Lymphoepithelioma-like neoplasm of the biliary tract with 'probable low malignant potential'.

AIMS: Lymphoepithelioma-like carcinomas (LELCs) are uncommon epithelial cancers characteristically showing two distinct components consisting of malignant epithelial cells and prominent dense lymphoid infiltrate. Hepatic LELCs consist of two types, the lymphoepithelioma-like hepatocellular carcinoma and lymphoepithelioma-like cholangiocarcinoma (LEL-CCA), with the latter being strongly associated with Epstein-Barr virus (EBV). METHODS AND RESULTS: We present a series of three cases of intrahepatic biliary EBV-associated LEL tumours in which the biliary epithelial component showed a distinctly benign appearance, instead of the usual malignant epithelial features of a typical CCA or EBV-associated LEL-CCA. In the lesions, the biliary epithelium showed interconnecting glands or cords of cells. All had a very low proliferation (Ki-67) index. Immunohistochemistry for IDH1 and TP53 performed on two cases was negative and molecular tests for EGFR and KRAS gene mutations performed on one were negative. Prognosis was very good in all three cases, with patients alive with no evidence of disease 24-62 months after surgery. Intriguingly, all three cases had co-infection of HBV and EBV. These cases are also discussed in the context of the 63 cases of LEL-CCA available in the literature, with a focus on epidemiology, clinicopathological features and potential research interests. CONCLUSIONS: Based on the distinct clinicopathological features and unique survival benefits, we believe these tumours represent the benign end of the spectrum of EBV-associated lymphoepithelial biliary carcinomas. Whether these tumours require a revision of the current nomenclature to 'lymphoepithelioma-like neoplasm of the biliary tract with probable low malignant potential' will require more detailed analysis with larger case-series.

cHCC-CCA: Consensus terminology for primary liver carcinomas with both hepatocytic and cholangiocytic differentation.

Primary liver carcinomas with both hepatocytic and cholangiocytic differentiation have been referred to as "combined (or mixed) hepatocellular-cholangiocarcinoma." These tumors, although described over 100 years ago, have attracted greater attention recently because of interest in possible stem cell origin and perhaps because of greater frequency and clinical recognition. Currently, because of a lack of common terminology in the literature, effective treatment and predictable outcome data have been challenging to accrue. This article represents a consensus document from an international community of pathologists, radiologists, and clinicians who have studied and reported on these tumors and recommends a working terminology for diagnostic and research approaches for further study and evaluation. CONCLUSION: It is recommended that diagnosis is based on routine histopathology with hematoxylin and eosin (H&E); immunostains are supportive, but not essential for diagnosis. (Hepatology 2018;68:113-126).

Gastric subtype of intraductal papillary neoplasm of the bile duct: The pathologic spectrum.

BACKGROUND AND AIMS: Intraductal papillary neoplasms of bile duct (IPNBs) remain a challenging entity to manage. METHODS: The pathologic spectrum of 34 gastric subtype of IPNB (gIPNB) cases was examined in consideration of the type 1 and 2 subclassification proposed by Japan-Korea consensus and compared with gastric subtype of pancreatic intraductal papillary mucinous neoplasm (gIPMN) (44 cases). RESULTS: Type 1 gIPNBs (17 cases) showed regular papillary foveola with variable tubular pyloric glands. Eight of the type 1 gIPNBs showed low-grade dysplasia. Type 2 cases (n = 17) showed complicated papillary and tubular structures and high-grade dysplastic foveola and pyloric glands. Foveolas were predominant in 15 cases, while pyloric glands were predominant in 10 cases, and considerable areas of foveolas and pyloric glands in the remaining: these three were found similarly in type 1 and 2 gIPNB. gIPMNs showed central foveola with a peripheral pyloric gland. Such a pattern was recognizable in type 1 but vague in type 2. Type 1 was frequently found in the intrahepatic bile ducts and showed abundant mucin, as in gIPMNs, while type 2 also occurred in the extrahepatic bile ducts and were pathologically more malignant. CONCLUSION: Type 1 lesions shared features of gIPMN, while type 2 lesions differed from gIPMN and were more pathologically malignant.

Telomere shortening and telomerase reactivation in dysplastic nodules of human hepatocarcinogenesis.

BACKGROUNDS/AIMS: The maintenance of telomere with telomerase reactivation, vital for carcinogenesis, was studied in human multistep hepatocarcinogenesis for the characterization of borderline lesions. METHODS: The terminal restriction fragment length (TRFL) and telomerase activity (TA) were examined in 3 chronic hepatitis (CH), 10 cirrhosis, 7 large regenerative nodules (LRNs), 30 low grade dysplastic nodules (LGDNs), 6 high grade DNs (HGDNs), 3 DNs with hepatocellular carcinoma (HCC) foci, 11 HCCs, and 4 normal livers by Southern hybridization and TRAPeze Elisa telomerase detection. RESULTS: The TRFL and TA showed significant differences between the LGDNs and HGDNs. Most LGDNs had similar levels of TRFL and TA to those of the CH, cirrhosis and LRNs, however, 17% of LGDNs revealed shortening of telomeres up to the levels of HGDNs and 7% of LGDNs showed high levels of TA. The levels of TRFL and TA in HGDNs showed no significant differences from those of DNs with HCC foci and HCCs. CONCLUSIONS: The shortening of telomeres and reactivation of telomerase occur in the DNs during the early stages of hepatocarcinogenesis, with a significant change in the transition of LGDNs to HGDNs. The characteristics of HGDNs are considered to be closer to those of HCCs.

Apoptosis of hepatic stellate cells in carbon tetrachloride induced acute liver injury of the rat: analysis of isolated hepatic stellate cells.

BACKGROUND/AIMS: Analysis of isolated hepatic stellate cells (HSCs) from the injured liver may provide direct information on HSC apoptosis. However, it has not been established whether apoptotic HSCs would be isolated using the usual density gradient centrifugation method. The aim of this study was to observe the serial pattern of proliferation and apoptosis in isolated HSCs in comparison with that of liver tissue sections in CCl4 induced acute liver injury. METHODS: Male Sprague-Dawley rats were treated with a single intraperitoneal injection of carbon tetrachloride (CCl4) and were killed at various time points after the treatment. RESULTS: HSC proliferation showed a maximal increase at 32 h after CCl4 injection. Apoptosis of HSC, examined by quantitative analysis of annexin-V-fluorescein isothiocyanate (FITC)staining, showed the maximal increase at 64 h. Apoptosis of HSC in liver tissue sections examined by counting desmin and Tdt-mediated-dUTP biotin nick end labeling (TUNEL) double staining cells, peaked at 64 h. The number of TUNEL positive HSCs in liver tissue sections correlated significantly with annexin-V-FITC binding of isolated HSC. CONCLUSIONS: Studying apoptosis using apoptotic HSCs isolated by a usual density gradient centrifugation method from injured tissue sections would be feasible since it correlated with in vivo apoptosis of HSC.