Hepatocellular Carcinoma

Torbenson, Michael

doi:10.1007/978-3-319-16089-4_7

Cited by 9 publications

(43 citation statements)

References 104 publications

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“…9 Glypican 3 (GPC3) was identified as a tumor marker for the diagnosis of HCC due to its specificity and sensitivity. 10,13–15 GPC3 shows a cytoplasmic, membranous and canalicular staining among HCCs. However, among livers with a cirrhotic background, GPC3 expression can also be found focally.…”

Section: Methodsmentioning

confidence: 93%

“…Tumors that retain a reticulin network are generally benign or pre-neoplastic, whereas HCC loses the reticulin fiber normal architecture. 9,10 CD34 is a marker of “capillarization”, a process by which sinusoid endothelial cells lose their fenestration. CD34 demonstrates neovascularization in HCC, while nontumorous hepatic sinusoids do not stain with CD34.…”

Section: Methodsmentioning

confidence: 99%

“…CD34 demonstrates neovascularization in HCC, while nontumorous hepatic sinusoids do not stain with CD34. 10–12 However, it was previously reported that in some cases, CD34 may occur diffusely or in areas of hepatocellular adenoma. 9 Glypican 3 (GPC3) was identified as a tumor marker for the diagnosis of HCC due to its specificity and sensitivity.…”

Section: Methodsmentioning

confidence: 99%

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Ectopic FVIII expression and misfolding in hepatocytes as a cause for hepatocellular carcinoma

Deng

Kapelanski-Lamoureux

Gao

et al. 2021

Preprint

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Clotting Factor VIII (FVIII) is the protein deficient in hemophilia A (HA), an X chromosome-linked bleeding disorder affecting 24.6 per 100,000 males at birth. Scientists and clinical physicians have been striving hard to find a cure for this disease. Presently, HA therapy involves prophylactic infusion of plasma-derived or recombinant-derived FVIII. Recent clinical studies have reported success using recent adeno-associated-virus (AAV) vector mediated delivery of a FVIII gene. FVIII is a 330 kDa glycoprotein comprised of three domains (A1-A2-B-A3-C1-C2). The B domain is dispensable and B domain-deleted (BDD) FVIII is used in the clinic as an effective protein replacement therapy for HA. Previously, we observed that hydrodynamic tail vein injection of the BDD-FVIII vector resulted in FVIII aggregation and endoplasmic reticulum (ER) stress in murine livers. Additionally, mice that were exposed to transient ER stress and then fed a high fat diet (HFD) for 9 months developed hepatocellular carcinoma (HCC). Therefore, we deduced that ectopic transient expression of FVIII in hepatocytes of mice with subsequent HFD feeding may also develop HCC. Here, we tested hepatocyte expression of two BDD-FVIII variants in vivo. BDD-FVIII aggregates in the ER and induces hepatocyte apoptosis, and N6-FVIII is more efficiently folded and secreted from the ER and causes less hepatocyte apoptosis. We performed tail vein injections of vectors directing expression of BDD-FVIII or N6-BDD to hepatocytes of 6-week old mice. One week after injection, mice were fed 60% HFD for 65 weeks. We found that 50% of mice that received N6-BDD developed liver tumors; in contrast, 90% of mice given BDD-FVIII developed liver tumors. Of the mice injected with BDD-FVIII, 30% developed carcinomas and 60% developed adenomas. Similar masses were not observed in mice that received empty vector. These findings raise concerns about the safety of long-term ectopic expression of FVIII in hepatocytes during FVIII gene therapy

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Section: Methodsmentioning

confidence: 93%

Section: Methodsmentioning

confidence: 99%

Section: Methodsmentioning

confidence: 99%

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Ectopic FVIII expression and misfolding in hepatocytes as a cause for hepatocellular carcinoma

Deng

Kapelanski-Lamoureux

Gao

et al. 2021

Preprint

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“…After independent detailed review, all four pathologists reviewed the cases together on a multi‐head microscope and reached a consensus. Based on the above cytological features, the 12 cases of HCC identified were classified as well‐differentiated, moderately differentiated, poorly differentiated, and fibrolamellar HCC 4 . Cell blocks were not made in any of the FNA samples collected as the technical procedure had not been standardised at that time in our department.…”

Section: Methodsmentioning

confidence: 99%

Cytomorphology of paediatric hepatocellular carcinoma: A useful diagnostic adjunct

et al. 2023

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IntroductionHepatocellular carcinoma (HCC) is a common primary malignancy of the liver but is rare in the paediatric age group; thus, it may be misdiagnosed as the more common tumour, hepatoblastoma. Management varies in both these tumours, and pathological diagnosis thus plays an important role for definitive therapy. Only a few case reports available in the literature have described the cytological characteristics of paediatric HCC. The present study was thus planned to evaluate the cytomorphological features of paediatric HCC.MethodsCases diagnosed with HCC on ultrasound‐guided fine needle aspiration cytology over a period of 14 years were retrieved. The cases were evaluated for detailed cytological features including cellularity, architecture, sinusoidal wrapping, trabecular thickness, necrosis, anisonucleosis, chromatin, nucleoli, nuclear contours, bi‐ or multinucleation, intranuclear and intracytoplasmic inclusions, naked nuclei, extra‐medullary haematopoiesis, monomorphism, and nuclear overlapping.ResultsTwelve cases of HCC were included in the study. The median age at diagnosis was 10 years. Serum alpha‐fetoprotein level was raised in most of them. Five of the 12 cases were characterised as moderately differentiated, three as poorly differentiated, two as well differentiated, and two as the fibrolamellar type of HCC. Cytohistological correlation was performed in seven cases.ConclusionsUltrasound‐guided fine needle aspiration serves as a useful tool to diagnose paediatric HCC and differentiate it from other primary hepatic malignancies, especially hepatoblastoma which closely mimics HCC in this age group, as serum alpha protein levels and imaging findings are unable to distinguish these two tumours.

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“…In tumors with a major HCC component, the cut surface resembles HCC and is a yellowish, green to tan color. It is usually well-demarcated, soft, and bulges out from the cut surface of the liver, with varying degrees of hemorrhage and necrosis [ 37 ]. In tumors with a major CCA component, the cut surface is grayish-white, fibrotic, and firm with an infiltrative tumor border [ 38 ].…”

Section: Pathological Featuresmentioning

confidence: 99%

Combined Hepatocellular-Cholangiocarcinoma: An Update on Pathology and Diagnostic Approach

Choi

2022

Biomedicines

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Combined hepatocellular-cholangiocarcinoma (cHCC-CCA) is a rare primary liver carcinoma displaying both hepatocytic and cholangiocytic differentiation within the same tumor. Relative to classic hepatocellular carcinoma (HCC), cHCC-CCA has more aggressive behavior and a poorer prognosis. Though recent advances have improved our understanding of the biology underlying cHCC-CCAs, they remain diagnostically challenging for pathologists because of their morphologic and phenotypic diversity. Accurate diagnosis of cHCC-CCA is important for patient management and prognostication. Herein, we review recent updates on cHCC-CCA, focusing on tumor classification, pathology, and diagnostic approach.

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Hepatocellular Carcinoma

Cited by 9 publications

References 104 publications

Ectopic FVIII expression and misfolding in hepatocytes as a cause for hepatocellular carcinoma

Ectopic FVIII expression and misfolding in hepatocytes as a cause for hepatocellular carcinoma

Cytomorphology of paediatric hepatocellular carcinoma: A useful diagnostic adjunct

Combined Hepatocellular-Cholangiocarcinoma: An Update on Pathology and Diagnostic Approach

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