Intrapancreatic Cholangiocarcinomas: A Clinicopathological and Immunohistochemical Analysis
J Shen, I Konstantinidis, CR Ferrone, V Deshpande. Massachusetts General Hospital, Boston, MA
Background: Intrapancreatic cholangiocarcinomas (ICC) are distal common bile duct (CBD) tumors that may be indistinguishable from pancreatic ductal adenocarcinomas (PDAC). The diagnosis of ICC is dependant on the pattern and extent of bile duct involvement, including the presence of dysplasia. However, there have been no prior attempts to explore ICC pathologically and genetically. The aim is to characterize the pathological features of ICC and their association with a panel of tumor suppressors or oncogenes.
Design: We reviewed 100 resections in which the tumors were located adjacent to the CBD. The tumor microscopically involved the CBD in 64 cases, and these formed the study group. Two patterns of tumor growth were recognized: type I tumors demonstrated circumferential and symmetrical involvement of the bile duct, whereas in type II tumors the epicenter of the tumor located away from the CBD. Pathological correlates were analyzed and compared between the two subtypes. A tissue microarray (TMA) was constructed, and immunohistochemical studies for p16, p53, EGFR, INI1, Her2/Neu, and B-catenin were evaluated and compared between two subtypes. A positive staining was recorded when more than 5% of cells are stained, and only nuclear positivity is recorded for B-cateinin, p16, INI1, and p53.
Results: We first classified 37 patients as type I and 27 as type II. Type I lesions were associated with bile duct dysplasia, (46% vs 11%, p=0.03) whereas type II lesions were statistically more likely to be associated with high-grade PanIN (41%vs 8%, p=0.002). Of these patients, 22 from type 1 and 7 from type 2 showed reliable results for immunohistochemical studies on TMA and were included for analysis. Type I showed more staining than type 2 for p53 (82% vs 29%;p=0.016), and p16 (45% vs 14%;p=NS). Neither nuclear positivity for B-cateinin nor loss of INI1 was observed in either group.
|Type 1 (n=22)||18 (82%)||10 (45%)||7 (32%)||1 (5%)|
|Type 2 (n=7)||2 (29%)||1 (14%)||2 (29%)||0 (0%)|