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Mixed Neuroendocrine-Nonneuroendocrine Carcinoma Arising in the Gallbladder: A Rare Case of a Three-Component Composite Neoplasm


 
 
 Neuroendocrine gallbladder neoplasms are rare, comprising 0.5% of all neuroendocrine cancers and about 2% of gallbladder cancers. Interestingly, those neoplasms can also be observed along with other malignant components of epithelial origin, mostly adenocarcinomas. Herein we report an unusual case of a patient with a gallbladder neoplasm composed of a neuroendocrine carcinoma, a squamous cell carcinoma, and an adenocarcinoma.
 
 
 
 The patient was a 62-year-old woman who presented with right upper quadrant abdominal pain with a positive Murphy’s sign on physical examination. She was clinically diagnosed with acute cholecystitis and underwent cholecystectomy. Gross examination showed a 5-cm exophytic mass at the gallbladder fundus. Histopathologic examination of the mass showed an infiltrating squamous cell carcinoma and an adjacent high-grade neuroendocrine carcinoma; each of these two components composed more than 30% of the neoplasm and infiltrated into the perimuscular connective tissue with no serosal involvement. Additionally, a superficial adenocarcinoma component was also seen composing 10% of the neoplasm. The squamous cell carcinoma showed moderate differentiation with areas of keratinization; it was positive for Ck7, p40, and p63. The neuroendocrine carcinoma showed areas of geographic necrosis, and the cells had inconspicuous nucleoli and granular chromatin, with numerous mitotic figures; it was positive for synaptophysin and chromogranin. The adenocarcinoma showed gland formation with mucicarmine stain, highlighting the mucin within the neoplastic cells; it was positive for Ck7 but negative for p40. Subsequently, the patient underwent resection of the liver bed, which was negative for metastasis, and was then referred for chemotherapy.
 
 
 
 Our review of the literature revealed seven documented cases of three-component gallbladder neuroendocrine neoplasms. Generally, patients with these tumors have a poor prognosis, and due to their rarity, no specific treatment guidelines have yet been established. It has been suggested that a multipotent common stem cell is the origin of these tumors.
