Question: A 71-year-old woman was admitted with intractable nausea and vomiting. The patient denied any abdominal pain but did note a 6-month history of intermittent thoracolumbar back pain. She denied any weight loss, changes to her bowel pattern, or bouts of acute pancreatitis. Her family history was notable for a sister who died of pancreatic adenocarcinoma at age 50. Physical examination revealed a palpable mass and a minimally tender abdomen to deep palpation in the epigastric region. Laboratory studies demonstrated normal electrolytes, liver function tests, complete blood count, CA 19-9, amylase and lipase levels. Abdominal and pelvic computed tomography (CT) demonstrated a 6.8 × 5.5-cm mass of the proximal pancreatic body encasing the celiac artery (Figure A). A positron emission tomography (PET) scan demonstrated FDG activity only in the pancreatic body and in a celiac lymph node (Figure B). Endoscopic ultrasonography (EUS) revealed a large, 38 × 40-mm, heterogeneous mass with areas of hypoechoic spaces compatible with necrosis arising from the pancreas (Figure C). A rounded and sharply demarcated lymph node, abutting the celiac plexus, was measured at 15 mm in diameter. What is your differential diagnosis? See the Gastroenterology web site (www.gastrojournal.org) for more information on submitting your favorite image to Clinical Challenges and Images in GI. Cytology from the EUS fine needle aspirate (FNA) of the pancreatic mass revealed poorly differentiated malignant cells with scant, eosinophilic cytoplasm, high nuclear–cytoplasmic ratios, granular chromatin, and inconspicuous nucleoli (Figure D). A cell block was made from the FNA material and immunohistochemistry noted positive stains for AE1/AE3, TTF-1, CK7, chromogranin and synaptophysin (Figure E, synaptophysin-positive staining) but negative for CK20, CD45, CD3, and CD20, consistent with a poorly differentiated small cell carcinoma. Extrapulmonary small cell carcinoma of the pancreas (ESCCP) was diagnosed in this patient in the context of no pulmonary involvement on CT or PET scans. The patient was treated with a chemotherapeutic regimen of cisplatin and etoposide. Although a subsequent CT scan indicated an initial marked decrease in tumor size, 6 months after initial diagnosis, the patient was found to have liver metastases and subsequently passed away. ESCCP is a very rare condition, which represents approximately 1% of all pancreatic malignancies, and is frequently under-recognized, leading to a delay in diagnosis.1Galanis E. Frytak S. Lloyd R.V. Extrapulmonary small cell carcinoma.Cancer. 1997; 79: 1729-1736Crossref PubMed Scopus (245) Google Scholar Since Duguid and Kennedy first described 2 cases of a mediastinal tumor with a small cell pattern without bronchial involvement in 1930, cases of primary extrapulmonary small cell carcinoma have been described in numerous other organs.1Galanis E. Frytak S. Lloyd R.V. Extrapulmonary small cell carcinoma.Cancer. 1997; 79: 1729-1736Crossref PubMed Scopus (245) Google Scholar The pancreas is a rare site of origin for small cell carcinoma: Reyes and Wang reported only 5 histologically confirmed cases of primary pancreatic small cell carcinoma out of 485 pancreatic malignancies over a 29-year period.2Reyes C.V. Wang T. Undifferentiated small cell carcinoma of the pancreas: a report of five cases.Cancer. 1981; 47: 2500-2502Crossref PubMed Scopus (86) Google Scholar The Mayo Clinic published a case series in which out of 81 cases of extrapulmonary small cell cancer, 29 cases (36%) involved the gastrointestinal tract with only 7 cases (8.6%) involving the pancreas.1Galanis E. Frytak S. Lloyd R.V. Extrapulmonary small cell carcinoma.Cancer. 1997; 79: 1729-1736Crossref PubMed Scopus (245) Google Scholar ESCCP carries a poor prognosis, and no consensus exists on the appropriate treatment of these patients. Patients who do not undergo chemotherapy survive a median of 1 month; the median survival increases to 6 months with cisplatin-based chemotherapy.3Vos B. Awada A. Hendlisz A. Primary small-cell carcinoma of the pancreas: An extensive review of the literature with emphasis on therapy and prognosis.Cancer Ther. 2008; 6: 857-864Google Scholar ESCCP is aggressive and often widely metastatic at presentation; therefore, operative resection with curative intent is frequently not possible. In prior reports, the histologic diagnosis of ESCCP was typically made by surgical pathology after resection or post mortem by autopsy; in our case, EUS-FNA allowed for a pathologic diagnosis.