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It is known that V-set and immunoglobulin domain containing 1 (VSIG1) is a cell-cell adhesion molecule that can serve as an indicator of better survival in patients with gastric cancer. Its interaction with cytoplasmic thyroid transcription factor 1 (TTF-1) has been hypothesized to characterize gastric-type HCC, but its clinical importance is far from understood. As VSIG1 has also been supposed to be involved in the epithelial-mesenchymal transition (EMT) phenomenon, we checked for the first time in the literature the supposed interaction between VSIG1, TTF-1, and Vimentin (VIM) in HCCs. Immunohistochemical (IHC) stains were performed on 217 paraffin-embedded tissue samples that included tumor cells and normal hepatocytes, which served as positive internal controls. VSIG1 positivity was seen in 113 cases (52.07%). In 71 out of 217 HCCs (32.71%), simultaneous positivity for VSIG1 and TTF-1 was seen, being more specific for G1/G2 carcinomas with a trabecular architecture and a longer OS ( p = 0.004). A negative association with VIM was revealed ( p < 0.0001). Scirrhous-type HCC proved negative for all three examined markers. The present paper validates the hypothesis of the existence of a gastric-type HCC, which shows a glandular-like architecture and is characterized by double positivity for VSIG1 and TTF-1, vimentin negativity, and a significant OS.

Hepatocellular carcinoma (HCC) and intrahepatic cholangiocarcinoma (ICC) are the most common primary liver cancers. Little is known about the combined hepatocellular-cholangiocarcinoma (cHCC-ICC) variant and the proper therapeutic strategies. Out of over 1200 available studies about cHCC-ICC, we selected the most representative ones that reflected updated information with application to individualized therapy. Based on literature data and own experience, we hypothesize that two molecular groups of cHCC-ICC can be identified. The proposed division might have a significant therapeutic role. Most cases develop, like HCC, on a background of cirrhosis and hepatitis and share characteristics with HCC; thus, they are named HCC-type cHCC-ICC and therapeutic strategies might be like those for HCC. This review also highlights a new carcinogenic perspective and identifies, based on literature data and the own experience, a second variant of cHCC-ICC called ICC-type cHCC-ICC. Contrary to HCC, these cases show a tendency for lymph node metastases and ICC components in the metastatic tissues. No guidelines have been established yet for such cases. Individualized therapy should be, however, oriented toward the immunoprofile of the primary tumor and metastatic cells, and different therapeutic strategies should be used in patients with HCC- versus ICC-type cHCC-ICC., (© 2024. The Author(s).)

In hepatocellular carcinomas (HCCs), the role of the cell surface protein V-set and immunoglobulin domain containing 1 (VSIG1), which is known as a specific marker of the gastric mucosa and testis, has not yet been determined. We examined VSIG1 immunohistochemical (IHC) expression in 105 consecutive samples provided by HCC patients, along with the IHC expression of three of the biomarkers known to be involved in the epithelial-mesenchymal transition (EMT): vimentin (VIM), and E- and N-cadherin (encoded by CDH1 and CDH2 genes). IHC subcellular localization of thyroid transcription factor 1 (TTF1), in which nuclear-to-cytoplasmic translocation is known to cause a lineage shift from lung to gastric-type adenocarcinoma, was also checked. The obtained data were validated using the miRNET program. In the examined HCC samples, VSIG1 expression was observed in the cytoplasm of normal hepatocytes and downregulated in 47 of the 105 HCCs (44.76%). In 29 cases (27.62%), VSIG1 was co-expressed with cytoplasmic TTF1. VSIG1 expression was positively correlated with both E-cadherin and N-cadherin and negatively correlated with VIM (p < 0.0001). The VSIG1+/E-cadherin+/N-cadherin-/VIM phenotype was seen in 13 cases (12.4%) and was characteristic of well-differentiated (G1/2) carcinomas diagnosed in pT1/2 stages. Like pulmonary carcinomas, simultaneous cytoplasmic positivity of HCC cells for VSIG1 and TTF1 may be a potential indicator of a lineage shift from conventional to gastric-type HCC. The E-cadherin/VSIG1 complex can help suppress tumor growth by limiting HCC dedifferentiation. The miRNET-based interaction between VSIG1/VIM/CDH1/CDH2 genes might be interconnected by miR-200b-3p, a central regulator of EMT which also targets VIM and VSIG1., (© 2021. The Author(s), under exclusive licence to Springer-Verlag GmbH Germany, part of Springer Nature.)

Purpose: We aimed to emphasize the prognostic impact of differences included in the 8th versus the previous 7th edition of AJCC (American Joint Committee on Cancer) Cancer Staging manual for hepatocellular carcinoma (HCC)., Methods: A number of 87 consecutive HCCs were retrospectively evaluated and staged, using the 7th and 8th edition of AJCC staging systems. The clinicopathological parameters were correlated with the overall survival rate. No preoperative chemotherapy was received by any of the patients., Results: According to the 7th edition of AJCC manual, 52 of the 87 cases were staged as pT2 and 35 as pT1. After restaging, according to the 8th edition, 23 of the 52 pT2 cases were understaged as pT1b, and the rest of the 29 remained as pT2. Regarding the 35 HCCs classified as pT1, using 7th edition, all of them were restaged as pT1a. Compared to the 7th staging system, using the 8th edition of AJCC manual, the percentage of pT2 tumors significantly decreased, from 59.77 to 33.33%. The patient's gender, age, tumor focality, and grade of differentiation did not prove to have any prognostic value. Regarding pT stage, it does not influence the overall survival rate, independently from the used staging system., Conclusion: The staging criteria, in the most recent edition of AJCC, are simplified and allowed tumor understaging. These changes do not have independent prognostic value. The prognostic impact of pT understaging should be evaluated in larger cohorts.

Purpose: To present a comprehensive review of the literature data, published between 2000 and 2019 on the PubMed and Web of Science databases, in the field of the tumor microenvironment in hepatocellular carcinoma (HCC). All the data were combined with the personal experiences of the authors., Design: From 1002 representative papers, we selected 86 representative publications which included data on epithelial-to-mesenchymal transition (EMT), angiogenesis, cancer stem-like cells (CSCs), and molecular background of chemoresistance or resistance to radiotherapy., Results: Although the central event concerns activation of the Wnt/ β -catenin pathway, other signal pathways, such as c-Met/HGF/Snail, Notch-1/NF- κ B, TGF- β /SMAD, and basic fibroblast growth factor-related signaling, play a role in the EMT of HCC cells. This pathway is targeted by specific miRNAs and long noncoding RNAs, as explored in this paper. A central player in the tumor microenvironment proved to be the CSCs which can be marked by CD133, CD44, CD90, EpCAM, and CD105. CSCs can induce resistance to cytotoxic therapy or, alternatively, can be synthesized, de novo, after chemo- or radiotherapy, especially after transarterial chemoembolization- or radiofrequency ablation-induced hypoxia. The circulating tumor cells proved to have epithelial, intermediate, or mesenchymal features; their properties have a critical prognostic role., Conclusion: The metastatic pathway of HCC seems to be related to the Wnt- or, rather, TGF β 1-mediated inflammation-angiogenesis-EMT-CSCs crosstalk link. Molecular therapy should target this molecular axis controlling the HCC microenvironment., Competing Interests: The authors have no conflicts of interest to report., (Copyright © 2019 Simona Gurzu et al.)

Rationale: Encephalopathy is a rare complication of hepatic metastases. In this paper we present a case of a patient with lung cancer and metastatic-related giant hepatomegaly., Patient Concerns: A 78-year-old previously healthy male was admitted in the Emergency room in hepatic coma., Diagnoses: The abdominal CT scan examination revealed a huge liver filled with solid nodules., Interventions: No interventions were performed., Outcomes: The patient died at few hours after hospitalization. The autopsy showed a 6.5 kilograms liver with several whitish metastatic nodules and an occult prostate adenocarcinoma. The hilum of both lungs was free of tumor and a 10 mm white nodule was identified surrounding a small bronchus. No peripheral nodules were macroscopically identified. Under microscope, cluster of small cells were observed encasing a small bronchus with multiple minute coin-shaped subpleural foci. A massive intrapulmonary angiolymphatic invasion and metastases from small cell carcinoma in liver, lymph nodes and iliac crest bone marrow were also diagnosed., Lessons: This case highlights the difficulty of diagnosis of aggressive lung carcinomas and the necessity of checking for metachronous tumors. The encephalopathy might be the result of metastatic damage of the liver parenchyma combined with the paraneoplastic effect of the tumor cells. Few than 25 cases of SCLCs with diffuse liver metastases and fulminant liver failure were reported to December 2016. This is the first reported case with a synchronous prostate cancer and a "coin-like" aspect of the SCLC.

Hemangiomas are the most common benign tumors of the liver, considered giant when they exceed 50-100 mm in diameter. In the present report, we present a case of a 5.2-kg hemangioma of the right hepatic lobe, with hemangiomatous foci in the left lobe, which was incidentally diagnosed in a 53-year-old obese female hospitalized for uterine bleeding. The computed tomographic scan and physical examination revealed a giant abdominal tumor and hepatic hemangioma of the right hepatic lobe was suspected. Right hepatectomy and total hysterectomy with bilateral ovariectomy was performed. The histological examination of the surgical specimens confirmed the extremely giant cavernous hepatic hemangioma, and a synchronous pT1a endometrioid endometrial adenocarcinoma was also diagnosed. The patient remains alive without postoperative disorders, 6 months after surgery. To our knowledge, this is the first reported case of such huge hemangioma incidentally diagnosed in an obese female, with a synchronous endometrial adenocarcinoma of the uterus. Because obesity may cause hyperestrogenism, it might both increase the growth rate of hemangioma and the genesis of endometrial cancer in perimenopausal females., (Copyright© 2016 International Institute of Anticancer Research (Dr. John G. Delinassios), All rights reserved.)

In this paper, we present the successful therapeutic approach of unresectable liver metastases in a patient with rectal cancer.A 63-year-old male underwent endoscopic polypectomy followed by rectosigmoid resection for an adenocarcinoma of the rectum diagnosed in pT2N0 stage. The angio-computed tomography (CT) revealed four metastatic hepatic nodules ranging from 12 to 130 mm in diameter. After one cure of trans-arterial chemoembolization (TACE) with lipiodol and 5-fluorouracil, combined with FOLFOX4 + capecitabine systemic chemotherapy, the diameter of all hepatic nodules decreased to half size, at 6 months after TACE. Further curative surgical hepatic metastasectomy was done and complete pathologic response was obtained. The patient is free of recurrences and metastases after 26 months of follow-up.This representative case shows that an efficient trans-disciplinary approach could lead to successful therapeutic management even in patients with advanced-staged colorectal carcinomas.

Atypical hepatocellular neoplasm (AHN) is an adenoma-like hepatic tumor that even occurs in noncirrhotic liver of males (any age) or females ≥ 50 years old, or associates focal atypical features. In this article, 2 unusual cases diagnosed in elderly cirrhotic patients, unrelated to steroids, are presented. The first case was incidentally diagnosed in an 83-year-old female. During laparoscopic surgery for cholecystectomy, hemoperitoneum was installed and laparotomy was necessary to remove a 70-mm nodular encapsulated hepatic tumor that was microscopically composed by hepatocyte-like cells with clear cytoplasm, arranged in 1- to 2-cell-thick plates and intermingled with areas of peliosis, negative for alpha fetoprotein (αFP), p53, and keratin 7, with low Ki67 index and intact reticulin framework. The second case was incidentally diagnosed at ultrasound examination in a 66-year-old male. The surgical specimen was a 50-mm solid multinodular tumor that microscopically consisted of 3-cell-thick plates of hepatocyte-like cells with acinar, pseudoglandular, and trabecular architecture, intermingled with peliotic areas, without nuclear atypia and disintegrated reticulin framework. Both of the cases occurred in cirrhotic liver. The tumor cells were marked by AE1/AE3 keratin, displayed a Ki67 index < 5% and were negative for αFP, p53, and keratin 7. No recurrences or any other disorder occurred 6 months after surgery. In cirrhotic liver, adenomas with peliosis that do not satisfy all the diagnosis criteria synthesized in the article should be considered AHNs and differential diagnosis includes hepatocellular carcinoma but also focal nodular hyperplasia, regenerative nodules, and dysplastic nodules. This histological entity is not yet included in the WHO Classification list.

Aim: The present study aimed to investigate the status of primary liver tumors diagnosed in the Emergency Hospital of Mures County, Romania., Materials and Methods: We performed a retrospective study based on data collected from histopathological bulletins stored in the archives of the Pathology Laboratories of Mures County. We selected those patients' data that were diagnosed with liver tumors during January 2004-August 2011. The acquired data were collected and processed statistically using the GraphPad InStat Demo 3 statistical software., Results: We identified 748 liver tumors out of which 264 were primary liver tumors (35.29%), whereof 108 were malignant primary liver tumors and 156 benign liver tumors. The male:female ratio in case of malignant tumors was 1.7:1 and for benign tumors it was 1:2.62. In case of malignant tumors, the mean age of male patients was 63.98±11.67 as for female patients it was 60.14±11.65 years. In case of benign tumors, the mean age of male patients was 59.29±9.58 as for female patients it was 55.55±12.86. 81.48% of the malignant tumors were hepatocellular carcinoma (HCC), followed by cholangiocarcinoma (14.81%). 40% of HCC presented associated cirrhosis, in the other 60% signs of chronic alcoholism being observed., Conclusions: Hepatocellular carcinoma remains the first on the list of malignant primary liver tumors in Romanian patients, probably due to a high rate of alcohol consumption.

The liver is the most common and critical site for the development of colon cancer metastases. Tumor angiogenesis in liver metastasis from colon carcinoma is a controversial subject. Liver microenvironment, immunophenotypical and morphological particularities of hepatic vessels are only few aspects, which establish difficulties in quantification of tumor vascularisation from liver metastasis. The aim of this work is to study the distribution of CD105 positive vessels and the proliferation rate of endothelial cells from liver metastasis of colon carcinoma based on double immunostaining CD105/Ki67. In liver metastasis from well-differentiated adenocarcinoma we found a high number of CD105+/Ki67- vessels. On the other hand, in liver metastasis from poorly differentiated adenocarcinoma we noticed rare CD105+/Ki67+ vessels. It is hypothesized that neoangiogenesis of liver metastasis is performed through intussusceptive mechanism rather than sprouting and could be supported by the presence of kissing phenomenon, CD105 positive transcapillary pillars and the absence of endothelial cells proliferation in this vessels. We conclude that in liver metastasis principal mechanism of neovascularisation formation is based on intussusception.