Intraductal papillary neoplasm of the bile duct accompanying biliary mixed adenoneuroendocrine carcinoma

Abstract

We present the first case of an intraductal papillary neoplasm of the bile duct (IPNB) accompanying a mixed adenoneuroendocrine carcinoma (MANEC). A 74-year-old woman presented with fever of unknown cause. Laboratory data revealed jaundice and liver injury. Contrast-enhanced computed tomography revealed a 20 mm polypoid tumor in the dilated distal bile duct, which exhibited early enhancement and papillary growth. Upper gastrointestinal endoscopy revealed mucus production from the papilla of Vater, characterized by its protruding and dilated orifice. Endoscopic ultrasonography visualized the polypoid tumor in the distal bile duct, but no invasive region was suggested by diagnostic imaging. Therefore, the initial diagnosis was IPNB. After endoscopic nasobiliary drainage, a pylorus-preserving pancreaticoduodenectomy was performed. Pathological examination of the resected bile duct revealed papillary proliferation of biliary-type cells with nuclear atypia, indicating pancreaticobiliary-type IPNB. In addition, solid portions comprised of tumor cells with characteristic salt-and-pepper nuclei were evident. Immunohistochemistry revealed expression of the neuroendocrine marker synaptophysin in this solid component, diagnosing it as a neuroendocrine tumor (NET). Furthermore, the MIB-1 proliferation index of NET was higher than that of IPNB, and microinvasion of the NET component was found, indicating neuroendocrine carcinoma (NET G3). This unique case of MANEC, comprising IPNB and NET, provides insight into the pathogenesis of biliary NET.

Keywords: Bile duct; Intraductal papillary neoplasm of bile duct; Intraductal papillary neoplasm of the bile duct; Neuroendocrine tumor.

Figure 1

Computed tomography of the bile duct. Computed tomography revealed dilatation of the bile duct and an elevated lesion (arrow) at the bottom of the lower bile duct.

Figure 2

Pathological findings from the resected bile duct (hematoxylin eosin staining). A: A semi macro cross-sectional image of the resected extrahepatic bile duct. In the dilated bile duct, the tumor was comprised of two distinct parts: papillary (P) and solid (S); B: The boundary between the papillary (right) and solid (left) areas. The papillary area consisted of a papillary proliferation of cholangiocyte-like columnar epithelial cells covering fine fibrovascular cores (arrows). In the solid area, a lacunar tumor was evident, but lacked distinct acinar/glandular structures. Magnification: × 100; C: The solid tumor at higher magnification. Tumor cells exhibited characteristic salt-and-pepper nuclei, a high nucleus-to-cytoplasm ratio, and increased nuclear chromatin. Magnification: × 400.

Figure 3

Immunohistochemistry for cytokeratin 19, synaptophysin, and Ki-67. A: Both the solid (asterisk) and papillary (arrows) components were positive for CK19. Magnification: × 200; B: Synaptophysin expression was evident in the solid component (left), indicating a neuroendocrine tumor, but not in the papillary component (right). Magnification: × 100; C: Although Ki-67-positive cells were scarce in the papillary component (arrows), many Ki-67-positive cells were identified in the solid component (asterisk). Magnification: × 200.