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.

We report a case of typical fibrolamellar hepatocellular carcinoma (FL-HCC) in a 16-year-old Japanese boy. This is very rare malignancy in Japan. The patient was referred for investigation of a large hepatic tumor and the results of tests for hepatitis B virus surface antigen and hepatitis C virus antibody were negative. Liver function test results and serum alpha-fetoprotein (AFP) levels were normal; however, the prothrombin induced by vitamin K absence/antagonist II was elevated. Computed tomography (CT) showed a large lobulated heterogeneously enhanced tumor in the posterior section of the liver. We diagnosed FL-HCC and performed posterior sectionectomy of the liver. The resected specimen contained a light brown and green tumor with a central fibrous scar, 10.0 cm in diameter. Microscopic and electron microscopic examinations revealed the typical features of FL-HCC. Immunohistochemically, the tumor cells were positive for cytokeratin (CK) 7, but negative for CK19 and AFP. The patient was alive without recurrence 48 months after surgery. Following this case report, we summarize the clinical features of the Japanese cases documented in the literature.

Fibrolamellar hepatocellular carcinoma (FHLCC) generally occurs in young individuals lacking a background of chronic liver disease and other risk factors for hepatocellular carcinoma. The clinical presentations of FLHCC are generally nonspecific, and the alpha-fetoprotein level is typically within the normal range in most cases. Imaging studies have a major role in clinical diagnosis, but pathology is the gold standard in confirming diagnosis. Pathological characteristics of FLHCC include the presence of tumor cells with a deeply eosinophilic cytoplasm and macronucleoli surrounded by abundant fibrous bands. The most effective treatment for FLHCC is aggressive surgical resection. This comprehensive literature review gives a full account of the clinical, pathological, and molecular features of FLHCC.

Since its first description 50 years ago, fibrolamellar carcinomas (FLCs) have been recognized as a unique type of primary liver cancer. FLCs occur principally in children and young adults and are not associated with chronic liver disease. Their etiology is unknown. The tumor is made up of large polygonal cells containing abundant eosinophilic cytoplasm, large vesiculated nuclei, and large nucleoli, with tumor cells that are embedded in lamellar bands of fibrosis. Although rare, the most common variant of FLC shows areas of glandular type differentiation with mucin production. The uniqueness of FLC extends to their molecular findings, as they show no evidence for involvement by many of the major pathways and genes that are dysregulated in typical hepatocellular carcinoma, including alpha-fetoprotein, TP53 mutations, and beta catenin mutations. FLCs are not indolent tumors, but have an overall better prognosis than hepatocellular carcinomas of the usual sort because of the younger age at presentation and lack of cirrhosis. The most important prognostic feature is resectability. Although their morphologic appearance on routine stains is well defined, their etiology is still unknown and much of their molecular biology remains poorly described and awaits future investigation.

A 17-year-old Japanese female underwent major hepatic resection for a huge fibrolamellar hepatocellular carcinoma that was compressing the inferior vena cava. The tumor was not exposed at the surgical margin but was very close to it. A recurrent lesion at the surgical margin of the liver and a lymph node metastasis were discovered 9 months postoperatively together with a marked elevation of vitamin B12 binding capacity. These lesions were resected, and vitamin B12 binding capacity decreased thereafter. Peritoneal dissemination was detected by CT 16 months postoperatively, together with recurrent elevation of vitamin B12 binding capacity. Several types of chemotherapy, including intraperitoneal injection of epirubicin, were applied and improved the patient's quality of life somewhat, but the patient died of recurrent disease 34 months after the initial hepatic resection. This is the first report in Japan of fibrolamellar hepatocellular carcinoma with increased vitamin B12 binding capacity as a useful marker. Fibrolamellar hepatocellular carcinomas, if resected, have a better prognosis than ordinary hepatocellular carcinoma in Japan, as well as in Western countries. An aggressive strategy should be chosen, which consists mainly of precise surgical resection and postoperative multimodality therapy, including chemotherapy.

The aim of this report is to describe the frequency, clinical, and morphologic characteristics of fibrolamellar hepatocellular carcinoma in Mexican patients. Fibrolamellar hepatocellular carcinoma (FLHCC) is a rare variant of hepatocellular carcinoma. Although this tumor appears to be predominant among the Caucasian population of the U.S, FLHCC has been described in many other countries. The frequency and characteristics of FLHCC in Latin American population is almost unknown. The clinico-pathologic characteristics of seven (5.8%) Mexican patients with FLHCC, obtained among 121 hepato-cellular carcinomas are described. The frequency of these tumors was compared with the frequency reported in other geographic areas in the international literature between 1980 and 1999. There were four women and three men. Two patients had taken oral contraceptives for six months and a year prior to diagnosis; another patient had positive serology for the hepatitis B virus. Common symptoms included a palpable mass, abdominal pain and weight loss; two patients presented jaundice. In two patients the tumor had been removed eight and three years previously, and they were readmitted when FLHCC recurred. In three patients the diagnosis was suspected in radiological studies (computed tomography and/or magnetic resonance). Laboratory tests were non-specific. In four patients, resection of the tumor was performed, and in the remaining three the neoplasm was diagnosed by percutaneous hepatic biopsy. Two patients had died of disease at the time of the study, and another was alive with recurrent disease.

fibrolamellar hepatocarcinoma is an uncommon, but not an exceptional neoplasm in our population and represents 5.8% of all hepatocarcinomas reviewed.

Fibrolamellar carcinoma (FLC) is a variant of hepatocellular carcinoma characterized by distinct pathological features. The presence of intracellular lumina resembling bile canaliculi was previously reported in tumor cells of FLC on electron microscopy. Using light microscopy, we describe the presence of intracellular lumina in FLC, which was resected from a 15-year-old Japanese girl, as round structures lined with a brush-like border. These lumina occasionally contained bile. Light microscopic examination of 1 micron thick serial sections of Epon-embedded tissue samples showed that the lumina were located in the intracellular space without any connection to the intercellular space. However, we also detected a small number of lumina that were lined by microvilli, which were present between adjacent tumor cells. Results suggest that the presence of the intracellular lumina in tumor cells probably represents a common histopathologic feature of FLC.