Characteristic of Perineural Invasion in Hilar Cholangiocarcinoma Based on Whole-Mount Histologic Large Sections of Liver

Abstract

Background & ObjectivePerineural invasion is an important biological feature of hilar cholangiocarcinoma (HCCA). We developed a whole-mount histologic large sections (WHLS) of the liver to evaluate peripheral nerve invasion (PNI) of HCCA.MethodsUsing sampling, fixation, dehydration, embedding, sectioning, hematoxylin and eosin (H&E) and immunohistochemical (IHC) staining, and scanning, the characteristics of intrahepatic and extrahepatic PNI in 20 patients with Bismuth type III and type IV HCCA were analyzed with WHLS. Correlation between the characteristics of nerve invasion and tumor size, vascular invasion (artery, portal vein), degree of differentiation, microvascular invasion (MVI), carbohydrate antigen19-9 (CA19-9), and differentiation degree of HCCA was statistically evaluated.ResultsThe WHLS of the liver was successfully established, which enabled us to observe intrahepatic and extrahepatic distribution of HCCA and whether surrounding tissues including nervous, blood, and lymph vessels were infiltrated. Extrahepatic and intrahepatic PNI were identified in 20 (100%) patients and 1 (5.0%) patient, respectively. Vessel density decreased in most invaded nerves presented by CD-34, which correlated with 100% of poorly differentiated and 83% of moderately differentiated tumors (P<0.008).ConclusionThis study established a WHLS of the liver that can be used for clinical diagnosis and research, and confirmed that extrahepatic PNI is prevalent, but intrahepatic nerve invasion is rare and does not accompany the invasion scope of bile ducts in types III and IV HCCA. In addition, moderately and poorly differentiated malignant tumors are more prone to PNI, independent of blood supply.

Periampullary cancer and neurological interactions: current understanding and future research directions

“…The intricate neural network in the periampullary region provides tumors with close proximity to nerves, thereby increasing the risk of neural invasion. Observations indicate that even though both belong to the category of cholangiocarcinomas, there exists a significant difference in the rate of neural invasion between intrahepatic and extrahepatic anatomical locations ( 10 ). Nerves influence the pathophysiological behaviors of tumor cells through various mechanisms, and in turn, they are affected by neurotrophic factors produced by the tumor and its microenvironment.…”

“…These fine fibers are connected to deeper, thicker nerve fibers and infiltrate along these fine fibers, gradually enveloping and expanding around the coarse fibers ( 62 ). The invasion of extrahepatic cholangiocarcinoma cells into surrounding tissues is notably correlated with PNI and is not dependent on blood supply ( 10 ). In pancreatic ductal adenocarcinoma, the occurrence of PNI is significantly associated with post-surgical recurrence due to microvascular invasion ( 63 ).…”

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