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

Abstract

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.

Keywords: Adenocarcinoma; Gallbladder; MiNENs; Neuroendocrine tumors; Non-neuroendocrine tumors; Squamous cell carcinoma.

Figure 1

Magnetic resonance cholangiopancreatographic image showing a distended gallbladder (red arrow) with debris and stones (about 1 cm) and two irregular septate nodules in the inferior fundus (about 1.5 cm) that enhanced after gadolinium administration.

Figure 2

Resected gallbladder specimen showing multiple exophytic masses in the lumen.

Figure 3

Representative photomicrographs of the MiNEN. (a) Infiltrating squamous cell carcinoma (*) and neuroendocrine carcinoma (†) adjacent to each other (× 20). (b) Squamous component with keratinization (× 100). (c) Neuroendocrine component with necrosis (× 200). (d) Adenocarcinoma component with gland formation (× 20). H&E stain. MiNEN: mixed neuroendocrine non-endocrine neoplasm; H&E: hematoxylin and eosin.

Figure 4

Immunohistochemical staining showing: (a) p63-positive squamous component and negative neuroendocrine component (× 40); (b) synaptophysin-positive neuroendocrine component and negative squamous cell component (× 40); (c) CK7-positive adenocarcinoma component (× 20).