Size-biology paradox in ampullary tumours - large-cell neuroendocrine carcinoma of the ampulla of Vater: A case report

BACKGROUND Ampullary adenocarcinoma is often associated with favourable outcomes due to early presentation and high resectability. Small ampullary lesions are more commonly well-differentiated neuroendocrine tumours, which typically demonstrate indolent behaviour. In contrast, poorly differentiated neuroendocrine carcinomas, including large-cell neuroendocrine carcinoma (LCNEC), are exceptionally rare and biologically aggressive, challenging prognostic assumptions based on tumour size. CASE SUMMARY A 69-year-old woman presented with painless obstructive jaundice. Imaging revealed a small ampullary lesion without evidence of metastatic disease. Endoscopic cytology suggested adenocarcinoma, and pancreaticoduodenectomy was performed. Histopathological examination demonstrated LCNEC characterised by large polygonal cells, extensive necrosis, high mitotic activity, and a Ki-67 index up to 70%. Immunohistochemistry was positive for synaptophysin and chromogranin A. The patient completed six cycles of adjuvant carboplatin and etoposide and remains disease-free at 8 months postoperatively. CONCLUSION This case highlights the size-biology paradox in ampullary tumours, where small lesions may harbour highly aggressive histology. LCNEC of the ampulla of Vater remains rare and carries a potentially poor prognosis, warranting accurate pathological diagnosis and multidisciplinary management.