Clinicopathologic and Molecular Features of Mixed Neuroendocrine Non-Neuroendocrine Neoplasms of the Gallbladder

Neuroendocrine neoplasms of the gallbladder are rare, comprising 0.5% of all neuroendocrine cancers and about 2% of gallbladder cancers. These neoplasms can also be found along with other malignant neoplasms of epithelial origin, mostly adenocarcinomas. Herein, we describe an unusual finding of a three-component mixed neuroendocrine non-neuroendocrine neoplasm (MiNEN) of the gallbladder. We also review the literature on 29 similar cases and summarize key features. We report on a 62-year-old woman who presented with right upper quadrant pain with a positive Murphy's sign. A clinical diagnosis of neoplasia was entertained and she underwent cholecystectomy. Gross examination of the specimen revealed a 5-cm exophytic mass at the gallbladder fundus. Histopathologic examination of the mass showed an infiltrating squamous cell carcinoma, an adjacent neuroendocrine carcinoma (each of these two components composed more than 30% of the neoplasm), and a superficial adenocarcinoma (composing 10% of the neoplasm). Gallbladder MiNENs present with similar symptoms and in the same age group as do carcinomas; however, their prognosis is often poor. Specific management and treatment guidelines have not been established since MiNENs are very rare.