Small-cell neuroendocrine carcinoma of ampulla of Vater

A 58-year-old woman presented to our emergency department with abdominal pain, chills, and fever for 2 weeks. Computed tomography of the abdomen showed obstructive common bile duct dilatation and gallbladder distension [Figure 1, right upper panel]. Multiple liver tumors were observed, consistent with liver metastases [Figure 1, left lower panel]. The patient had a history of uterus myoma, for which she underwent myomectomy 5 years ago, and acute appendicitis, for which she underwent appendectomy 10 years ago. On admission, the laboratory data revealed an increased CA199 level to 153 units/mL, and the CA125 and carcinoembryonic antigen levels were within the normal range. The upper gastrointestinal endoscopy showed a polypoid tumor in the region of the ampulla of Vater [Figure 1, left upper panel]. Magnetic resonance imaging showed a high-signal-intensity tumor in the ampulla of Vater [Figure 2, right lower panel]. Biopsy, endoscopic sphincterotomy, and endoscopic retrograde biliary drainage were performed. The histopathologic analysis of the biopsy specimen revealed a sheet of tumor cells. The tumor cells showed round-to-ovoid nuclei with scanty cytoplasm and salt and pepper chromatin [Figure 2, upper panel]. The immunohistochemical staining revealed a Ki-67 index [Figure 2, right lower panel] of 60%, and tumor cells were positive for CK (AE1/AE3) [Figure 2, right upper panel], synaptophysin [Figure 2, left lower panel], and chromogranin A and negative for cytokeratin 7, CK20, caudal-related homeobox gene 2, and thyroid transcription factor-1. Based on these findings, the patient was diagnosed with small-cell neuroendocrine carcinoma of the ampulla of Vater.Figure 1:: Gastroscopy findings of the polypoid tumor in the region of the ampulla of Vater (left upper panel, blue encircle area indicating tumor). Computed tomography of the abdomen showed gallbladder distension (red arrow, right upper panel) and common bile duct dilation (blue arrow, right upper panel). Computed tomography of the abdomen showed multiple liver metastases (red arrow, left lower panel) and intrahepatic bile duct dilation (blue arrow, left lower panel). Magnetic resonance imaging of the abdomen showed a high-signal-intensity tumor in the ampulla of Vater (red arrow, right lower panel)Figure 2:: Histopathologic analysis revealed a sheet of tumor cells with closely packed uniform cells with round uniform nuclei, salt and pepper chromatin, and scanty cytoplasm (upper panel, H&E stain, 400×). Immunohistochemically, the tumor cells showed membranous and positive cytoplasmic staining for cytokeratin (AE1/AE3, right upper panel, 400×) and synaptophysin (left lower panel, 400×) and positive nuclear staining for Ki-67 (right lower panel, 400×). H&E = hematoxylin and eosinThe patient received platinum-based chemotherapy, followed by triweekly cyclophosphamide + adriamycin + vincristine. Fifteen months after histopathologic diagnosis, the patient died of disease progression with multiple liver tumors, consistent with liver metastases. The maximum diameter of the liver tumor was more than 10 cm. The patient also developed Klebsiella pneumonia and acute bacteremia with a blood culture showing Escherichia coli. Neuroendocrine tumors are very rare tumors of the ampulla of Vater. In total, less than 150 cases have been reported. The ampulla of Vater is highly vascularized, which contributes to liver dissemination and lymph node metastases. Regardless of tumor size, published data showed that tumors metastasized in half of the cases in a retrospective case series of 20 patients. Overall, the 10-year survival for resected ampulla of Vater neuroendocrine tumors is 71% for well-differentiated tumors but only 15% for poorly differentiated neuroendocrine carcinoma.[1] According to the World Health Organization Classification of Tumors of the Digestive System (fifth edition) for poorly differentiated neuroendocrine carcinoma, the diagnostic criteria include Ki-67 index of more than 20% or mitotic index of more than 20 mitoses/2 mm2, equaling 10 high-power fields. Previous studies showed that pancreatic poorly differentiated neuroendocrine carcinoma responded to platinum-based chemotherapy. However, its prognosis was very poor. The Japanese guidelines for the management of pancreatic and gastrointestinal tract neuroendocrine carcinoma recommend chemotherapy instead of surgery.[2] Generally, the prognosis of small-cell neuroendocrine carcinomas is very poor, because early metastasis to the liver and regional lymph nodes is common. The 5-year survival rate was 8% for small-cell neuroendocrine carcinoma of the gall bladder and 0% for small-cell neuroendocrine carcinoma of the extrahepatic bile duct.[3] Declaration of patient consent The authors certify that they have obtained all appropriate patient consent forms. In the form, the patient has given her consent for her images and other clinical information to be reported in the journal. The patient understands that her name and initials will not be published and due efforts will be made to conceal identity, but anonymity cannot be guaranteed. Data availability statement All data generated or analyzed during this study are included in this published article. Financial support and sponsorship Nil. Conflict of interest Dr. Hong-Wei Gao, an section editor at Tungs’ Medical Journal, had no role in the peer review process of or decision to publish this article. The other authors declared no conflicts of interest in writing this paper.