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Qin Z, Li Y, Shao X, Li K, Bai Y, Wang B, Ma F, Shi W, Song L, Zhuang A, He F, Ding C, Yang W. HNF4A functions as a hepatocellular carcinoma oncogene or tumor suppressor depending upon the AMPK pathway activity status. Cancer Lett 2025; 623:217732. [PMID: 40254090 DOI: 10.1016/j.canlet.2025.217732] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/28/2024] [Revised: 04/10/2025] [Accepted: 04/17/2025] [Indexed: 04/22/2025]
Abstract
Cancer cells frequently undergo energy metabolic stress induced by the increased dynamics of nutrient supply. Hepatocyte nuclear factor 4A (HNF4A) is a master transcription factor (TF) in hepatocytes that regulates metabolism and differentiation. However, the mechanism underlying how HNF4A functions in cancer progression remains unclear due to conflicting results observed in numerous studies. To address the roles of HNF4A in hepatocellular carcinoma (HCC), we investigated the regulatory functions of HNF4A in HCC cells under different glucose supply conditions. We found that HNF4A exhibited tumor-suppressive effects on the proliferation and migration of HCC cells in glucose-sufficient conditions and tumor-promotive effects on HCC cells in glucose-insufficient conditions. Further investigation revealed that this diverse function of HNF4A was dependent upon the AMPK pathway activity. Similarly, the prognosis predicted by HNF4A was also correlated with whether the AMPKa expression levels were low or high in clinical HCC patients. Multiomics approaches consisting of proteomics and ChIP-seq revealed that key HNF4A target genes, including NEDD4 and RPS6KA2, are involved in the diverse function of HNF4A in HCC in response to the AMPK activity status. Specifically, HNF4A could bind to the promoter region of NEDD4 and RPS6KA2, and upregulating their expression. Our study has demonstrated the relationship between and synergism of AMPK and HNF4A in the progression of HCC under diverse nutrient conditions.
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Affiliation(s)
- Zhaoyu Qin
- Department of Pediatric Orthopedics, Xinhua Hospital Affiliated to Shanghai Jiao Tong University School of Medicine, Shanghai, 200092, China; State Key Laboratory of Genetics and Development of Complex Phenotypes, Institutes of Biomedical Sciences, School of Life Sciences, Human Phenome Institute, Fudan University, Shanghai 200032, China
| | - Yan Li
- State Key Laboratory of Genetics and Development of Complex Phenotypes, Institutes of Biomedical Sciences, School of Life Sciences, Human Phenome Institute, Fudan University, Shanghai 200032, China
| | - Xiexiang Shao
- Department of Pediatric Orthopedics, Xinhua Hospital Affiliated to Shanghai Jiao Tong University School of Medicine, Shanghai, 200092, China
| | - Kai Li
- State Key Laboratory of Genetics and Development of Complex Phenotypes, Institutes of Biomedical Sciences, School of Life Sciences, Human Phenome Institute, Fudan University, Shanghai 200032, China
| | - Yihe Bai
- State Key Laboratory of Genetics and Development of Complex Phenotypes, Institutes of Biomedical Sciences, School of Life Sciences, Human Phenome Institute, Fudan University, Shanghai 200032, China
| | - Bing Wang
- State Key Laboratory of Genetics and Development of Complex Phenotypes, Institutes of Biomedical Sciences, School of Life Sciences, Human Phenome Institute, Fudan University, Shanghai 200032, China
| | - Fahan Ma
- State Key Laboratory of Genetics and Development of Complex Phenotypes, Institutes of Biomedical Sciences, School of Life Sciences, Human Phenome Institute, Fudan University, Shanghai 200032, China
| | - Wenhao Shi
- State Key Laboratory of Proteomics, Beijing Proteome Research Center, Beijing Institute of Radiation Medicine, National Center for Protein Sciences (The PHOENIX Center, Beijing), Beijing, 102206, China; School of Life Sciences, Tsinghua University, Beijing, 100084, China
| | - Lei Song
- State Key Laboratory of Proteomics, Beijing Proteome Research Center, Beijing Institute of Radiation Medicine, National Center for Protein Sciences (The PHOENIX Center, Beijing), Beijing, 102206, China
| | - Aojia Zhuang
- State Key Laboratory of Genetics and Development of Complex Phenotypes, Institutes of Biomedical Sciences, School of Life Sciences, Human Phenome Institute, Fudan University, Shanghai 200032, China
| | - Fuchu He
- State Key Laboratory of Genetics and Development of Complex Phenotypes, Institutes of Biomedical Sciences, School of Life Sciences, Human Phenome Institute, Fudan University, Shanghai 200032, China; State Key Laboratory of Proteomics, Beijing Proteome Research Center, Beijing Institute of Radiation Medicine, National Center for Protein Sciences (The PHOENIX Center, Beijing), Beijing, 102206, China; School of Life Sciences, Tsinghua University, Beijing, 100084, China
| | - Chen Ding
- State Key Laboratory of Genetics and Development of Complex Phenotypes, Institutes of Biomedical Sciences, School of Life Sciences, Human Phenome Institute, Fudan University, Shanghai 200032, China; State Key Laboratory of Proteomics, Beijing Proteome Research Center, Beijing Institute of Radiation Medicine, National Center for Protein Sciences (The PHOENIX Center, Beijing), Beijing, 102206, China
| | - Wenjun Yang
- Department of Pediatric Orthopedics, Xinhua Hospital Affiliated to Shanghai Jiao Tong University School of Medicine, Shanghai, 200092, China.
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Moris D, Martinino A, Schiltz S, Allen PJ, Barbas A, Sudan D, King L, Berg C, Kim C, Bashir M, Palta M, Morse MA, Lidsky ME. Advances in the treatment of hepatocellular carcinoma: An overview of the current and evolving therapeutic landscape for clinicians. CA Cancer J Clin 2025. [PMID: 40392748 DOI: 10.3322/caac.70018] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 11/25/2024] [Revised: 04/10/2025] [Accepted: 04/11/2025] [Indexed: 05/22/2025] Open
Abstract
Hepatocellular carcinoma (HCC) is the sixth most common malignancy and the third leading cause of cancer-related death worldwide. Contemporary advances in systemic and locoregional therapies have led to changes in peer-reviewed guidelines regarding systemic therapy as well as the possibility of downstaging disease that may enable some patients with advanced disease to ultimately undergo partial hepatectomy or transplantation with curative intent. This review focuses on all modalities of therapy for HCC, guided by modern-day practice-changing randomized data where available. The surgical management of HCC, including resection and transplantation, both of which have evolving criteria for what is considered biologically resectable and transplantable, as well as locoregional therapy (i.e., therapeutic embolization, ablation, radiation, and hepatic arterial infusion), are discussed. Historical and modern-day practice-changing trials evaluating immunotherapy with targeted therapies for advanced disease, as well as adjuvant systemic therapy, are also summarized. In addition, this article examines the critical dimension of toxicities and patient-oriented considerations to ensure a comprehensive and balanced discourse on treatment implications.
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Affiliation(s)
- Dimitrios Moris
- Division of Surgical Oncology, Department of Surgery, Duke University Medical Center, Durham, North Carolina, USA
| | - Alessandro Martinino
- Division of Abdominal Transplantation, Department of Surgery, Duke University Medical Center, Durham, North Carolina, USA
| | - Sarah Schiltz
- Patient Advocate Steering Committee, National Cancer Institute Hepatobiliary Task Force, Los Gatos, California, USA
- Blue Faery, Simi Valley, California, USA
- Cancer CAREpoint, Los Gatos, California, USA
| | - Peter J Allen
- Division of Surgical Oncology, Department of Surgery, Duke University Medical Center, Durham, North Carolina, USA
| | - Andrew Barbas
- Division of Abdominal Transplantation, Department of Surgery, Duke University Medical Center, Durham, North Carolina, USA
| | - Debra Sudan
- Division of Abdominal Transplantation, Department of Surgery, Duke University Medical Center, Durham, North Carolina, USA
| | - Lindsay King
- Division of Gastroenterology and Hepatology, Department of Medicine, Duke University Medical Center, Durham, North Carolina, USA
| | - Carl Berg
- Division of Gastroenterology and Hepatology, Department of Medicine, Duke University Medical Center, Durham, North Carolina, USA
| | - Charles Kim
- Department of Radiology, Duke University Medical Center, Durham, North Carolina, USA
| | - Mustafa Bashir
- Department of Radiology, Duke University Medical Center, Durham, North Carolina, USA
| | - Manisha Palta
- Department of Radiation Oncology, Duke University Medical Center, Durham, North Carolina, USA
| | - Michael A Morse
- Division of Medical Oncology, Department of Medicine, Duke University Medical Center, Durham, North Carolina, USA
| | - Michael E Lidsky
- Division of Surgical Oncology, Department of Surgery, Duke University Medical Center, Durham, North Carolina, USA
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Sun RQ, Ye YH, Xu Y, Wang B, Pan SY, Li N, Chen L, Pan JY, Hu ZQ, Fan J, Zhou ZJ, Zhou J, Song CL, Zhou SL. Integrated molecular characterization of sarcomatoid hepatocellular carcinoma. Clin Mol Hepatol 2025; 31:426-444. [PMID: 39657751 PMCID: PMC12016616 DOI: 10.3350/cmh.2024.0686] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 08/21/2024] [Revised: 11/15/2024] [Accepted: 12/06/2024] [Indexed: 12/12/2024] Open
Abstract
BACKGROUNDS/AIMS Sarcomatoid hepatocellular carcinoma (HCC) is a rare histological subtype of HCC characterized by extremely poor prognosis; however, its molecular characterization has not been elucidated. METHODS In this study, we conducted an integrated multiomics study of whole-exome sequencing, RNA-seq, spatial transcriptome, and immunohistochemical analyses of 28 paired sarcomatoid tumor components and conventional HCC components from 10 patients with sarcomatoid HCC, in order to identify frequently altered genes, infer the tumor subclonal architectures, track the genomic evolution, and delineate the transcriptional characteristics of sarcomatoid HCCs. RESULTS Our results showed that the sarcomatoid HCCs had poor prognosis. The sarcomatoid tumor components and the conventional HCC components were derived from common ancestors, mostly accessing similar mutational processes. Clonal phylogenies demonstrated branched tumor evolution during sarcomatoid HCC development and progression. TP53 mutation commonly occurred at tumor initiation, whereas ARID2 mutation often occurred later. Transcriptome analyses revealed the epithelial-mesenchymal transition (EMT) and hypoxic phenotype in sarcomatoid tumor components, which were confirmed by immunohistochemical staining. Moreover, we identified ARID2 mutations in 70% (7/10) of patients with sarcomatoid HCC but only 1-5% of patients with non-sarcomatoid HCC. Biofunctional investigations revealed that inactivating mutation of ARID2 contributes to HCC growth and metastasis and induces EMT in a hypoxic microenvironment. CONCLUSION We offer a comprehensive description of the molecular basis for sarcomatoid HCC, and identify genomic alteration (ARID2 mutation) together with the tumor microenvironment (hypoxic microenvironment), that may contribute to the formation of the sarcomatoid tumor component through EMT, leading to sarcomatoid HCC development and progression.
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Affiliation(s)
- Rong-Qi Sun
- Department of Liver Surgery and Transplantation, Zhongshan Hospital, Fudan University, Shanghai, China
- Liver Cancer Institute, Zhongshan Hospital, Fudan University, Shanghai, China
| | - Yu-Hang Ye
- Department of Liver Surgery and Transplantation, Zhongshan Hospital, Fudan University, Shanghai, China
- Liver Cancer Institute, Zhongshan Hospital, Fudan University, Shanghai, China
| | - Ye Xu
- Department of Liver Surgery and Transplantation, Zhongshan Hospital, Fudan University, Shanghai, China
- Liver Cancer Institute, Zhongshan Hospital, Fudan University, Shanghai, China
| | - Bo Wang
- Department of General Surgery, Second Affiliated Hospital, Dalian Medical University, Dalian, China
| | - Si-Yuan Pan
- Department of Liver Surgery and Transplantation, Zhongshan Hospital, Fudan University, Shanghai, China
- Liver Cancer Institute, Zhongshan Hospital, Fudan University, Shanghai, China
| | - Ning Li
- Department of Liver Surgery and Transplantation, Zhongshan Hospital, Fudan University, Shanghai, China
- Liver Cancer Institute, Zhongshan Hospital, Fudan University, Shanghai, China
| | - Long Chen
- Department of Liver Surgery and Transplantation, Zhongshan Hospital, Fudan University, Shanghai, China
- Liver Cancer Institute, Zhongshan Hospital, Fudan University, Shanghai, China
| | - Jing-Yue Pan
- Department of Liver Surgery and Transplantation, Zhongshan Hospital, Fudan University, Shanghai, China
- Liver Cancer Institute, Zhongshan Hospital, Fudan University, Shanghai, China
| | - Zhi-Qiang Hu
- Department of Liver Surgery and Transplantation, Zhongshan Hospital, Fudan University, Shanghai, China
- Liver Cancer Institute, Zhongshan Hospital, Fudan University, Shanghai, China
| | - Jia Fan
- Department of Liver Surgery and Transplantation, Zhongshan Hospital, Fudan University, Shanghai, China
- Liver Cancer Institute, Zhongshan Hospital, Fudan University, Shanghai, China
| | - Zheng-Jun Zhou
- Department of Liver Surgery and Transplantation, Zhongshan Hospital, Fudan University, Shanghai, China
- Liver Cancer Institute, Zhongshan Hospital, Fudan University, Shanghai, China
| | - Jian Zhou
- Department of Liver Surgery and Transplantation, Zhongshan Hospital, Fudan University, Shanghai, China
- Liver Cancer Institute, Zhongshan Hospital, Fudan University, Shanghai, China
| | - Cheng-Li Song
- Institute of Cancer Stem Cell, Dalian Medical University, Dalian, China
| | - Shao-Lai Zhou
- Department of Liver Surgery and Transplantation, Zhongshan Hospital, Fudan University, Shanghai, China
- Liver Cancer Institute, Zhongshan Hospital, Fudan University, Shanghai, China
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Dhiman B, Kundu R, Mitra S, Kalra N, Premkumar M, Duseja AK, Srinivasan R. Hepatocellular carcinoma: Morphological spectrum and subtyping as per the World Health Organization classification on FNA biopsy with cell block samples. Cancer Cytopathol 2025; 133:e70009. [PMID: 40045688 DOI: 10.1002/cncy.70009] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/01/2024] [Revised: 01/28/2025] [Accepted: 01/29/2025] [Indexed: 05/13/2025]
Abstract
BACKGROUND Hepatocellular carcinoma (HCC) may be diagnosed and further subclassified in surgical specimen as per the recent World Health Organization (WHO) classification into several distinct subtypes with prognostic implications. The aim of this study was to apply this WHO classification on fine-needle aspiration biopsy (FNAB) samples of HCC and describe their features. METHODS This was a retrospective analysis of all ultrasound-guided FNAB of liver mass lesions in patients with suspected HCC (n = 164) over a 7-year period. Detailed morphological assessment of cytopathological features and grading was done and correlated with each other. HCC was subtyped further in cases with available cell blocks (n = 126). RESULTS A total of 164 cases of HCC were evaluated on FNAB with age range of 18-88 years (mean, 60 years), and with 140 (85.4%) male and 24 (14.6%) female patients. Grading performed on 160 cases of HCC (after excluding fibrolamellar HCC) revealed 23 well differentiated, 127 moderately differentiated, and 10 poorly differentiated HCCs. Subtyping was feasible in 126 cases, of which 26 cases (20.6%) showed specific subtypes that were steatohepatitic (8), lymphocyte-rich (8), fibrolamellar (4), neutrophil-rich (3), macrotrabecular massive (2), and clear cell HCC (1) with remaining cases (100) being conventional HCC, no special type. CONCLUSION The study demonstrates the feasibility of subtyping HCC (as per the current WHO classification) for the first time on FNAB with cell blocks that carries implication for prognostication and emphasizes the importance of obtaining tissue diagnosis by FNAB with cell blocks.
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Affiliation(s)
- Bhawana Dhiman
- Department of Cytology and Gynaecological Pathology, Post Graduate Institute of Medical Education and Research, Chandigarh, India
| | - Reetu Kundu
- Department of Cytology and Gynaecological Pathology, Post Graduate Institute of Medical Education and Research, Chandigarh, India
| | - Suvradeep Mitra
- Department of Histopathology, Post Graduate Institute of Medical Education and Research, Chandigarh, India
| | - Naveen Kalra
- Department of Radiodiagnosis and Imaging, Post Graduate Institute of Medical Education and Research, Chandigarh, India
| | - Madhumita Premkumar
- Department of Hepatology, Post Graduate Institute of Medical Education and Research, Chandigarh, India
| | - Ajay Kumar Duseja
- Department of Hepatology, Post Graduate Institute of Medical Education and Research, Chandigarh, India
| | - Radhika Srinivasan
- Department of Cytology and Gynaecological Pathology, Post Graduate Institute of Medical Education and Research, Chandigarh, India
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Saler CHA, Shuai S, Beckervordersandforth JC, Rennspiess D, Roemen G, Gevers T, Stoehr‐Kleinegris MCF, Bouwense SAW, Dewulf MJL, Coolsen MME, Bemelmans MHA, Damink SWO, Winnepenninckx V, zur Hausen A, Kramer M, Samarska IV. Clinicopathological Study on Morphological Subtypes of Hepatocellular Carcinoma: A Single Tertiary Referral Center Experience. Cancer Rep (Hoboken) 2025; 8:e70127. [PMID: 39953652 PMCID: PMC11828739 DOI: 10.1002/cnr2.70127] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/31/2024] [Revised: 12/09/2024] [Accepted: 01/16/2025] [Indexed: 02/17/2025] Open
Abstract
AIM We aimed to analyze hepatocellular carcinoma (HCC) morphological subtypes characterized according to the WHO classification and the International Collaboration on Cancer Reporting (ICCR) recommendations, and their prognostic features in a Dutch population. METHODS AND RESULTS This retrospective study in a tertiary referral center included the histopathological revision of 62 HCC resection specimens, obtained from 22 female and 40 male patients (median age: 67 years), in a period between 2011 and 2021 at the Maastricht University Medical Center +. Clinical data, morphological subtypes, growth pattern (GP), tumor grade, tumor extension, margins, and vascular and perineural invasion were collected. Eighteen cases were assigned a specific morphologic subtype and steatohepatic HCC was the most common in our cohort. Twenty-one tumors classified as conventional type HCC (HCC-NOS), commonly exhibiting two concurrent GPs. Twenty-three cases revealed a heterogeneous morphologic differentiation, compromising the combination of HCC-NOS with another morphologic subtype, most frequently a steatohepatitic component. Comparison of HCC-NOS and HCC with heterogeneous morphology did not show significant differences in the main clinicopathological characteristics and survival. CONCLUSION Although the most common morphologic subtype was steatohepatitic HCC, the majority of cases demonstrated multiple morphologic patterns. In case of HCC-NOS, heterogeneous GPs were often observed. Therefore, a histomorphological diagnosis based on a single tumor biopsy specimen may lead to incorrect classification of HCC. Sufficient tumor sampling of HCC resection specimens is required for the complete evaluation of all histomorphological features followed by correct subclassification in order to meet the clinical needs regarding prognostic relevance and patient follow-up.
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Affiliation(s)
- C. H. A. Saler
- Department of PathologyGROW‐School for Oncology and Reproduction, Maastricht University Medical Center +Maastrichtthe Netherlands
- Department of Internal MedicineGROW‐School for Oncology and Reproduction, Maastricht University Medical Center +Maastrichtthe Netherlands
| | - S. Shuai
- Department of PathologyGROW‐School for Oncology and Reproduction, Maastricht University Medical Center +Maastrichtthe Netherlands
| | - J. C. Beckervordersandforth
- Department of PathologyGROW‐School for Oncology and Reproduction, Maastricht University Medical Center +Maastrichtthe Netherlands
| | - D. Rennspiess
- Department of PathologyGROW‐School for Oncology and Reproduction, Maastricht University Medical Center +Maastrichtthe Netherlands
| | - G. Roemen
- Department of PathologyGROW‐School for Oncology and Reproduction, Maastricht University Medical Center +Maastrichtthe Netherlands
| | - T. Gevers
- Department of Internal MedicineGROW‐School for Oncology and Reproduction, Maastricht University Medical Center +Maastrichtthe Netherlands
| | - M. C. F. Stoehr‐Kleinegris
- Department of Internal MedicineGROW‐School for Oncology and Reproduction, Maastricht University Medical Center +Maastrichtthe Netherlands
| | - S. A. W. Bouwense
- Department of SurgerySchool of Nutrition and Translational Research in Metabolism (NUTRIM), School of Nutrition and Translational Research in Metabolism, Maastricht UniversityMaastrichtthe Netherlands
| | - M. J. L. Dewulf
- Department of SurgerySchool of Nutrition and Translational Research in Metabolism (NUTRIM), School of Nutrition and Translational Research in Metabolism, Maastricht UniversityMaastrichtthe Netherlands
| | - M. M. E. Coolsen
- Department of SurgerySchool of Nutrition and Translational Research in Metabolism (NUTRIM), School of Nutrition and Translational Research in Metabolism, Maastricht UniversityMaastrichtthe Netherlands
| | - M. H. A. Bemelmans
- Department of SurgerySchool of Nutrition and Translational Research in Metabolism (NUTRIM), School of Nutrition and Translational Research in Metabolism, Maastricht UniversityMaastrichtthe Netherlands
| | - S. W. Olde Damink
- Department of SurgerySchool of Nutrition and Translational Research in Metabolism (NUTRIM), School of Nutrition and Translational Research in Metabolism, Maastricht UniversityMaastrichtthe Netherlands
| | - V. Winnepenninckx
- Department of PathologyGROW‐School for Oncology and Reproduction, Maastricht University Medical Center +Maastrichtthe Netherlands
| | - A. zur Hausen
- Department of PathologyGROW‐School for Oncology and Reproduction, Maastricht University Medical Center +Maastrichtthe Netherlands
| | - M. Kramer
- Department of Internal MedicineGROW‐School for Oncology and Reproduction, Maastricht University Medical Center +Maastrichtthe Netherlands
| | - I. V. Samarska
- Department of PathologyGROW‐School for Oncology and Reproduction, Maastricht University Medical Center +Maastrichtthe Netherlands
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Ben-Slama S, Mallek I, Ghorbeli E, Hajri M, Labidi T, Mestiri H, Lahmar A, Bacha D. CHROMOPHOBE HEPATOCELLULAR CARCINOMA: DIAGNOSTIC CHALLENGES. ARQUIVOS BRASILEIROS DE CIRURGIA DIGESTIVA : ABCD = BRAZILIAN ARCHIVES OF DIGESTIVE SURGERY 2025; 37:e1863. [PMID: 39841766 PMCID: PMC11745479 DOI: 10.1590/0102-6720202400069e1863] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Subscribe] [Scholar Register] [Received: 07/07/2024] [Accepted: 09/11/2024] [Indexed: 01/24/2025]
Abstract
BACKGROUND Hepatocellular carcinoma (HCC) encompasses rare variants like chromophobe hepatocellular carcinoma (CHCC) characterized by distinct histological features and molecular profiles. CASE REPORT A 56-year-old male with chronic hepatitis C, presenting pain in the right hypochondrium. Imaging revealed a solitary liver lesion, subsequently resected and histologically diagnosed as HCC. Macroscopic examination found a 4×4 cm encapsulated liver nodule with necrotic areas, surrounded by numerous smaller satellite nodules in Segment 6. The liver was in micronodular cirrhosis. Histologically, the tumor had focal trabecular or pseudoglandular patterns within a vascularized stroma. The cells were large, with clear to eosinophilic cytoplasm and hyperchromatic and pleomorphic nuclei with focal anaplastic features. No vascular invasion was noted in adjacent cirrhotic liver tissue. RESULTS The final diagnosis was CHCC. Due to its rarity and overlapping characteristics with other hepatic tumors, CHCC poses diagnostic challenges. Accurate diagnosis necessitates thorough histopathological assessment and molecular testing. The identification of the alternative lengthening of telomeres phenotype may distinguish CHCC from conventional HCC and hold potential implications for targeted therapeutic approaches. CONCLUSIONS Recognition of HCC variants is critical for effective management and underscores the need for continued research into its clinical behavior and therapeutic responses.
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Affiliation(s)
- Sana Ben-Slama
- Mongi Slim Hospital, Department of Pathology – Marsa, Tuni, Tunísia
- University of Tunis, Faculty of Medicine of Tunis, – El Manar, Tunis, Tunísia
| | - Ines Mallek
- Mongi Slim Hospital, Department of Pathology – Marsa, Tuni, Tunísia
| | - Eya Ghorbeli
- Salah Azaiez Institute, Department of Oncologic Surgery, Tunis, Tunísia
| | - Mohamed Hajri
- University of Tunis, Faculty of Medicine of Tunis, – El Manar, Tunis, Tunísia
| | - Taher Labidi
- Mongi Slim Hospital, Department of General Surgery, Tunis, Tunísia
| | - Hafedh Mestiri
- University of Tunis, Faculty of Medicine of Tunis, – El Manar, Tunis, Tunísia
| | - Ahlem Lahmar
- Mongi Slim Hospital, Department of Pathology – Marsa, Tuni, Tunísia
- University of Tunis, Faculty of Medicine of Tunis, – El Manar, Tunis, Tunísia
| | - Dhouha Bacha
- Mongi Slim Hospital, Department of Pathology – Marsa, Tuni, Tunísia
- University of Tunis, Faculty of Medicine of Tunis, – El Manar, Tunis, Tunísia
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Santarsiero A, Convertini P, Iacobazzi D, Infantino V, Todisco S. Metabolic Crossroad Between Macrophages and Cancer Cells: Overview of Hepatocellular Carcinoma. Biomedicines 2024; 12:2684. [PMID: 39767591 PMCID: PMC11727080 DOI: 10.3390/biomedicines12122684] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/27/2024] [Revised: 11/17/2024] [Accepted: 11/22/2024] [Indexed: 01/16/2025] Open
Abstract
The metabolic interplay between macrophages and cancer cells mirrors the plasticity of both kinds of cells, which adapt to the microenvironment by sustaining cell growth and proliferation. In this way, cancer cells induce macrophage polarization, and, on the other hand, tumor-associated macrophages (TAMs) contribute to the survival of cancer cells. In a simplified manner, macrophages can assume two opposite subtypes: M1, pro-inflammatory and anti-tumor phenotype, and M2, anti-inflammatory and protumor phenotype. How do cancer cells induce macrophage polarization? Any actor involved in tumor growth, including the mitochondria, releases molecules into the tumor microenvironment (TME) that trigger a subtype transition. These metabolic changes are the primary cause of this polarization. Hepatocellular carcinoma (HCC), the prevalent type of liver primary tumor, is characterized by cells with extensive metabolic adaptions due to high flexibility in different environmental conditions. This review focuses on the main metabolic features of M1 and M2 macrophages and HCC cells underlying their metabolic behavior in response to TME.
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Affiliation(s)
- Anna Santarsiero
- Department of Health Sciences, University of Basilicata, 85100 Potenza, Italy; (A.S.); (V.I.)
| | - Paolo Convertini
- Department of Basic and Applied Science, University of Basilicata, 85100 Potenza, Italy;
| | - Dominga Iacobazzi
- Bristol Medical School, Translational Health Sciences, University of Bristol, Bristol BS2 8HW, UK;
| | - Vittoria Infantino
- Department of Health Sciences, University of Basilicata, 85100 Potenza, Italy; (A.S.); (V.I.)
| | - Simona Todisco
- Department of Basic and Applied Science, University of Basilicata, 85100 Potenza, Italy;
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Vij M, Raju LP, Jothimani D, Subbiah K, Simon E, Gowrishankar G, Rajalingam R, Kaliamoorthy I, Rammohan A, Rela M. Clinicopathological Characteristics of Neutrophil-Rich Hepatocellular Carcinoma: An Uncommon Subtype of Primary Liver Cancer. Int J Surg Pathol 2024:10668969241291882. [PMID: 39533751 DOI: 10.1177/10668969241291882] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/16/2024]
Abstract
Introduction. Neutrophil-rich hepatocellular carcinoma (HCC) is an extremely uncommon subtype of HCC with an overall incidence of <1%. Neutrophil-rich HCC shows poor cellular differentiation and sarcomatoid transformation in most patients. There is prominent neutrophilic inflammatory cell infiltration in the tumor. These tumors are associated with poor prognosis, high rate of recurrence, and metastasis. Methods. Herein, we investigated 4 patients with neutrophil-rich HCC reported at our center. Clinical, radiological, and pathological findings were reviewed. Immunophenotypic characterization of the tumors were done. Granulocyte colony-stimulating factor (G-CSF), programmed cell death ligand 1 (PD-L1), and mismatch repair immunostains were performed in all 4 tumors. Results. We report 4 neutrophil-rich HCCs in 3 male patients and one female patient with an age range of 43 to 64 years. Three underwent living donor liver transplantation and one underwent right hepatectomy. Tumor measured 0.5 cm to 12 cm in maximum dimension. Histologically, tumors demonstrated moderate to marked cellular pleomorphism. Spindle cell transformation was noted in 3 tumors. Three tumors showed vascular invasion, and one tumor showed bile duct invasion. Immunopositivity for Hep Par-1, arginase-1, and glypican-3 was present in all tumors. Tumors also expressed stemness markers including KRT19 and EpCAM. Cytoplasmic positivity for G-CSF and immunoexpression of PD-L1 was demonstrated. We also report proficient mismatch repair by immunohistochemistry in all tumors. Conclusion. Neutrophil-rich HCC is an aggressive primary liver cancer which demonstrates stemness-related features. Programmed cell death ligand 1 expression in tumor cells suggests distinct immunogenic features and potential role of anti-PD-L1 therapies in inoperable disease.
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Affiliation(s)
- Mukul Vij
- Department of Pathology, Dr Rela Institute & Medical Centre, Chennai, Tamil Nadu, India
| | - Lexmi Priya Raju
- Department of Pathology, Dr Rela Institute & Medical Centre, Chennai, Tamil Nadu, India
| | - Dinesh Jothimani
- The Institute of Liver Disease & Transplantation, Dr Rela Institute & Medical Centre, Chennai, Tamil Nadu, India
| | - Komalavalli Subbiah
- The Institute of Liver Disease & Transplantation, Dr Rela Institute & Medical Centre, Chennai, Tamil Nadu, India
| | - Evangeline Simon
- The Institute of Liver Disease & Transplantation, Dr Rela Institute & Medical Centre, Chennai, Tamil Nadu, India
| | | | - Rajesh Rajalingam
- The Institute of Liver Disease & Transplantation, Dr Rela Institute & Medical Centre, Chennai, Tamil Nadu, India
| | - Ilankumaran Kaliamoorthy
- The Institute of Liver Disease & Transplantation, Dr Rela Institute & Medical Centre, Chennai, Tamil Nadu, India
| | - Ashwin Rammohan
- The Institute of Liver Disease & Transplantation, Dr Rela Institute & Medical Centre, Chennai, Tamil Nadu, India
| | - Mohamed Rela
- The Institute of Liver Disease & Transplantation, Dr Rela Institute & Medical Centre, Chennai, Tamil Nadu, India
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9
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Numata Y, Akutsu N, Idogawa M, Wagatsuma K, Numata Y, Ishigami K, Nakamura T, Hirano T, Kawakami Y, Masaki Y, Murota A, Sasaki S, Nakase H. Genomic analysis of an aggressive hepatic leiomyosarcoma case following treatment for hepatocellular carcinoma. Hepatol Res 2024; 54:859-865. [PMID: 38459823 DOI: 10.1111/hepr.14034] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 08/08/2023] [Revised: 02/05/2024] [Accepted: 02/17/2024] [Indexed: 03/10/2024]
Abstract
A 70-year-old man undergoing treatment for immunoglobulin G4-related disease developed a liver mass on computed tomography during routine imaging examination. The tumor was located in the hepatic S1/4 region, was 38 mm in size, and showed arterial enhancement on dynamic contrast-enhanced computed tomography. We performed a liver biopsy and diagnosed moderately differentiated hepatocellular carcinoma. The patient underwent proton beam therapy. The tumor remained unchanged but enlarged after 4 years. The patient was diagnosed with hepatocellular carcinoma recurrence and received hepatic arterial chemoembolization. However, 1 year later, the patient developed jaundice, and the liver tumor grew in size. Unfortunately, the patient passed away. Autopsy revealed that the tumor consisted of spindle-shaped cells exhibiting nuclear atypia and a fission pattern and tested positive for α-smooth muscle actin and vimentin. No hepatocellular carcinoma components were observed, and the patient was pathologically diagnosed with hepatic leiomyosarcoma. Next-generation sequencing revealed somatic mutations in CACNA2D4, CTNNB1, DOCK5, IPO8, MTMR1, PABPC5, SEMA6D, and ZFP36L1. Based on the genetic mutation, sarcomatoid hepatocarcinoma was the most likely pathogenesis in this case. This mutation is indicative of the transition from sarcomatoid hepatocarcinoma to hepatic leiomyosarcoma.
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Affiliation(s)
- Yuto Numata
- Department of Gastroenterology and Hepatology, Sapporo Medical University School of Medicine, Sapporo, Japan
| | - Noriyuki Akutsu
- Department of Gastroenterology and Hepatology, Sapporo Medical University School of Medicine, Sapporo, Japan
| | - Masashi Idogawa
- Department of Gastroenterology and Hepatology, Sapporo Medical University School of Medicine, Sapporo, Japan
- Department of Medical Genome Sciences, Cancer Research Institute, Sapporo Medical University School of Medicine, Sapporo, Japan
| | - Kohei Wagatsuma
- Department of Gastroenterology and Hepatology, Sapporo Medical University School of Medicine, Sapporo, Japan
| | - Yasunao Numata
- Department of Gastroenterology and Hepatology, Sapporo Medical University School of Medicine, Sapporo, Japan
| | - Keisuike Ishigami
- Department of Gastroenterology and Hepatology, Sapporo Medical University School of Medicine, Sapporo, Japan
| | - Tomoya Nakamura
- Department of Gastroenterology and Hepatology, Sapporo Medical University School of Medicine, Sapporo, Japan
| | - Takehiro Hirano
- Department of Gastroenterology and Hepatology, Sapporo Medical University School of Medicine, Sapporo, Japan
| | - Yujiro Kawakami
- Department of Gastroenterology and Hepatology, Sapporo Medical University School of Medicine, Sapporo, Japan
| | - Yoshiharu Masaki
- Department of Gastroenterology and Hepatology, Sapporo Medical University School of Medicine, Sapporo, Japan
| | - Ayako Murota
- Department of Gastroenterology and Hepatology, Sapporo Medical University School of Medicine, Sapporo, Japan
| | - Shigeru Sasaki
- Department of Gastroenterology and Hepatology, Sapporo Medical University School of Medicine, Sapporo, Japan
| | - Hiroshi Nakase
- Department of Gastroenterology and Hepatology, Sapporo Medical University School of Medicine, Sapporo, Japan
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10
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Song M, Tao Y, He K, Du M, Guo L, Hu C, Zhang W. Clear cell hepatocellular carcinoma: Gd-EOB-DTPA-enhanced MR imaging features and prognosis. Abdom Radiol (NY) 2024; 49:2606-2621. [PMID: 38557768 DOI: 10.1007/s00261-024-04263-2] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/09/2023] [Revised: 02/17/2024] [Accepted: 02/20/2024] [Indexed: 04/04/2024]
Abstract
PURPOSE To investigate imaging findings on gadolinium-ethoxybenzyl-diethylenetriamine pentaacetic acid-enhanced magnetic resonance imaging (Gd-EOB-DTPA-enhanced MRI) and prognosis of clear cell hepatocellular carcinoma (CCHCC) comparing with non-otherwise specified hepatocellular carcinoma (NOS-HCC). METHODS The clinical, pathological and MR imaging features of 42 patients with CCHCC and 84 age-matched patients with NOS-HCC were retrospectively analyzed from January 2015 to October 2021. Univariate and multivariate logistic regression and Cox regression analyses were performed to identify independent diagnostic and prognostic factors for CCHCC. Disease-free survival (DFS) and overall survival (OS) were determined by Kaplan-Meier analysis. RESULTS CCHCC showed fat content more frequently (P < 0.001) and relatively higher Edmondson tumor grade (P = 0.001) compared with NOS-HCC. The lesion-to-muscle ratio (LMR) and lesion-to-liver ratio (LLR) of CCHCC on pre-enhancement T1-weighted imaging (pre-T1WI) (P = 0.001, P = 0.003) and hepatobiliary phase (HBP) (P = 0.007, P = 0.048) were significantly higher than those of NOS-HCC. The area under the curve (AUC) for fat content, LLR on pre-T1WI and their combination with better diagnostic performance in predicting CCHCC were 0.678, 0.666, and 0.750, respectively. There was no statistically significant difference in clinical outcomes between CCHCC and NOS-HCC. Multivariate Cox analysis confirmed that tumor size > 2 cm and enhancing capsule were independent prognostic factors for DFS and OS among CCHCC patients. CONCLUSION Fat content and adjusted lesion signal intensity on pre-T1WI and HBP could be used to differentiate CCHCC from NOS-HCC. CCHCC had similar prognosis with NOS-HCC.
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Affiliation(s)
- Mingyue Song
- Department of Radiology, The Fourth Affiliated Hospital of Soochow University, Suzhou, 215028, China
- Department of Radiology, The First Affiliated Hospital of Soochow University, Suzhou, 215006, China
| | - Yuhao Tao
- Department of Radiology, The Fourth Affiliated Hospital of Soochow University, Suzhou, 215028, China
- Department of Radiology, The First Affiliated Hospital of Soochow University, Suzhou, 215006, China
| | - Kuang He
- Department of Pathology, The First Affiliated Hospital of Soochow University, Suzhou, 215006, China
| | - Mingzhan Du
- Department of Pathology, The First Affiliated Hospital of Soochow University, Suzhou, 215006, China
| | - Lingchuan Guo
- Department of Pathology, The First Affiliated Hospital of Soochow University, Suzhou, 215006, China
| | - Chunhong Hu
- Department of Radiology, The First Affiliated Hospital of Soochow University, Suzhou, 215006, China
| | - Weiguo Zhang
- Department of Radiology, The Fourth Affiliated Hospital of Soochow University, Suzhou, 215028, China.
- Department of Radiology, The First Affiliated Hospital of Soochow University, Suzhou, 215006, China.
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11
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Suddle A, Reeves H, Hubner R, Marshall A, Rowe I, Tiniakos D, Hubscher S, Callaway M, Sharma D, See TC, Hawkins M, Ford-Dunn S, Selemani S, Meyer T. British Society of Gastroenterology guidelines for the management of hepatocellular carcinoma in adults. Gut 2024; 73:1235-1268. [PMID: 38627031 PMCID: PMC11287576 DOI: 10.1136/gutjnl-2023-331695] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 12/06/2023] [Accepted: 03/19/2024] [Indexed: 05/01/2024]
Abstract
Deaths from the majority of cancers are falling globally, but the incidence and mortality from hepatocellular carcinoma (HCC) is increasing in the United Kingdom and in other Western countries. HCC is a highly fatal cancer, often diagnosed late, with an incidence to mortality ratio that approaches 1. Despite there being a number of treatment options, including those associated with good medium to long-term survival, 5-year survival from HCC in the UK remains below 20%. Sex, ethnicity and deprivation are important demographics for the incidence of, and/or survival from, HCC. These clinical practice guidelines will provide evidence-based advice for the assessment and management of patients with HCC. The clinical and scientific data underpinning the recommendations we make are summarised in detail. Much of the content will have broad relevance, but the treatment algorithms are based on therapies that are available in the UK and have regulatory approval for use in the National Health Service.
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Affiliation(s)
- Abid Suddle
- King's College Hospital NHS Foundation Trust, London, UK
| | - Helen Reeves
- Newcastle University Translational and Clinical Research Institute, Newcastle upon Tyne, UK
| | - Richard Hubner
- Department of Oncology, The Christie NHS Foundation Trust, Manchester, UK
| | | | - Ian Rowe
- University of Leeds, Leeds, UK
- St James's University Hospital, Leeds, UK
| | - Dina Tiniakos
- Institute of Cellular Medicine, Newcastle University, Newcastle upon Tyne, UK
| | - Stefan Hubscher
- Department of Pathology, University of Birmingham, Birmingham, UK
| | - Mark Callaway
- Division of Diagnostics and Therapies, University Hospitals Bristol NHS Trust, Bristol, UK
| | | | - Teik Choon See
- Department of Radiology, Cambridge University Hospitals NHS Foundation Trust, Cambridge, UK
| | - Maria Hawkins
- Department of Medical Physics and Biomedical Engineering, University College London, London, UK
| | | | - Sarah Selemani
- King's College Hospital NHS Foundation Trust, London, UK
| | - Tim Meyer
- Department of Oncology, University College, London, UK
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12
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Soon GST, Callea F, Burt AD, Cook S, Terracciano L, Ercan C, Dienes HP, Goodman ZD, Roberts EA, Clouston AD, Gouw ASH, Kleiner DE, Park YN, Chung T, Schirmacher P, Tiniakos D, Dimopoulou K, Weber A, Endhardt K, Torbenson M. Steatohepatitic hepatocellular Carcinoma:A new approach to classifying morphological subtypes of hepatocellular carcinoma. Hum Pathol 2024; 149:55-65. [PMID: 38876199 DOI: 10.1016/j.humpath.2024.06.007] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 03/21/2024] [Revised: 06/07/2024] [Accepted: 06/11/2024] [Indexed: 06/16/2024]
Abstract
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.
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Affiliation(s)
- Gwyneth S T Soon
- Department of Pathology, National University Hospital, Singapore
| | | | - Alastair D Burt
- Translational and Clinical Research Institute, Faculty of Medical Sciences, Newcastle University, Newcastle Upon Tyne, United Kingdom
| | - Sam Cook
- Translational and Clinical Research Institute, Faculty of Medical Sciences, Newcastle University, Newcastle Upon Tyne, United Kingdom
| | - Luigi Terracciano
- Department of Biomedical Sciences, Humanitas University, Via Rita Levi Montalcini 4, 20090 Pieve Emanuele, Milan, Italy; IRCCS Humanitas Research Hospital, Via Manzoni 56, 20089 Rozzano, Milan, Italy
| | - Caner Ercan
- Institute of Pathology and Medical Genetics, University Hospital Basel, Basel, Switzerland
| | - Hans-Peter Dienes
- Institute of Pathology, Meduniwien, Medical University of Vienna, 1090 Wien, Austria
| | - Zachary D Goodman
- Center for Liver Diseases, Inova Fairfax Hospital, Falls Church, VA 22042, USA
| | - Eve A Roberts
- Division of Gastroenterology, Hepatology and Nutrition, The Hospital for Sick Children, Toronto, Ontario M5G1X8, Canada
| | - Andrew D Clouston
- Centre for Liver Disease Research, School of Medicine (Southern), University of Queensland, Princess Alexandra Hospital, Ipswich Rd Woolloongabba 4109, Australia
| | - Annette S H Gouw
- Department of Pathology and Medical Biology, University Medical Center Groningen, 9700 RB Groningen, the Netherlands
| | - David E Kleiner
- Laboratory of Pathology, National Cancer Institute, National Institutes of Health, Bethesda, USA
| | - Young Nyun Park
- Department of Pathology, Yonsei University College of Medicine, Seoul Korea
| | - Taek Chung
- Department of Pathology, Yonsei University College of Medicine, Seoul Korea.
| | - Peter Schirmacher
- Institute of Pathology, University Hospital, Im Neuenheimer Feld 224, 69120 Heidelberg, Germany
| | - Dina Tiniakos
- Translational and Clinical Research Institute, Faculty of Medical Sciences, Newcastle University, Newcastle Upon Tyne, United Kingdom; Department of Pathology, Aretaieion Hospital, Medical School, National & Kapodistrian University of Athens, Athens, Greece
| | - Konstantina Dimopoulou
- Department of Pathology, Aretaieion Hospital, Medical School, National & Kapodistrian University of Athens, Athens, Greece
| | - Achim Weber
- Department of Pathology and Molecular Pathology, University Hospital Zurich and University of Zurich, Zurich, Switzerland
| | - Katharina Endhardt
- Department of Pathology and Molecular Pathology, University Hospital Zurich and University of Zurich, Zurich, Switzerland
| | - Michael Torbenson
- Department of Laboratory Medicine and Pathology, Mayo Clinic, Rochester, MN, USA.
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13
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Lehrich BM, Zhang J, Monga SP, Dhanasekaran R. Battle of the biopsies: Role of tissue and liquid biopsy in hepatocellular carcinoma. J Hepatol 2024; 80:515-530. [PMID: 38104635 PMCID: PMC10923008 DOI: 10.1016/j.jhep.2023.11.030] [Citation(s) in RCA: 45] [Impact Index Per Article: 45.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 08/09/2023] [Revised: 10/27/2023] [Accepted: 11/27/2023] [Indexed: 12/19/2023]
Abstract
The diagnosis and management of hepatocellular carcinoma (HCC) have improved significantly in recent years. With the introduction of immunotherapy-based combination therapy, there has been a notable expansion in treatment options for patients with unresectable HCC. Simultaneously, innovative molecular tests for early detection and management of HCC are emerging. This progress prompts a key question: as liquid biopsy techniques rise in prominence, will they replace traditional tissue biopsies, or will both techniques remain relevant? Given the ongoing challenges of early HCC detection, including issues with ultrasound sensitivity, accessibility, and patient adherence to surveillance, the evolution of diagnostic techniques is more relevant than ever. Furthermore, the accurate stratification of HCC is limited by the absence of reliable biomarkers which can predict response to therapies. While the advantages of molecular diagnostics are evident, their potential has not yet been fully harnessed, largely because tissue biopsies are not routinely performed for HCC. Liquid biopsies, analysing components such as circulating tumour cells, DNA, and extracellular vesicles, provide a promising alternative, though they are still associated with challenges related to sensitivity, cost, and accessibility. The early results from multi-analyte liquid biopsy panels are promising and suggest they could play a transformative role in HCC detection and management; however, comprehensive clinical validation is still ongoing. In this review, we explore the challenges and potential of both tissue and liquid biopsy, highlighting that these diagnostic methods, while distinct in their approaches, are set to jointly reshape the future of HCC management.
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Affiliation(s)
- Brandon M Lehrich
- Department of Pathology and Pittsburgh Liver Institute, University of Pittsburgh, School of Medicine and University of Pittsburgh Medical Center, Pittsburgh, Pennsylvania, USA
| | - Josephine Zhang
- Division of Gastroenterology and Hepatology, Department of Medicine, Stanford University, Staford, CA, 94303, USA
| | - Satdarshan P Monga
- Department of Pathology and Pittsburgh Liver Institute, University of Pittsburgh, School of Medicine and University of Pittsburgh Medical Center, Pittsburgh, Pennsylvania, USA.
| | - Renumathy Dhanasekaran
- Division of Gastroenterology and Hepatology, Department of Medicine, Stanford University, Staford, CA, 94303, USA.
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14
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Nakamura T, Teo R, Shih AR, Latham K, Bethea ED, Kalva S, Tomosugi T, Yamamoto T, Dageforde LA, Yeh H, Elias N, Bozorgzadeh A, Kawai T, Markmann JF, Kimura S. Rapidly Progressive Pulmonary Lymphangitic Carcinomatosis After Liver Transplantation Due to Diffuse Infiltrative Sarcomatoid Hepatocellular Carcinoma. Transplant Direct 2024; 10:e1594. [PMID: 39877648 PMCID: PMC11774559 DOI: 10.1097/txd.0000000000001594] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/21/2023] [Revised: 12/19/2023] [Accepted: 01/04/2024] [Indexed: 01/31/2025] Open
Affiliation(s)
- Tsukasa Nakamura
- Division of Transplant Surgery, Massachusetts General Hospital, Harvard Medical School, Boston, MA
| | - Richard Teo
- Division of Transplant Surgery, Massachusetts General Hospital, Harvard Medical School, Boston, MA
| | - Angela R. Shih
- Department of Pathology, Massachusetts General Hospital, Harvard Medical School, Boston, MA
| | - Katherine Latham
- Department of Pathology, Massachusetts General Hospital, Harvard Medical School, Boston, MA
| | - Emily D. Bethea
- Department of Gastroenterology, Massachusetts General Hospital, Harvard Medical School, Boston, MA
| | - Sanjeeva Kalva
- Department of Radiology, Massachusetts General Hospital, Harvard Medical School, Boston, MA
| | - Toshihide Tomosugi
- Division of Transplant Surgery, Massachusetts General Hospital, Harvard Medical School, Boston, MA
| | - Takayuki Yamamoto
- Division of Transplant Surgery, Massachusetts General Hospital, Harvard Medical School, Boston, MA
| | - Leigh Anne Dageforde
- Division of Transplant Surgery, Massachusetts General Hospital, Harvard Medical School, Boston, MA
| | - Heidi Yeh
- Division of Transplant Surgery, Massachusetts General Hospital, Harvard Medical School, Boston, MA
| | - Nahel Elias
- Division of Transplant Surgery, Massachusetts General Hospital, Harvard Medical School, Boston, MA
| | - Adel Bozorgzadeh
- Division of Transplant Surgery, Massachusetts General Hospital, Harvard Medical School, Boston, MA
| | - Tatsuo Kawai
- Division of Transplant Surgery, Massachusetts General Hospital, Harvard Medical School, Boston, MA
| | - James F. Markmann
- Division of Transplant Surgery, Massachusetts General Hospital, Harvard Medical School, Boston, MA
| | - Shoko Kimura
- Division of Transplant Surgery, Massachusetts General Hospital, Harvard Medical School, Boston, MA
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15
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Yoshida T, Sakai K, Kaibori M, Ishida M, Tanaka S, Kubo S, Nakai T, De Velasco MA, Matsushima H, Tsuta K, Sekimoto M, Nishio K. Downregulated expression of PBRM1 in sarcomatoid hepatocellular carcinoma. Oncol Lett 2024; 27:124. [PMID: 38348389 PMCID: PMC10859838 DOI: 10.3892/ol.2024.14257] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/08/2023] [Accepted: 01/03/2024] [Indexed: 02/15/2024] Open
Abstract
Sarcomatoid hepatocellular carcinoma (SHCC) is a rare and highly lethal subtype of HCC. The present study aimed to explore the unique markers of SHCC using whole gene expression analysis. Subsequently, gene expression analysis was performed using five sarcomatoid and seven carcinomatoid components of seven tissues from patients with SHCC. The results demonstrated a significant downregulation of polybromo 1 (PBRM1) gene expression in the sarcomatoid components. Immunohistochemical staining also indicated a decreased expression of PBRM1 in the sarcomatoid components. Moreover, gene ontology enrichment analysis revealed that most of the 336 differentially expressed genes between the sarcomatoid and carcinomatoid components were involved in functions associated with DNA replication and histone methylation, which was consistent with the loss of function of PBRM1 which encodes Switch/sucrose-non-fermentable chromatin remodeling complex protein. Therefore, the results of the present study suggested that PBRM1 may be a candidate biomarker for the evaluation of SHCC.
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Affiliation(s)
- Terufumi Yoshida
- Department of Surgery, Kansai Medical University, Hirakata, Osaka 573-1010, Japan
| | - Kazuko Sakai
- Department of Genome Biology, Kindai University Faculty of Medicine, Osakasayama, Osaka 589-8511, Japan
| | - Masaki Kaibori
- Department of Surgery, Kansai Medical University, Hirakata, Osaka 573-1010, Japan
| | - Mitsuaki Ishida
- Department of Pathology, Osaka Medical and Pharmaceutical University, Takatsuki, Osaka 569-8686, Japan
| | - Shogo Tanaka
- Department of Hepato-Biliary-Pancreatic Surgery, Osaka Metropolitan University Graduate School of Medicine, Osaka, Osaka 545-8585, Japan
| | - Shoji Kubo
- Department of Hepato-Biliary-Pancreatic Surgery, Osaka Metropolitan University Graduate School of Medicine, Osaka, Osaka 545-8585, Japan
| | - Takuya Nakai
- Department of Surgery, Kindai University Faculty of Medicine, Osakasayama, Osaka 589-8511, Japan
| | - Marco A. De Velasco
- Department of Genome Biology, Kindai University Faculty of Medicine, Osakasayama, Osaka 589-8511, Japan
| | - Hideyuki Matsushima
- Department of Surgery, Kansai Medical University, Hirakata, Osaka 573-1010, Japan
| | - Koji Tsuta
- Department of Pathology, Kansai Medical University, Hirakata, Osaka 573-1010, Japan
| | - Mitsugu Sekimoto
- Department of Surgery, Kansai Medical University, Hirakata, Osaka 573-1010, Japan
| | - Kazuto Nishio
- Department of Genome Biology, Kindai University Faculty of Medicine, Osakasayama, Osaka 589-8511, Japan
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16
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Scholer AJ, Marcus RK, Garland-Kledzik M, Ghosh D, Ensenyat-Mendez M, Germany J, Santamaria-Barria JA, Khader A, Orozco JIJ, Goldfarb M. Exploring the Genomic Landscape of Hepatobiliary Cancers to Establish a Novel Molecular Classification System. Cancers (Basel) 2024; 16:325. [PMID: 38254814 PMCID: PMC10814719 DOI: 10.3390/cancers16020325] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/17/2023] [Revised: 12/15/2023] [Accepted: 01/04/2024] [Indexed: 01/24/2024] Open
Abstract
Taxonomy of hepatobiliary cancer (HBC) categorizes tumors by location or histopathology (tissue of origin, TO). Tumors originating from different TOs can also be grouped by overlapping genomic alterations (GA) into molecular subtypes (MS). The aim of this study was to create novel HBC MSs. Next-generation sequencing (NGS) data from the AACR-GENIE database were used to examine the genomic landscape of HBCs. Machine learning and gene enrichment analysis identified MSs and their oncogenomic pathways. Descriptive statistics were used to compare subtypes and their associations with clinical and molecular variables. Integrative analyses generated three MSs with different oncogenomic pathways independent of TO (n = 324; p < 0.05). HC-1 "hyper-mutated-proliferative state" MS had rapidly dividing cells susceptible to chemotherapy; HC-2 "adaptive stem cell-cellular senescence" MS had epigenomic alterations to evade immune system and treatment-resistant mechanisms; HC-3 "metabolic-stress pathway" MS had metabolic alterations. The discovery of HBC MSs is the initial step in cancer taxonomy evolution and the incorporation of genomic profiling into the TNM system. The goal is the development of a precision oncology machine learning algorithm to guide treatment planning and improve HBC outcomes. Future studies should validate findings of this study, incorporate clinical outcomes, and compare the MS classification to the AJCC 8th staging system.
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Affiliation(s)
- Anthony J. Scholer
- Division of Surgical Oncology, University of South Carolina School of Medicine, Greenville, SC 29605, USA;
| | - Rebecca K. Marcus
- Department of Surgery, Saint John’s Cancer Institute at Providence St. John’s Health Center, Santa Monica, CA 90404, USA; (R.K.M.); (J.I.J.O.); (M.G.)
| | - Mary Garland-Kledzik
- Department of Surgery, Division of Surgical Oncology, West Virginia University, Morgantown, WV 26506, USA;
| | - Debopriya Ghosh
- Janssen Research and Development LLC, Early Development and Oncology, Biostatistics, Raritan, NJ 08869, USA;
| | - Miquel Ensenyat-Mendez
- Cancer Epigenetics Laboratory, Health Research Institute of the Balearic Islands, 07120 Palma, Spain;
| | - Joshua Germany
- Division of Surgical Oncology, University of South Carolina School of Medicine, Greenville, SC 29605, USA;
| | - Juan A. Santamaria-Barria
- Department of Surgery, Division of Surgical Oncology, University of Nebraska Medical Center, Omaha, NE 68105, USA;
| | - Adam Khader
- Department of Surgery, Division of Surgical Oncology, Hunter Holmes McGuire Veterans Affairs Medical Center, Richmond, VA 23249, USA;
| | - Javier I. J. Orozco
- Department of Surgery, Saint John’s Cancer Institute at Providence St. John’s Health Center, Santa Monica, CA 90404, USA; (R.K.M.); (J.I.J.O.); (M.G.)
| | - Melanie Goldfarb
- Department of Surgery, Saint John’s Cancer Institute at Providence St. John’s Health Center, Santa Monica, CA 90404, USA; (R.K.M.); (J.I.J.O.); (M.G.)
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17
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van der Meeren PE, de Wilde RF, Sprengers D, IJzermans JNM. Benefit and harm of waiting time in liver transplantation for HCC. Hepatology 2023:01515467-990000000-00646. [PMID: 37972979 DOI: 10.1097/hep.0000000000000668] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 07/07/2023] [Accepted: 10/26/2023] [Indexed: 11/19/2023]
Abstract
Liver transplantation is the most successful treatment for limited-stage HCC. The waiting time for liver transplantation (LT) can be a critical factor affecting the oncological prognosis and outcome of patients with HCC. Efficient strategies to optimize waiting time are essential to maximize the benefits of LT and to reduce the harm of delay in transplantation. The ever-increasing demand for donor livers emphasizes the need to improve the organization of the waiting list for transplantation and to optimize organ availability for patients with and without HCC. Current progress in innovations to expand the donor pool includes the implementation of living donor LT and the use of grafts from extended donors. By expanding selection criteria, an increased number of patients are eligible for transplantation, which necessitates criteria to prevent futile transplantations. Thus, the selection criteria for LT have evolved to include not only tumor characteristics but biomarkers as well. Enhancing our understanding of HCC tumor biology through the analysis of subtypes and molecular genetics holds significant promise in advancing the personalized approach for patients. In this review, the effect of waiting time duration on outcome in patients with HCC enlisted for LT is discussed.
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Affiliation(s)
- Pam Elisabeth van der Meeren
- Department of Surgery, Division of HPB & Transplant Surgery, Erasmus MC Transplant Institute, University Medical Center Rotterdam, Rotterdam, the Netherlands
| | - Roeland Frederik de Wilde
- Department of Surgery, Division of HPB & Transplant Surgery, Erasmus MC Transplant Institute, University Medical Center Rotterdam, Rotterdam, the Netherlands
| | - Dave Sprengers
- Department of Gastroenterology & Hepatology, Erasmus MC Transplant Institute, University Medical Center Rotterdam, Rotterdam, the Netherlands
| | - Jan Nicolaas Maria IJzermans
- Department of Surgery, Division of HPB & Transplant Surgery, Erasmus MC Transplant Institute, University Medical Center Rotterdam, Rotterdam, the Netherlands
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Jiang Y, Miao X, Wu Z, Xie W, Wang L, Liu H, Gong W. Targeting SIRT1 synergistically improves the antitumor effect of JQ-1 in hepatocellular carcinoma. Heliyon 2023; 9:e22093. [PMID: 38045194 PMCID: PMC10692793 DOI: 10.1016/j.heliyon.2023.e22093] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/25/2023] [Revised: 10/31/2023] [Accepted: 11/03/2023] [Indexed: 12/05/2023] Open
Abstract
Bromodomain and extraterminal domain protein inhibitors have shown therapeutic promise in hepatocellular carcinoma. However, resistance to bromodomain and extraterminal domain protein inhibitors has emerged in preclinical trials, presenting an immense clinical challenge, and the mechanisms are unclear. In this study, we found that overexpression of SIRT1 induced by JQ-1, a bromodomain and extraterminal domain protein inhibitor, may confer resistance to JQ-1 in hepatocellular carcinoma. SIRT1 protein expression was higher in hepatocellular carcinoma tissues than in normal tissues, and this phenotype was correlated with a poor prognosis. Cotreatment with JQ-1 and the SIRT1 inhibitor EX527 synergistically suppressed proliferation and blocked cell cycle progression in hepatocellular carcinoma cells. Combined administration of JQ-1 and EX527 successfully reduced the tumor burden in vivo. In addition, JQ-1 mediated AMPK/p-AMPK axis activation to upregulate SIRT1 protein expression and enhanced autophagy to inhibit cell apoptosis. Activation of AMPK could alleviate the antitumor effect of the combination of JQ-1 and EX527 on hepatocellular carcinoma cells. Furthermore, inhibition of SIRT1 further enhanced the antitumor effect of JQ-1 by blocking protective autophagy in hepatocellular carcinoma. Our study proposes a novel and efficacious therapeutic strategy of a BET inhibitor combined with a SIRT1 inhibitor for hepatocellular carcinoma.
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Affiliation(s)
- Yuancong Jiang
- Department of Surgery, Second Affiliated Hospital of School of Medicine, Zhejiang University, Hangzhou, China
- Department of Surgery, Shaoxing People's Hospital (Shaoxing Hospital, Zhejiang University School of Medicine), Shaoxing, China
| | - Xiaolong Miao
- Department of Surgery, Second Affiliated Hospital of School of Medicine, Zhejiang University, Hangzhou, China
- The Institute of Transplantation Science, The Affiliated Hospital of Qingdao University, Qingdao, China
| | - Zelai Wu
- Department of Surgery, Second Affiliated Hospital of School of Medicine, Zhejiang University, Hangzhou, China
| | - Weixun Xie
- Department of Surgery, Second Affiliated Hospital of School of Medicine, Zhejiang University, Hangzhou, China
| | - Li Wang
- Department of Surgery, Second Affiliated Hospital of School of Medicine, Zhejiang University, Hangzhou, China
| | - Han Liu
- Department of Surgery, Second Affiliated Hospital of School of Medicine, Zhejiang University, Hangzhou, China
| | - Weihua Gong
- Department of Surgery, Second Affiliated Hospital of School of Medicine, Zhejiang University, Hangzhou, China
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19
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Vij M, Veerankutty FH, Raju LP, Gowrishankar G, Rajalingam R, Jothimani D, Kaliamoorthy I, Rammohan A, Rela M. Frequent expression of PD-L1 in lymphocyte-rich hepatocellular carcinoma: A report of 4 cases. Ann Diagn Pathol 2023; 66:152172. [PMID: 37348413 DOI: 10.1016/j.anndiagpath.2023.152172] [Citation(s) in RCA: 2] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/31/2023] [Revised: 06/09/2023] [Accepted: 06/13/2023] [Indexed: 06/24/2023]
Abstract
BACKGROUND Programmed death ligand 1 (PD-L1) is an immune checkpoint inhibitor. PD-L1 binds to its receptor programmed death receptor (PD-1) expressed by immune cells and plays a key role in regulating immune responses. Engagement of PD-L1 on cancer cells and PD-1 on immune cells avoid destruction of tumour cells by immune cells. Immunostaining with PD-L1 has been suggested as a biomarker predictive of antiPD-L1 immunotherapy. Lymphocyte-rich hepatocellular carcinoma (LrHCC) is a rare histological HCC subtype which is characterised by neoplastic epithelial cells intermixed with numerous immune cells. METHODS Here in we investigated immunohistochemical PD-L1 expression in 4 cases of LrHCC. Tumour proportion score (TPS) and immune cell score was recorded. Immunophenotypic characterization of the tumour and inflammatory cells was also done. Epstein-Barr encoding region (EBER) in situ hybridization (ISH) assay as performed in all four tumours. RESULTS Expression of PD-L1 was demonstrated in tumour epithelial cells and immune cells in all four cases. Incomplete to membranous staining was demonstrated in the tumour cells. Tumour proportion score (TPS) was 1.2-20 %. Immune cells demonstrated membranous and cytoplasmic immunostaining. Immune cell score was ≥1 % to >10 %. CONCLUSION PD-L1 expression in both tumour and immune cells suggests distinct immunogenic feature and potential role of antiPD-L1 therapies in cases with inoperable disease.
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Affiliation(s)
- Mukul Vij
- Department of Pathology, Dr.Rela Institute & Medical Centre, No. 7 CLC Works Road Chromepet, Chennai 44, Tamil Nadu, India.
| | - Fadl H Veerankutty
- The Institute of Liver Disease & Transplantation, Dr.Rela Institute & Medical Centre, No. 7 CLC Works Road Chromepet, Chennai 44, Tamil Nadu, India
| | - Lexmi Priya Raju
- Department of Pathology, Dr.Rela Institute & Medical Centre, No. 7 CLC Works Road Chromepet, Chennai 44, Tamil Nadu, India
| | - Gowripriya Gowrishankar
- Department of Pathology, Dr.Rela Institute & Medical Centre, No. 7 CLC Works Road Chromepet, Chennai 44, Tamil Nadu, India.
| | - Rajesh Rajalingam
- The Institute of Liver Disease & Transplantation, Dr.Rela Institute & Medical Centre, No. 7 CLC Works Road Chromepet, Chennai 44, Tamil Nadu, India
| | - Dinesh Jothimani
- The Institute of Liver Disease & Transplantation, Dr.Rela Institute & Medical Centre, No. 7 CLC Works Road Chromepet, Chennai 44, Tamil Nadu, India.
| | - Ilankumaran Kaliamoorthy
- The Institute of Liver Disease & Transplantation, Dr.Rela Institute & Medical Centre, No. 7 CLC Works Road Chromepet, Chennai 44, Tamil Nadu, India.
| | - Ashwin Rammohan
- The Institute of Liver Disease & Transplantation, Dr.Rela Institute & Medical Centre, No. 7 CLC Works Road Chromepet, Chennai 44, Tamil Nadu, India
| | - Mohamed Rela
- The Institute of Liver Disease & Transplantation, Dr.Rela Institute & Medical Centre, No. 7 CLC Works Road Chromepet, Chennai 44, Tamil Nadu, India.
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20
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Auer TA, Halskov S, Fehrenbach U, Nevermann NF, Pelzer U, Mohr R, Hamm B, Schöning W, Horst D, Ihlow J, Geisel D. Gd-EOB MRI for HCC subtype differentiation in a western population according to the 5 th edition of the World Health Organization classification. Eur Radiol 2023; 33:6902-6915. [PMID: 37115216 PMCID: PMC10511376 DOI: 10.1007/s00330-023-09669-y] [Citation(s) in RCA: 3] [Impact Index Per Article: 1.5] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/27/2023] [Revised: 03/29/2023] [Accepted: 04/10/2023] [Indexed: 04/29/2023]
Abstract
OBJECTIVES To investigate the value of gadoxetic acid (Gd-EOB)-enhanced magnetic resonance imaging (MRI) for noninvasive subtype differentiation of HCCs according to the 5th edition of the WHO Classification of Digestive System Tumors in a western population. METHODS This retrospective study included 262 resected lesions in 240 patients with preoperative Gd-EOB-enhanced MRI. Subtypes were assigned by two pathologists. Gd-EOB-enhanced MRI datasets were assessed by two radiologists for qualitative and quantitative imaging features, including imaging features defined in LI-RADS v2018 and area of hepatobiliary phase (HBP) iso- to hyperintensity. RESULTS The combination of non-rim arterial phase hyperenhancement with non-peripheral portal venous washout was more common in "not otherwise specified" (nos-ST) (88/168, 52%) than other subtypes, in particular macrotrabecular massive (mt-ST) (3/15, 20%), chromophobe (ch-ST) (1/8, 13%), and scirrhous subtypes (sc-ST) (2/9, 22%) (p = 0.035). Macrovascular invasion was associated with mt-ST (5/16, p = 0.033) and intralesional steatosis with steatohepatitic subtype (sh-ST) (28/32, p < 0.001). Predominant iso- to hyperintensity in the HBP was only present in nos-ST (16/174), sh-ST (3/33), and clear cell subtypes (cc-ST) (3/13) (p = 0.031). Associations were found for the following non-imaging parameters: age and sex, as patients with fibrolamellar subtype (fib-ST) were younger (median 44 years (19-66), p < 0.001) and female (4/5, p = 0.023); logarithm of alpha-fetoprotein (AFP) was elevated in the mt-ST (median 397 µg/l (74-5370), p < 0.001); type II diabetes mellitus was more frequent in the sh-ST (20/33, p = 0.027). CONCLUSIONS Gd-EOB-MRI reproduces findings reported in the literature for extracellular contrast-enhanced MRI and CT and may be a valuable tool for noninvasive HCC subtype differentiation. CLINICAL RELEVANCE STATEMENT Better characterization of the heterogeneous phenotypes of HCC according to the revised WHO classification potentially improves both diagnostic accuracy and the precision of therapeutic stratification for HCC. KEY POINTS • Previously reported imaging features of common subtypes in CT and MRI enhanced with extracellular contrast agents are reproducible with Gd-EOB-enhanced MRI. • While uncommon, predominant iso- to hyperintensity in the HBP was observed only in NOS, clear cell, and steatohepatitic subtypes. • Gd-EOB-enhanced MRI offers imaging features that are of value for HCC subtype differentiation according to the 5th edition of the WHO Classification of Digestive System Tumors.
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Affiliation(s)
- Timo A Auer
- Department of Radiology, Charité - Universitätsmedizin Berlin, Augustenburger Platz 1, 13353, Berlin, Germany.
- Berlin Institute of Health (BIH), Anna-Louisa-Karsch-Straße 2, 10178, Berlin, Germany.
| | - Sebastian Halskov
- Department of Radiology, Charité - Universitätsmedizin Berlin, Augustenburger Platz 1, 13353, Berlin, Germany
| | - Uli Fehrenbach
- Department of Radiology, Charité - Universitätsmedizin Berlin, Augustenburger Platz 1, 13353, Berlin, Germany
| | - Nora F Nevermann
- Department of Surgery - CVK/CCM, Charité - Universitätsmedizin Berlin, Augustenburger Platz 1, 13353, Berlin, Germany
| | - Uwe Pelzer
- Department of Hematology, Oncology and Cancer Immunology, Charité - Universitätsmedizin Berlin, Augustenburger Platz 1, 13353, Berlin, Germany
| | - Raphael Mohr
- Department of Hepatology and Gastroenterology, Charité - Universitätsmedizin Berlin, Augustenburger Platz 1, 13353, Berlin, Germany
| | - Bernd Hamm
- Department of Radiology, Charité - Universitätsmedizin Berlin, Augustenburger Platz 1, 13353, Berlin, Germany
| | - Wenzel Schöning
- Department of Surgery - CVK/CCM, Charité - Universitätsmedizin Berlin, Augustenburger Platz 1, 13353, Berlin, Germany
| | - David Horst
- Institute of Pathology, Charité - Universitätsmedizin Berlin, corporate member of Freie Universität Berlin and Humboldt-Universität Zu Berlin, Charitéplatz 1, 10117, Berlin, Germany
| | - Jana Ihlow
- Institute of Pathology, Charité - Universitätsmedizin Berlin, corporate member of Freie Universität Berlin and Humboldt-Universität Zu Berlin, Charitéplatz 1, 10117, Berlin, Germany
| | - Dominik Geisel
- Department of Radiology, Charité - Universitätsmedizin Berlin, Augustenburger Platz 1, 13353, Berlin, Germany
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21
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Choi JH, Thung SN. Advances in Histological and Molecular Classification of Hepatocellular Carcinoma. Biomedicines 2023; 11:2582. [PMID: 37761023 PMCID: PMC10526317 DOI: 10.3390/biomedicines11092582] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/13/2023] [Revised: 09/06/2023] [Accepted: 09/08/2023] [Indexed: 09/29/2023] Open
Abstract
Hepatocellular carcinoma (HCC) is a primary liver cancer characterized by hepatocellular differentiation. HCC is molecularly heterogeneous with a wide spectrum of histopathology. The prognosis of patients with HCC is generally poor, especially in those with advanced stages. HCC remains a diagnostic challenge for pathologists because of its morphological and phenotypic diversity. However, recent advances have enhanced our understanding of the molecular genetics and histological subtypes of HCC. Accurate diagnosis of HCC is important for patient management and prognosis. This review provides an update on HCC pathology, focusing on molecular genetics, histological subtypes, and diagnostic approaches.
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Affiliation(s)
- Joon Hyuk Choi
- Department of Pathology, Yeungnam University College of Medicine, Daegu 42415, Republic of Korea
| | - Swan N. Thung
- Department of Pathology, Molecular and Cell-Based Medicine, Icahn School of Medicine at Mount Sinai, 1468 Madison Avenue, New York, NY 10029, USA;
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22
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Pan YJ, Liu W, Qiu QX, Miao SL, Zeng MS, Shan Y, Lin J, Xu PJ. Prognostic value of LI-RADS category on MRI in patients with primary hepatic lymphoepithelioma-like carcinoma. Eur Radiol 2023; 33:5993-6000. [PMID: 37014407 DOI: 10.1007/s00330-023-09598-w] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/14/2022] [Revised: 01/18/2023] [Accepted: 02/10/2023] [Indexed: 04/05/2023]
Abstract
OBJECTIVES To compare the clinical and MRI features of primary hepatic lymphoepithelioma-like carcinoma (LELC) categorized as LR-M or LR-4/5 using the Liver Imaging Reporting and Data System (LI-RADS) version 2018 and to determine the prognostic factors for recurrence-free survival (RFS). METHODS In this retrospective study, 37 patients with surgically confirmed LELC were included. Two independent observers evaluated preoperative MRI features according to the LI-RADS version 2018. Clinical and imaging features were compared between two groups. RFS and the associated factors were evaluated using Cox proportional hazards regression analysis, Kaplan-Meier analysis, and log-rank test. RESULTS In total, 37 patients (mean age, 58.5 ± 10.3 years) were evaluated. Sixteen (43.2%) LELCs were categorized as LR-M and twenty-one (56.8%) LELCs were categorized as LR-4/5. In the multivariate analysis, the LR-M category was an independent factor for RFS (HR 7.908, 95% CI 1.170-53.437; p = 0.033). RFS rates were significantly lower in patients with LR-M LELCs than in patients with LR-4/5 LELCs (5-year RFS rate, 43.8% vs.85.7%; p = 0.002). CONCLUSION The LI-RADS category was significantly associated with postsurgical prognosis of LELC, with tumor categorized as LR-M having a worse RFS than those categorized as LR-4/5. KEY POINTS • Lymphoepithelioma-like carcinoma patients categorized as LR-M have worse recurrence-free survival than those categorized as LR-4/5. • MRI-based LI-RADS categorization was an independent factor for postoperative prognosis of primary hepatic lymphoepithelioma-like carcinoma.
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Affiliation(s)
- Yi-Jun Pan
- Department of Radiology, Zhongshan Hospital, Fudan University, No. 180 Fenglin Road, Xuhui District, Shanghai, 200032, China
- Shanghai Institute of Medical Imaging, No. 180 Fenglin Road, Xuhui District, Shanghai, 200032, China
| | - Wei Liu
- Department of Nuclear Medicine, Fudan University Shanghai Cancer Center, No. 270 Dong'an Road, Xuhui District, Shanghai, 200032, China
| | - Qi-Xuan Qiu
- Department of Radiology, Zhongshan Hospital, Fudan University, No. 180 Fenglin Road, Xuhui District, Shanghai, 200032, China
| | - Shou-Liang Miao
- Department of Radiology, The First Affiliated Hospital of Wenzhou Medical University, Nanbaixiang, Ouhai District, Wenzhou, 325015, Zhejiang, China
| | - Meng-Su Zeng
- Department of Radiology, Zhongshan Hospital, Fudan University, No. 180 Fenglin Road, Xuhui District, Shanghai, 200032, China
- Shanghai Institute of Medical Imaging, No. 180 Fenglin Road, Xuhui District, Shanghai, 200032, China
| | - Yan Shan
- Department of Radiology, Zhongshan Hospital, Fudan University, No. 180 Fenglin Road, Xuhui District, Shanghai, 200032, China.
- Shanghai Institute of Medical Imaging, No. 180 Fenglin Road, Xuhui District, Shanghai, 200032, China.
| | - Jiang Lin
- Department of Radiology, Zhongshan Hospital, Fudan University, No. 180 Fenglin Road, Xuhui District, Shanghai, 200032, China.
- Shanghai Institute of Medical Imaging, No. 180 Fenglin Road, Xuhui District, Shanghai, 200032, China.
| | - Peng-Ju Xu
- Department of Radiology, Zhongshan Hospital, Fudan University, No. 180 Fenglin Road, Xuhui District, Shanghai, 200032, China.
- Shanghai Institute of Medical Imaging, No. 180 Fenglin Road, Xuhui District, Shanghai, 200032, China.
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23
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Wang PY, Kuo YH, Sheu MJ, Kuo HT, Lee WY, Kuo YT, Wang SH. Lymphocyte-Rich Hepatocellular Carcinoma with Multiple Lymphadenopathy and Positive Epstein-Barr Virus Encoding Region. Case Reports Hepatol 2023; 2023:4797233. [PMID: 37583793 PMCID: PMC10425252 DOI: 10.1155/2023/4797233] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 02/25/2023] [Revised: 05/22/2023] [Accepted: 07/19/2023] [Indexed: 08/17/2023] Open
Abstract
Lymphocyte-rich hepatocellular carcinoma (HCC) represents the rarest subtype among the various subgroups of HCC, and limited clinical data are available for this particular subtype. It is commonly observed as a solitary lesion and tends to present at an early stage. Histopathological examination typically reveals tumor cells infiltrated by a lymphocyte-rich background, leading to its designation as lymphoepithelioma-like HCC. Unlike other lymphoepithelioma-like tumors associated with the Epstein-Barr virus (EBV), lymphocyte-rich HCC is predominantly negative for EBV. This subtype is characterized by more favorable clinical outcomes and prognosis compared to conventional HCC. Here, we present a case of lymphocyte-rich hepatocellular carcinoma (HCC) characterized by the presence of bilateral hepatic tumors and concurrent multiple lymphadenopathy. Interestingly, contrary to previous literature, the examination for the Epstein-Barr virus (EBV) revealed a positive result in this particular case.
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Affiliation(s)
- Pin-Yi Wang
- Division of Hepatogastroenterology, Department of Internal Medicine, Chi Mei Medical Center, Tainan, Taiwan
| | - Yu-Hsuan Kuo
- Division of Hematology and Oncology, Department of Internal Medicine, Chi Mei Medical Center, Tainan, Taiwan
| | - Ming-Jen Sheu
- Division of Hepatogastroenterology, Department of Internal Medicine, Chi Mei Medical Center, Tainan, Taiwan
| | - Hsing-Tao Kuo
- Division of Hepatogastroenterology, Department of Internal Medicine, Chi Mei Medical Center, Tainan, Taiwan
| | - Wen-Ying Lee
- Department of Pathology, Chi Mei Medical Center, Tainan, Taiwan
| | - Yu-Ting Kuo
- Department of Radiology, Chi Mei Medical Center, Tainan, Taiwan
| | - Su-Hung Wang
- Division of Hepatogastroenterology, Department of Internal Medicine, Chi Mei Medical Center, Tainan, Taiwan
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24
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Fowler KJ, Chernyak V, Ronot M, Vilgrain V, Kitao A, Lee JM, Motosugi U, Song B, Jiang H, Sirlin CB, Bashir MR. Hepatocellular Carcinoma: It Is Time to Focus on Prognosis. Radiology 2023; 307:e220884. [PMID: 37014249 PMCID: PMC10140632 DOI: 10.1148/radiol.220884] [Citation(s) in RCA: 2] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/25/2022] [Revised: 07/05/2022] [Accepted: 07/12/2022] [Indexed: 04/05/2023]
Affiliation(s)
- Kathryn J. Fowler
- From the Department of Radiology, University of California San Diego,
6206 Lakewood St, San Diego, CA 92122 (K.J.F., C.B.S.); Department of Radiology,
Beth Israel Deaconess Medical Center, Boston, Mass (V.C.); Department of
Radiology, Université Paris Cité, Paris, France (M.R., V.V.);
Department of Radiology, Hôpital Beaujon, APHP.Nord, Clichy, France
(M.R., V.V.); Department of Radiology, Kanazawa University Graduate School of
Medicine, Kanazawa, Japan (A.K.); Department of Radiology, Seoul National
University College of Medicine, Seoul, Korea (J.M.L.); Department of Radiology,
Kofu Kyoritsu Hospital, Kofu, Japan (U.M.); Department of Radiology, West China
Hospital, Chengdu, China (B.S., H.J.); and Department of Radiology, Duke
University Medical Center, Durham, NC (M.R.B.)
| | - Victoria Chernyak
- From the Department of Radiology, University of California San Diego,
6206 Lakewood St, San Diego, CA 92122 (K.J.F., C.B.S.); Department of Radiology,
Beth Israel Deaconess Medical Center, Boston, Mass (V.C.); Department of
Radiology, Université Paris Cité, Paris, France (M.R., V.V.);
Department of Radiology, Hôpital Beaujon, APHP.Nord, Clichy, France
(M.R., V.V.); Department of Radiology, Kanazawa University Graduate School of
Medicine, Kanazawa, Japan (A.K.); Department of Radiology, Seoul National
University College of Medicine, Seoul, Korea (J.M.L.); Department of Radiology,
Kofu Kyoritsu Hospital, Kofu, Japan (U.M.); Department of Radiology, West China
Hospital, Chengdu, China (B.S., H.J.); and Department of Radiology, Duke
University Medical Center, Durham, NC (M.R.B.)
| | - Maxime Ronot
- From the Department of Radiology, University of California San Diego,
6206 Lakewood St, San Diego, CA 92122 (K.J.F., C.B.S.); Department of Radiology,
Beth Israel Deaconess Medical Center, Boston, Mass (V.C.); Department of
Radiology, Université Paris Cité, Paris, France (M.R., V.V.);
Department of Radiology, Hôpital Beaujon, APHP.Nord, Clichy, France
(M.R., V.V.); Department of Radiology, Kanazawa University Graduate School of
Medicine, Kanazawa, Japan (A.K.); Department of Radiology, Seoul National
University College of Medicine, Seoul, Korea (J.M.L.); Department of Radiology,
Kofu Kyoritsu Hospital, Kofu, Japan (U.M.); Department of Radiology, West China
Hospital, Chengdu, China (B.S., H.J.); and Department of Radiology, Duke
University Medical Center, Durham, NC (M.R.B.)
| | - Valerie Vilgrain
- From the Department of Radiology, University of California San Diego,
6206 Lakewood St, San Diego, CA 92122 (K.J.F., C.B.S.); Department of Radiology,
Beth Israel Deaconess Medical Center, Boston, Mass (V.C.); Department of
Radiology, Université Paris Cité, Paris, France (M.R., V.V.);
Department of Radiology, Hôpital Beaujon, APHP.Nord, Clichy, France
(M.R., V.V.); Department of Radiology, Kanazawa University Graduate School of
Medicine, Kanazawa, Japan (A.K.); Department of Radiology, Seoul National
University College of Medicine, Seoul, Korea (J.M.L.); Department of Radiology,
Kofu Kyoritsu Hospital, Kofu, Japan (U.M.); Department of Radiology, West China
Hospital, Chengdu, China (B.S., H.J.); and Department of Radiology, Duke
University Medical Center, Durham, NC (M.R.B.)
| | - Azusa Kitao
- From the Department of Radiology, University of California San Diego,
6206 Lakewood St, San Diego, CA 92122 (K.J.F., C.B.S.); Department of Radiology,
Beth Israel Deaconess Medical Center, Boston, Mass (V.C.); Department of
Radiology, Université Paris Cité, Paris, France (M.R., V.V.);
Department of Radiology, Hôpital Beaujon, APHP.Nord, Clichy, France
(M.R., V.V.); Department of Radiology, Kanazawa University Graduate School of
Medicine, Kanazawa, Japan (A.K.); Department of Radiology, Seoul National
University College of Medicine, Seoul, Korea (J.M.L.); Department of Radiology,
Kofu Kyoritsu Hospital, Kofu, Japan (U.M.); Department of Radiology, West China
Hospital, Chengdu, China (B.S., H.J.); and Department of Radiology, Duke
University Medical Center, Durham, NC (M.R.B.)
| | - Jeong Min Lee
- From the Department of Radiology, University of California San Diego,
6206 Lakewood St, San Diego, CA 92122 (K.J.F., C.B.S.); Department of Radiology,
Beth Israel Deaconess Medical Center, Boston, Mass (V.C.); Department of
Radiology, Université Paris Cité, Paris, France (M.R., V.V.);
Department of Radiology, Hôpital Beaujon, APHP.Nord, Clichy, France
(M.R., V.V.); Department of Radiology, Kanazawa University Graduate School of
Medicine, Kanazawa, Japan (A.K.); Department of Radiology, Seoul National
University College of Medicine, Seoul, Korea (J.M.L.); Department of Radiology,
Kofu Kyoritsu Hospital, Kofu, Japan (U.M.); Department of Radiology, West China
Hospital, Chengdu, China (B.S., H.J.); and Department of Radiology, Duke
University Medical Center, Durham, NC (M.R.B.)
| | - Utaroh Motosugi
- From the Department of Radiology, University of California San Diego,
6206 Lakewood St, San Diego, CA 92122 (K.J.F., C.B.S.); Department of Radiology,
Beth Israel Deaconess Medical Center, Boston, Mass (V.C.); Department of
Radiology, Université Paris Cité, Paris, France (M.R., V.V.);
Department of Radiology, Hôpital Beaujon, APHP.Nord, Clichy, France
(M.R., V.V.); Department of Radiology, Kanazawa University Graduate School of
Medicine, Kanazawa, Japan (A.K.); Department of Radiology, Seoul National
University College of Medicine, Seoul, Korea (J.M.L.); Department of Radiology,
Kofu Kyoritsu Hospital, Kofu, Japan (U.M.); Department of Radiology, West China
Hospital, Chengdu, China (B.S., H.J.); and Department of Radiology, Duke
University Medical Center, Durham, NC (M.R.B.)
| | - Bin Song
- From the Department of Radiology, University of California San Diego,
6206 Lakewood St, San Diego, CA 92122 (K.J.F., C.B.S.); Department of Radiology,
Beth Israel Deaconess Medical Center, Boston, Mass (V.C.); Department of
Radiology, Université Paris Cité, Paris, France (M.R., V.V.);
Department of Radiology, Hôpital Beaujon, APHP.Nord, Clichy, France
(M.R., V.V.); Department of Radiology, Kanazawa University Graduate School of
Medicine, Kanazawa, Japan (A.K.); Department of Radiology, Seoul National
University College of Medicine, Seoul, Korea (J.M.L.); Department of Radiology,
Kofu Kyoritsu Hospital, Kofu, Japan (U.M.); Department of Radiology, West China
Hospital, Chengdu, China (B.S., H.J.); and Department of Radiology, Duke
University Medical Center, Durham, NC (M.R.B.)
| | - Hanyu Jiang
- From the Department of Radiology, University of California San Diego,
6206 Lakewood St, San Diego, CA 92122 (K.J.F., C.B.S.); Department of Radiology,
Beth Israel Deaconess Medical Center, Boston, Mass (V.C.); Department of
Radiology, Université Paris Cité, Paris, France (M.R., V.V.);
Department of Radiology, Hôpital Beaujon, APHP.Nord, Clichy, France
(M.R., V.V.); Department of Radiology, Kanazawa University Graduate School of
Medicine, Kanazawa, Japan (A.K.); Department of Radiology, Seoul National
University College of Medicine, Seoul, Korea (J.M.L.); Department of Radiology,
Kofu Kyoritsu Hospital, Kofu, Japan (U.M.); Department of Radiology, West China
Hospital, Chengdu, China (B.S., H.J.); and Department of Radiology, Duke
University Medical Center, Durham, NC (M.R.B.)
| | - Claude B. Sirlin
- From the Department of Radiology, University of California San Diego,
6206 Lakewood St, San Diego, CA 92122 (K.J.F., C.B.S.); Department of Radiology,
Beth Israel Deaconess Medical Center, Boston, Mass (V.C.); Department of
Radiology, Université Paris Cité, Paris, France (M.R., V.V.);
Department of Radiology, Hôpital Beaujon, APHP.Nord, Clichy, France
(M.R., V.V.); Department of Radiology, Kanazawa University Graduate School of
Medicine, Kanazawa, Japan (A.K.); Department of Radiology, Seoul National
University College of Medicine, Seoul, Korea (J.M.L.); Department of Radiology,
Kofu Kyoritsu Hospital, Kofu, Japan (U.M.); Department of Radiology, West China
Hospital, Chengdu, China (B.S., H.J.); and Department of Radiology, Duke
University Medical Center, Durham, NC (M.R.B.)
| | - Mustafa R. Bashir
- From the Department of Radiology, University of California San Diego,
6206 Lakewood St, San Diego, CA 92122 (K.J.F., C.B.S.); Department of Radiology,
Beth Israel Deaconess Medical Center, Boston, Mass (V.C.); Department of
Radiology, Université Paris Cité, Paris, France (M.R., V.V.);
Department of Radiology, Hôpital Beaujon, APHP.Nord, Clichy, France
(M.R., V.V.); Department of Radiology, Kanazawa University Graduate School of
Medicine, Kanazawa, Japan (A.K.); Department of Radiology, Seoul National
University College of Medicine, Seoul, Korea (J.M.L.); Department of Radiology,
Kofu Kyoritsu Hospital, Kofu, Japan (U.M.); Department of Radiology, West China
Hospital, Chengdu, China (B.S., H.J.); and Department of Radiology, Duke
University Medical Center, Durham, NC (M.R.B.)
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25
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Madani SP, Mirza-Aghazadeh-Attari M, Mohseni A, Pawlik T, Kamel IR. Diffuse infiltrative hepatocellular carcinoma: Multimodality imaging manifestations. J Surg Oncol 2023; 127:385-393. [PMID: 36374195 DOI: 10.1002/jso.27138] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/21/2022] [Accepted: 10/23/2022] [Indexed: 11/16/2022]
Abstract
Hepatocellular carcinoma (HCC) is the most prevalent primary liver cancer, being the third most common cause of cancer-related death globally. HCC most frequently develops in the context of hepatic cirrhosis. HCC can manifest as various morphologic subtypes. Each pattern exhibits distinct behaviors in terms of imaging features, disease progression, response to therapy, and prognosis. While the nodular pattern is the most frequent subtype, infiltrative HCC is the least prevalent and makes up about 8%-20% of all HCC cases. Infiltrative HCC manifests as small tumor nodules that often spread across the entire liver or across a hepatic segment/lobe and is not identified as a focal tumor. On ultrasonography, infiltrative HCC presents as a markedly heterogeneous area with ill-defined echotexture, making it difficult to distinguish from background hepatic cirrhosis. On magnetic resonance imaging (MRI), infiltrating HCC typically manifests as a mild, poorly defined hepatic region with heterogeneous or homogenous aberrant signal intensity. Specifically, on T1-weighted MRI scans, infiltrating HCC frequently appears as largely hypointense and typically homogenous and mildly to moderately hyperintense on T2-weighted imaging. Infiltrative HCC frequently lacks a clearly defined boundary on cross-sectional imaging and can consequently fade into the background of the cirrhotic liver. As a result, infiltrating HCC is frequently not discovered until an advanced stage and has an associated poor prognosis. Thus, understanding imaging features associated with infiltrative HCC diagnosis is crucial for abdominal radiologists to ensure effective and timely care. We herein review imaging characteristics of infiltrative HCC.
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Affiliation(s)
- Seyedeh Panid Madani
- Russell H. Morgan Department of Radiology and Radiological Science, School of Medicine, Johns Hopkins Hospital, Johns Hopkins University, Baltimore, Maryland, USA
| | - Mohammad Mirza-Aghazadeh-Attari
- Russell H. Morgan Department of Radiology and Radiological Science, School of Medicine, Johns Hopkins Hospital, Johns Hopkins University, Baltimore, Maryland, USA
| | - Alireza Mohseni
- Russell H. Morgan Department of Radiology and Radiological Science, School of Medicine, Johns Hopkins Hospital, Johns Hopkins University, Baltimore, Maryland, USA
| | - Timothy Pawlik
- Department of Surgery, Wexner Medical Center, The James Comprehensive Cancer Center, The Ohio State University, Columbus, Ohio, USA
| | - Ihab R Kamel
- Russell H. Morgan Department of Radiology and Radiological Science, School of Medicine, Johns Hopkins Hospital, Johns Hopkins University, Baltimore, Maryland, USA
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26
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Kierans AS, Chernyak V, Mendiratta-Lala M, Sirlin CB, Hecht EM, Fowler KJ. The Organ Procurement and Transplantation Network hepatocellular carcinoma classification: Alignment with Liver Imaging Reporting and Data System, current gaps, and future direction. Liver Transpl 2023; 29:206-216. [PMID: 37160075 DOI: 10.1002/lt.26570] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 07/08/2022] [Revised: 08/08/2022] [Accepted: 08/24/2022] [Indexed: 01/25/2023]
Abstract
The Organ Procurement and Transplantation Network (OPTN) updated its allocation policy for liver transplantation to align with the Liver Imaging Reporting and Data System (LI-RADS) for the diagnosis of hepatocellular carcinoma (HCC). LI-RADS computed tomography/magnetic resonance imaging algorithm had achieved congruency with the American Association for the Study of Liver Diseases (AASLD) HCC Practice Guidance in 2018, and therefore, alignment of OPTN, LI-RADS, and AASLD unifies HCC diagnostic approaches. The two changes to the OPTN HCC classification are adoption of LI-RADS terminology or lexicon for HCC major imaging features as well as the modification of OPTN Class-5A through the adoption of LI-RADS-5 criteria. However, despite this significant milestone, the OPTN allocation policy may benefit from further refinements such as adoption of treatment response assessment criteria after locoregional therapy and categorization criteria for lesions with atypical imaging appearances that are not specific for HCC. In this review, we detail the changes to the OPTN HCC classification to achieve alignment with LI-RADS, discuss current limitations of the OPTN classification, and explore future directions.
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Affiliation(s)
- Andrea S Kierans
- Department of Radiology , Weill Cornell Medical College , New York , New York , USA
| | - Victoria Chernyak
- Department of Radiology , Memorial Sloan Kettering Cancer Center , New York , New York , USA
| | | | - Claude B Sirlin
- Department of Radiology , University of California San Diego , La Jolla , California , USA
| | - Elizabeth M Hecht
- Department of Radiology , Weill Cornell Medical College , New York , New York , USA
| | - Kathryn J Fowler
- Department of Radiology , University of California San Diego , La Jolla , California , USA
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27
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Invited Commentary: Augmented Reality for Central Liver Resection: To See or Not to See. J Am Coll Surg 2023; 236:337-338. [PMID: 36648261 DOI: 10.1097/xcs.0000000000000461] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 01/18/2023]
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28
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Yasir S, Thompson S, Chen ZE, Knudson R, Knutson D, Kloft-Nelson S, Graham RP, Jain D, Simon SM, Wu TT, Torbenson M. Alternative lengthening of telomeres in primary hepatic neoplasms. Hum Pathol 2023; 131:79-86. [PMID: 36370823 PMCID: PMC10756352 DOI: 10.1016/j.humpath.2022.11.003] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 08/16/2022] [Revised: 10/31/2022] [Accepted: 11/04/2022] [Indexed: 11/11/2022]
Abstract
The alternative lengthening of telomeres (ALT) phenotype is characterized by ultra-bright telomeres on fluorescence in situ hybridization (FISH) and is a marker of a unique mechanism of telomere maintenance in tumors. ALT does not occur in normal tissues. ALT has been described in hepatocellular carcinoma (5-10%) and in primary hepatic angiosarcomas (75%). To study the frequency of ALT in other primary hepatic tumors, a wide range of primary hepatic neoplasms were retrieved. The tumors included the following: intrahepatic and hilar cholangiocarcinomas (N = 110), hepatic adenomas (N = 35), hepatocellular carcinomas (N = 30), fibrolamellar carcinomas (n = 11), combined cholangiocarcinoma-hepatocellular carcinomas (N = 8), carcinosarcoma (N = 10), hepatoblastomas (N = 5), hemangiomas (N = 4), angiosarcomas (N = 8), epithelioid hemangioendotheliomas (N = 10), calcified nested stromal epithelial tumor (N = 2), embryonal sarcoma (N = 2), rhabdoid tumor (N = 1), bile duct adenoma (N = 1), and angiomyolipoma (N = 1). For epithelial tumors, ALT-FISH was positive in one carcinosarcoma (10% of cases), one cholangiocarcinoma (1% of cases), and one combined hepatocellular carcinoma-cholangiocarcinoma (13% of cases). In the hepatocellular carcinoma component of both the carcinosarcoma and the combined hepatocellular carcinoma-cholangiocarcinoma, the tumor cells showed patchy marked nuclear pleomorphism akin to that described previously for chromophobe hepatocellular carcinoma, which are typically ALT FISH positive. The ALT-positive cholangiocarcinoma also showed patchy, striking nuclear pleomorphism. For soft tissue tumors, ALT was positive in two angiosarcomas (N = 2; 25% of cases). In summary, this study shows that ALT-FISH is positive in rare carcinosarcomas, cholangiocarcinomas, and combined cholangiocarcinoma-hepatocellular carcinoma. ALT is not a significant mechanism of telomere maintenance in hepatocellular adenomas or fibrolamellar carcinomas and was negative in all other tested primary hepatic neoplasms. ALT-FISH is also positive in a subset of primary hepatic angiosarcomas.
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Affiliation(s)
- Saba Yasir
- Department of Laboratory Medicine and Pathology, Mayo Clinic Rochester, MN, 55905, USA
| | - Scott Thompson
- Department of Radiology, Mayo Clinic Rochester, MN, 55905, USA
| | - Zongming Eric Chen
- Department of Laboratory Medicine and Pathology, Mayo Clinic Rochester, MN, 55905, USA
| | - Ryan Knudson
- Medical Genome Facility, Cytogenetics Core Laboratory, Mayo Clinic Rochester, MN, 55905, USA
| | - Darlene Knutson
- Medical Genome Facility, Cytogenetics Core Laboratory, Mayo Clinic Rochester, MN, 55905, USA
| | - Sara Kloft-Nelson
- Medical Genome Facility, Cytogenetics Core Laboratory, Mayo Clinic Rochester, MN, 55905, USA
| | - Rondell P Graham
- Department of Laboratory Medicine and Pathology, Mayo Clinic Rochester, MN, 55905, USA
| | | | - Sanford M Simon
- Laboratory of Cellular Biophysics, The Rockefeller University, 1230 York Avenue, NY, NY, 10065, USA
| | - Tsung-Teh Wu
- Department of Laboratory Medicine and Pathology, Mayo Clinic Rochester, MN, 55905, USA
| | - Michael Torbenson
- Department of Laboratory Medicine and Pathology, Mayo Clinic Rochester, MN, 55905, USA.
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29
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Bilal Masokano I, Pei Y, Chen J, Liu W, Xie S, Liu H, Feng D, He Q, Li W. Development and validation of MRI-based model for the preoperative prediction of macrotrabecular hepatocellular carcinoma subtype. Insights Imaging 2022; 13:201. [PMID: 36544029 PMCID: PMC9772375 DOI: 10.1186/s13244-022-01333-1] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.7] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/24/2022] [Accepted: 11/20/2022] [Indexed: 12/24/2022] Open
Abstract
BACKGROUND Macrotrabecular hepatocellular carcinoma (MTHCC) has a poor prognosis and is difficult to diagnose preoperatively. The purpose is to build and validate MRI-based models to predict the MTHCC subtype. METHODS Two hundred eight patients with confirmed HCC were enrolled. Three models (model 1: clinicoradiologic model; model 2: fusion radiomics signature; model 3: combined model 1 and model 2) were built based on their clinical data and MR images to predict MTHCC in training and validation cohorts. The performance of the models was assessed using the area under the curve (AUC). The clinical utility of the models was estimated by decision curve analysis (DCA). A nomogram was constructed, and its calibration was evaluated. RESULTS Model 1 is easier to build than models 2 and 3, with a good AUC of 0.773 (95% CI 0.696-0.838) and 0.801 (95% CI 0.681-0.891) in predicting MTHCC in training and validation cohorts, respectively. It performed slightly superior to model 2 in both training (AUC 0.747; 95% CI 0.689-0.806; p = 0.548) and validation (AUC 0.718; 95% CI 0.618-0.810; p = 0.089) cohorts and was similar to model 3 in the validation (AUC 0.866; 95% CI 0.801-0.928; p = 0.321) but inferior in the training (AUC 0.889; 95% CI 0.851-0.926; p = 0.001) cohorts. The DCA of model 1 had a higher net benefit than the treat-all and treat-none strategy at a threshold probability of 10%. The calibration curves of model 1 closely aligned with the true MTHCC rates in the training (p = 0.355) and validation sets (p = 0.364). CONCLUSION The clinicoradiologic model has a good performance in diagnosing MTHCC, and it is simpler and easier to implement, making it a valuable tool for pretherapeutic decision-making in patients.
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Affiliation(s)
- Ismail Bilal Masokano
- grid.216417.70000 0001 0379 7164Department of Radiology, Xiangya Hospital, Central South University, No. 168 Xiangya Road, Kaifu District, Changsha, 410008 Hunan China ,grid.216417.70000 0001 0379 7164National Clinical Research Center for Geriatric Disorders, Xiangya Hospital, Central South University, Changsha, 410008 Hunan China ,grid.216417.70000 0001 0379 7164Department of Radiology, The Third Xiangya Hospital, Central South University, Changsha, 410013 Hunan China
| | - Yigang Pei
- grid.216417.70000 0001 0379 7164Department of Radiology, Xiangya Hospital, Central South University, No. 168 Xiangya Road, Kaifu District, Changsha, 410008 Hunan China ,grid.216417.70000 0001 0379 7164National Clinical Research Center for Geriatric Disorders, Xiangya Hospital, Central South University, Changsha, 410008 Hunan China
| | - Juan Chen
- grid.216417.70000 0001 0379 7164Department of Radiology, Xiangya Hospital, Central South University, No. 168 Xiangya Road, Kaifu District, Changsha, 410008 Hunan China ,grid.216417.70000 0001 0379 7164National Clinical Research Center for Geriatric Disorders, Xiangya Hospital, Central South University, Changsha, 410008 Hunan China
| | - Wenguang Liu
- grid.216417.70000 0001 0379 7164Department of Radiology, Xiangya Hospital, Central South University, No. 168 Xiangya Road, Kaifu District, Changsha, 410008 Hunan China ,grid.216417.70000 0001 0379 7164National Clinical Research Center for Geriatric Disorders, Xiangya Hospital, Central South University, Changsha, 410008 Hunan China
| | - Simin Xie
- grid.216417.70000 0001 0379 7164Department of Radiology, Xiangya Hospital, Central South University, No. 168 Xiangya Road, Kaifu District, Changsha, 410008 Hunan China ,grid.216417.70000 0001 0379 7164National Clinical Research Center for Geriatric Disorders, Xiangya Hospital, Central South University, Changsha, 410008 Hunan China
| | - Huaping Liu
- grid.216417.70000 0001 0379 7164Department of Radiology, The Third Xiangya Hospital, Central South University, Changsha, 410013 Hunan China
| | - Deyun Feng
- grid.216417.70000 0001 0379 7164Department of Pathology, Xiangya Hospital, Central South University, Changsha, 410008 Hunan China
| | - Qiongqiong He
- grid.216417.70000 0001 0379 7164Department of Pathology, Xiangya Hospital, Central South University, Changsha, 410008 Hunan China
| | - Wenzheng Li
- grid.216417.70000 0001 0379 7164Department of Radiology, Xiangya Hospital, Central South University, No. 168 Xiangya Road, Kaifu District, Changsha, 410008 Hunan China ,grid.216417.70000 0001 0379 7164National Clinical Research Center for Geriatric Disorders, Xiangya Hospital, Central South University, Changsha, 410008 Hunan China
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30
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Da BL, Suchman KI, Lau L, Rabiee A, He AR, Shetty K, Yu H, Wong LL, Amdur RL, Crawford JM, Fox SS, Grimaldi GM, Shah PK, Weinstein J, Bernstein D, Satapathy SK, Chambwe N, Xiang X, Mishra L. Pathogenesis to management of hepatocellular carcinoma. Genes Cancer 2022; 13:72-87. [PMID: 36533190 PMCID: PMC9746873 DOI: 10.18632/genesandcancer.226] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/07/2022] [Accepted: 11/17/2022] [Indexed: 12/15/2022] Open
Abstract
Hepatocellular carcinoma (HCC) is the most common primary liver cancer whose incidence continues to rise in many parts of the world due to a concomitant rise in many associated risk factors, such as alcohol use and obesity. Although early-stage HCC can be potentially curable through liver resection, liver-directed therapies, or transplantation, patients usually present with intermediate to advanced disease, which continues to be associated with a poor prognosis. This is because HCC is a cancer with significant complexities, including substantial clinical, histopathologic, and genomic heterogeneity. However, the scientific community has made a major effort to better characterize HCC in those aspects via utilizing tissue sampling and histological classification, whole genome sequencing, and developing viable animal models. These efforts ultimately aim to develop clinically relevant biomarkers and discover molecular targets for new therapies. For example, until recently, there was only one approved systemic therapy for advanced or metastatic HCC in the form of sorafenib. Through these efforts, several additional targeted therapies have gained approval in the United States, although much progress remains to be desired. This review will focus on the link between characterizing the pathogenesis of HCC with current and future HCC management.
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Affiliation(s)
- Ben L. Da
- Department of Internal Medicine, Division of Hepatology, Sandra Atlas Bass Center for Liver Diseases and Transplantation, Donald and Barbara Zucker School of Medicine at Hofstra/Northwell Health, Manhasset, NY 11030, USA
| | - Kelly I. Suchman
- Department of Internal Medicine, Donald and Barbara Zucker School of Medicine at Hofstra/Northwell Health, Manhasset, NY 11030, USA
| | - Lawrence Lau
- Department of Surgery, North Shore University Hospital, Northwell Health, Manhasset, NY 11030, USA
| | - Atoosa Rabiee
- Department of Gastroenterology and Hepatology, VA Medical Center, Washington, DC 20422, USA
| | - Aiwu Ruth He
- Lombardi Comprehensive Cancer Center, Georgetown University Medical Center, Washington, DC 20007, USA
| | - Kirti Shetty
- Division of Gastroenterology and Hepatology, University of Maryland, Baltimore, MD 21201, USA
| | - Herbert Yu
- Department of Epidemiology, University of Hawaii Cancer Center, Honolulu, HI 96813-5516, USA
| | - Linda L. Wong
- Department of Surgery, University of Hawaii, Honolulu, HI 96813-5516, USA
| | - Richard L. Amdur
- Quantitative Intelligence, The Institutes for Health Systems Science and Bioelectronic Medicine, The Feinstein Institutes for Medical Research, Northwell Health, Manhasset, NY 10022, USA
| | - James M. Crawford
- Department of Pathology and Laboratory Medicine, Donald and Barbara Zucker School of Medicine at Hofstra/Northwell, Hempstead, NY 11549, USA
| | - Sharon S. Fox
- Department of Pathology and Laboratory Medicine, Donald and Barbara Zucker School of Medicine at Hofstra/Northwell, Hempstead, NY 11549, USA
| | - Gregory M. Grimaldi
- Department of Radiology, Northwell Health, Donald and Barbara Zucker School of Medicine at Hofstra/Northwell, Manhasset, NY 11030, USA
| | - Priya K. Shah
- Department of Radiology, Northwell Health, Donald and Barbara Zucker School of Medicine at Hofstra/Northwell, Manhasset, NY 11030, USA
| | - Jonathan Weinstein
- Division of Vascular and Interventional Radiology, Department of Radiology, Northwell Health, Donald and Barbara Zucker School of Medicine at Hofstra/Northwell, Manhasset, NY 11030, USA
| | - David Bernstein
- Department of Internal Medicine, Division of Hepatology, Sandra Atlas Bass Center for Liver Diseases and Transplantation, Donald and Barbara Zucker School of Medicine at Hofstra/Northwell Health, Manhasset, NY 11030, USA
| | - Sanjaya K. Satapathy
- Department of Internal Medicine, Division of Hepatology, Sandra Atlas Bass Center for Liver Diseases and Transplantation, Donald and Barbara Zucker School of Medicine at Hofstra/Northwell Health, Manhasset, NY 11030, USA
| | - Nyasha Chambwe
- The Institute of Molecular Medicine, The Feinstein Institutes for Medical Research, Northwell Health, Manhasset, NY 11030, USA
| | - Xiyan Xiang
- The Institute for Bioelectronic Medicine, The Feinstein Institutes for Medical Research and Cold Spring Harbor Laboratory, Department of Medicine, Division of Gastroenterology and Hepatology, Northwell Health, Manhasset, NY 11030, USA
| | - Lopa Mishra
- The Institute for Bioelectronic Medicine, The Feinstein Institutes for Medical Research and Cold Spring Harbor Laboratory, Department of Medicine, Division of Gastroenterology and Hepatology, Northwell Health, Manhasset, NY 11030, USA
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31
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Meier MA, Nuciforo S, Coto-Llerena M, Gallon J, Matter MS, Ercan C, Vosbeck J, Terracciano LM, Soysal SD, Boll D, Kollmar O, Delaloye R, Piscuoglio S, Heim MH. Patient-derived tumor organoids for personalized medicine in a patient with rare hepatocellular carcinoma with neuroendocrine differentiation: a case report. COMMUNICATIONS MEDICINE 2022; 2:80. [PMID: 35789568 PMCID: PMC9249908 DOI: 10.1038/s43856-022-00150-3] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/21/2021] [Accepted: 06/21/2022] [Indexed: 11/20/2022] Open
Abstract
Background Hepatocellular carcinoma with neuroendocrine differentiation (HCC-NED) is a very rare subtype of primary liver cancer. Treatment allocation in these patients therefore remains a challenge. Methods We report the case of a 74-year-old man with a HCC-NED. The tumor was surgically removed in curative intent. Histopathological work-up revealed poorly differentiated hepatocellular carcinoma (Edmondson-Steiner grade IV) with diffuse expression of neuroendocrine markers synaptophysin and chromogranin. Three months after resection, multifocal recurrence of the HCC-NED was observed. In the meantime, tumor organoids have been generated from the resected HCC-NED and extensively characterized. Sensitivity to a number of drugs approved for the treatment of HCC or neuroendocrine carcinomas was tested in vitro. Results Based on the results of the in vitro drug screening, etoposide and carboplatin are used as first line palliative combination treatment. With genomic analysis revealing a NTRK1-mutation of unknown significance (kinase domain) and tumor organoids found to be sensitive to entrectinib, a pan-TRK inhibitor, the patient was treated with entrectinib as second line therapy. After only two weeks, treatment is discontinued due to deterioration of the patient’s general condition. Conclusion The rapid establishment of patient-derived tumor organoids allows in vitro drug testing and thereby personalized treatment choices, however clinical translation remains a challenge. To the best of our knowledge, this report provides a first proof-of-principle for using organoids for personalized medicine in this rare subtype of primary liver cancer. Tumors that simultaneously display features of liver, nerve and hormone-producing cells are very rare. In such cases, the most appropriate treatment choice is not well defined. Here, we describe the generation of three-dimensional miniature tumors, called organoids, from the patient’s tumor tissue, that can be grown and studied in a culture dish. These organoids closely mimic the patient’s tumor and allowed us to test different drugs to identify the most effective therapy for informed treatment choice. What we describe in this study is an emerging approach for a practice known as personalized medicine, that aims to provide a more tailored treatment to patients. In summary, we demonstrate that this approach can be useful in a rare cancer type and that it holds significant potential to guide treatment decision in other patients with aggressive cancers. Meier, Nuciforo, Coto-Llerena et al. report a rare case of a patient with hepatocellular carcinoma with neuroendocrine differentiation. The authors establish organoids that recapitulate the genetic features of the patient’s tumor and are used for ex vivo drug testing to guide therapy selection in the patient.
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Chung A, Nasralla D, Quaglia A. Understanding the Immunoenvironment of Primary Liver Cancer: A Histopathology Perspective. J Hepatocell Carcinoma 2022; 9:1149-1169. [PMID: 36349146 PMCID: PMC9637345 DOI: 10.2147/jhc.s382310] [Citation(s) in RCA: 3] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/14/2022] [Accepted: 09/01/2022] [Indexed: 11/26/2022] Open
Abstract
One of the most common cancers worldwide, primary liver cancer remains a major cause of cancer-related mortality. Hepatocellular carcinoma and cholangiocarcinoma represent the majority of primary liver cancer cases. Despite advances in the development of novel anti-cancer therapies that exploit targets within the immune system, survival rates from liver cancer remain poor. Furthermore, responses to immunotherapies, such as immune checkpoint inhibitors, have revealed limited and variable responses amongst patients with hepatocellular carcinoma, although combination immunotherapies have shown recent breakthroughs in clinical trials. This has shifted the focus towards improving our understanding of the underlying immune and molecular characteristics of liver tumours that may influence their response to immune-modulating treatments. In this review, we outline the complex interactions that occur in the tumour microenvironment of hepatocellular carcinoma and cholangiocarcinoma, respectively, from a histopathological perspective. We explore the potential role of a classification system based on immune-specific characteristics within each cancer type, the importance of understanding inter- and intra-tumoural heterogeneity and consider the future role of histopathology and novel technologies within this field.
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Affiliation(s)
- Annabelle Chung
- Department of Cellular Pathology, Royal Free Hospital, London, UK
| | - David Nasralla
- Department of Hepato-Pancreato-Biliary Surgery, Royal Free Hospital, London, UK
| | - Alberto Quaglia
- Department of Cellular Pathology, Royal Free Hospital, London, UK
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33
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Sweed D, Sweed E, Moaz I, Mosbeh A, Fayed Y, Elhamed SMA, Sweed E, Macshut M, Abdelsattar S, Kilany S, Saied SA, Badr R, Abdallah MS, Ehsan N. The clinicopathological and prognostic factors of hepatocellular carcinoma: a 10-year tertiary center experience in Egypt. World J Surg Oncol 2022; 20:298. [PMID: 36117166 PMCID: PMC9484175 DOI: 10.1186/s12957-022-02764-2] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.7] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/07/2022] [Accepted: 09/06/2022] [Indexed: 02/08/2023] Open
Abstract
BACKGROUND Hepatocellular carcinoma (HCC) remains a major health problem despite the emergence of several preventive and therapeutic modalities. HCC has heterogeneous and wide morpho-molecular patterns, resulting in unique clinical and prognostic criteria. Therefore, we aimed to study the clinical and pathological criteria of HCC to update the morpho-molecular classifications and provide a guide to the diagnosis of this disease. METHODS Five hundred thirty pathologically analyzed HCC cases were included in this study. The clinical and survival data of these cases were collected. RESULTS Hepatitis C virus is still the dominant cause of HCC in Egypt. Post-direct-acting antiviral agent HCC showed an aggressive course compared to interferon-related HCC. Old age, male gender, elevated alpha-fetoprotein level, tumor size, and background liver were important prognostic parameters. Special HCC variants have characteristic clinical, laboratory, radiological, prognostic, and survival data. Tumor-infiltrating lymphocytes rather than neutrophil-rich HCC have an excellent prognosis. CONCLUSIONS HCC is a heterogenous tumor with diverse clinical, pathological, and prognostic parameters. Incorporating the clinicopathological profile per specific subtype is essential in the treatment decision of patients with HCC. TRIAL REGISTRATION This was a retrospective study that included 530 HCC cases eligible for analysis. The cases were obtained from the archives of the Pathology Department, during the period between January 2010 and December 2019. Clinical and survival data were collected from the patients' medical records after approval by the institutional review board (IRB No. 246/2021) of Liver National Institute, Menoufia University. The research followed the guidelines outlined in the Declaration of Helsinki and registered on ClinicalTrials.gov (NCT05047146).
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Affiliation(s)
- Dina Sweed
- Pathology Department, National Liver Institute, Menoufia University, Shebin Elkom, Menoufia Egypt
| | - Enas Sweed
- Radiology Department, Faculty of Medicine, Benha University, Benha, Egypt
| | - Inas Moaz
- Epidemiology, and Preventive Medicine Department, National Liver Institute, Menoufia University, Shebin Elkom, Menoufia Egypt
| | - Asmaa Mosbeh
- Pathology Department, National Liver Institute, Menoufia University, Shebin Elkom, Menoufia Egypt
| | - Yahya Fayed
- Hepatopancreatobiliary Surgery Department, National Liver Institute, Menoufia University, Shebin Elkom, Menoufia Egypt
| | - Sara Mohamed Abd Elhamed
- Pathology Department, National Liver Institute, Menoufia University, Shebin Elkom, Menoufia Egypt
| | - Eman Sweed
- Clinical Pharmacology Department, Faculty of Medicine, Menoufia University, Shebin Elkom, Menoufia Egypt
| | - Mahmoud Macshut
- Hepatopancreatobiliary Surgery Department, National Liver Institute, Menoufia University, Shebin Elkom, Menoufia Egypt
| | - Shimaa Abdelsattar
- Clinical Biochemistry and Molecular Diagnostics Department, National Liver Institute, Menoufia University, Shebin Elkom, Menoufia Egypt
| | - Shimaa Kilany
- Hepatology and Gastroenterology Department, National Liver Institute, Menoufia University, Shebin Elkom, Menoufia Egypt
| | - Sara A. Saied
- Clinical Pathology Department, National Liver Institute, Menoufia University, Shebin Elkom, Menoufia Egypt
| | - Reda Badr
- Hepatology and Gastroenterology Department, National Liver Institute, Menoufia University, Shebin Elkom, Menoufia Egypt
| | - Mahmoud S. Abdallah
- Clinical Pharmacy, Faculty of Pharmacy, University of Sadat City, Sadat City, Menoufia Egypt
| | - Nermine Ehsan
- Pathology Department, National Liver Institute, Menoufia University, Shebin Elkom, Menoufia Egypt
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Brandão ABDM, Rodriguez S, Fleck Jr ADM, Marroni CA, Wagner MB, Hörbe A, Fernandes MV, Cerski CTS, Coral GP. Propensity-matched analysis of patients with intrahepatic cholangiocarcinoma or mixed hepatocellular-cholangiocarcinoma and hepatocellular carcinoma undergoing a liver transplant. World J Clin Oncol 2022; 13:688-701. [PMID: 36160465 PMCID: PMC9476608 DOI: 10.5306/wjco.v13.i8.688] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.7] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 04/08/2022] [Revised: 06/14/2022] [Accepted: 07/11/2022] [Indexed: 11/08/2022] Open
Abstract
BACKGROUND Cholangiocarcinoma (CC) is a rare tumor that arises from the epithelium of the bile ducts. It is classified according to anatomic location as intrahepatic, perihilar, and distal. Intrahepatic CC (ICC) is rare in patients with cirrhosis due to causes other than primary sclerosing cholangitis. Mixed hepatocellular carcinoma-CC (HCC-CC) is a rare neoplasm that shows histologic findings of both HCC and ICC within the same tumor mass. Due to the difficulties in arriving at the correct diagnosis, patients eventually undergo liver transplantation (LT) with a presumptive diagnosis of HCC on imaging when, in fact, they have ICC or HCC-CC.
AIM To evaluate the outcomes of patients with intrahepatic cholangiocarcinoma or mixed hepatocellular-cholangiocarcinoma on pathological examination after liver transplant.
METHODS Propensity score matching was used to analyze tumor recurrence (TR), overall mortality (OM), and recurrence-free survival (RFS) in LT recipients with pathologically confirmed ICC or HCC-CC matched 1:8 to those with HCC. Progression-free survival and overall mortality rates were computed with the Kaplan-Meier method using Cox regression for comparison.
RESULTS Of 475 HCC LT recipients, 1.7% had the diagnosis of ICC and 1.5% of HCC-CC on pathological examination of the explant. LT recipients with ICC had higher TR (46% vs 11%; P = 0.006), higher OM (63% vs 23%; P = 0.002), and lower RFS (38% vs 89%; P = 0.002) than those with HCC when matched for pretransplant tumor characteristics, as well as higher TR (46% vs 23%; P = 0.083), higher OM (63% vs 35%; P = 0.026), and lower RFS (38% vs 59%; P = 0.037) when matched for posttransplant tumor characteristics. Two pairings were performed to compare the outcomes of LT recipients with HCC-CC vs HCC. There was no significant difference between the outcomes in either pairing.
CONCLUSION Patients with ICC had worse outcomes than patients undergoing LT for HCC. The outcomes of patients with HCC-CC did not differ significantly from those of patients with HCC.
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Affiliation(s)
- Ajacio Bandeira de Mello Brandão
- Graduate Program in Medicine: Hepatology, School of Medicine, Universidade Federal de Ciências da Saúde de Porto Alegre, Porto Alegre 90050170, RS, Brazil
- Liver Transplantation Group, Santa Casa de Misericórdia de Porto Alegre, Porto Alegre 90020090, RS, Brazil
| | - Santiago Rodriguez
- Graduate Program in Medicine: Hepatology, School of Medicine, Universidade Federal de Ciências da Saúde de Porto Alegre, Porto Alegre 90050170, RS, Brazil
- Department of Hepatology, Hospital Vozandes Quito-HVQ, Quito 170521, Ecuador
| | - Alfeu de Medeiros Fleck Jr
- Liver Transplantation Group, Santa Casa de Misericórdia de Porto Alegre, Porto Alegre 90020090, RS, Brazil
| | - Claudio Augusto Marroni
- Graduate Program in Medicine: Hepatology, School of Medicine, Universidade Federal de Ciências da Saúde de Porto Alegre, Porto Alegre 90050170, RS, Brazil
- Liver Transplantation Group, Santa Casa de Misericórdia de Porto Alegre, Porto Alegre 90020090, RS, Brazil
| | - Mário B Wagner
- School of Medicine, Universidade Federal do Rio Grande do Sul (UFRGS), Porto Alegre 90035002, RS, Brazil
| | - Alex Hörbe
- Interventional Radiology Unit, Santa Casa de Misericórdia de, Porto Alegre 90020090, RS, Brazil
| | - Matheus V Fernandes
- Graduate Program in Medicine: Hepatology, School of Medicine, Universidade Federal de Ciências da Saúde de Porto Alegre, Porto Alegre 90050170, RS, Brazil
| | - Carlos TS Cerski
- Department of Pathology, School of Medicine, Universidade Federal do Rio Grande do Sul, Porto Alegre 90035002, RS, Brazil
| | - Gabriela Perdomo Coral
- Graduate Program in Medicine: Hepatology, School of Medicine, Universidade Federal de Ciências da Saúde de Porto Alegre, Porto Alegre 90050170, RS, Brazil
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Loy LM, Low HM, Choi JY, Rhee H, Wong CF, Tan CH. Variant Hepatocellular Carcinoma Subtypes According to the 2019 WHO Classification: An Imaging-Focused Review. AJR Am J Roentgenol 2022; 219:212-223. [PMID: 35170359 DOI: 10.2214/ajr.21.26982] [Citation(s) in RCA: 22] [Impact Index Per Article: 7.3] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/18/2022]
Abstract
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.
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Affiliation(s)
- Liang Meng Loy
- Department of Diagnostic Radiology, Tan Tock Seng Hospital, 11 Jalan Tan Tock Seng, Singapore 308433, Singapore
| | - Hsien Min Low
- Department of Diagnostic Radiology, Tan Tock Seng Hospital, 11 Jalan Tan Tock Seng, Singapore 308433, Singapore
| | - Jin-Young Choi
- Department of Radiology, Severance Hospital, Research Institute of Radiological Science and Center for Clinical Imaging Data Science, Yonsei University College of Medicine, Seoul, Republic of Korea
| | - Hyungjin Rhee
- Department of Radiology, Severance Hospital, Research Institute of Radiological Science and Center for Clinical Imaging Data Science, Yonsei University College of Medicine, Seoul, Republic of Korea
| | - Chin Fong Wong
- Department of Pathology, Tan Tock Seng Hospital, Singapore, Singapore
| | - Cher Heng Tan
- Department of Diagnostic Radiology, Tan Tock Seng Hospital, 11 Jalan Tan Tock Seng, Singapore 308433, Singapore
- Lee Kong Chian School of Medicine, Nanyang Technological University, Singapore, Singapore
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de Souza AJS, Malheiros AP, da Silva VL, da Silva TC, Cogliati B, de Sá LRM. Hepatocellular Carcinoma in a Free-Ranging Three-Toed Sloth (Bradypus variegatus). Animals (Basel) 2022; 12:ani12151921. [PMID: 35953911 PMCID: PMC9367539 DOI: 10.3390/ani12151921] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/02/2022] [Revised: 06/15/2022] [Accepted: 06/21/2022] [Indexed: 11/16/2022] Open
Abstract
The increasing interest of tumors in wildlife is important for biodiversity conservation and for monitoring environmental agents and/or contaminants with potential impact on human health. Here we described the occurrence of hepatocellular carcinoma (HCC) in noncirrhotic liver of a free-ranging three-toed sloth (Bradypus variegatus) from the Atlantic Forest biome in Brazil. The HCC showed a moderate mononuclear inflammatory infiltrate within the tumor tissue but with no inflammation and fibrosis in the adjacent liver tissue. Upon immunohistochemistry, neoplastic cells were diffusely positive for HepPar-1 and glutamine-synthetase presenting an irregular and random immunostaining pattern; β-catenin was positive in the cytoplasmic membrane of malignant hepatocytes; and cytokeratin 19 immunostaining was restricted to bile duct epithelial cells. The liver tissue was negative for HBV-like and HCV-like viruses assessed by molecular tests. The potential similarity of pathogenesis may reinforce the need for research on environmental and/or infectious agents associated with HCC that may contribute to the understanding of cancer in wildlife.
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Affiliation(s)
- Alex Junior Souza de Souza
- Department of Pathology, School of Veterinary Medicine and Animal Science, University of São Paulo, São Paulo 05508-270, SP, Brazil; (A.J.S.d.S.); (T.C.d.S.); (B.C.)
| | | | | | - Tereza Cristina da Silva
- Department of Pathology, School of Veterinary Medicine and Animal Science, University of São Paulo, São Paulo 05508-270, SP, Brazil; (A.J.S.d.S.); (T.C.d.S.); (B.C.)
| | - Bruno Cogliati
- Department of Pathology, School of Veterinary Medicine and Animal Science, University of São Paulo, São Paulo 05508-270, SP, Brazil; (A.J.S.d.S.); (T.C.d.S.); (B.C.)
| | - Lilian Rose Marques de Sá
- Department of Pathology, School of Veterinary Medicine and Animal Science, University of São Paulo, São Paulo 05508-270, SP, Brazil; (A.J.S.d.S.); (T.C.d.S.); (B.C.)
- Correspondence:
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Etiology, Pathogenesis, Diagnosis, and Practical Implications of Hepatocellular Neoplasms. Cancers (Basel) 2022; 14:cancers14153670. [PMID: 35954333 PMCID: PMC9367411 DOI: 10.3390/cancers14153670] [Citation(s) in RCA: 8] [Impact Index Per Article: 2.7] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/10/2022] [Revised: 07/18/2022] [Accepted: 07/25/2022] [Indexed: 11/16/2022] Open
Abstract
Hepatocellular carcinoma (HCC), a major global contributor of cancer death, usually arises in a background of chronic liver disease, as a result of molecular changes that deregulate important signal transduction pathways. Recent studies have shown that certain molecular changes of hepatocarcinogenesis are associated with clinicopathologic features and prognosis, suggesting that subclassification of HCC is practically useful. On the other hand, subclassification of hepatocellular adenomas (HCAs), a heterogenous group of neoplasms, has been well established on the basis of genotype–phenotype correlations. Histologic examination, aided by immunohistochemistry, is the gold standard for the diagnosis and subclassification of HCA and HCC, while clinicopathologic correlation is essential for best patient management. Advances in clinico-radio-pathologic correlation have introduced a new approach for the diagnostic assessment of lesions arising in advanced chronic liver disease by imaging (LI-RADS). The rapid expansion of knowledge concerning the molecular pathogenesis of HCC is now starting to produce new therapeutic approaches through precision oncology. This review summarizes the etiology and pathogenesis of HCA and HCC, provides practical information for their histologic diagnosis (including an algorithmic approach), and addresses a variety of frequently asked questions regarding the diagnosis and practical implications of these neoplasms.
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Sessa A, Mulé S, Brustia R, Regnault H, Galletto Pregliasco A, Rhaiem R, Leroy V, Sommacale D, Luciani A, Calderaro J, Amaddeo G. Macrotrabecular-Massive Hepatocellular Carcinoma: Light and Shadow in Current Knowledge. J Hepatocell Carcinoma 2022; 9:661-670. [PMID: 35923611 PMCID: PMC9342198 DOI: 10.2147/jhc.s364703] [Citation(s) in RCA: 6] [Impact Index Per Article: 2.0] [Reference Citation Analysis] [Abstract] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/02/2022] [Accepted: 06/22/2022] [Indexed: 12/11/2022] Open
Abstract
The subject of this narrative review is macrotrabecular-massive hepatocellular carcinoma (MTM‐HCC). Despite their rarity, these tumours are of general interest because of their epidemiological and clinical features and for representing a distinct model of the interaction between the angiogenetic system and neoplastic cells. The MTM‐HCC subtype is associated with various adverse biological and pathological parameters (the Alfa-foetoprotein (AFP) serum level, tumour size, vascular invasion, and satellite nodules) and is a key determinant of patient prognosis, with a strong and independent predictive value for early and overall tumour recurrence. Gene expression profiling has demonstrated that angiogenesis activation is a hallmark feature of MTM-HCC, with overexpression of both angiopoietin 2 (ANGPT2) and vascular endothelial growth factor A (VEGFA).
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Affiliation(s)
- Anna Sessa
- Hepatology Department, APHP, Henri Mondor University Hospital, Créteil, France
- Université Paris-Est Créteil, Faculté de Médecine, Créteil, France
- Inserm, U955, Team 18, Créteil, France
- Correspondence: Giuliana Amaddeo; Anna Sessa, Hepatology Department, APHP, Henri Mondor University Hospital, 1 rue Gustave Eiffel, Créteil, 94000, France, Tel +33 149812353, Email ;
| | - Sébastien Mulé
- Université Paris-Est Créteil, Faculté de Médecine, Créteil, France
- Inserm, U955, Team 18, Créteil, France
- Medical Imaging Department, AP-HP, Henri Mondor University Hospital, Créteil, France
| | - Raffaele Brustia
- Université Paris-Est Créteil, Faculté de Médecine, Créteil, France
- Inserm, U955, Team 18, Créteil, France
- Department of Digestive and Hepato-Pancreato-Biliary Surgery, AP-HP, Henri Mondor University Hospital, Créteil, France
| | - Hélène Regnault
- Hepatology Department, APHP, Henri Mondor University Hospital, Créteil, France
- Inserm, U955, Team 18, Créteil, France
| | | | - Rami Rhaiem
- Department of Hepato-Biliary Pancreatic and Digestive Oncological Surgery, Robert Debré University Hospital, Reims, France
- Reims Champagne-Ardenne University, Reims, France
| | - Vincent Leroy
- Hepatology Department, APHP, Henri Mondor University Hospital, Créteil, France
- Université Paris-Est Créteil, Faculté de Médecine, Créteil, France
- Inserm, U955, Team 18, Créteil, France
| | - Daniele Sommacale
- Université Paris-Est Créteil, Faculté de Médecine, Créteil, France
- Inserm, U955, Team 18, Créteil, France
- Department of Digestive and Hepato-Pancreato-Biliary Surgery, AP-HP, Henri Mondor University Hospital, Créteil, France
| | - Alain Luciani
- Université Paris-Est Créteil, Faculté de Médecine, Créteil, France
- Inserm, U955, Team 18, Créteil, France
- Medical Imaging Department, AP-HP, Henri Mondor University Hospital, Créteil, France
| | - Julien Calderaro
- Université Paris-Est Créteil, Faculté de Médecine, Créteil, France
- Inserm, U955, Team 18, Créteil, France
- Department of Pathology, APHP, Henri Mondor University Hospital, Créteil, France
| | - Giuliana Amaddeo
- Hepatology Department, APHP, Henri Mondor University Hospital, Créteil, France
- Université Paris-Est Créteil, Faculté de Médecine, Créteil, France
- Inserm, U955, Team 18, Créteil, France
- Correspondence: Giuliana Amaddeo; Anna Sessa, Hepatology Department, APHP, Henri Mondor University Hospital, 1 rue Gustave Eiffel, Créteil, 94000, France, Tel +33 149812353, Email ;
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Yuan RH, Hsu CL, Jhuang YL, Liu YR, Hsieh TH, Jeng YM. Tumor-matrix interaction induces phenotypic switching in liver cancer cells. Hepatol Int 2022; 16:562-576. [PMID: 35525880 DOI: 10.1007/s12072-022-10315-w] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 11/06/2021] [Accepted: 02/13/2022] [Indexed: 01/16/2023]
Abstract
BACKGROUND 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. METHODS AND RESULTS 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. CONCLUSIONS 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.
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Affiliation(s)
- Ray-Hwang Yuan
- Department of Surgery, National Taiwan University Hospital, Taipei, Taiwan
- Department of Surgery, Hsinchu Branch, National Taiwan University Hospital, Hsinchu, Taiwan
| | - Chia-Lang Hsu
- Department of Medical Research, National Taiwan University Hospital, Taipei, Taiwan
| | - Yu-Lin Jhuang
- Graduate Institute of Pathology, National Taiwan University, Taipei, Taiwan
- Department of Pathology, National Taiwan University Hospital, Taipei, Taiwan
| | - Yun-Ru Liu
- Joint Biobank Office of Human Research, Taipei Medical University, Taipei, Taiwan
| | - Tsung-Han Hsieh
- Joint Biobank Office of Human Research, Taipei Medical University, Taipei, Taiwan
| | - Yung-Ming Jeng
- Graduate Institute of Pathology, National Taiwan University, Taipei, Taiwan.
- Department of Pathology, National Taiwan University Hospital, Taipei, Taiwan.
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40
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Yang T, Zou MH, Zou Q, Jiao J, Zhang Y. 18F-FDG PET/CT Imaging in Sarcomatoid Hepatocellular Carcinoma. Clin Nucl Med 2022; 47:427-429. [PMID: 35293354 DOI: 10.1097/rlu.0000000000004121] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/25/2022]
Abstract
Sarcomatoid hepatocellular carcinoma is a rare subtype of hepatocellular carcinoma. We present a 53-year-old man with a hepatic IV/VIII segment neoplasm whose tumor markers were all in the reference range. The neoplasm presented intense uptake of 18F-FDG and was confirmed as sarcomatoid hepatocellular carcinoma by immunohistochemistry. After 6 cycles of PD-1 treatment, no recurrence or metastasis was found by follow-up CT over 2 years. Thus, we reported a case of sarcomatoid hepatocellular carcinoma with complete remission to PD-1 treatment and provided some help for the diagnosis and treatment of sarcomatoid hepatocellular carcinoma.
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Affiliation(s)
- Ting Yang
- From the Departments of Nuclear Medicine
| | - Min-Hong Zou
- Ultrasonic Diagnosis, Third Affiliated Hospital of Sun Yat-Sen University, Guangzhou, Guangdong, China
| | - Qiong Zou
- From the Departments of Nuclear Medicine
| | - Ju Jiao
- From the Departments of Nuclear Medicine
| | - Yong Zhang
- From the Departments of Nuclear Medicine
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41
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Nguyen RY, Xiao H, Gong X, Arroyo A, Cabral AT, Fischer TT, Flores KM, Zhang X, Robert ME, Ehrlich BE, Mak M. Cytoskeletal dynamics regulates stromal invasion behavior of distinct liver cancer subtypes. Commun Biol 2022; 5:202. [PMID: 35241781 PMCID: PMC8894393 DOI: 10.1038/s42003-022-03121-5] [Citation(s) in RCA: 8] [Impact Index Per Article: 2.7] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/13/2021] [Accepted: 02/08/2022] [Indexed: 02/07/2023] Open
Abstract
Drug treatment against liver cancer has limited efficacy due to heterogeneous response among liver cancer subtypes. In addition, the functional biophysical phenotypes which arise from this heterogeneity and contribute to aggressive invasive behavior remain poorly understood. This study interrogated how heterogeneity in liver cancer subtypes contributes to differences in invasive phenotypes and drug response. Utilizing histological analysis, quantitative 2D invasion metrics, reconstituted 3D hydrogels, and bioinformatics, our study linked cytoskeletal dynamics to differential invasion profiles and drug resistance in liver cancer subtypes. We investigated cytoskeletal regulation in 2D and 3D culture environments using two liver cancer cell lines, SNU-475 and HepG2, chosen for their distinct cytoskeletal features and invasion profiles. For SNU-475 cells, a model for aggressive liver cancer, many cytoskeletal inhibitors abrogated 2D migration but only some suppressed 3D migration. For HepG2 cells, cytoskeletal inhibition did not significantly affect 3D migration but did affect proliferative capabilities and spheroid core growth. This study highlights cytoskeleton driven phenotypic variation, their consequences and coexistence within the same tumor, as well as efficacy of targeting biophysical phenotypes that may be masked in traditional screens against tumor growth.
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Affiliation(s)
- Ryan Y Nguyen
- Department of Biomedical Engineering, Yale University, New Haven, CT, USA
| | - Hugh Xiao
- Department of Biomedical Engineering, Yale University, New Haven, CT, USA
| | - Xiangyu Gong
- Department of Biomedical Engineering, Yale University, New Haven, CT, USA
| | - Alfredo Arroyo
- Department of Pharmacology, Yale University, New Haven, CT, USA
| | - Aidan T Cabral
- Department of Biomedical Engineering, Yale University, New Haven, CT, USA
| | - Tom T Fischer
- Department of Pharmacology, Yale University, New Haven, CT, USA
- Institute of Pharmacology, University of Heidelberg, Heidelberg, Germany
| | - Kaitlin M Flores
- Department of Biomedical Engineering, Yale University, New Haven, CT, USA
| | - Xuchen Zhang
- Department of Pathology, Yale University, New Haven, CT, USA
| | - Marie E Robert
- Department of Pathology, Yale University, New Haven, CT, USA
| | | | - Michael Mak
- Department of Biomedical Engineering, Yale University, New Haven, CT, USA.
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42
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Nahm JH, Park YN. [Up-to-date Knowledge on the Pathological Diagnosis of Hepatocellular Carcinoma]. THE KOREAN JOURNAL OF GASTROENTEROLOGY 2021; 78:268-283. [PMID: 34824185 DOI: 10.4166/kjg.2021.140] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Subscribe] [Scholar Register] [Received: 10/12/2021] [Revised: 10/21/2021] [Accepted: 10/22/2021] [Indexed: 11/09/2022]
Abstract
Hepatocellular carcinoma (HCC) has heterogeneous molecular and pathological features and biological behavior. Large-scale genetic studies of HCC were accumulated, and a pathological-molecular classification of HCC was proposed. Approximately 35% of HCCs can be classified into distinct histopathological subtypes according to their molecular characteristics. Among recently identified subtypes, macrotrabecular massive HCC, neutrophil-rich HCC, vessels encapsulating tumor clusters HCC, and progenitor phenotype HCC (HCC with CK19 expression) are associated with a poor prognosis, whereas the lymphocyte-rich HCC subtype is related to a better prognosis. This review provides up-to-date knowledge on the pathological diagnosis of HCC according to the updated World Health Organization Classification of Digestive System Tumors 5th ed.
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Affiliation(s)
- Ji Hae Nahm
- Department of Pathology, Yonsei University College of Medicine, Seoul, Korea
| | - Young Nyun Park
- Department of Pathology, Yonsei University College of Medicine, Seoul, Korea.,Graduate School of Medical Science, Brain Korea 21 Project, Yonsei University College of Medicine, Seoul, Korea
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Murtha-Lemekhova A, Fuchs J, Schulz E, Sterkenburg AS, Mayer P, Pfeiffenberger J, Hoffmann K. Scirrhous Hepatocellular Carcinoma: Systematic Review and Pooled Data Analysis of Clinical, Radiological, and Histopathological Features. J Hepatocell Carcinoma 2021; 8:1269-1279. [PMID: 34712626 PMCID: PMC8547765 DOI: 10.2147/jhc.s328198] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/06/2021] [Accepted: 09/16/2021] [Indexed: 12/29/2022] Open
Abstract
Background Aberrant subtypes of hepatocellular carcinoma (HCC) account for 20–30% of all HCCs and habitually present a challenge in diagnosis and treatment. Scirrhous hepatocellular carcinoma (s-HCC) is often misdiagnosed as cholangiocarcinoma, fibrolamellar hepatocellular carcinoma, or metastasis. Methods Electronic databases (PubMed, Web of Knowledge, Google Scholar, Cochrane Library, and WHO International Clinical Trials Registry Platform) were searched for publications on scirrhous hepatocellular carcinoma without date or language restrictions. Quality assessment was performed using a tool proposed by Murad et al for case reports and series. For observational studies, MINORS quality assessment tool was used. This study was registered at PROSPERO (CRD42020212323). Results S-HCC arises in patients with chronic hepatitis (hepatitis B in 60% and hepatitis C in 21%). S-HCC primarily affects men with a mean age of 55.8 years. Serum AFP is elevated above 20IU/mL in 66.7% of the patients. On ultrasound, s-HCC presents as hypoechoic or mosaic pattern lesions (47.6% each) and causes a retraction of the liver surface (70%) when near the capsule. Delayed enhancement of the tumor is evident in 87.0%. On MRI, 65.0% of s-HCCs show a target appearance. Histopathologic pattern is mostly irregular (97.6%). Lesions show a bulging appearance (100%), septae (85.6%) and a central scar (63.5%), and usually lack central necrosis (75%). Immunohistochemistry shows HepPar 1 positivity in 64.6%, CK7 in 40.7%, and EMA in 41.9%. The 5-year overall survival rate estimates 45.2% and 45.5% of the patients experience a recurrence after hepatectomy. Conclusion S-HCC is a rare subtype of HCC primarily arising in hepatitis- or cirrhosis-afflicted livers and incorporates atypical radiological and histopathological HCC features. Despite lower recurrence rates, overall survival of patients with s-HCC is poorer than generally for HCC, underlining the need for individualized treatment. Patients with atypical lesions of the liver should be referred to tertiary hospitals for interdisciplinary assessment and treatment.
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Affiliation(s)
- Anastasia Murtha-Lemekhova
- Department of General, Visceral, and Transplantation Surgery, Heidelberg University Hospital, Heidelberg, Germany.,RELIVE Initiative, Heidelberg University Hospital, Heidelberg, Germany
| | - Juri Fuchs
- Department of General, Visceral, and Transplantation Surgery, Heidelberg University Hospital, Heidelberg, Germany.,RELIVE Initiative, Heidelberg University Hospital, Heidelberg, Germany
| | - Erik Schulz
- Department of General, Visceral, and Transplantation Surgery, Heidelberg University Hospital, Heidelberg, Germany.,RELIVE Initiative, Heidelberg University Hospital, Heidelberg, Germany
| | - Anthe Suzan Sterkenburg
- Department of General, Visceral, and Transplantation Surgery, Heidelberg University Hospital, Heidelberg, Germany
| | - Philipp Mayer
- RELIVE Initiative, Heidelberg University Hospital, Heidelberg, Germany.,Department of Diagnostic and Interventional Radiology, Heidelberg University Hospital, Heidelberg, Germany
| | - Jan Pfeiffenberger
- RELIVE Initiative, Heidelberg University Hospital, Heidelberg, Germany.,Department of Gastroenterology and Hepatology, Heidelberg University Hospital, Heidelberg, Germany
| | - Katrin Hoffmann
- Department of General, Visceral, and Transplantation Surgery, Heidelberg University Hospital, Heidelberg, Germany.,RELIVE Initiative, Heidelberg University Hospital, Heidelberg, Germany
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Gene Expression Characteristics of Liver Tissue Reveal the Underlying Pathogenesis of Hepatocellular Carcinoma. BIOMED RESEARCH INTERNATIONAL 2021; 2021:9458328. [PMID: 34651050 PMCID: PMC8506137 DOI: 10.1155/2021/9458328] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Subscribe] [Scholar Register] [Received: 07/05/2021] [Revised: 09/06/2021] [Accepted: 09/07/2021] [Indexed: 11/17/2022]
Abstract
Background Hepatocellular carcinoma (HCC) is high-mortality primary liver cancer and the most common malignant tumor in the world. This study is based on a hepatocellular carcinoma-related dysfunction module designed to explore the dysregulation of genes in liver cancer tissue. Methods By downloading the relevant data on the GEO database, we performed a differential analysis of healthy liver tissue and liver cancer tissues as well as healthy liver tissue and hepatocellular carcinoma tissue and then obtained two sets of differential genes and combined them. We performed a cointerpretation analysis of these differential genes and constructed related functional disorder modules. A hypergeometric test was performed to calculate the potential regulatory effects of multiple factors on the module, and a series of ncRNA and TF regulators were identified. We obtained a total of 4479 differentially expressed genes in hepatocellular carcinoma, and these genes were clustered into ten hepatocellular carcinoma-related functional interpretation disorder modules. Results Enrichment analysis revealed that these modular genes are mainly involved in signal transduction including cell cycle, TGF-beta signal transduction, and p53 signal transduction. Depending on the predictive analysis of multidimensional regulators, 323 ncRNAs and 52 TF-mediated hepatocellular carcinoma-related dysregulation modules were found to regulate disease progression. Conclusions Based on a series of investigations, it was found that miR-30b-5p may participate in the peroxisome signal transduction by downregulating ABCD3-mediated module 1, thereby promoting the development and progression of hepatocellular carcinoma. Our research results not only provide a theoretical basis for biologists to study hepatocellular carcinoma further but also offer new methods and new ideas for the personalized care and treatment of hepatocellular carcinoma.
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Sadiq AM, Mjemmas MG, Sadiq AM, Nkya GZ. Sarcomatoid hepatocellular carcinoma in a young African female. SAGE Open Med Case Rep 2021; 9:2050313X211052452. [PMID: 34646567 PMCID: PMC8504208 DOI: 10.1177/2050313x211052452] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/03/2021] [Accepted: 09/23/2021] [Indexed: 12/24/2022] Open
Abstract
Sarcomatoid hepatocellular carcinoma is a rare primary malignant liver cancer. The pathogenesis is unclear; however, the risk factors may be similar to that of conventional hepatocellular carcinoma. We present an 18-year-old female who was admitted due to generalized tonic-clonic convulsions. On examination, we palpated a large non-tender mass in the right upper quadrant. An abdominal computed tomography identified it as hepatocellular carcinoma, and spindle-shaped cells were seen on histopathology. She was counseled on her prognosis but opted for local herbal medications rather than chemotherapy, but unfortunately passed away. We present a rare subtype of hepatocellular carcinoma in a young female which is commonly seen in males above the age of 50 years, and despite its grade and stage, overall survival is poor.
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Affiliation(s)
- Abid M Sadiq
- Department of Internal Medicine, Kilimanjaro Christian Medical Centre, Moshi, Tanzania.,Kilimanjaro Christian Medical University College, Moshi, Tanzania
| | - Minael G Mjemmas
- Department of Internal Medicine, Kilimanjaro Christian Medical Centre, Moshi, Tanzania
| | - Adnan M Sadiq
- Kilimanjaro Christian Medical University College, Moshi, Tanzania.,Department of Radiology, Kilimanjaro Christian Medical Centre, Moshi, Tanzania
| | - Gilbert Z Nkya
- Kilimanjaro Christian Medical University College, Moshi, Tanzania.,Department of Pathology, Kilimanjaro Christian Medical Centre, Moshi, Tanzania
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Chen J, Xia C, Duan T, Cao L, Jiang H, Liu X, Zhang Z, Ye Z, Wu Z, Gao R, Shi Y, Song B. Macrotrabecular-massive hepatocellular carcinoma: imaging identification and prediction based on gadoxetic acid-enhanced magnetic resonance imaging. Eur Radiol 2021; 31:7696-7704. [PMID: 33856520 DOI: 10.1007/s00330-021-07898-7] [Citation(s) in RCA: 25] [Impact Index Per Article: 6.3] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/07/2021] [Revised: 03/06/2021] [Accepted: 03/16/2021] [Indexed: 02/05/2023]
Abstract
OBJECTIVES To identify image features of macrotrabecular-massive (MTM) hepatocellular carcinoma (HCC) and to determine its role in predicting MTM-HCC. METHODS Patients who underwent preoperative gadoxetic acid-enhanced MRI and with surgery proven HCC were retrospectively included. Imaging features were assessed according to Liver Imaging Reporting and Data System. Quantitative measurements were recorded. Clinical characteristics and imaging findings were compared between MTM-HCCs and non-MTM-HCCs. Predictive factors of MTM-HCC were screened with univariate analyses and then identified with multivariate logistic regression. A regression-based diagnostic model was constructed. ROC analyses were used to determine cutoff values, AUC, and corresponding 95% confidence interval (CI) of findings. The diagnostic performance was validated by 10-fold cross-validation. RESULTS One hundred and forty-one patients with 37 MTM-HCCs were included. Multivariate analyses identified high platelet count (≥ 163.5 × 103/ul, odds ratio = 3.20; 95% CI: 1.29, 7.96; p = 0.012), low tumor-to-liver ADC ratio (≤ 1.05, odds ratio = 3.05; 95% CI, 1.23 - 7.55; p = 0.016), and necrosis or severe ischemia (odds ratio = 11.61; 95% CI, 3.99 - 33.76, p < 0.001) as independent predictors of MTM-HCC. Necrosis or severe ischemia alone helped identify 86% MTM-HCCs with a specificity of 66%. The average AUCs were 0.81 (95% CI: 0.71, 0.90) for the regression-based diagnostic model, with a sensitivity of 57% and specificity of 92%. CONCLUSIONS Necrosis or severe ischemia was a sensitive imaging feature of MTM-HCC. Noninvasive prediction of this subtype can be achieved with good accuracy and excellent specificity when findings were combined. KEY POINTS • The macrotrabecular-massive (MTM) hepatocellular carcinoma (HCC) represents an aggressive subtype of HCC and is associated with poor prognosis. • Imaging features of necrosis or severe ischemia alone helped identify 86% MTM-HCCs with a specificity of 66%. • A regression-based diagnostic model including high platelet count (≥ 163.5 × 103/ul), low tumor-to-liver ADC ratio (≤ 1.05), and necrosis or severe ischemia can provide noninvasive assessment of MTM-HCC with good accuracy and high specificity.
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Affiliation(s)
- Jie Chen
- Department of Radiology, West China Hospital, Sichuan University, No.37 Guoxue Alley, Chengdu, 610041, China
| | - Chunchao Xia
- Department of Radiology, West China Hospital, Sichuan University, No.37 Guoxue Alley, Chengdu, 610041, China
| | - Ting Duan
- Department of Radiology, West China Hospital, Sichuan University, No.37 Guoxue Alley, Chengdu, 610041, China
| | - Likun Cao
- Department of Radiology, Peking Union Medical College Hospital (Dongdan campus), No.1 Shuaifuyuan Wangfujing Dongcheng District, Beijing, 100730, China
| | - Hanyu Jiang
- Department of Radiology, West China Hospital, Sichuan University, No.37 Guoxue Alley, Chengdu, 610041, China
| | - Xijiao Liu
- Department of Radiology, West China Hospital, Sichuan University, No.37 Guoxue Alley, Chengdu, 610041, China
| | - Zhen Zhang
- Department of Radiology, West China Hospital, Sichuan University, No.37 Guoxue Alley, Chengdu, 610041, China
| | - Zheng Ye
- Department of Radiology, West China Hospital, Sichuan University, No.37 Guoxue Alley, Chengdu, 610041, China
| | - Zhenru Wu
- Laboratory of Pathology, West China Hospital, Sichuan University, No.88 South Keyuan Road, Chengdu, 610041, China
| | - Ronghui Gao
- Department of Radiology, West China Hospital, Sichuan University, No.37 Guoxue Alley, Chengdu, 610041, China
| | - Yujun Shi
- Laboratory of Pathology, West China Hospital, Sichuan University, No.88 South Keyuan Road, Chengdu, 610041, China.
| | - Bin Song
- Department of Radiology, West China Hospital, Sichuan University, No.37 Guoxue Alley, Chengdu, 610041, China.
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Kang HJ, Oh JH, Kim YW, Kim W, An J, Sung CO, Kim J, Shim JH, Hwang S, Yu E, Heaphy CM, Hong SM. Clinicopathological and molecular characterization of chromophobe hepatocellular carcinoma. Liver Int 2021; 41:2499-2510. [PMID: 34036718 DOI: 10.1111/liv.14975] [Citation(s) in RCA: 5] [Impact Index Per Article: 1.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 02/23/2021] [Revised: 05/04/2021] [Accepted: 05/20/2021] [Indexed: 12/13/2022]
Abstract
BACKGROUND AND AIMS Chromophobe hepatocellular carcinoma (HCC) is a newly included subtype of HCC in the 5th edition of the WHO classification with distinctive histological features (chromophobic cytoplasm with anaplastic nuclei and pseudocyst formation) and is strongly associated with the alternative lengthening of telomeres (ALT) phenotype. However, the clinicopathologic characterization and molecular features of chromophobe HCC are unknown. METHODS To comprehensively characterize chromophobe HCC, whole exome sequencing, copy number variation, and transcriptomic analyses were performed in 224 surgically resected HCC cases. Additionally, telomere-specific fluorescence in situ hybridization was used to assess ALT. These genomic profiles and ALT status were compared with clinicopathological features among subtypes of HCC, particularly chromophobe HCC and conventional HCC. RESULTS Chromophobe HCC was observed in 10.3% (23/224) cases and, compared to conventional HCC, was more frequent in females (P = .023). The overall and recurrence-free survival outcomes were similar between patients with chromophobe HCC and conventional HCC. However, chromophobe HCC displayed significantly more upregulated genes involving cell cycle progression and DNA repair. Additionally, ALT was significantly enriched in chromophobe HCC (87%; 20/23) compared to conventional HCC (2.2%, 4/178; P < .001). Somatic mutations in ALT-associated genes, including ATRX, SMARCAL1, FANCG, FANCM, SP100, TSPYL5, and RAD52 were more frequent in chromophobe HCC (30.4%, 7/23 cases) compared to conventional HCC (11.8%, 21/178 cases; P = .024). CONCLUSIONS Chromophobe HCC is a unique subtype of HCC with a prevalence of ~10%. Compared to conventional HCC, chromophobe HCC is associated with female predominance and ALT, although overall and recurrence-free outcomes are similar to conventional HCC.
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Affiliation(s)
- Hyo Jeong Kang
- Department of Pathology, Asan Medical Center, University of Ulsan College of Medicine, Seoul, Republic of Korea.,Asan Liver Center, Asan Medical Center, University of Ulsan College of Medicine, Seoul, Republic of Korea
| | - Ji-Hye Oh
- Department of Medical Science, Asan Medical Institute of Convergence Science and Technology, University of Ulsan College of Medicine, Seoul, Republic of Korea
| | - Yeon Wook Kim
- Asan Institute for Life Science, Asan Medical Center, Seoul, Republic of Korea
| | - Wonkyung Kim
- Department of Medical Science, Asan Medical Institute of Convergence Science and Technology, University of Ulsan College of Medicine, Seoul, Republic of Korea
| | - Jihyun An
- Department of Gastroenterology and Hepatology, Hanyang University of Medicine, Guri, Republic of Korea
| | - Chang Ohk Sung
- Department of Pathology, Asan Medical Center, University of Ulsan College of Medicine, Seoul, Republic of Korea
| | - Jihun Kim
- Department of Pathology, Asan Medical Center, University of Ulsan College of Medicine, Seoul, Republic of Korea.,Asan Liver Center, Asan Medical Center, University of Ulsan College of Medicine, Seoul, Republic of Korea
| | - Ju Hyun Shim
- Asan Liver Center, Asan Medical Center, University of Ulsan College of Medicine, Seoul, Republic of Korea.,Department of Gastroenterology, Asan Medical Center, University of Ulsan College of Medicine, Seoul, Republic of Korea
| | - Shin Hwang
- Asan Liver Center, Asan Medical Center, University of Ulsan College of Medicine, Seoul, Republic of Korea.,Department of Surgery, Asan Medical Center, University of Ulsan College of Medicine, Seoul, Republic of Korea
| | - Eunsil Yu
- Department of Pathology, Asan Medical Center, University of Ulsan College of Medicine, Seoul, Republic of Korea.,Asan Liver Center, Asan Medical Center, University of Ulsan College of Medicine, Seoul, Republic of Korea
| | - Christopher M Heaphy
- Department of Medicine, Boston University School of Medicine, Boston, MA, USA.,Department of Pathology and Laboratory Medicine, Boston University School of Medicine, Boston, MA, USA
| | - Seung-Mo Hong
- Department of Pathology, Asan Medical Center, University of Ulsan College of Medicine, Seoul, Republic of Korea.,Asan Institute for Life Science, Asan Medical Center, Seoul, Republic of Korea
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Ji W, Xing Y, Ma J, Zhao Z, Xu H, Zheng S, Li W, Li X. Primary Liver Sarcomatoid Carcinoma: A Case Series and Literature Review. J Hepatocell Carcinoma 2021; 8:1117-1127. [PMID: 34522692 PMCID: PMC8434859 DOI: 10.2147/jhc.s325182] [Citation(s) in RCA: 5] [Impact Index Per Article: 1.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/16/2021] [Accepted: 08/25/2021] [Indexed: 12/12/2022] Open
Abstract
Background Primary liver sarcomatoid carcinoma (PLSC) is rare. To improve the understanding of PLSC, cases were described and reviewing the literature. Methods A retrospective analysis was performed on 14 cases of PLSC diagnosed by pathology in Northeastern China from 2010 to 2020. An individual participant data analysis based on reported cases was conducted to determine epidemiological characteristics, clinical characteristics, and prognoses of PLSC. Results A total of 136 cases involved our 14 cases and 122 cases from previous reports. The percentages of sarcomatoid hepatocellular carcinoma, sarcomatoid cholangiolocellular carcinoma, and mixed and unclassified types were 36.8%, 41.9%, 5.9%, and 15.4%, respectively. A total of 95.6% PLSC was found in Asia. There was a lower percentage of hepatitis-infected patients in Japan, when compared with the Republic of Korea (38.5% vs 70.0%, P<0.05). Five cases were initially misdiagnosed as a hepatic abscess by imaging. A total of 36.7% cases had metastases when being diagnosed, and 68.9% cases relapsed during the follow-up. The median disease-free survival and overall survival (OS) were 3 months and 5 months, respectively. Only radical surgery (hazard ratio = 0.308, 95% confidence interval 0.186–0.512, P<0.001) indicated a better OS. Conclusion PLSC was more prevalent in Asia and there were possibilities of misdiagnoses. Surgery is still an effective treatment and can significantly prolong the OS. Only limited strategies for recurrent or advanced PLSC, immunotherapy may be possible treatment.
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Affiliation(s)
- Wei Ji
- Cancer Center, The First Hospital of Jilin University, Changchun, People's Republic of China
| | - Yunlong Xing
- Plastic Surgery, China-Japan Union Hospital, Jilin University, Changchun, People's Republic of China
| | - Jinshu Ma
- Department of Pathology, China-Japan Union Hospital, Jilin University, Changchun, People's Republic of China
| | - Zhuo Zhao
- Cardiology Department, The Second Hospital of Jilin University, Changchun, People's Republic of China
| | - Hongqin Xu
- Department of Hepatology, The First Hospital of Jilin University, Changchun, People's Republic of China
| | - Shuang Zheng
- Department of Radiology, The First Hospital of Jilin University, Changchun, People's Republic of China
| | - Wei Li
- Cancer Center, The First Hospital of Jilin University, Changchun, People's Republic of China
| | - Xu Li
- Department of Hepatology, The First Hospital of Jilin University, Changchun, People's Republic of China
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Abstract
Malignant primary liver tumors are rare in children. Yet a wide histologic spectrum is seen, particularly in hepatoblastoma, the most common malignant liver tumor in children. Furthermore, there can be significant morphologic overlap with hepatocellular carcinoma, the second most common pediatric liver malignancy, and tumors with hybrid features of hepatoblastoma and hepatocellular carcinoma are also reported (currently placed in the provisional category of malignant hepatocellular neoplasm, not otherwise specified). This review provides detailed morphologic descriptions and updates in the evolving clinical context of these tumors, and presents recent molecular advances that may further help in accurate classification of these tumors, which is critical in their management.
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Affiliation(s)
- Soo-Jin Cho
- Department of Pathology, University of California San Francisco, 1825 4th Street Room M2369, Box 4066, San Francisco, CA 94143, USA.
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50
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Shyu S, Ali SZ. Significance of hepatocyte atypia in liver fine needle aspiration. Diagn Cytopathol 2021; 50:186-195. [PMID: 34459153 DOI: 10.1002/dc.24851] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/16/2021] [Revised: 08/04/2021] [Accepted: 08/05/2021] [Indexed: 11/06/2022]
Abstract
Fine needle aspiration (FNA) of the liver is frequently the diagnostic procedure of choice for sampling hepatic lesions. One of the main diagnostic challenges in the interpretation of liver FNA is distinguishing dysplastic lesions and well-differentiated hepatocellular carcinoma (WD-HCC) from benign processes, as they share significant cytomorphologic overlap. Furthermore, the diagnosis of HCC often requires evaluation of stroma for invasion, which may not be present on cytology and small needle biopsy specimens. A reporting system for liver cytopathology has yet to be instituted. Without standardized and well-defined criteria for hepatocyte atypia, we recommend limiting the use of atypia in evaluation of liver FNA specimens to describe a diagnosis of exclusion, in which all known benign and neoplastic processes have been ruled out. The cytologic findings on the FNA of a liver nodule may be best reported as atypical hepatocytes in the absence of a core needle biopsy or cell block sufficient to render a definitive diagnosis of HCC.
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Affiliation(s)
- Susan Shyu
- Department of Pathology, Johns Hopkins University, Baltimore, Maryland, USA
| | - Syed Z Ali
- Department of Pathology, Johns Hopkins University, Baltimore, Maryland, USA
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