Mixed adenoneuroendocrine carcinoma of the gallbladder, amphicrine type: Case report and review of literature.

Amphicrine type mixed adenoneuroendocrine carcinoma (MANEC), also known as amphicrine carcinoma, is an exceedingly rare neoplasm comprising of tumor cells simultaneously demonstrating both neuroendocrine and exocrine differentiation. Majority of reported cases were found in tubular gastrointestinal tracts such as colon. Herein, we report the first case of amphicrine carcinoma in gallbladder in a 57-year-old female who presented with abdominal pain, vomiting, and gallbladder mass on imaging followed by radical cholecystectomy. Macroscopically, the tumor was a polypoid solid mass with a firm and tan-white cut surface located at the gallbladder fundus. Histologically, the tumor cells were composed of monotonous-appearing signet-ring cells with fine chromatin, variably conspicuous nucleoli, brisk mitotic figures, and spotty necrosis. They were loosely clustered, forming nests and cords but no glandular formation. Immunohistochemically, the entire tumor showed strong and diffuse immunoreactivity for CDX2, p53, and synaptophysin, with patchy positivity for CD56, chromogranin, and INSM1. Kreyberg stain highlighted both intracytoplasmic and extracellular mucin. Ki-67 proliferation index was approximately 70%. Next-generation sequencing performed on a 724 cancer-related gene panel identified TP53 mutation at c.844C>T (p.R282W). To our knowledge, this is the first case of amphicrine carcinoma in gallbladder. It highlights the complex dynamism and controversial pathogenesis of this unique entity, the exact mechanism and clinicopathologic behavior of which are not yet understood.