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World J Hepatol 2021 Apr;13(4):393-410

Department of Pathology, Groupe Hospitalier Henri Mondor, Creteil F-94010, France.

Morphological diversity and several new distinct pathologic subtypes of hepatocellular carcinoma (HCC) are now well-recognized. Recent advances in tumor genomics and transcriptomics have identified several recurrent somatic/genetic alterations that are closely related with histomorphological subtypes and have therefore, greatly improved our understanding of HCC pathogenesis. Pathologic subtyping allows for a diagnosis which is clinically helpful and can have important implication in patient prognostication as some of these subtypes are extremely aggressive with vascular invasion, early recurrence, and worst outcomes. Read More

Pediatr Radiol 2021 Apr 14. Epub 2021 Apr 14.

Department of Radiology, University of Pittsburgh Medical Center, Pittsburgh, PA, USA.

Liver tumors in children can be benign or malignant. Although several clinical factors are important in the evaluation of these lesions, MRI is particularly important for lesion characterization and tumor staging. In children, use of a hepatobiliary contrast agent is recommended to evaluate a known or suspected liver lesion. Read More

Children (Basel) 2021 Mar 16;8(3). Epub 2021 Mar 16.

Department of Surgery, St. Jude Children's Research Hospital, Memphis, TN 38105, USA.

Pulmonary ossification (PO) is a rare finding, characterized by mature bone formation in the lung parenchyma. We report a 20-year-old female patient diagnosed with fibrolamellar hepatocellular carcinoma (FL-HCC) and bilateral diffuse nodular PO. The patient presented with a unifocal left liver mass and multiple bilateral pulmonary lesions, which were treated as metastatic disease. Read More

J Pediatr Hematol Oncol 2021 Mar 23. Epub 2021 Mar 23.

Michael E. DeBakey Department of Surgery, Division of Pediatric Surgery, Texas Children's Surgical Oncology Program, Texas Children's Liver Tumor Program, Dan L. Duncan Cancer Center, Baylor College of Medicine Department of Pathology and Immunology, Texas Children's Hospital Liver Tumor Center, Dan L. Duncan Cancer Center, Baylor College of Medicine E. DeBakey Department of Surgery, Division of Abdominal Transplantation, Michael Texas Children's Hospital Liver Tumor Center, Dan L. Duncan Cancer Center, Baylor College of Medicine Department of Pediatrics, Texas Children's Cancer Center, Center for Cell and Gene Therapy, Texas Children's Liver Tumor Center, Dan L. Duncan Cancer Center, Baylor College of Medicine Singleton Department of Pediatric Radiology, Texas Children's Hospital Liver Tumor Program, Baylor College of Medicine Department of Interventional Radiology, MD Anderson Cancer Center Singleton Department of Pediatric Radiology, Division of Interventional Radiology, Texas Children's Hospital Liver Tumor Program, Baylor College of Medicine, Houston Department of Pediatrics, Texas Tech University Health Sciences Center, El Paso, TX Division of Hematology and Oncology, The University of Oklahoma Health Sciences Center, Oklahoma City, OK School of Medicine, Royal College of Surgeons in Ireland, Dublin, Ireland.

Background: Children with unresectable hepatocellular carcinoma (HCC) have a poor prognosis and limited treatment options. Transarterial radioembolization (TARE) using Yttrium-90 (Y90) has emerged as a potential bridge therapy to hepatic resection or transplantation for HCC with very limited studies in children.

Observations: Here we present the clinical course of 2 children successfully treated with TARE Y90 for initially unresectable fibrolamellar HCC (FL-HCC) and bridged to partial hemihepatectomy with >1-year overall survival post-TARE. Read More

Pediatr Radiol 2021 Mar 10. Epub 2021 Mar 10.

Department of Diagnostic Imaging, The Hospital for Sick Children, 555 University Ave., Toronto, ON, M5G 1X8, Canada.

Background: Hepatocellular carcinoma (HCC) is rare in children and there is limited data on its imaging features.

Objective: To describe imaging features of pediatric HCC and correlate them with clinical and laboratory findings.

Materials And Methods: We retrospectively reviewed imaging in all pediatric HCC cases seen between January 2000 and January 2019. Read More

J Med Case Rep 2021 Mar 16;15(1):132. Epub 2021 Mar 16.

Department of Medical Oncology, Comprehensive Cancer Center, King Fahad Medical City, Makkah Al Mukarramah Branch Road, Riyadh, 12231, Kingdom of Saudi Arabia.

Background: Fibrolamellar hepatocellular carcinoma is a unique tumor of the liver that differs from the classical hepatocellular carcinoma in diagnosis, behavior, and possibly treatment. There is usually absent underlying liver disease, and it usually occurs in young patients. The survival outcomes in localized fibrolamellar hepatocellular carcinoma are perhaps better than in classical hepatocellular carcinoma if treated early and radically. Read More

Commun Biol 2021 Mar 10;4(1):321. Epub 2021 Mar 10.

Department of Biochemistry, Molecular Biology, and Biophysics, University of Minnesota, Minneapolis, MN, USA.

An aberrant fusion of the DNAJB1 and PRKACA genes generates a chimeric protein kinase (PKA-C) in which the J-domain of the heat shock protein 40 is fused to the catalytic α subunit of cAMP-dependent protein kinase A (PKA-C). Deceivingly, this chimeric construct appears to be fully functional, as it phosphorylates canonical substrates, forms holoenzymes, responds to cAMP activation, and recognizes the endogenous inhibitor PKI. Nonetheless, PKA-C has been recognized as the primary driver of fibrolamellar hepatocellular carcinoma and is implicated in other neoplasms for which the molecular mechanisms remain elusive. Read More

Oncology 2021 9;99(5):310-317. Epub 2021 Mar 9.

Department of Pediatrics, Division of Hematology and Oncology, Rush University Medical Center, Chicago, Illinois, USA,

Introduction: There are no standard systemic therapies for the treatment of fibrolamellar carcinoma (FLC), as surgery remains the only definitive option. We share our experiences using systemic "triple therapy" (TT) with 5-fluorouracil, interferon, and nivolumab for the treatment of relapsed, refractory, metastatic, or unresectable FLC.

Methods: Data from all patients who received TT from May 2018 to July 2020 were reviewed to assess response, survival, and toxicity. Read More

Cureus 2021 Jan 10;13(1):e12609. Epub 2021 Jan 10.

Gastroenterology and Hepatology, University of Nebraska Medical Center, Omaha, USA.

Liver transplantation (LT) is an accepted form of therapy for selected cases of malignant tumors of the liver that include primary and fibrolamellar hepatocellular carcinoma, cholangiocarcinoma limited to Klatskin distribution, neuroendocrine tumors, epithelioid hemangioendothelioma, and hepatoblastoma. This is the case of a 61-year-old previously healthy female transferred from an outside hospital for a second opinion for a liver transplant. Computed tomography of the abdomen with contrast showed cirrhosis and multiple masses with arterial enhancement in her liver. Read More

Clin J Gastroenterol 2021 Feb 10. Epub 2021 Feb 10.

Department of Gastroenterology, Teikyo University Mizonokuchi Hospital, Kawasaki, Japan.

A 25-year-old woman with fever and epigastric pain was referred to our hospital. Blood examination showed significant liver dysfunction, markedly high C-reactive protein (CRP 19.1 mg/dL) and procalcitonin (48. Read More

Gan To Kagaku Ryoho 2020 Dec;47(13):2326-2328

Dept. of Surgery, Japan Community Health care Organization(JCHO)Osaka Hospital.

We report a rare case of hepatic fibrolamellar hepatocellular carcinoma(FLC). A 25-year-old Vietnamese male experienced loss of appetite and abdominal pain. He was referred for further examination of a 20 cm tumor in the left lobe of the liver detected in mass screening ultrasonography. Read More

Hum Pathol 2020 Dec 30. Epub 2020 Dec 30.

Department of Laboratory Medicine and Pathology, Mayo Clinic, Rochester, MN, 55905, USA. Electronic address:

Hepatocellular carcinomas are not a homogenous group of tumors but have multiple layers of heterogeneity. This heterogeneity has been studied for many years with the goal to individualize care for patients and has led to the identification of numerous hepatocellular carcinoma subtypes, defined by morphology and or molecular methods. This article reviews both gross and histological levels of heterogeneity within hepatocellular carcinoma, with a focus on histological findings, reviewing how different levels of histological heterogeneity are used as building blocks to construct morphological hepatocellular carcinoma subtypes. Read More

PLoS Biol 2020 12 28;18(12):e3001018. Epub 2020 Dec 28.

Department of Chemistry and Biochemistry, University of California, San Diego, La Jolla, California, United States of America.

When the J-domain of the heat shock protein DnaJB1 is fused to the catalytic (C) subunit of cAMP-dependent protein kinase (PKA), replacing exon 1, this fusion protein, J-C subunit (J-C), becomes the driver of fibrolamellar hepatocellular carcinoma (FL-HCC). Here, we use cryo-electron microscopy (cryo-EM) to characterize J-C bound to RIIβ, the major PKA regulatory (R) subunit in liver, thus reporting the first cryo-EM structure of any PKA holoenzyme. We report several differences in both structure and dynamics that could not be captured by the conventional crystallography approaches used to obtain prior structures. Read More

Front Oncol 2020 20;10:570479. Epub 2020 Nov 20.

Department of Paediatrics and Adolescent Medicine, The University of Hong Kong, Queen Mary Hospital, Hong Kong, Hong Kong.

Background: Hepatocellular carcinoma (HCC) is a rare hepatic malignancy in children. Hepatitis B virus (HBV) infection is a key predisposing factor in endemic regions but its impact on outcome has not been studied. We aim to evaluate the prognostic implication of HBV seropositivity and role of cancer surveillance in children with HCC from East Asian populations with national HBV vaccination. Read More

J Clin Exp Hepatol 2020 Nov-Dec;10(6):636-640. Epub 2020 Mar 7.

Department of Cytology and Gynecologic Pathology, Postgraduate Institute of Medical Education and Research, Chandigarh.

Ovaries are a common niche for metastasis. Metastatic malignancies account for 5-30% of all ovarian malignancies. Hepatocellular carcinoma (HCC) is one of the rare malignancies to metastasize to the ovaries. Read More

GE Port J Gastroenterol 2020 Nov 15;27(6):429-433. Epub 2020 Apr 15.

Medical Oncology Department, Centro Hospitalar Universitário Lisboa Central, Lisbon, Portugal.

Fibrolamellar carcinoma is a rare variant of hepatocellular carcinoma not associated with cirrhosis or viral hepatitis. Serum alpha-fetoprotein levels are usually normal; the histology is of a well-differentiated tumor, and the staging is the same as for hepatocellular carcinoma. We describe the case of a female patient in her 4th decade of life with a diagnosis of fibrolamellar hepatocellular carcinoma with a multimodal approach. Read More

J Hepatol 2021 Apr 26;74(4):931-943. Epub 2020 Nov 26.

Department of Medicine I, University Medical Center of the Johannes-Gutenberg University Mainz, Germany.

Recent years have seen significant progress in the systemic treatment of hepatocellular carcinoma (HCC), including the advent of immunotherapy. While several large phase III trials have provided the evidence for a multi-line treatment paradigm, they have focused on a highly selected group of patients by excluding potentially confounding comorbidities. As a result, high quality evidence for the systemic treatment of HCC in patients with various comorbidities is missing. Read More

JHEP Rep 2021 Feb 24;3(1):100174. Epub 2020 Aug 24.

Service d'hépatologie, Hôpital Avicenne, Hôpitaux Universitaires Paris-Seine-Saint-Denis, Assistance-Publique Hôpitaux de Paris, Bobigny, France.

Hepatocholangiocarcinoma, fibrolamellar carcinoma, hepatic haemangioendothelioma and hepatic angiosarcoma represent less than 5% of primary liver cancers. Fibrolamellar carcinoma and hepatic haemangioendothelioma are driven by unique somatic genetic alterations ( and fusions, respectively), while the pathogenesis of hepatocholangiocarcinoma remains more complex, as suggested by its histological diversity. Histology is the gold standard for diagnosis, which remains challenging even in an expert centre because of the low incidences of these liver cancers. Read More

Curr Probl Diagn Radiol 2020 Nov 2. Epub 2020 Nov 2.

Department of Radiodiagnosis, All India Institute of Medical Sciences (A.I.I.M.S), New Delhi, India.

The radiological appearance of common primary hepatic tumors such as hepatocellular carcinoma (HCC) and cholangiocarcinoma (CCA) is widely recognized. Hepatic masses with unusual histology are occasionally encountered, but seldom suspected on imaging. However, many possess characteristic imaging findings, which when assessed along with the clinical and demographic background and serum tumor markers, may enable a prospective diagnosis. Read More

Surg Pathol Clin 2020 Dec;13(4):601-623

Department of Pathology, University of California San Francisco, 1825 4th Street Room M2369, Box 4066, San Francisco, CA 94143, USA. Electronic address:

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). Read More

Radiol Case Rep 2020 Dec 12;15(12):2613-2616. Epub 2020 Oct 12.

Department of Radiology, Beth Israel Deaconess Medical Center, 330 Brookline Ave, Boston, MA 02215, USA.

Fibrolamellar hepatocellular carcinoma (FL-HCC) is a rare primary liver tumor that typically presents at an advanced stage in early adolescents and adults with no underlying liver disease. Surgical resection is the first-line treatment, and patients who are not surgical candidates face limited treatment options with poor long-term outcomes. Herein we report the first documented, technically successful treatment of FL-HCC with extrahepatic spread using transarterial radioembolization (TARE) in a 16-year-old male patient with surgically unresectable disease. Read More

Clin Hemorheol Microcirc 2021 ;77(1):49-60

School of Computer Science and Engineering, Nanyang Technological University, Singapore, Singapore.

Background: Fibrolamellar hepatocellular carcinoma (FLHCC) is an unusual variant of hepatocellular carcinoma (HCC). Revealing the imaging features is important to the diagnosis of FLHCC.

Objective: The aim of this study was to investigate the imaging characteristics of FLHCCs. Read More

Cancer Res Treat 2021 Jan 7;53(1):283-288. Epub 2020 Sep 7.

Department of Pediatrics, Center for Pediatric Cancer, National Cancer Center, Goyang, Korea.

Fibrolamellar hepatocellular carcinoma (FLHCC) is a rare liver cancer affecting adolescents and young adults without any pre existing liver disease. Hyperammonemic encephalopathy (HAE) is a serious paraneoplastic syndrome, and several cases of HAE have been reported in patients with FLHCC. This condition is rare; hence, there are currently no management guidelines for cancer-related HAE. Read More

J Gastrointest Cancer 2020 Dec;51(4):1187-1192

Liver Institute, Pathology Department, Inonu University, School of Medicine, Malatya, Turkey.

Purpose: We aimed to distinguish between fibrolamellar hepatocellular carcinoma and scirrhous hepatocellular carcinoma histopathologically.

Methods And Results: In this review, fibrolamellar hepatocellular carcinoma and scirrhous hepatocellular carcinoma two specific and rare variants of hepatocellular carcinoma, which are difficult to diagnose histopathologically are discussed.

Conclusion: The clinical, radiological, gross, histopathological, immunohistochemical, and molecular features of these two tumors, which are defined by the World Health Organization (WHO), are mentioned. Read More

Cell 2020 09 25;182(6):1531-1544.e15. Epub 2020 Aug 25.

Department of Pharmacology, University of California, San Diego, La Jolla, CA 92093, USA; Department of Bioengineering, University of California, San Diego, La Jolla, CA 92093, USA; Department of Chemistry and Biochemistry, University of California, San Diego, La Jolla, CA 92093, USA; Department of Pharmacology and Molecular Sciences, The Johns Hopkins University School of Medicine, Baltimore, MD 21205, USA. Electronic address:

The fidelity of intracellular signaling hinges on the organization of dynamic activity architectures. Spatial compartmentation was first proposed over 30 years ago to explain how diverse G protein-coupled receptors achieve specificity despite converging on a ubiquitous messenger, cyclic adenosine monophosphate (cAMP). However, the mechanisms responsible for spatially constraining this diffusible messenger remain elusive. Read More

Eur J Cancer 2020 09 5;137:144-147. Epub 2020 Aug 5.

Department of Medical Oncology, The Christie NHS Foundation Trust, Manchester, United Kingdom; Division Cancer Sciences, University of Manchester; Manchester, United Kingdom. Electronic address:

Fibrolamellar carcinoma (FLC) is a rare and poorly understood malignancy, which seems to be more prevalent in young patients compared with conventional hepatocellular carcinoma (HCC). Performing prospective clinical trials recruiting patients diagnosed with FLC has proven challenging with scarce data available guiding clinical management. The use of a number of chemotherapy compounds in these patients, including cisplatin, epirubicin, 5-fluorouracil (5-FU) and recombinant interferon α-2B (IFN-α-2B), has been reported in the literature, mainly in the form of case reports. Read More

Am J Med 2020 12 31;133(12):e745-e746. Epub 2020 Jul 31.

Mayo Clinic, Gastroenterology, Rochester, Minn.

Cancer 2020 Sep 14;126(18):4126-4135. Epub 2020 Jul 14.

Memorial Sloan Kettering Cancer Center, New York, New York, USA.

Background: Fibrolamellar carcinoma (FLC) is a rare primary liver cancer of young adults. A functional chimeric transcript resulting from the in-frame fusion of the DNAJ homolog, subfamily B, member 1 (DNAJB1), and the catalytic subunit of protein kinase A (PRKACA) genes on chromosome 19 is believed to be unique in FLC, with a possible role in pathogenesis, yet with no established therapeutic value. The objective of the current study was to understand the molecular landscape of FLC and to identify potential novel therapeutic targets. Read More

J Pediatr Surg 2020 Jun 18. Epub 2020 Jun 18.

Department of Surgery, Division of Hepatobiliary Surgery and Liver Transplantation, Vanderbilt University Medical Center, Nashville, TN 37232, USA. Electronic address:

Purpose: This study evaluates overall survival (OS) between liver transplantation (LT) and liver resection (LR), while assessing the effect of margin status, in children with hepatocellular carcinoma (HCC).

Methods: The National Cancer Database was queried (2004-2015) for children (<18 years) with non-metastatic HCC undergoing surgery.

Results: One hundred six children with HCC treated surgically (LT 34, LR 72) were identified. Read More