm squamous cell carcinoma of the ampulla of Vater based on positive p40 and CK5 on immunohistochemistry. It was noted to be invading the pancreatic head and duodenal mucosal. Surgical margins were negative. Adjuvant chemotherapy with mFOLFIRINOX (irinotecan, 5-fluorouracil, oxaliplatin) was not performed because of active Hepatitis C infection. Chemoradiotherapy with capecitabine and radiation therapy was initiated however patient had progression of disease despite that. The patient was transitioned to Pembrolizumab in the context of MSI high tumor with palliative intent. He had an excellent response to immunotherapy. The therapy was stopped after 18 cycles at patient's request because of persistent symptoms of dizziness and lethargy. At the eight-month follow-up after the last cycle of immunotherapy (2.5 years after surgical resection), the patient had no evidence of relapse on the CT scan.