Combined Adenosquamous and Large Cell Neuroendocrine Carcinoma of the Gallbladder

Abstract

Large cell neuroendocrine carcinoma (LCNEC) of the gallbladder is extremely rare and usually combined with other type of malignancy, mostly adenocarcinoma. We report an unusual case of combined adenosquamous carcinoma and LCNEC of the gallbladder in a 54-year-old woman. A radical cholecystectomy specimen revealed a 4.3×4.0 cm polypoid mass in the fundus with infiltration of adjacent liver parenchyma. Microscopically, the tumor consisted of two distinct components. Adenosquamous carcinoma was predominant and abrupt transition from adenocarcinoma to squamous cell carcinoma was observed. LCNEC showed round cells with large, vesicular nuclei, abundant mitotic figures, and occasional pseudorosette formation. The patient received adjuvant chemotherapy. However, multiple liver metastases were identified at 3-month follow-up. Metastatic nodules were composed of LCNEC and squamous cell carcinoma components. Detecting LCNEC component is important in gallbladder cancer, because the tumor may require a different chemotherapy regimen and show early metastasis and poor prognosis.

Keywords: Carcinoma, adenosquamous; Gallbladder; Large cell neuroendocrine carcinoma; Prognosis.

Fig. 1.

Imaging and gross findings. (A) On abdominal computed tomography, the tumor of the gallbladder shows direct invasion of the adjacent liver. (B) On opening the gallbladder, a fungating mass is observed in the fundus. (C) The cut surface shows a relatively well-circumscribed, yellowish fibrotic mass, with hemorrhage and necrosis, invading the liver parenchyma.

Fig. 2.

Microscopic findings. (A, B) Adenosquamous carcinoma component consisted of variable-sized glands lined by atypical columnar epithelium (left) and atypical stratified squamous epithelium (right). (C) Neuroendocrine carcinoma component, transition from adenocarcinomatous component (left) and composed of large cells arranged in solid sheets (right). (D) The neuroendocrine component shows solid and pseudorosette patterns.

Fig. 3.

Immunohistochemical findings. Large cell neuroendocrine carcinoma component was diffusely positive for synaptophysin (A), and chromogranin (B), and focal positive for CD56 (C). (D) The Ki-67 proliferating index was up to 25%.