Intraductal neoplasm of the intrahepatic bile duct: clinicopathological study of 24 cases

Abstract

Aim: To investigate the clinicopathological features of intraductal neoplasm of the intrahepatic bile duct (INihB).

Methods: Clinicopathological features of 24 cases of INihB, which were previously diagnosed as biliary papillomatosis or intraductal growth of intrahepatic biliary neoplasm, were reviewed. Mucin immunohistochemistry was performed for mucin (MUC)1, MUC2, MUC5AC and MUC6. Ki-67, P53 and β-catenin immunoreactivity were also examined. We categorized each tumor as adenoma (low grade), borderline (intermediate grade), and malignant (carcinoma in situ, high grade including tumors with microinvasion).

Results: Among 24 cases of INihB, we identified 24 tumors. Twenty of 24 tumors (83%) were composed of a papillary structure; the same feature observed in intraductal papillary neoplasm of the bile duct (IPNB). In contrast, the remaining four tumors (17%) showed both tubular and papillary structures. In three of the four tumors (75%), macroscopic mucin secretion was limited but microscopic intracellular mucin was evident. Histologically, 16 tumors (67%) were malignant, three (12%) were borderline, and five (21%) were adenoma. Microinvasion was found in four cases (17%). Immunohistochemical analysis revealed that MUC1 was not expressed in the borderline/adenoma group but was expressed only in malignant lesions (P = 0.0095). Ki-67 labeling index (LI) was significantly higher in the malignant group than in the borderline/adenoma group (22.2 ± 15.5 vs 7.5 ± 6.3, P < 0.01). In the 16 malignant cases, expression of MUC5AC showed borderline significant association with high Ki-67 LI (P = 0.0622). Nuclear expression of β-catenin was observed in two (8%) of the 24 tumors, and these two tumors also showed MUC1 expression. P53 was negative in all tumors.

Conclusion: Some cases of INihB have a tubular structure, and are subcategorized as IPNB with tubular structure. MUC1 expression in INihB correlates positively with degree of malignancy.

Keywords: Intraductal biliary neoplasm; Intraductal papillary neoplasm of the bile duct; Intraductal tubular neoplasm of the bile duct; Intraductal tubulopapillary neoplasm of the bile duct; Mucin expression.

Figure 1

Gross findings. A: Duct-ectatic type. Tumor filled the dilated intrahepatic bile duct. Surrounding bile duct was also dilated; B: Cystic type. Cystic dilatation of intrahepatic bile duct. Papillary tumor was found in the dilated intrahepatic bile duct. Significant retention of mucin was observed.

Figure 2

Histopathology of intraductal neoplasm of the intrahepatic bile duct. Tumor shows papillary proliferation within the dilated bile duct (hematoxylin and eosin stain, × 20).

Figure 3

Microinvasion of tumor. Tumor cells infiltrating into the bile duct wall (hematoxylin and eosin stain, × 40).

Figure 4

Tubular structure within intraductal neoplasm of the intrahepatic bile duct. Cells with intracellular mucin and mild atypia forming a pyloric gland-like structure (hematoxylin and eosin stain, × 200).

Figure 5

Histology of intraductal neoplasm of the intrahepatic bile duct with papillary and tubular structure (case 1). A: Histological structure was mainly tubular, but papillary structure was also present [hematoxylin and eosin (HE) stain, × 40]; B: Tubular structure (HE stain, × 200); C: Papillary structure (HE stain, × 200); D: Tumor cells were positive for mucin (MUC)1 immunohistochemistry (MUC1 stain, × 200).

Figure 6

Box plot for Ki-67 labeling index by histological degree of malignancy and MUC5AC expression. A: The Ki-67 labeling index (LI) was significantly higher in the malignant group than in the benign/borderline group; B: There was an association with borderline significance between MUC5AC expression and Ki-67 LI (P = 0.0622). MUC: Mucin.

Figure 7

Nuclear expression of β-catenin in pancreaticobiliary type. A: Hematoxylin and eosin stain, × 200; B: β-catenin stain, × 200.