Fibrolamellar Carcinoma: A Review with Focus on Genetics and Comparison to Other Malignant Primary Liver Tumors

The Lillian and Henry M. Stratton-Hans Popper Department of Pathology, Mount Sinai School of Medicine, New York, USA.
Seminars in Liver Disease (Impact Factor: 4.95). 02/2011; 31(1):61-70. DOI: 10.1055/s-0031-1272835
Source: PubMed


Fibrolamellar carcinoma is a rare primary malignant liver neoplasm that usually affects adolescents and young adults with no underlying liver disease. Morphologically, the tumor cells resemble oncocytic hepatocytes arranged in cords with a stroma of lamellated collagen fibers. Immunohistochemical studies have found that fibrolamellar carcinomas express markers associated with both biliary (CK7 and epithelial membrane antigen) and hepatocytic (heppar-1and glypican-3) differentiation, as well as markers associated with hepatic progenitor cells (CK19 and EpCAM) and stem cells (CD133 and CD44). Genetic studies show fewer alterations compared with classic hepatocellular carcinoma. Pooled data from comparative genomic hybridization studies show that fibrolamellar carcinomas have fewer and less frequent genomic alterations when compared with classic hepatocellular carcinoma, cholangiocarcinoma, and hepatoblastoma. Of the alterations seen in fibrolamellar carcinoma, the most frequent are gains in 1q and 8q (also frequently seen in other hepatic tumors) and loss of 18q. Fibrolamellar carcinoma also has less frequent methylation of tumor suppressor promoters compared with hepatocellular carcinoma and minimal alterations in mitochondrial DNA. Fibrolamellar carcinoma is associated with better survival than hepatocellular carcinoma and cholangiocarcinoma, presumably due to the young age of the patients and the lack of cirrhosis. These features make more aggressive surgical therapy possible. There is currently very little information on the effectiveness of chemotherapy for fibrolamellar carcinoma.

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    • "Fibrolamellar hepatocellular carcinoma (FLHCC), a rare variant of hepatocellular carcinoma (HCC) comprising 1-2% of the US HCC cases. FLHCC was first described by Edmondson in 1956;1,2 it histologically consists of polygonal, eosinophilic hepatocyte cords separated by bands of fibrous stroma.1,3 FLHCC tumors typically present with symptoms of abdominal pain, fullness, and nausea.1,3 "
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    ABSTRACT: Fibrolamellar hepatocellular carcinoma (FLHCC) is a rare variant of hepatocellular carcinoma (HCC) that commonly affects young individuals without a prior history of liver disease. FLHCC commonly results in a better prognosis than HCC; however, the risk of recurrence and metastatic disease is high. FLHCC is typically treated by primary resection of the tumor with 50-75% cure rates. The use of radiation therapy in FLHCC has not been assessed on its own, and may show some success in a very few reported combination therapy cases. We report on the successful use of radiation therapy in a case of metastatic FLHCC to the lung following primary and secondary resections. Our treatment of the large, metastatic, pulmonary FLHCC tumor with 40 Gy in 10 fractions resulted in an 85.9% tumor volume decrease over six months. This suggests FLHCC may be a radiosensitive tumor and radiotherapy may be valuable in unresectable or metastatic tumors.
    Rare tumors 07/2013; 5(3):e28. DOI:10.4081/rt.2013.e28
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    • "Subsequent case reports and cases series have confirmed and expanded the unique clinical and pathologic features of FLC. Major review articles on the clinical, pathological, and biological findings have been published in 2007 [3], 2009 [4], and 2011 [5]. "
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    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.
    09/2012; 2012(2):743790. DOI:10.6064/2012/743790
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    • "Fibrolamellar hepatocellular carcinoma (HCC) is a rare liver tumour [1]. In contrast to conventional HCC, this tumour occurs in non-cirrhotic liver. "
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    ABSTRACT: The only currently validated treatment for advanced hepatocellular carcinoma (HCC) is sorafenib. However, sorafenib has been mainly studied in patients with HCC developed in cirrhotic liver. Chemotherapy might be more suitable for patients with HCC in non-cirrhotic liver. We report the case of a young woman with fibrolamellar HCC in a non-cirrhotic liver, with histologically proven metastatic ganglionary relapse after surgical resection of the primary tumour. Chemotherapy with gemcitabine and oxaliplatin (GEMOX regimen) achieved a complete response without relapse five years after discontinuation of chemotherapy. This exceptional case raises the question of clinical trials specifically designed for patients with HCC in non-cirrhotic liver.
    Case Reports in Oncology 04/2012; 5(1):169-72. DOI:10.1159/000338242
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