Macrotrabecular‐massive hepatocellular carcinoma: A distinctive histological subtype with clinical relevance

Ziol, Marianne; Poté, Nicolas; Amaddeo, Giuliana; Laurent, Alexis; Nault, Jean‐Charles; Oberti, Frédéric; Costentin, Charlotte; Michalak, Sophie; Bouattour, Mohamed; Francoz, Claire; Pageaux, Georges Philippe; Ramos, Jeanne; Decaens, Thomas; Luciani, Alain; Guiu, Boris; Vilgrain, Valérie; Aubé, Christophe; Derman, Jonathan; Charpy, Cécile; Zucman‐Rossi, Jessica; Barget, Nathalie; Séror, Olivier; Ganne-Carrié, Nathalie; Paradis, Valérie; Caldéraro, Julien

doi:10.1002/hep.29762

Cited by 169 publications

(143 citation statements)

References 33 publications

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“…74,75,77,78 The main signalling pathways specifically activated in the progenitor subclass are IGF1R and AKT. 67,74 The ''Wnt-TGFb subclass" also includes a more aggressive subgroup of HCC ''G3", distinguished by a specific histological phenotype designated ''macrotrabecular massive", 77,83 the occurrence of TSC1 and TSC2 mutations, a more pronounced enrichment in FGF19/CCND1 amplification, as well as overexpression of genes related to the cell cycle and nucleus pore. 74,77 The ''non-proliferation class" of HCC is more heterogeneous and includes less aggressive, chromosomally stable, tumours related to HCV or alcohol.…”

Section: Key Pointsmentioning

confidence: 99%

Advances in molecular classification and precision oncology in hepatocellular carcinoma

Rebouissou

Nault

2020

Journal of Hepatology

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Hepatocellular carcinoma (HCC) arises from hepatocytes through the sequential accumulation of multiple genomic and epigenomic alterations resulting from Darwinian selection. Genes from various signalling pathways such as telomere maintenance, Wnt/b-catenin, P53/cell cycle regulation, oxidative stress, epigenetic modifiers, AKT/mTOR and MAP kinase are frequently mutated in HCC. Several subclasses of HCC have been identified based on transcriptomic dysregulation and genetic alterations that are closely related to risk factors, pathological features and prognosis. Undoubtedly, integration of data obtained from both preclinical models and human studies can help to accelerate the identification of robust predictive biomarkers of response to targeted biotherapy and immunotherapy. The aim of this review is to describe the main advances in HCC in terms of molecular biology and to discuss how this knowledge could be used in clinical practice in the future.

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Section: Key Pointsmentioning

confidence: 99%

Advances in molecular classification and precision oncology in hepatocellular carcinoma

Rebouissou

Nault

2020

Journal of Hepatology

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341

283

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“…Four major growth patterns in HCC are trabecular (70%), solid (20%), pseudo glandular (10%) and macrotrabecular (1%)[ 72 ]. Of these, macrotrabecular pattern has recently been shown to have significant clinical relevance[ 73 , 74 ]. Morphology based segregation into histological subtypes[ 72 , 75 ] such as fibro lamellar carcinoma[ 76 , 77 ], lymphoepithelioma like carcinoma[ 78 ], steatohepatitis HCC[ 79 ], combined hepatocholangiocarcinoma[ 75 ], and histological subtype with stem cell markers[ 80 , 81 ] have independent prognostic importance.…”

Section: Role Of Morphological Parameters and Histological Subtypesmentioning

confidence: 99%

“…In a recent study by Ziol et al[ 74 ] Macrotrabecular-massive is a newly described subtype of HCC, found in 12% of the cohort of 237 HCC surgical samples and 284 HCC liver biopsies. Authors have defined this entity by the presence of a predominant (> 50%) macrotrabecular architecture (more than 6 cells thick).…”

Section: Role Of Morphological Parameters and Histological Subtypesmentioning

confidence: 99%

“…Authors have defined this entity by the presence of a predominant (> 50%) macrotrabecular architecture (more than 6 cells thick). This phenotype was associated with poor prognostic factors like tumor size, α-Feto protein (AFP) level, satellite nodules, and vascular invasion and was found to be an independent predictor of early and overall recurrence[ 74 ]. Lauwers et al[ 86 ] noted macrotrabecular -predominant architecture in 26.6% of their 425 cases of resected HCC.…”

Section: Role Of Morphological Parameters and Histological Subtypesmentioning

confidence: 99%

“…In comparison to the compact architecture they had worse overall survival. Prognostic information derived from phenotypes reemphasizes the potential benefits of biopsy add to reviving its importance[ 74 ].…”

Section: Role Of Morphological Parameters and Histological Subtypesmentioning

confidence: 99%

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Changing role of histopathology in the diagnosis and management of hepatocellular carcinoma

Rastogi

2018

WJG

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Hepatocellular carcinoma (HCC) is one of the most common and fatal cancer in the world. HCC frequently presents with advanced disease, has a high recurrence rate and limited treatment options, which leads to very poor prognosis. This warrants urgent improvement in the diagnosis and treatment. Liver biopsy plays very important role in the diagnosis and prognosis of HCC, but with technical advancements and progression in the field of imaging, clinical guidelines have restricted the role of biopsy to very limited situations. Biopsy also has its own problems of needle tract seeding of tumor, small risk of complications, technical and sampling errors along with interpretative errors. Despite this, tissue analysis is often required because imaging is not always specific, limited expertise and lack of advanced imaging in many centers and limitations of imaging in the diagnosis of small, mixed and other variant forms of HCC. In addition, biopsy confirmation is often required for clinical trials of new drugs and targeted therapies. Tissue biomarkers along with certain morphological features, phenotypes and immune-phenotypes that serve as important prognostic and outcome predictors and as decisive factors for therapy decisions, add to the continuing role of histopathology. Advancements in cancer biology and development of molecular classification of HCC with clinic pathological correlation, lead to discovery of HCC phenotypic surrogates of prognostic and therapeutically significant molecular signatures. Thus tissue characteristics and morphology based correlates of molecular subtypes provide invaluable information for management and prognosis. This review thus focuses on the importance of histopathology and resurgence of role of biopsy in the diagnosis, management and prognostication of HCC.

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Blockade of PD‐1 and CTLA‐4: A potent immunotherapeutic approach for hepatocellular carcinoma

Hou,

Xu,

et al. 2023

BioFactors

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Immune checkpoints (ICPs) can promote tumor growth and prevent immunity‐induced cancer cell apoptosis. Fortunately, targeting ICPs, such as programmed cell death 1 (PD‐1) or cytotoxic T lymphocyte associated protein 4 (CTLA‐4), has achieved great success in the past few years and has gradually become an effective treatment for cancers, including hepatocellular carcinoma (HCC). However, many patients do not respond to ICP therapy due to acquired resistance and recurrence. Therefore, clarifying the specific mechanisms of ICP in the development of HCC is very important for enhancing the efficacy of anti‐PD‐1 and anti‐CTLA‐4 therapy. In particular, antigen presentation and interferon‐γ (IFN‐γ) signaling were reported to be involved in the development of resistance. In this review, we have explained the role and regulatory mechanisms of ICP therapy in HCC pathology. Moreover, we have also elaborated on combinations of ICP inhibitors and other treatments to enhance the antitumor effect. Collectively, recent advances in the pharmacological targeting of ICPs provide insights for the development of a novel alternative treatment for HCC.

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Macrotrabecular‐massive hepatocellular carcinoma: A distinctive histological subtype with clinical relevance

Abstract: The MTM-HCC subtype, reliably observed in 12% of patients eligible for curative treatment, represents an aggressive form of HCC that may require more specific therapeutic strategies. (Hepatology 2018;68:103-112).

Cited by 169 publications

References 33 publications

Advances in molecular classification and precision oncology in hepatocellular carcinoma

Advances in molecular classification and precision oncology in hepatocellular carcinoma

Changing role of histopathology in the diagnosis and management of hepatocellular carcinoma

Blockade of PD‐1 and CTLA‐4: A potent immunotherapeutic approach for hepatocellular carcinoma

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