Scirrhous Hepatocellular Carcinoma Research Articles

Steatohepatitic hepatocellular Carcinoma:A new approach to classifying morphological subtypes of hepatocellular carcinoma

Histological subtyping of hepatocellular carcinoma (HCC) is challenging in the presence of histological heterogeneity, where distinctly different morphological patterns are present within the same tumor. Current approaches rely on percent cut-offs. We hypothesized that morphologic intratumor heterogeneity is a non-random biological feature and that incorporating recurrent patterns would improve histological subtyping of HCC. Resected HCC were studied and the overall frequency of morphologic intratumor heterogeneity was 45% in 242 specimens. Steatohepatitic HCC (SH-HCC) had the highest frequency of morphologic intratumor heterogeneity (91%); this was confirmed in additional cohorts of SH-HCC from different medical centers (overall frequency of 78% in SH-HCC). Morphologic intratumor heterogeneity in SH-HCC showed distinct and recurrent patterns that could be classified as early, intermediate, and advanced. Incorporating these patterns into the definition of SH-HCC allowed successful resolution of several persistent challenges: the problem of the best cut-off for subtyping SH-HCC, the problem of the relationship between SH-HCC and scirrhous HCC, and the classification for HCC with abundant microvesicular steatosis. This approach also clarified the relationship between SH-HCC and CTNNB1 mutations, showing that CTNNB1 mutations occur late in a subset of SH-HCC. In summary, there is a high frequency of morphologic intratumor heterogeneity in HCC. Incorporating this finding into histological subtyping resolved several persistent problems with the SH-HCC subtype.

Hypoxia-driven tumor stromal remodeling and immunosuppressive microenvironment in scirrhous HCC.

Scirrhous HCC (SHCC) is one of the unique subtypes of HCC, characterized by abundant fibrous stroma in the tumor microenvironment. However, the molecular traits of SHCC remain unclear, which is essential to develop specialized therapeutic approaches for SHCC. We presented an integrative analysis containing single-cell RNA-sequencing, whole-exome sequencing, and bulk RNA-sequencing in SHCC and usual HCC samples from 134 patients to delineate genomic features, transcriptomic profiles, and stromal immune microenvironment of SHCC. Multiplexed immunofluorescence staining, flow cytometry, and functional experiments were performed for validation. Here, we identified SHCC presented with less genomic heterogeneity while possessing a unique transcriptomic profile different from usual HCC. Insulin-like growth factor 2 was significantly upregulated in SHCC tumor cells compared to usual HCC, and could serve as a potential diagnostic biomarker for SHCC. Significant tumor stromal remodeling and hypoxia were observed in SHCC with enrichment of matrix cancer-associated fibroblasts and upregulation of hypoxic pathways. Insulin-like growth factor 2 was identified as a key mediator in shaping the hypoxic stromal microenvironment of SHCC. Under this microenvironment, SHCC exhibited an immunosuppressive niche correlated to enhanced VEGFA signaling activity, where CD4 + T cells and CD8 + T cells were dysfunctional. Furthermore, we found that another hypoxic-related molecule SPP1 from SHCC tumor cells suppressed the function of dendritic cells via the SPP1-CD44 axis, which also probably hindered the activation of T cells. We uncovered the genomic characteristics of SHCC, and revealed a hypoxia-driven tumor stroma remodeling and immunosuppressive microenvironment in SHCC.

Imaging features of concurrent scirrhous hepatocellular carcinoma and primary clear cell carcinoma of the liver: A case report and literature review

Multiple lesions commonly appear in the liver of patients with hepatocellular carcinoma (HCC), and the prognosis is associated with the subtype. However, simultaneous occurrence of scirrhous HCC (SHCC) and primary clear cell carcinoma of the liver (PCCCL) has not been reported to date. The diagnosis of SHCC and PCCCL is uncommon using the traditional imaging examination methods such as ultrasound (US), computed tomography (CT), and magnetic resonance imaging. We herein summarize the imaging features of SHCC and PCCCL to provide a reference for accurate preoperative diagnosis and appropriate treatment. A 55-year-old male was diagnosed with two hepatic tumors by the US examination. On the 2nd day after the US examination, he was diagnosed with HCC with intrahepatic metastasis by enhanced CT examination. His alpha-fetoprotein level was 3272 ng/mL (reference range, 0–7 ng/mL). Two weeks after enhanced CT examination, the patient underwent hepatectomy and cholecystectomy. Pathological examination showed that the tumor in liver segments 2 and 3 was SHCC and that the tumor in liver segment 4 was PCCCL. One year postoperatively, digital subtraction angiography showed no obvious tumor staining. Five years postoperatively, enhanced CT examination showed no recurrence or metastasis. Radiologists usually diagnose multiple tumors in the liver as malignant tumors with intrahepatic metastasis. Simultaneous occurrence of SHCC and PCCCL in the liver is occasionally found. The US imaging features, CT enhancement types, and location of the tumors can help radiologists to accurately diagnose SHCC and PCCCL, allowing clinicians to choose appropriate treatment.

DNA methylation status of the SPHK1 and LTB genes underlies the clinicopathological diversity of non-alcoholic steatohepatitis-related hepatocellular carcinomas

PurposeThis study was performed to identify the DNA methylation profiles underlying the clinicopathological diversity of non-alcoholic steatohepatitis (NASH)-related hepatocellular carcinomas (HCCs). MethodsGenome-wide DNA methylation analysis of 88 liver tissue samples was performed using the Infinium assay. ResultsPrincipal component analysis revealed that distinct DNA methylation profiles differing from such profiles in normal control liver tissue had already been established in non-cancerous liver tissue showing NASH, which is considered to be a precancerous condition. Hierarchical clustering separated 26 NASH-related HCCs into Cluster I (n = 8) and Cluster II (n = 18). Such epigenetic clustering was significantly correlated with histopathological diversity, i.e. poorer tumor differentiation, tumor steatosis and development of a scirrhous HCC component. Significant differences in DNA methylation levels between the two clusters were accumulated in molecular pathways participating in cell adhesion and cytoskeletal remodeling, as well as cell proliferation and apoptosis. Among tumor-related genes characterizing Clusters I and II, differences in the levels of DNA methylation and mRNA expression for the SPHK1, INHBA, LTB and PDE3B genes were correlated with poorer tumor differentiation. 5-Aza-2′-deoxycytidine treatment of HCC cells revealed epigenetic regulation of the SPHK1 and LTB genes. Knockdown experiments showed that SPHK1 promotes cell proliferation, represses apoptosis and enhances migration, whereas LTB enhances migration of HCC cells. DNA hypomethylation resulting in increased expression of SPHK1 and LTB in poorly differentiated HCCs may underlie the aggressive phenotype of such HCCs. ConclusionThese data indicate that DNA methylation profiles may determine the clinicopathological heterogeneity of NASH-related HCCs via alterations of tumor-related gene expression.

Update in Pathology of Practically Encountered Lesions and Diseases in the Liver

This issue of the American Journal of Surgical Pathology, Reviews and Reports is devoted to recent advances and update in the pathology of the liver. The articles provide insights into the current nomenclature, classification, diagnosis, differential diagnoses, clinical and prognostic aspects of various liver diseases, and lesions that are informative to pathologists in their daily practice. Hepatocellular adenomas (HCAs) is generally a benign liver neoplasm that typically arises in the noncirrhotic liver; however, malignant transformation does occur, and hence, subtyping is critical. Drs Jung and Liu present a case of HCA that was initially diagnosed as inflammatory HCA on a biopsy and subsequently was confirmed to be β-catenin–activated inflammatory HCA on the resection specimen. They then comprehensively review recent updates on molecular classification and the key histologic features of each subtype and discuss common diagnostic pitfalls. Over the past decades, hepatocellular carcinoma (HCC) and intrahepatic cholangiocarcinoma (iCCA) have been recognized to be heterogeneous in morphology, molecular features, and biological behavior. Recent World Health Organization classification describes various histomorphological subtypes of HCC and iCCA, some with characteristic molecular profiles, clinical correlates, and prognostic implications. In their review, Drs Hwang and Kim nicely discuss recently described subtypes of HCC and iCCA: macrotrabecular HCC, steatohepatitic HCC, scirrhous HCC, and small duct iCCA. Congestive hepatopathy shows a unique pattern of fibrosis, that is, pericentral fibrosis at early stage, which may progress to bridging fibrosis and cirrhosis. Making a diagnosis of congestive hepatopathy and staging its fibrosis are important tasks for pathologists, as patients may undergo liver biopsies before cardiac transplantation to assess the degree of liver fibrosis, which may impact clinical decision-making. Besides patients' own cardiac dysfunction, congestive hepatopathy can also be seen after a Fontan procedure. Drs Gosse and Bosch describe a case of congestive hepatopathy due to altered circulation with a Fontan procedure. They then discuss the fibrosis scoring systems recently described for Fontan-associated liver disease and congestive heart disease–associated hepatopathy. Combined hepatocellular-cholangiocarcinoma is a rare primary liver tumor with neoplastic components of both hepatocytic and cholangiocytic differentiation within the same tumor. There is recent consensus paper and World Health Organization classification of this unique tumor. Drs Kondo, Akiba, and Yano herein report a case of this tumor and thoughtfully review the terminology, classification, and clinical and pathological characteristics of combined hepatocellular-cholangiocarcinoma and its differential diagnosis. Hemophagocytic lymphohistiocytosis is a rare disease with a high mortality. Liver involvement is common, with most patients demonstrating acute hepatitis. Therefore, liver biopsies are frequently performed when this entity is suspected. Dr Xiong and colleagues summarize the clinical features of hemophagocytic lymphohistiocytosis, emphasizing its hepatic manifestations. They describe the highly variable histologic patterns and address difficulties encountered by pathologists. We are extremely grateful to all the contributors for sharing their expertise and knowledge in forming this issue. We hope that the information provides highlights and elucidates the practically encountered lesions in the liver. Guest Editors

Histomorphological Subtypes of Hepatocellular Carcinoma and Intrahepatic Cholangiocarcinoma: Review and Update

AbstractPrimary liver cancers comprise a heterogeneous group of neoplasms, with the 2 main entities being hepatocellular carcinoma (HCC) and intrahepatic cholangiocarcinoma (iCCA). Over the past decades, HCC and iCCA have been recognized to be heterogeneous in morphology, molecular features, and biological behavior, and the most recent World Health Organization classification of digestive system tumors describes various histomorphological subtypes of HCC and iCCA, some of which also have characteristic molecular features, clinical correlates, and prognostic implications. In this review, we discuss 4 recently described subtypes of HCC and iCCA—macrotrabecular HCC, steatohepatitic HCC, scirrhous HCC, and small duct iCCA—based on a series of cases.

Morphomolecular Classification Update on Hepatocellular Adenoma, Hepatocellular Carcinoma, and Intrahepatic Cholangiocarcinoma

Hepatocellular adenomas (HCAs), hepatocellular carcinomas (HCCs), and intrahepatic cholangiocarcinomas (iCCAs) are a highly heterogeneous group of liver tumors with diverse pathomolecular features and prognoses. High-throughput gene sequencing techniques have allowed discovery of distinct genetic and molecular underpinnings of these tumors and identified distinct subtypes that demonstrate varied clinicobiologic behaviors, imaging findings, and complications. The combination of histopathologic findings and molecular profiling form the basis for the morphomolecular classification of liver tumors. Distinct HCA subtypes with characteristic imaging findings and complications include HNF1A-inactivated, inflammatory, β-catenin-activated, β-catenin-activated inflammatory, and sonic hedgehog HCAs. HCCs can be grouped into proliferative and nonproliferative subtypes. Proliferative HCCs include macrotrabecular-massive, TP53-mutated, scirrhous, clear cell, fibrolamellar, and sarcomatoid HCCs and combined HCC-cholangiocarcinoma. Steatohepatitic and β-catenin-mutated HCCs constitute the nonproliferative subtypes. iCCAs are classified as small-duct and large-duct types on the basis of the level of bile duct involvement, with significant differences in pathogenesis, molecular signatures, imaging findings, and biologic behaviors. Cross-sectional imaging modalities, including multiphase CT and multiparametric MRI, play an essential role in diagnosis, staging, treatment response assessment, and surveillance. Select imaging phenotypes can be correlated with genetic abnormalities, and identification of surrogate imaging markers may help avoid genetic testing. Improved understanding of morphomolecular features of liver tumors has opened new areas of research in the targeted therapeutics and management guidelines. The purpose of this article is to review imaging findings of select morphomolecular subtypes of HCAs, HCCs, and iCCAs and discuss therapeutic and prognostic implications. Online supplemental material is available for this article. ©RSNA, 2022.

State-of-the-art review on the correlations between pathological and magnetic resonance features of cirrhotic nodules.

Hepatocellular carcinoma (HCC) has become the second greatest cause of cancer-related mortality worldwide and the newest advancements in liver imaging have improved the diagnosis of both overt malignancies and premalignant lesions, such as cirrhotic or dysplastic nodules, which is crucial to improve overall patient survival rate and to choose the best treatment options. The role of Computed Tomography (CT) and Magnetic Resonance Imaging (MRI) has grown in the last 20 years. In particular, the introduction of hepatospecific contrast agents has strongly increased the definition of precursor nodules and detection of high-grade dysplastic nodules and early HCCs. Nevertheless, the diagnosis of liver tumours in cirrhotic patients sometimes remains challenging for radiologists, thus, in doubtful cases, biopsy and histological analysis become critical in clinical practice. This current review briefly summarizes the history of imaging and histology for HCC, covering the newest techniques and their limits. Then, the article discusses the links between radiological and pathological characteristics of liver lesions in cirrhotic patients, by describing the multistep process of hepatocarcinogenesis. Explaining the evolution of pathologic change from cirrhotic nodules to malignancy, the list of analyzed lesions provides regenerative nodules, low-grade and high-grade dysplastic nodules, small HCC and progressed HCC, including common subtypes (steatohepatitic HCC, scirrhous HCC, macrotrabecular massive HCC) and more rare forms (clear cell HCC, chromophobe HCC, neutrophil-rich HCC, lymphocyte-rich HCC, fibrolamellar HCC). The last chapter covers the importance of the new integrated morphological-molecular classification and its association with radiological features.

Tumor-matrix interaction induces phenotypic switching in liver cancer cells.

Intrahepatic cholangiocarcinoma (ICC) is characterized by fibrous stroma and clinical behavior more aggressive than that of hepatocellular carcinoma (HCC). Scirrhous HCC is a subtype of HCC with fibrous stroma, frequently has partial cholangiocytic differentiation, and is more likely to have an aggressive behavior. This study explored the interaction of liver cancer cells with the extracellular matrix. Liver cancer cells grown on collagen 1-coated plates showed upregulation of cholangiocytic marker expression but downregulation of hepatocytic marker expression. Three-dimensional sphere culture and Boyden chamber assay showed enhanced invasion and migration ability in collagen 1-conditioned liver cancer cells. Interaction with collagen 1 reduced liver cancer cell proliferation. RNA sequencing showed that in the liver cancer cells, collagen 1 upregulated cell cycle inhibitor expression and cell-matrix interaction, tumor migration, and angiogenesis pathways, but downregulated liver metabolic function pathways. Cholangiocytic differentiation and invasiveness induced by collagen 1 was mediated by the mitogen-activated protein kinase (MAPK) pathway, which was regulated by cell-matrix interaction-induced Src activation. Analysis of the Cancer Genome Atlas cohort showed that collagen 1 induced and suppressed genes were highly enriched in ICC and HCC, respectively. In HCC samples, collagen 1-regulated genes were strongly coexpressed and correlated with COL1A1 expression. Liver cancer cell-matrix interaction induces cholangiocytic differentiation and switches liver cancer cells from a proliferative to an invasive phenotype through the Src/MAPK pathway, which may partly explain the differences in the behaviors of HCC and ICC.

Variant Hepatocellular Carcinoma Subtypes According to the 2019 WHO Classification: An Imaging-Focused Review.

The 2019 5th edition of the WHO classification of digestive system tumors estimates that up to 35% of hepatocellular carcinomas (HCCs) can be classified as one of eight subtypes defined by molecular characteristics: steatohepatitic, clear cell, macrotrabecular-massive, scirrhous, chromophobe, fibrolamellar, neutrophil-rich, and lymphocyte-rich HCCs. Due to their distinct cellular and architectural characteristics, these subtypes may not display arterial phase hyperenhancement and washout appearance, which are the classic MRI features of HCC, creating challenges in noninvasively diagnosing such lesions as HCC. Moreover, certain subtypes with atypical imaging features have a worse prognosis than other HCCs. A range of distinguishing imaging features may help raise suspicion that a liver lesion represents one of these HCC subtypes. In this review, we describe the MRI features that have been reported in association with various HCC subtypes according to the 2019 WHO classification, with attention given to the current understanding of these subtypes' pathologic and molecular bases and relevance to clinical practice. Imaging findings that differentiate the subtypes from benign liver lesions and non-HCC malignancies are highlighted. Familiarity with these sub-types and their imaging features may allow the radiologist to suggest their presence, though histologic analysis remains needed to establish the diagnosis.

Imaging Spectrum of Intrahepatic Mass-Forming Cholangiocarcinoma and Its Mimickers: How to Differentiate Them Using MRI.

Intrahepatic cholangiocarcinoma (ICC) is the second most common primary hepatic malignancy, with mass-forming growth pattern being the most common. The typical imaging appearance of mass-forming ICC (mICC) consists of irregular ring enhancement in the arterial phase followed by the progressive central enhancement on portal venous and delayed phases. However, atypical imaging presentation in the form of hypervascular mICC might also be seen, which can be attributed to distinct pathological characteristics. Ancillary imaging features such as lobular shape, capsular retraction, segmental biliary dilatation, and vascular encasement favor the diagnosis of mICC. Nevertheless, these radiological findings may also be present in certain benign conditions such as focal confluent fibrosis, sclerosing hemangioma, organizing hepatic abscess, or the pseudosolid form of hydatid disease. In addition, a few malignant lesions including primary liver lymphoma, hemangioendothelioma, solitary hypovascular liver metastases, and atypical forms of hepatocellular carcinoma (HCC), such as scirrhous HCC, infiltrative HCC, and poorly differentiated HCC, may also pose a diagnostic dilemma by simulating mICC in imaging studies. Diffusion-weighted imaging and the use of hepatobiliary contrast agents might be helpful for differential diagnosis in certain cases. The aim of this manuscript is to provide a comprehensive overview of mICC imaging features and to describe useful tips for differential diagnosis with its potential mimickers.

Gadoxetate-enhanced MRI Features of Proliferative Hepatocellular Carcinoma Are Prognostic after Surgery.

Background Hepatocellular carcinomas (HCCs) are heterogeneous neoplasms, and the prognosis varies based on the subtype. Two broad molecular classes of HCC have been proposed: a proliferative and a nonproliferative class. Purpose To evaluate the gadoxetate-enhanced MRI findings of the proliferative class HCC and its prognostic significance after surgery. Materials and Methods This retrospective cohort study evaluated patients with surgically resected treatment-naive single HCC (≤5 cm) who underwent hepatic resection from January 2010 through February 2013 and preoperative gadoxetate-enhanced MRI. A Cox proportional hazards model was used to determine the predictive factors for overall survival (OS), intrahepatic distant recurrence, and extrahepatic metastasis (EM). The mean follow-up period was 75.5 months ± 30.2 (standard deviation). Multivariable logistic regression was performed to determine factors associated with proliferative class HCC. Results A total of 158 patients (mean age, 57 years ± 11; 128 men and 30 women) were evaluated. Forty-two of the 158 HCCs (26.6%) were proliferative class HCCs (17 macrotrabecular-massive HCCs, 14 keratin 19-positive HCCs, 10 scirrhous HCCs, and one sarcomatoid HCC). The proliferative class was associated with worse OS (hazard ratio [HR], 3.1; 95% CI: 1.5, 6.0; P = .01) and higher rates of intrahepatic distant recurrence (HR, 1.83; 95% CI: 1.1, 2.9; P = .01) and EM (HR, 9.97; 95% CI: 3.2, 31.4; P < .001). Rim arterial phase hyperenhancement (APHE) at gadoxetate-enhanced MRI (odds ratio [OR], 6.35; 95% CI: 1.9, 21.7; P = .01) and high serum α-fetoprotein (>100 ng/mL) (OR, 4.18; 95% CI: 1.64, 10.7; P = .01) were independent predictors for proliferative HCC. The presence of rim APHE was associated with poor OS (HR, 2.4; 95% CI: 1.2, 4.9; P = .02) and higher rates of EM (HR, 7.4; 95% CI: 2.5, 21.7; P < .01). Conclusion The proliferative class of hepatocellular carcinoma (HCC) is an independent factor for poor overall survival with increased rates of intrahepatic and extrahepatic metastasis. Rim arterial phase hyperenhancement at gadoxetate-enhanced MRI may help to identify proliferative class HCC and predict poor overall survival and an increased incidence of extrahepatic metastasis. © RSNA, 2021 Online supplemental material is available for this article. See also the editorial by Krinsky and Shanbhogue in this issue.

Clinical manifestations and outcomes of patients with scirrhous hepatocellular carcinoma.

The scirrhous hepatocellular carcinoma (HCC) is a rare subtype characterized by prominent fibrous stroma separating nests of tumor cells histologically. The clinical characteristics of scirrhous HCC have not been clearly elucidated due to limited literatures. We aimed to investigate the clinical manifestations and outcomes of patients with scirrhous HCC. A total of 4012 patients with histologically proven HCC from the Cancer Registry Database (2004-2016) of the National Taiwan University Hospital (NTUH) were enrolled; whereas, 30 patients with scirrhous HCC were identified from the pathology database of NTUH. We matched 120 patients with non-scirrhous HCC through propensity score according to sex, age, Barcelona Clinic Liver Cancer stage and initial treatment modality for comparison. No significant difference in baseline characteristics and presentations was observed between the patients with scirrhous and non-scirrhous HCC except baseline alpha-fetoprotein level. The overall survival was comparable in these two groups. For the patients undergoing curative therapy, the risk of recurrence in the patients with scirrhous HCC was significantly higher within 24months after curative therapy (hazard ratio [HR], 2.88, 95% confidence interval [CI], 1.43-5.80, p value, 0.003) as compared with those with non-scirrhous HCC. The overall recurrence rate was comparable in these two groups. Using propensity score matching, the risk of recurrence in the patients with scirrhous HCC was significantly higher in the first 2years after curative therapy as compared to those with non-scirrhous HCC. An individualized post-curative treatment monitoring strategy should be considered for the patients with scirrhous HCC.

Co-existence of clear cell hepatocellular carcinoma and scirrhous hepatocellular carcinoma in the same liver segment: A case report

Co-existence of clear cell hepatocellular carcinoma and scirrhous hepatocellular carcinoma in the same liver segment: A case report

Clinicopathological Features of Two Extremely Rare Hepatocellular Carcinoma Variants: a Brief Review of Fibrolamellar and Scirrhous Hepatocellular Carcinoma.

We aimed to distinguish between fibrolamellar hepatocellular carcinoma and scirrhous hepatocellular carcinoma histopathologically. In this review, fibrolamellar hepatocellular carcinoma and scirrhous hepatocellular carcinoma two specific and rare variants of hepatocellular carcinoma, which are difficult to diagnose histopathologically are discussed. The clinical, radiological, gross, histopathological, immunohistochemical, and molecular features of these two tumors, which are defined by the World Health Organization (WHO), are mentioned.

Fibronodular hepatocellular carcinoma—a new variant of liver cancer: clinical, pathological and radiological correlation

AimsTo establish and define a new, not previously reported hepatocellular carcinoma (HCC) variant, termed fibronodular HCC (FN-HCC).MethodsWe retrospectively reviewed 290 HCC cases and identified 29 FN-HCC and 24 scirrhous HCC...

Outcomes of Patients with Scirrhous Hepatocellular Carcinoma: Insights from the National Cancer Database

IntroductionScirrhous hepatocellular carcinoma (HCC) is a rare primary liver tumor characterized by extensive fibrosis and production of parathyroid hormone–related peptide. There have been conflicting reports on patient survival in scirrhous versus non-scirrhous HCC. The objective of the present study was to define the clinical features, practice patterns, and long-term outcomes of patients with scirrhous HCC versus non-scirrhous HCC in a propensity score–matched cohort. MethodsA propensity score–matched cohort was created using data from the National Cancer Database for 2004 to 2015. A multivariable Cox proportional hazards regression analysis was performed to assess the effect of the scirrhous HCC variant on overall survival. ResultsAmong the 70,426 patients with a diagnosis of HCC who met the inclusion criteria, 99.8% had non-scirrhous HCC (n = 70,290) whereas a small subset had scirrhous HCC (n = 136, 0.19%). While 20,330 (28.9%) patients underwent liver-directed therapy (resection, ablation, and transplantation), the majority did not (n = 50,096, 71.1%). After propensity matching, there were no difference in 1-, 3-, or 5-year overall survival among patients with scirrhous versus non-scirrhous HCC (1-year overall survival (OS), 53.7% versus 51.0%; 3-year OS, 34.6% versus 28.7%; and 5-year OS, 18.0% versus 21.0%, respectively; p = 0.52). While the scirrhous HCC variant was not associated with survival (hazard ratio [HR] 0.93, 95% CI 0.74–1.16), non-receipt of liver-directed therapy (HR 0.24, 95% CI 0.18–0.32), advanced AJCC stage (III/IV) (HR 2.14, 95% CI 1.55–2.95), and non-academic facilities (HR 0.60, 95% CI 0.49–0.73) remained associated with worse survival. ConclusionPatients with the scirrhous variant had a comparable overall survival compared with individuals who had non-scirrhous HCC. Failure to receive liver-directed therapy, advanced AJCC stage (III/IV), and treatment at a non-academic facility was strongly associated with a worse long-term prognosis.

Steatotic and nonsteatotic scirrhous hepatocellular carcinomas reveal distinct clinicopathological features

We investigated the clinicopathological and molecular characteristics of scirrhous hepatocellular carcinoma (HCC) to elucidate its uniqueness. Samples from 120 resected HCC cases underwent immunohistochemical analysis. Tumor area containing fibrous stroma and the percentage of steatotic cells within the tumor were evaluated. In our previous report, tumors were immunohistochemically subclassified as biliary/stem cell markers-positive (B/S) (cytokeratin 19 and/or sal-like protein 4 and/or epithelial cell adhesion molecule positive), Wnt/β-catenin signaling-related markers-positive (W/B) (β-catenin and/or glutamine synthetase positive), or all markers-negative (-/-) groups. Thirty-seven cases (31%) with fibrous stroma making up ≥50% of the largest tumor area were defined as scirrhous HCC (sHCC); the other 83 cases (69%) were categorized as common HCC (cHCC). Clinicopathologically, sHCC had fewer poorly differentiated tumors (P = .037) and a higher percentage of cases with steatosis (P = .025) than cHCC. sHCC cases were further divided into two subgroups: those with ≥5% steatotic cells (steatotic sHCC) and those with <5% steatotic cells (nonsteatotic sHCC). Hepatitis B virus infection was more frequent in nonsteatotic sHCC (P = .029), and non-B, non-C cases were more frequent in steatotic sHCC (P = .006). Steatotic sHCC tended to have a longer time to recurrence than nonsteatotic sHCC and cHCC. Most nonsteatotic sHCC cases belonged to B/S group, whereas most steatotic sHCC belonged to -/- group. The same tendency in sHCC was shown in another cohort. Distinct features were seen in steatotic and nonsteatotic sHCC, and both sHCC subgroups exhibited different clinicopathological and molecular features from cHCC. These findings support the hypothesis that sHCC is an independent entity.

Synchronous Occurrence of Classic and Scirrhous Hepatocellular Carcinomas: A Case Report

: Scirrhous hepatocellular carcinoma (HCC) is a subtype of HCC that is characterized by abundant fibrous stroma admixed with tumor cells. Although imaging findings of scirrhous HCC differ from those of classic HCC, it is difficult to diagnose this rare neoplasm. Like classic HCC, scirrhous HCC frequently develops in patients with liver cirrhosis, but there has been no report of synchronous occurrence of classic and scirrhous HCCs. Here, we report synchronous classic and scirrhous HCCs in a 62-year-old man with early liver cirrhosis who underwent gadoxetic acid-enhanced and diffusion-weighted magnetic resonance imaging.

Multiple hepatic sclerosing hemangiomas: a case report and review of the literature

BackgroundHepatic sclerosing hemangioma, a very rare benign tumor, is characterized by fibrosis and hyalinization occurring in association with degeneration of a hepatic cavernous hemangioma. Such atypical hemangiomas can be diagnosed incorrectly as primary or metastatic malignancies based on imaging characteristics. We present herein a rare case of giant and multiple hepatic sclerosing hemangiomas that are difficult to differentiate from hepatic malignancies and review the relevant literature.Case presentationThe patient was a 48-year-old male who was found to have multiple hepatic tumors and a giant tumor (67 × 53 mm) superior to the inferior vena cave by an abdominal ultrasonography during a routine medical examination. The patient was referred to our hospital for further evaluations and diagnosis of the multiple hepatic tumors. Dynamic CT showed low-density tumors in the delayed phase suggestive of membrane-covered lesions. EOB-MRI demonstrated a mass with low-signal intensity mass on T1-weighted images and areas of high-signal intensity on T2-weighted images and a hypointense mass in the hepatobiliary phase, which showed high intensity on DWI-based ADC map. FDG-PET showed no accumulation of [18F]-FDG. A provisional diagnosis of multiple scirrhous hepatocellular carcinomas was made on the basis of these imaging studies, and caudate lobectomy of the liver and partial hepatectomy of S2 and S6 were performed. Histopathological examination showed that the tumors were composed of various sized irregularly dilated vessels with some blood thrombi, inflammatory cell infiltration, fibrous and hyalinized sclerotic or myxomatous stroma, resulting in a diagnosis of multiple hepatic sclerosing hemangiomas.ConclusionsDifferentiation of multiple sclerosing hemangiomas from other hepatic malignant tumors, such as intrahepatic cholangiocarcinoma, metastatic liver cancer, and scirrhous hepatocellular carcinoma characterized by abundant fibrous stroma, is difficult because the radiological findings are very similar. Inclusion of hepatic sclerosing hemangioma in the differential diagnosis of multiple liver tumors could enable optimal management; this possibility is important to consider before planning invasive therapies.