A 48-year-old male diagnosed recently with LFS as a result of genetic testing he underwent following the patient’s son’s diagnosis of LFS and leukemia earlier in the year. The patient also has one young daughter who is well and does not have LFS. The patient’s sister died at age of 14 years old following a diagnosis of a brain tumor. His father died at age of 50 years after diagnosis of hematological malignancy. It is assumed the patient’s sister and father had LFS, although there was no formal diagnosis (see ). The patient presented to emergency room with a 3-month history of abdominal pain in the epigastric region associated with lower back pain. He had history of weight loss of approximately 20 pounds over a few weeks. Imaging showed a pancreatic head mass with distal common bile duct dilatation, a gastric mass with wall thickening, left adrenal nodule, and necrotic para-aortic lymphadenopathy, deemed highly suspicious for malignancy involving potentially more than one primary. CT spine, CT head, and bone scan revealed no obvious evidence of metastasis. He underwent gastroscopy and endoscopic ultrasound which revealed a large gastric cardia mass with involvement of the esophagus and extension along the lesser curvature, which was biopsied, as well as a cystic lesion within the pancreas head with soft tissue component, which was biopsied as well. Pathology of gastric biopsy showed a poorly differentiated invasive adenocarcinoma, CK 8/18 positive, P40 negative, p53 overexpressed, MMR deficient with loss of nuclear expression of MLH1 and PMS2 via immunohistochemistry (see, a–e), MLH promoter hypermethylated, estimated CPS = 5 and HER 2 neu negative. Pathology of the pancreatic head lesion showed a well-differentiated neuroendocrine tumor, positive for synaptophysin, chromogranin, pancytokeratin, Ki 67 < 1% without necrosis or mitotic activity (see a–d). NM PET scan showed hypermetabolic mass involving gastric cardia, fundus, and lesser curvature. Hypermetabolic pancreatic head mass. Foci of FDG avid lesions in the liver highly suspicious for hypermetabolic metastasis (see ). Gallium 68 scan showed somatostatin avid receptor rich tumor in the pancreatic head. Malignant process in the gastric cardia demonstrates relatively low somatostatin receptor expression, in keeping with the known diagnosis of invasive adenocarcinoma. Likewise, the lymphadenopathy seen in the subcarinal region and upper abdomen showed similar characteristics, favoring metastatic disease from the gastric adenocarcinoma, rather than the pancreatic neuroendocrine tumor. The previously seen liver foci on FDG PET scan are not identified with confidence, favoring adenocarcinoma origin as well. We selected a treatment regimen directed toward the metastatic MSI-H gastric cancer. The patient started on chemotherapy-immunotherapy in the form of FOLFOX + Nivolumab every 2 weeks. He was compliant with the treatment plan. After eight cycles of treatment, CT scan follow-up showed significant response (more than 50%) regression in metastatic gastric cancer and stable disease in pancreatic neuroendocrine tumor. The patient tolerated the treatment well. Regular assessment in oncology clinic prior/post each cycle of treatment showed no adverse events.