Primary Mixed Adenoneuroendocrine Carcinoma (MANEC) of Gallbladder, Report of Two Cases with Different Histologic and Immunohistochemical Features

Abstract

Since implementation of immunohistochemistry, the occurrence of neuroendocrine cells in adenocarcinomas of gastrointestinal tract has been well documented and is not uncommon. The mixture of neuroendocrine carcinoma and adenocarcinoma (MANEC), where each represents at least 30% of the neoplasm, is however very uncommon and occurs mostly in the stomach, appendix, and large intestine. Their occurrence in the gallbladder, as the primary site, is exceptionally rare. We present two elderly patients, one male and one female with clinical manifestations of cholecystitis. The cholecystectomy specimens from these patients revealed MANEC. In one patient, the epithelial component was conspicuously papillary and well-differentiated. In our second case, the epithelial component was variably poorly differentiated carcinoma with mixed neuroendocrine collision features. In this paper we describe the clinicopathologic features of these two cases with emphasis on differences in their gross, histologic, and immunohistochemical findings. These differences may be attributed to the proposed varied pathways for the origin of neuroendocrine cells in the gallbladder.

Rare Mixed Adenoneuroendocrine Carcinoma of the Gallbladder: Case Report and Review of Literature

“…However, due to the tumor’s rarity and histological heterogeneity, there are no established adjuvant chemotherapy protocols for gMANEC, which makes it difficult to determine its effectiveness [ 4 , 27 , 28 ]. Therefore, the adjuvant therapy usually targets the most aggressive component of the tumor [ 5 , 6 , 29 ].…”

“…The prognosis depends on the size of the tumor, infiltration, differentiation, and metastasis [ 24 , 30 ]. The unpredictable biological behavior of MANECs contributes to an uncertain prognosis that seems to be poor [ 5 ]. There is evidence that the neuroendocrine component of the tumor may present a higher proliferative rate than the adenocarcinomatous, suggesting that this component may influence the long-term results in these patients [ 1 ].…”

“…To define the presence of MANEC, at least 30% of each tumor component must be determined [ 3 ]. In most cases, this tumor appears in the colon, appendix, rectum, or stomach, and is rarely found in the biliary tract, pancreas, or gallbladder [ 4 , 5 ].…”

“…Herein, we report a case of primary gMANEC, the first reported in Latin America and the 24 th worldwide [ 5 – 22 ]. This case has been reported in line with the SCARE criteria [ 23 ].…”