Primary Mixed Adenoneuroendocrine Carcinoma of the Gallbladder in a 55-Year-Old Female Patient

Abstract

Mixed adenoneuroendocrine carcinomas (MANECs) of the biliary tract are rare tumors, and to date only a few cases arising in the gallbladder have been reported. Their histogenesis is a matter of debate, since the biliary tract normally lacks neuroendocrine cells. However, the immunohistochemical identification of nonneoplastic neuroendocrine cells in both biliary adenocarcinomas and intestinal metaplasia has been documented. Here we report a case of a 55-year-old female patient presenting with right upper quadrant pain, cholelithiasis, and a gallbladder mass identified after cholecystectomy. The histopathologic examination showed a MANEC, composed of an intestinal-type adenocarcinoma and a large cell neuroendocrine carcinoma, arising in a background of enteric metaplasia with extensive high-grade dysplasia. Moreover, we report the presence of focal pancreatic intraepithelial neoplasia-like epithelial lesions, which has not been described for these tumors yet. The histopathologic features of this case provide further support for the theory that MANECs arise following a metaplasia-dysplasia-carcinoma pathway.

Primary Biliary Mixed Adenoneuroendocrine Carcinoma (MANEC): A Short Review

“…17,20,24,25 MACROSCOPIC AND MICROSCOPIC FEATURES Macroscopically, biliary MANECs are solid, polypoid, nodular, or papillary tumors with a firm consistency and a homogeneous tan to gray-white cut surface (Figure 1, A). 14,19,21 Focal hemorrhage, necrosis, and mucin-filled cysts can also be evidenced on gross examination. 19,21 Microscopically, biliary MANECs usually have 2 (AC/ SCC-NET) or more histologic components without a Abbreviations: ChT, chemotherapy; ChXrT, chemoradiotherapy.…”

“…transition zone (collision pattern in Lewin's original classification; Figure 1, B). 2,14,17,27,28 Less frequently, the NET and AC/SCC components are tightly intermingled, without a clear separation (combined pattern). 19,25 A biliary MANEC containing biphenotypic (NE-AC) tumor cells has been reported only once, to the best of our knowledge.…”

“…17 The AC can display either intestinal or pancreatobiliary phenotype, and it is usually of a low grade. 14,17,19,25,27 In contrast, the NET is often of a high grade (most commonly grade 3/NE carcinoma), with either small or large cell cytomorphology (Figure 1, C). 14,15,25 It can show a nested organoid configuration, rosette formation, and sheetlike, cordlike, or solid growth.…”

“…14,17,19,25,27 In contrast, the NET is often of a high grade (most commonly grade 3/NE carcinoma), with either small or large cell cytomorphology (Figure 1, C). 14,15,25 It can show a nested organoid configuration, rosette formation, and sheetlike, cordlike, or solid growth. 14,17,19,25 Perineural and vascular invasion reveal pure high-grade NET in the overwhelming majority of cases (Figure 1, D).…”

A case of neuroendocrine carcinoma in the hepatic hilar lymph nodes concomitant with an adenocarcinoma of the gallbladder

“…CDX2, a homeobox gene, is involved in the differentiation and maintenance of enteric epithelium [16] and is known to be a useful immunohistochemical marker of intestinal metaplasia of the gallbladder [17]. Acosta et al reported a case of gallbladder MANEC that was positive for CDX2 in both tumor components and concluded that the finding supported the metaplasia–dysplasia–carcinoma sequence [18]. In the present case which is non-matching as MANEC, the adenocarcinoma component of the primary tumor and the intestinal metaplasia lesions were positive for CDX2 but the neuroendocrine cells were not (Fig.…”