Impact of large regenerative, low grade and high grade dysplastic nodules in hepatocellular carcinoma development

2003 ◽  
Vol 39 (2) ◽  
pp. 208-214 ◽  
Author(s):  
Mauro Borzio ◽  
Silvia Fargion ◽  
Franco Borzio ◽  
Anna Ludovica Fracanzani ◽  
Anna Maria Croce ◽  
...  
2021 ◽  
Vol 58 (1) ◽  
pp. 82-86
Author(s):  
Gabriela Perdomo CORAL ◽  
Fernanda BRANCO ◽  
Rosalva MEURER ◽  
Patrícia dos Santos MARCON ◽  
Paulo Roberto Ott FONTES ◽  
...  

ABSTRACT BACKGROUND: Hepatocellular carcinoma (HCC) is the most frequent primary cancer of the liver and cirrhosis is considered a pre-malignant disease. In this context, the evolutionary sequence from low grade dysplastic nodule and high grade dysplastic nodule (HGDN) to early HCC and advanced HCC has been studied. The differential diagnosis between HGDN and early HCC is still a challenge, especially in needle biopsies OBJECTIVE: To evaluate an immunohistochemistry panel to differentiate dysplastic nodules and HCC. METHODS: Patients with cirrhosis who underwent surgical resection or liver transplantation were included. The sensitivity, specificity and accuracy for the diagnosis of neoplasia were analyzed by evaluating five markers: heat shock protein 70, glypican 3, glutamine synthetase, clathrin heavy chain and beta-catenin. P≤0.05 was considered statistically significant. RESULTS: One hundred and fifty-six nodules were included; of these, 57 were HCC, 14 HGDN, 18 low grade dysplastic nodules and 67 regenerative macronodules. Sensitivity of HCC diagnosis was 64.9% for glypican 3 and 77.2% for glutamine syntetase, while specificity was 96.0% and 96.0% respectively. When the panel of four markers was considered (excluding beta catenin), the specificity ranged from 87.9% for one positive marker to 100% for at least three markers. The best accuracy for HCC diagnosis was obtained with at least two positive markers, which was associated with a sensitivity of 82.5% and specificity of 99%. CONCLUSION: Differential diagnosis of dysplastic nodules and HCC by morphological criteria can be challenging. Immunomarkers are useful and should be used for the differential diagnosis between HCC and HGDN.


2016 ◽  
Vol 2 (4) ◽  
pp. 179
Author(s):  
Omar Abdel-Rahman

<p>Primary liver cancer is one of the most commonly occur-ring malignancies, albeit one with a deadly consequence as it ranks second in males and sixth in females as a cause of cancer-related death [1, 2]. In this regard, hepatocellular carcinoma (HCC) constitutes almost 90% of confirmed primary liver cancer cases [3]. Despite the advances in clinical classifications of HCC according to patient-related and disease-related criteria (e.g., the Barcelona Clinic liver cancer system) [4], exploring the biological diversity of HCC have lagged behind. The biological diversity of HCC is ex-pected to come from a diverse set of etiological factors (Hepatitis-B virus, Hepatitis-C virus, non-alcoholic stea-tohepatitis, and aflatoxin, among other things), all of which are expected to drive the pathogenesis of HCC via various pathways. In the current issue of AMOR, Youssef and co-workers explored the potential involvement of the cofactor of BRCA1 (COBRA1) in HCC pathogenesis [5]. COBRA1 has been incriminated in the pathogenesis of a number of other solid tumors, notably breast cancer. In the current study, the authors investigated the expression of COBRA1 in several HCC cell lines, ranging from low- to high-grade HCC cell lines. Their results showed that the COBRA1 protein was highly expressed in the low-grade HCC cell line, while significantly down-regulated in high-grade HCC cell lines. This preliminary study indicates that COBRA1 may indeed play a role in HCC pathogenesis and progression, and should be further investigated moving forward.</p><p>Primary liver cancer is one of the most commonly occurring malignancies, albeit one with a deadly consequence as it ranks second in males and sixth in females as a cause of cancer-related death [1,2]. In this regard, hepatocellular carcinoma (HCC) constitutes almost 90% of confirmed primary liver cancer cases [3].</p><p>Despite the advances in clinical classifications of HCC according to patient-related and disease-related criteria (<em>e.g.</em>, the Barcelona Clinic liver cancer system) [4], exploring the biological diversity of HCC have lagged behind. The biological diversity of HCC is expected to come from a diverse set of etiological factors (Hepatitis-B virus, Hepatitis-C virus, non-alcoholic steatohepatitis, and aflatoxin, among other things), all of which are expected to drive the pathogenesis of HCC via various pathways.</p><p>In the current issue of AMOR, Youssef and co-workers explored the potential involvement of the cofactor of BRCA1 (COBRA1) in HCC pathogenesis [5].  COBRA1 has been incriminated in the pathogenesis of a number of other solid tumors, notably breast cancer. In the current study, the authors investigated the expression of COBRA1 in several HCC cell lines, ranging from low- to high-grade HCC cell lines. Their results showed that the COBRA1 protein was highly expressed in the low-grade HCC cell line, while significantly down-regu- lated in high-grade HCC cell lines. This preliminary study indicates that COBRA1 may indeed play a role in HCC pathogenesis and progression, and should be further investigated moving forward.</p>


2014 ◽  
Vol 94 (4) ◽  
pp. 479-484 ◽  
Author(s):  
Ryo Hasegawa ◽  
Kyoko Fujiwara ◽  
Daisuke Obinata ◽  
Hiroyuki Kawashima ◽  
Yui Shinojima ◽  
...  

Introduction: Aberrant methylation levels in the cytosine-phosphate-guanine island (CpGi) region from exon 1 to intron 1 of the zygote arrest 1 (ZAR1) gene have been reported in several types of human cancers, including melanoma, brain tumor, and hepatocellular carcinoma. In the present study, methylation levels at the CpGi of ZAR1 exon 1/intron 1 in bladder cancer specimens were analyzed using mass spectrometry. Materials and Methods: Genomic DNA was extracted from 20 sporadic bladder cancers, and the methylation levels at ZAR1 CpGi were quantitatively examined by the MassARRAY EpiTYPER method. Result: The methylation levels at specific CpG sites of the ZAR1 CpGi were significantly lower in high-grade bladder cancers than in low-grade tumors. Conclusions: The results of the present study indicated a decreased methylation level at CpG sites of ZAR1 exon 1/intron 1. CpGi could serve as a biomarker for invasive bladder cancer.


Gut ◽  
2018 ◽  
Vol 67 (9) ◽  
pp. 1674-1682 ◽  
Author(s):  
Matteo Renzulli ◽  
Maurizio Biselli ◽  
Stefano Brocchi ◽  
Alessandro Granito ◽  
Francesco Vasuri ◽  
...  

ObjectiveMany improvements have been made in diagnosing hepatocellular carcinoma (HCC), but the radiological hallmarks of HCC have remained the same for many years. We prospectively evaluated the imaging criteria of HCC, early HCC and high-grade dysplastic nodules (HGDNs) in patients under surveillance for chronic liver disease, using gadolinium-ethoxybenzyl-diethylenetriamine pentaacetic acid (Gd-EOB-DTPA) MRI and diffusion-weighted imaging.DesignOur study population included 420 nodules >1 cm in 228 patients. The MRI findings of each nodule were collected in all sequences/phases. The diagnosis of HCC was made according to the American Association for the Study of Liver Diseases (AASLD) criteria; all atypical nodules were diagnosed using histology.ResultsA classification and regression tree was developed using three MRI findings which were independently significant correlated variables for early HCC/HCC, and the best sequence of their application in a new diagnostic algorithm (hepatobiliary hypointensity, arterial hyperintensity and diffusion restriction) was suggested. This algorithm demonstrated, both in the entire study population and for nodules ≤2 cm, higher sensitivity (96% [95% CI 93.5% to 97.6%] and 96.6% [95% CI 93.9% to 98.5%], P<0.001, respectively) and slightly lower specificity (91.8% [95% CI 88.6% to 94.1%], P=0.063, and 92.7% [95% CI 88.9% to 95.4%], P=0.125, respectively) than those of the AASLD criteria. Our new diagnostic algorithm also showed a very high sensitivity (94.7%; 95% CI 92% to 96.6%) and specificity (99.3%; 95% CI 97.7% to 99.8%) in classifying HGDN.ConclusionOur new diagnostic algorithm demonstrated significantly higher sensitivity and comparable specificity than those of the AASLD imaging criteria for HCC in patients with cirrhosis evaluated using Gd-EOB-DTPA MRI, even for lesions ≤2 cm. Moreover, this diagnostic algorithm allowed evaluating other lesions which could arise in a cirrhotic liver, such as early HCC and HGDN.


2010 ◽  
Vol 134 (12) ◽  
pp. 1818-1822
Author(s):  
Mario Pirisi ◽  
Monica Leutner ◽  
David J. Pinato ◽  
Claudio Avellini ◽  
Luca Carsana ◽  
...  

Abstract Context—It has been claimed that the Edmondson and Steiner grading system (EGS) values should be obtained preoperatively to select patients with hepatocellular carcinoma for liver transplantation. However, EGS reliability in biopsy specimens has been questioned. Objective—To verify the reliability of the EGS using core biopsy specimens and its reproducibility among pathologists. Design—Paired biopsy and surgical specimens obtained from 40 patients (subset 1) were retrieved by means of computer-aided search of the pathology records and blindly and independently reviewed. The EGS interrater agreement was measured using κ statistics. After having held a consensus meeting, pathologists graded an additional 21 paired hepatocellular carcinoma specimens (subset 2). Results—Analyzing subset 1, pathologists gave significantly lower EGS grades to the biopsy specimens (P &lt; .001), for which the observed agreement was 32.5% (κ  =  0.021), which increased to 82.5% (κ  =  0.186) if only 2 categories were considered (low grade, EGS I–II; high grade, EGS III–IV). The observed agreement in the case of the surgical specimens was 52.5% (κ  =  0.199), which increased to 62.5% (κ  =  0.275) when the low- and high-grade scores were merged. The observed agreement between the assessments of paired biopsy and surgical specimens was 50.0% for pathologist 1 (κ  =  0.057) and 35.0% for pathologist 2 (κ  =  0.078). Merging the EGS grades did not improve the strength of the agreement. Analyzing subset 2 (after the consensus meeting), the observed agreement between pathologists improved more on biopsies (76.2%, κ  =  0.614) than on surgical specimens (61.9%, κ  =  0.434). Conclusions—The EGS is easily underestimated in core biopsy specimens, and interrater disagreement between pathologists can be significant unless consensus meetings are held.


2019 ◽  
Vol 72 (4) ◽  
pp. 295-303
Author(s):  
Dingbao Chen ◽  
Zhao Li ◽  
Weihua Zhu ◽  
Qian Cheng ◽  
Qiujing Song ◽  
...  

AimsTo evaluate stromal histopathological features and immunostaining expression for differential diagnosis of low- and high-grade dysplastic nodules (HGDN) to early and progressed hepatocellular carcinomas (eHCC, pHCC).MaterialsWe evaluated sinusoid capillarisation (SC), solitary artery (SA), ductular reaction (DR), stromal invasion and expression of six biomarkers (GPC3, HSP70, GS, CD34, CK19, EpCAM) in a series of 97 cases.ResultsStromal morphological changes, including SC, DR and SA, exhibited significant differences in differential diagnosis. In one indicator, SC had the best sensitivity (90.00%) and accuracy (85.42%), and SA had the best specificity at 88.89 %. In combinations, SC +and SA +were favourable and optimal. The immunoreactivity of GPC3, HSP70 and GS increased significantly in line with the stepwise progression of hepatocarcinogenesis.ConclusionsStromal histopathology features are useful for diagnosing HGDN, eHCC and small HCC. The immunostaining panel of GPC3, HSP70 and GS can also be supplementary.


2021 ◽  
Vol 11 ◽  
Author(s):  
Wen Chen ◽  
Tao Zhang ◽  
Lin Xu ◽  
Liang Zhao ◽  
Huan Liu ◽  
...  

ObjectivesTo investigate the value of contrast-enhanced computer tomography (CT)-based on radiomics in discriminating high-grade and low-grade hepatocellular carcinoma (HCC) before surgery.MethodsThe retrospective study including 161 consecutive subjects with HCC which was approved by the institutional review board, and the patients were divided into a training group (n = 112) and test group (n = 49) from January 2013 to January 2018. The least absolute shrinkage and selection operator (LASSO) was used to select the most valuable features to build a support vector machine (SVM) model. The performance of the predictive model was evaluated using the area under the curve (AUC), accuracy, sensitivity, and specificity.ResultsThe SVM model showed an acceptable ability to differentiate high-grade from low-grade HCC, with an AUC of 0.904 in the training dataset and 0.937 in the test dataset, accuracy (92.2% versus 95.7%), sensitivity(82.5% versus 88.0%), and specificity (92.7% versus 95.8%), respectively.ConclusionThe machine learning-based radiomics reflects a better evaluating performance in differentiating HCC between low-grade and high-grade, which may contribute to personalized treatment.


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