scholarly journals Expression of CD34 in cirrhotic liver: Reliance to dedifferentiation

2010 ◽  
Vol 67 (6) ◽  
pp. 459-462 ◽  
Author(s):  
Jasmina Gligorijevic ◽  
Biljana Djordjevic ◽  
Aleksandar Petrovic ◽  
Aleksandra Radicevic ◽  
Simonida Stojanovic
Keyword(s):  
Hepatocellular Carcinoma ◽  
Liver Tissue ◽  
Vascular Supply ◽  
Cirrhotic Liver ◽  
Low Grade ◽  
Dysplastic Nodules ◽  
Regenerative Nodules ◽  
Early Hcc ◽  
Statistical Program ◽  
Isolated Arteries

Background/Aim. The vascular supply of dysplastic nodules (DN) is altered compared with surrounding cirrhotic nodules. Dysplastic nodules contain unpaired arteries which are isolated arteries unaccompained by bille ducts. In adition, capillarization or neovascularization is evident on CD34 and CD31 staining. The investigation of angiogenic profile of regenerative, dysplastic and nodules of hepatocellular carcinoma aimed at assessing whether vascular profile is in reliance to the process of dedifferentiation of hepatocytes during the course of cirrhosis. Methods. Thirty four liver nodules from surgical biopsies of 12 patients previously undiagnosed to have cirrhosis, were classified as regenerative, dysplastic and small hepatocellular carcinomas (HCC). The investigation included 8 large regenerative nodules (LRN), 11 low grade dysplastic nodules (LGDN), 12 high grade dysplastic nodules (HGDN) and 3 early HCC. Serial sections of the nodules and surrounding cirrhotic liver tissue were immunostained against CD34. The vascular counting method was performed. The results were analysed using SPSS computer statistical program. Results. The number of capillary unites showed significant differences among nodular types, with the largest number of capillaries in hepatocellular carcinoma as well as strong reliance to dedifferentiation. Conclusion. There is a significant correlation of sinusoidal capillarization to dediferentiation of the liver tissue during the course of cirrhosis. From diagnostic view, capillary counting may be helpfull to distinguish dysplastic from nondysplastic nodules. The appearance of dysplastic nodules in nonselected surgical biopsies is frequent enough to challenge caution during the follow-up of cirrhotic patients.

scholarly journals RESULTS OF IMMUNOHISTOCHEMISTRY IN THE DIFFERENTIAL DIAGNOSIS OF EARLY HEPATOCELLULAR CARCINOMA AND NODULES WITH HIGH-GRADE DYSPLASIA IN PATIENTS WITH CIRRHOSIS

2021 ◽  
Vol 58 (1) ◽  
pp. 82-86
Author(s):  
Gabriela Perdomo CORAL ◽  
Fernanda BRANCO ◽  
Rosalva MEURER ◽  
Patrícia dos Santos MARCON ◽  
Paulo Roberto Ott FONTES ◽  
...  
Keyword(s):  
Hepatocellular Carcinoma ◽  
Differential Diagnosis ◽  
Low Grade ◽  
Beta Catenin ◽  
High Grade ◽  
Dysplastic Nodule ◽  
Dysplastic Nodules ◽  
Morphological Criteria ◽  
Early Hcc ◽  
Sensitivity Specificity

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.

scholarly journals Magnetic resonance imaging of the cirrhotic liver: diagnosis of hepatocellular carcinoma and evaluation of response to treatment - Part 1

2017 ◽  
Vol 50 (1) ◽  
pp. 38-47 ◽  
Author(s):  
Miguel Ramalho ◽  
António P. Matos ◽  
Mamdoh AlObaidy ◽  
Fernanda Velloni ◽  
Ersan Altun ◽  
...  
Keyword(s):  
Magnetic Resonance Imaging ◽  
Hepatocellular Carcinoma ◽  
Liver Cirrhosis ◽  
Magnetic Resonance ◽  
Cirrhotic Liver ◽  
Response To Treatment ◽  
Arterial Phase ◽  
Resonance Imaging ◽  
Regenerative Nodules ◽  
Magnetic Resonance Imaging Mri

Abstract Magnetic resonance imaging (MRI) is the modern gold standard for the noninvasive evaluation of the cirrhotic liver. The combination of arterial phase hyperenhancement and delayed wash-out allows a definitive diagnosis of hepatocellular carcinoma (HCC) in patients with liver cirrhosis or chronic liver disease, without the requirement for confirmatory biopsy. That pattern is highly specific and has been endorsed in Western and Asian diagnostic guidelines. However, the sensitivity of the combination is relatively low for small HCCs. In this two-part review paper, we will address MRI of the cirrhotic liver. In this first part, we provide a brief background on liver cirrhosis and HCC, followed by descriptions of imaging surveillance of liver cirrhosis and the diagnostic performance of the different imaging modalities used in clinical settings. We then describe some of the requirements for the basic MRI technique, as well as the standard MRI protocol, and provide a detailed description of the appearance of various types of hepatocellular nodules encountered in the setting of the carcinogenic pathway in the cirrhotic liver, ranging from regenerative nodules to HCC.

Squamous cell carcinoma antigen in human liver carcinogenesis

2007 ◽  
Vol 61 (4) ◽  
pp. 445-447 ◽  
Author(s):  
M Guido ◽  
T Roskams ◽  
P Pontisso ◽  
M Fassan ◽  
S N Thung ◽  
...  
Keyword(s):  
Squamous Cell Carcinoma ◽  
Cell Carcinoma ◽  
Squamous Cell ◽  
Early Event ◽  
Low Grade ◽  
Squamous Cell Carcinoma Antigen ◽  
Liver Carcinogenesis ◽  
Dysplastic Nodules ◽  
Significant Difference ◽  
Regenerative Nodules

Background:Squamous cell carcinoma antigen (SCCA) is a serine protease inhibitor that can be overexpressed in hepatocellular carcinoma (HCC) at both molecular and protein level, but no data are available on its expression in pre-malignant stages.Aim:To assess SCCA expression by immunohistochemistry in HCC and its nodular precursors in cirrhotic livers.Methods:55 nodules from 42 explanted livers were evaluated: 7 large regenerative nodules (LRNs), 7 low-grade dysplastic nodules (LG-DNs), 10 high-grade DNs (HG-DNs), and 31 HCC. SCCA expression was semiquantitatively scored on a four-tiered scale.Results:SCCA hepatocyte immunostaining was always restricted to the cytoplasm, mainly exhibiting a granular pattern. Stain intensity varied, ranging from weak to very strong. Within the nodules, positive cells were unevenly distributed, either scattered or in irregular clusters. The prevalence of SCCA expression was 29% in LRNs, 100% in DNs and 93% in HCC. A significant difference emerged in both prevalence and score for LRNs versus LG-DNs (p<0.039), HG-DNs (p = 0.001), and HCC (p = 0.000). A barely significant difference (p = 0.49) was observed between LG-DNs and HG-DNs, while no difference in SCCA expression was detected between HG-DNs and HCC. Cirrhotic tissue adjacent to the nodules was positive in 96% of cases, with a significant difference in the score (p = 0.000) between hepatocytes adjacent to HCC and those surrounding LRNs.Discussion:This study provides the first evidence that aberrant SCCA expression is an early event in liver cell carcinomatous transformation.

scholarly journals Expression of hnRNPK & Claudin-4 in HCV-Induced Early HCC and Adjacent Liver Tissue

2017 ◽  
Vol 5 (5) ◽  
pp. 595-602
Author(s):  
Olfat Hammam ◽  
Mona Magdy ◽  
Amgad Anas ◽  
Ali Abdel Rahim ◽  
Mohamed Heedaya ◽  
...  
Keyword(s):  
Liver Tissue ◽  
Epithelial Mesenchymal Transition ◽  
Low Grade ◽  
High Grade ◽  
Fibrosis Score ◽  
Immunohistochemical Expression ◽  
Mesenchymal Transition ◽  
Curative Therapy ◽  
Egyptian Patients ◽  
Early Hcc

BACKGROUND: HCC in Egypt usually occurs in HCV cirrhotic livers with poor prognosis due to late diagnosis. High hnRNPK & low Claudin-4 profiles indicate Epithelial Mesenchymal Transition (EMT), malignant transformation and high-grade tumours.AIM: We studied the immunohistochemical expression of hnRNPK and Claudin-4 in HCV induced early HCC (eHCC) and adjacent liver tissue in Egyptian patients to improve eHCC detection in cirrhotic livers with better curative therapy options.METHOD: We studied the immunohistochemical expression of hnRNPK and Claudin-4 in 100 Egyptian patients resection specimens of HCV induced early HCC (eHCC) and adjacent liver tissue, in order to improve eHCC detection in cirrhotic livers, thus improving their therapeutic options.RESULTS: Early HCC grade significantly directly correlated with nuclear hnRNPK/5HPFs count and inversely correlated with Claudin-4 expression %, with a converse correlation between hnRNPK and Claudin-4. Moreover in eHCC, combined hnRNPK ³ 30/5HPFs & Claudin-4 ³ 40% significantly distinguished low grade eHCC (G1) from high grade eHCC (G2&G3), with sensitivity 97% & specificity 69.7% for hnRNPK ³ 30/5HPFs, and with sensitivity 70% & specificity 94.3% for Claudin-4 ³ 40%. Moreover in the adjacent liver, both markers expressions significantly directly correlated with each other and with METAVIR fibrosis score but not with activity. Furthermore, 58% of eHCCs showed hnRNPK ³ 30 Claudin-4 < 40% profile, indicating EMT type3, compared to 26% with hnRNPK ³ 30 Claudin-4 £ 10% profile in adjacent cirrhotic/ precirrhotic liver, with significant use of combined hnRNPK ³30/5HPFs & Claudin 4 £ 10% as eHCC prediction cut offs in cirrhosis (p < 0.05).CONCLUSION: Combination of hnRNPK and Claudin-4 can indicate early HCC development in HCV cirrhotic livers using hnRNPK ³ 30/5HPFs & Claudin-4 £ 10% cut offs. Also, combination of hnRNPK ³ 30/5HPFs & Claudin-4 ³ 40% can distinguish low grade eHCC (G1) from high grade eHCC (G2&G3).

New hallmark of hepatocellular carcinoma, early hepatocellular carcinoma and high-grade dysplastic nodules on Gd-EOB-DTPA MRI in patients with cirrhosis: a new diagnostic algorithm

Gut ◽  
2018 ◽  
Vol 67 (9) ◽  
pp. 1674-1682 ◽  
Author(s):  
Matteo Renzulli ◽  
Maurizio Biselli ◽  
Stefano Brocchi ◽  
Alessandro Granito ◽  
Francesco Vasuri ◽  
...  
Keyword(s):  
Hepatocellular Carcinoma ◽  
Diagnostic Algorithm ◽  
High Grade ◽  
Mri Findings ◽  
Entire Study ◽  
Dysplastic Nodules ◽  
Early Hcc ◽  
Study Population ◽  
And Diffusion ◽  
Higher Sensitivity

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.

scholarly journals Molecular aspects of hepatic carcinogenesis

2002 ◽  
Vol 44 (1) ◽  
pp. 39-48 ◽  
Author(s):  
Marcelo Eidi NITA ◽  
Venâncio Avancini Ferreira ALVES ◽  
Flair José CARRILHO ◽  
Suzane Kioko ONO-NITA ◽  
Evandro Sobroza de MELLO ◽  
...  
Keyword(s):  
Hepatocellular Carcinoma ◽  
Special Focus ◽  
Molecular Alterations ◽  
Dysplastic Nodules ◽  
Hepatic Carcinogenesis ◽  
Great Progress ◽  
Regenerative Nodules ◽  
Exogenous Agents ◽  
The Subject ◽  
Molecular Aspects

Exogenous agents correlated with hepatocellular carcinoma (HCC) have been identified and well characterized. These agents, including the different viruses that cause chronic hepatitis and cirrhosis, can lead to regenerative nodules and dysplastic nodules/adenomatous hyperplasia. These conditions associated with several molecular alterations of hepatocyte ultimately culminate in hepatocellular carcinoma. Recently, there has been a great progress in the identification of somatic and germinative mutations that may be correlated with the development of HCC, justifying a review on the subject. Hence, the factors involved in the process of hepatic carcinogenesis, such as infection by the hepatitis B and C viruses, with a special focus in the molecular alterations described in recent years are discussed herein, pointing out areas potentially relevant for clinical development.

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