Perineural invasion of hilar cholangiocarcinoma in Chinese population: One center's experience

Abstract

Background: Hilar cholangiocarcinoma (HCCA) often produces perineural invasion (PNI) extending to extra-biliary sites, while significant confusion in the incidence of PNI in HCCA has occurred in the literature, and the mechanism of that procedure remains unclear.

Aim: To summarize the incidence of PNI in HCCA and to provide the distribution of nerve plexuses around hepatic portal to clinical surgeons.

Methods: Reported series with PNI in HCCA since 1996 were reviewed. A clinicopathological study was conducted on sections from 75 patients with HCCA to summarize the incidence and modes of PNI. Immunohistochemical stains for CD34 and D2-40 in the cancer tissue were performed to clarify the association of PNI with microvessel and lymph duct. Sections of the hepatoduodenal ligament from autopsy cases were scanned and handled by computer to display the distribution of nerve plexuses around the hepatic portal.

Results: The overall incidence of PNI in this study was 92% (69 of 75 patients), while the rate of PNI in HCCA in the literature ranging from 38% to 100%. The incidence of PNI did not show any remarkable differences among various differentiated groups and Bismuth-Corlette classification groups. Logistic regression analysis identified the depth of tumor invasion was the only factor that correlated significantly with PNI (P < 0.01). In spite of finding tumor cells that could invade microvessels and lymph ducts in HCCA, we did not find tumor cells invaded nerves via microvessels or lymph ducts. Three nerve plexuses in the hepatoduodenal ligament and Glisson's sheath were classified, and they all surrounded the great vessels very closely.

Conclusion: The incidence of PNI of HCCA in Chinese population is around 92% and correlated significantly with a depth of tumor invasion. It also should be considered when stratifying HCCA patients for further treatment.

Keywords: Hilar cholangiocarcinoma; Incidence; Nerve plexus; Pathology; Perineural invasion; Treatment.

Figure 1

Perineural invasion in human hilar cholangiocarcinoma. A: Tumor cells (arrow) located within the peripheral nerve sheath in clusters [Hematoxylin-eosin (HE) staining, ×100]; B: Tumor cells (arrow) from glandular elements in perineural space (HE staining, ×100); C: Tumor cells invaded more than 33% of the circumference of the nerve (HE staining, ×100); D: Modes of perineural invasion (arrows) in one patient (HE staining, ×100).

Figure 2

Correlation of perineural invasion and microvessel. A: Tumor cells (arrow) invaded microvessel (CD34, original magnification ×400); B: Tumor cell clump (arrow) in the microvessel (CD34, original magnification ×400); C, D: Tumor cells (arrow) invaded nerve fiber (N) with vascular proliferation (CD34, original magnification ×100).

Figure 3

Correlation between perineural invasion and lymphatics. A: Lymphatic microvessel (arrow) was stained brown (D2-40, original magnification ×400); B: A great of lymph ducts were observed in primary tumor (D2-40, original magnification ×100); C, D: Tumor cells (arrow) invaded nerve fiber and lymph ducts (arrowhead) were stained (D2-40, original magnification ×100).

Figure 4

Distribution of nerve plexus around hepatic portal. A: Delineation of cutting parts; B: Transection of hepatoduodenal ligament including common hepatic duct [Hematoxylin-eosin (HE) staining, original magnification ×200]; C: Figure B without fibrous connective tissue and adipose tissue; D: Transection of the beginning part of Glisson’s sheath, including left hepatic duct (HE staining, original magnification ×200); E: Transection of the beginning part of Glisson’s sheath, including right hepatic duct (HE staining, original magnification ×200); F: Transection of furcation of right hepatic duct (HE staining, original magnification ×200). CHD: Common hepatic duct; PV: Portal vein; PHA: Proper hepatic artery; N: Nerve plexus; LHD: Left hepatic duct; LPV: Left branch of portal vein; LHA: Left hepatic artery; RHD: Right hepatic duct; RPV: Right branch of portal vein; RFID: Right front hepatic duct; RPHD: Right posterior hepatic duct.