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Alshareefy Y, Shen CY, Prekash RJ. Exploring the molecular pathogenesis, diagnosis and treatment of fibrolamellar hepatocellular carcinoma: A state of art review of the current literature. Pathol Res Pract 2023; 248:154655. [PMID: 37429175 DOI: 10.1016/j.prp.2023.154655] [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: 04/13/2023] [Accepted: 06/25/2023] [Indexed: 07/12/2023]
Abstract
This paper aims to present a detailed overview of fibrolamellar carcinoma (FLC), a variant of hepatocellular carcinoma (HCC) that accounts for approximately 1-9% of all cases a. according to the SEER database. Despite ongoing research, the aetiology of FLC tumours remains unclear. Nevertheless, FLC is believed to have a better overall prognosis than other primary liver tumours, such as hepatocellular carcinoma (HCC) and intrahepatic cholangiocarcinoma. This study aims to present a comprehensive overview of fibrolamellar carcinoma (FLC), with a focus on its epidemiology, pathogenesis, diagnosis, treatment, and prognosis. FLC frequently incorporate features of stomach pain, weight loss, and malaise in their clinical signs and symptoms, which are generally nonspecific Ultimately, the most common physical finding is an abdominal mass or hepatomegaly. With this said, several unusual presentations have been documented such as Budd Chiari syndrome, severe anaemia, non-bacterial thrombotic endocarditis and many more. In regards to this tumour's genetic analysis, it is characterised by a 400 kb deletion on chromosome 19 leading to a functional DNAJB1-PRKACA chimeric transcript in addition to tetraploidy in 50% of cases. FLC is chromosomally stable as compared to typical HCC. mTOR pathway activation has also been found to play a critical role in 47% of these tumours and EFGR over-expression is also evident. Fibrolamellar carcinomas (FLCs) exhibit a distinctive gross appearance, characterized by a yellow to pale tan colour, with a consistency that can vary from soft to firm and hard. In addition, a central scar is observed in 60-70% of FLC cases. The central scar is typically white or grey in colour and has a fibrous appearance, which is often surrounded by nodular, tumour-like tissue. Its histologic appearance is characterized by large polygonal cells with abundant eosinophilic cytoplasm, large vesiculated nuclei, large nucleoli, and arranged in lamellar bands of collagen fibres. Lamellar bands of fibrosis, consisting of collagen type I, III and IV, have also been identified as a distinctive histologic feature that is observed under low power magnification. Ultrasound, CT and MRI along with image guided biopsy are the primary modalities in diagnosis. Current management options include systemic therapy which has thus far been unremarkable with platinum-based therapies as well combination therapy with interferon alpha-2b being the most successful options. Surgical resection remains the primary treatment modality and there have been no advances in targeted therapies. Although the prognosis for FLC is favourable as compared to other hepatic cancer subtypes such as intrahepatic cholangiocarcinoma, there is a high rate of recurrence ranging from 33% to 100% with a median recurrence-free survival of 20-48 months. As a result of this there is a low overall cure rate associated with this tumour type and much more research is required to gain an in-depth understanding of the molecular mechanisms occurring in order to provide more adequate treatment to patients who suffer from this condition.
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Affiliation(s)
- Yasir Alshareefy
- School of Medicine, Trinity College Dublin, University of Dublin, Ireland.
| | - Chai Yu Shen
- Department of Medicine, Manipal University College, Malaysia
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Abdelhamed W, El-Kassas M. Fibrolamellar hepatocellular carcinoma: A rare but unpleasant event. World J Gastrointest Oncol 2022; 14:1103-1114. [PMID: 35949219 PMCID: PMC9244987 DOI: 10.4251/wjgo.v14.i6.1103] [Citation(s) in RCA: 7] [Impact Index Per Article: 2.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 01/15/2022] [Revised: 03/19/2022] [Accepted: 05/08/2022] [Indexed: 02/06/2023] Open
Abstract
Fibrolamellar carcinoma (FLC) is a rare variant of hepatocellular carcinoma (HCC), comprising 1%-9% of all HCCs. FLC is a poorly understood malignancy, which seems to be more prevalent in young patients with no underlying liver diseases. The term "fibrolamellar" is derived from thick fibrous collagen bands surrounding the tumor cells. Unlike HCC, cirrhosis and viral hepatitis infection are not predisposing to FLC, and it is not associated with elevations in serum alpha-fetoprotein. FLC patients often present with vague abdominal pain, nausea, malaise, and weight loss. Most cases present are at an advanced stage at the time of initial diagnosis. However, curative treatment options can still be offered to up to 70% of patients. Surgery (resection/liver transplantation) is the mainstay of treatment and the only potentially curative option. FLCs have been less chemo-responsive than the conventional HCC, however, in advanced cases, multimodality treatments can be effective. Recent advances in molecular studies of FLC have found a unique DNAJB1-PRKACA fusion transcript in most of the cases studied. The review aims to describe clinical characteristics, diagnostic methods, and therapeutic modalities for this rare tumor to raise awareness among clinicians and surgeons.
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Affiliation(s)
- Walaa Abdelhamed
- Department of Endemic Medicine, Sohag University, Sohag 14322, Egypt
| | - Mohamed El-Kassas
- Department of Endemic Medicine, Faculty of Medicine, Helwan University, Cairo 11795, Egypt
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Xiong J, Kwong Chian S, Li J, Liu X. Iodine-125 seed implantation for synchronous pancreatic metastases from hepatocellular carcinoma: A case report and literature review. Medicine (Baltimore) 2017; 96:e8726. [PMID: 29145315 PMCID: PMC5704860 DOI: 10.1097/md.0000000000008726] [Citation(s) in RCA: 6] [Impact Index Per Article: 0.8] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 02/05/2023] Open
Abstract
RATIONALE The image-guided iodine-125 seed implantation has been widely used for a variety of tumors, including prostatic cancer, pulmonary cancer, hepatocellular carcinoma and pancreatic cancer. However, the clinical value of iodine-125 seed implantation for the treatment of pancreatic metastasis from hepatocellular carcinoma has not been reported. We presented the first case with ultrasound-guided iodine-125 seed implantation for this disease. PATIENT CONCERNS We presented the case of a 48-year-old man patient with primary hepatocellular carcinoma and pancreatic metastasis who was managed with ultrasound-guided iodine-125 seeds implantation. DIAGNOSES She was diagnosed with synchronous pancreatic metastases from hepatocellular carcinoma. INTERVENTIONS Puncture biopsy and ultrasound-guided iodine-125 seeds implantation. OUTCOMES The hepatic and pancreatic tumors were obviously reduced after 15 months. Moreover, the liver function test was mildly abnormal in glutamic-oxalacetic transaminase and glutamic-pyruvic transaminase. LESSONS The image-guided iodine-125 seeds implantation was an important therapeutic approache to unresectable hepatocellular carcinoma with pancreatic metastasis. However, more related cases should be reported for further evaluating the value of the way.
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Affiliation(s)
| | | | - Jiao Li
- Department of Emergency, West China Hospital, Sichuan University, Chengdu, Sichuan Province, China
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Lafaro KJ, Pawlik TM. Fibrolamellar hepatocellular carcinoma: current clinical perspectives. J Hepatocell Carcinoma 2015; 2:151-7. [PMID: 27508204 PMCID: PMC4918295 DOI: 10.2147/jhc.s75153] [Citation(s) in RCA: 29] [Impact Index Per Article: 2.9] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/15/2022] Open
Abstract
Fibrolamellar carcinoma (FLC) is a variant of hepatocellular carcinoma (HCC), which comprises ∼1%–9% of all HCCs. Although FLC is a variant of HCC, it is distinct from HCC in that it most often affects younger patients (10–35 years of age) with no underlying liver disease. FLC often presents with vague abdominal pain, nausea, abdominal fullness, malaise, and weight loss. Surgery is the current mainstay of treatment for FLC and remains the only potentially curative option. While FLCs are considered less responsive to chemotherapy than their classic HCC counterparts, there have been suggestions that multimodality treatments may be effective, especially in advanced cases. Further research is necessary to determine effective systemic therapies as an adjunct to surgery for FLC.
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Affiliation(s)
- Kelly J Lafaro
- Center for Pancreatic Cancer Research, Memorial Sloan Kettering Cancer Center, New York, NY
| | - Timothy M Pawlik
- Department of Surgery, The Johns Hopkins University School of Medicine, Baltimore, MD, USA
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Villa NA, Pannala R, Faigel DO, Haakinson DJ, Katariya N, Ramanathan R, Jaroszewski D, Lidner TK, Byrne T. Metastatic Fibrolamellar Hepatocellular Carcinoma to the Pancreas. Case Rep Gastroenterol 2015; 9:266-71. [PMID: 26351415 PMCID: PMC4560303 DOI: 10.1159/000437290] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.2] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 12/30/2022] Open
Abstract
Fibrolamellar hepatocellular carcinoma (FL-HCC) is a rare variant of hepatocellular carcinoma, usually presenting in the younger population (<40 years) without underlying liver disease. Although it has a better prognosis than hepatocellular carcinoma, it has a high rate of recurrence months to years after primary resection. While sites of recurrence usually involve the liver, regional lymph nodes, peritoneum, and lung, metastasis to the pancreas is extremely rare, with only 2 other cases reported in the literature. We present the case of a 46-year-old patient with metastatic FL-HCC to the pancreas 30 years after diagnosis and 26 years since his last resected liver recurrence.
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Affiliation(s)
- Nicolas A Villa
- Division of Gastroenterology and Hepatology, Scottsdale, Ariz., USA
| | - Rahul Pannala
- Division of Gastroenterology and Hepatology, Scottsdale, Ariz., USA
| | - Douglas O Faigel
- Division of Gastroenterology and Hepatology, Scottsdale, Ariz., USA
| | | | - Nitin Katariya
- Division of Transplant Surgery, Mayo Clinic Arizona, Scottsdale, Ariz., UAS
| | - Ramesh Ramanathan
- Division of Hematology and Oncology, Mayo Clinic Arizona, Scottsdale, Ariz., USA
| | - Dawn Jaroszewski
- Division of Cardiothoracic Surgery, Mayo Clinic Arizona, Scottsdale, Ariz., USA
| | - Thomas K Lidner
- Department of Pathology, Mayo Clinic Arizona, Scottsdale, Ariz., USA
| | - Thomas Byrne
- Division of Gastroenterology and Hepatology, Scottsdale, Ariz., USA
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Olson MT, Wakely PE, Ali SZ. Metastases to the pancreas diagnosed by fine-needle aspiration. Acta Cytol 2013; 57:473-80. [PMID: 24021904 DOI: 10.1159/000352006] [Citation(s) in RCA: 31] [Impact Index Per Article: 2.6] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/14/2013] [Accepted: 05/06/2013] [Indexed: 01/28/2023]
Abstract
BACKGROUND Metastatic cancer infrequently involves the pancreas. When the pancreas hosts a metastatic tumor, cytopathological evaluation of fine-needle aspirate material is a crucial part of the diagnostic process. In this study, we show two institutions' experience with cytopathological diagnosis of pancreatic metastasis. METHODS Databases of institutional experience at The Johns Hopkins Hospital and Ohio State University Medical Center were queried for cases of metastatic tumors in the pancreas that underwent fine-needle aspiration. Demographic and pathological features were compiled and the cytomorphology was reviewed. RESULTS Forty-two cases of tumor metastasis to the pancreas were found. Over the time of this review, 5,495 aspirates were performed, and 43% (2,389/5,495) had malignant cytological findings. Thus, the 42 cases of metastatic disease to the pancreas comprised 0.8% of all pancreas aspirates and 1.8% of the malignant ones. Renal cell carcinoma was the most common metastasis, followed by melanoma and non-small cell lung carcinoma. Among the other tumors in this series, 2 cases each of rare metastases such as the fibrolamellar variant of hepatocellular carcinoma and solitary fibrous tumor were also seen. CONCLUSION The pancreas is rarely involved with metastatic disease, but when it is involved the most common tumor is renal cell carcinoma followed by melanoma and non-small cell lung cancer. Clinical history and awareness of the primary pancreatic mimickers are necessary for arriving at the correct diagnosis. As conventional pancreatic adenocarcinoma is uncommon in children and young adults, history of other tumors - even ones that usually follow an indolent course - is essential.
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Affiliation(s)
- Matthew T Olson
- Department of Pathology, The Johns Hopkins Hospital, Baltimore, Md., USA
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Torbenson M. Fibrolamellar carcinoma: 2012 update. SCIENTIFICA 2012; 2012:743790. [PMID: 24278737 PMCID: PMC3820672 DOI: 10.6064/2012/743790] [Citation(s) in RCA: 65] [Impact Index Per Article: 5.0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Figures] [Subscribe] [Scholar Register] [Received: 07/26/2012] [Accepted: 08/22/2012] [Indexed: 06/02/2023]
Abstract
Fibrolamellar carcinomas are a unique type of primary liver cancer. They occur most commonly in children and young adults. Their etiology remains a mystery, as they are not associated with chronic liver disease. Fibrolamellar carcinomas are not indolent tumors, but have an overall better prognosis than typical hepatocellular carcinomas, in part because of the younger age at presentation and the lack of cirrhosis. The most important prognostic feature is whether the tumor is resectable. Histologically, the tumor is made up of large cells that contain abundant mitochondria. The nuclei of the tumor cells have prominent nucleoli. The tumor cells induce the formation of extensive intratumoral fibrosis, which often grows in parallel, or lamellar bands. The tumor cells clearly show hepatocellular features but are also unique in showing both biliary and neuroendocrine differentiation. The uniqueness of fibrolamellar carcinoma extends to their molecular findings. While the genetic abnormalities that lead to fibrolamellar carcinomas are not yet known, studies have shown that they lack mutations in the genes most commonly mutated in typical hepatocellular carcinoma (TP53 and CTNNB1). In this paper, the clinical, pathological, and basic science literature on fibrolamellar carcinoma is comprehensively reviewed. Key areas of needed research are also discussed.
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Affiliation(s)
- Michael Torbenson
- Department of Pathology, The Johns Hopkins University School of Medicine, Room B314, 1503 E. Jefferson, Bond Street Building, Baltimore, MD 21231, USA
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Liu S, Wah Chan K, Tong J, Wang Y, Wang B, Qiao L. PET-CT scan is a valuable modality in the diagnosis of fibrolamellar hepatocellular carcinoma: a case report and a summary of recent literature. QJM 2011; 104:477-483. [PMID: 21493692 DOI: 10.1093/qjmed/hcr040] [Citation(s) in RCA: 15] [Impact Index Per Article: 1.1] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 01/01/2023] Open
Abstract
We report a case of liver cancer with features consistent with fibrolamellar hepatocellular carcinoma (FLHCC) detected by PET-CT scan. A 20-year-old female with a large liver tumor was diagnosed with 'malignant hepatic tumor' 2 years earlier and received five courses of transhepatic arterial chemoembolization (TACE) before she presented to our hospital with abdominal distension and mild pain at the right upper quadrant. Ultrasound and CT scan showed a large tumor in the right lobe of the liver. Contrast CT scan and (18)F-FDG PET-CT showed metastatic lesions in multiple organs. The imaging diagnosis was confirmed by an ultrasound-guided fine needle biopsy of the hepatic lesion which showed features of FLHCC. Immunohistochemical staining showed a marked increase in the expressions of Hepar, CD99, MIB1, proliferating cell nuclear antigen (PCNA), Fibronectin, E-cadherin and CK7. The recent knowledge on the FLHCC and the possible applications of PET-CT were discussed.
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Affiliation(s)
- S Liu
- Department of Cadres, The First Affiliated Hospital of China Medical University, Shenyang, Liaoning Province, 110001, China
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Abstract
To determine the variety of chemotherapy drugs administrable for malignant pancreatic neoplasm as a result of typification with endoscopic ultrasonography-fine needle aspiration (EUS-FNA). A retrospective assessment, in one center, over a period of 1 year. Only malignant pancreatic neoplasm diagnosed by EUS-FNA was recorded. Benign (serous cystic neoplasm) and potentially malignant lesions (mucinous cystic neoplasm and intraductal papillary-mucinous neoplasm) were excluded. Medical data were recorded and Oncological Pharmacy records were studied. Ductal adenocarcinoma were detected in 17 patients (N = 17/22), 2 of them with adenocarcinoma in signet ring and 1 with mucinous adenocarcinoma. The primary therapies used were as follows: Whipple pancreaticoduodenectomy (3), biliary stent by endoscopic retrograde cholangiopancreatography (3), radiological transhepatic percutaneous stent (2), intestinal bypass (2), and a gastric stent (1). The adjuvant drugs used were gemcitabine (10), erlotinib (3), and cetuximab (1), and also radiotherapy was used (1). An unresectable squamous cell carcinoma (N = 1) of the tail was detected, and gemcitabine + vinorelbine + fluorouracil + cisplatin used. Nonfunctioning neuroendocrine tumors were seen in 3 (N = 3) cases and long-acting somatostatin analogues were used (1); the remaining 2 patients showed resectable tumors and were resected accordingly. A metastasis to the pancreatic head in a hepatocellular carcinoma was found in 1 patient (N = 1), allowing specific treatment with sorafenib. Histopathologic analysis with EUS-FNA implies a variety of different treatments. Optimal management was achieved as a result of improved diagnosis, with the advent of new molecular genetic diagnostic methods facilitating the design of specific new therapy and neoadjuvant targeting strategies.
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