Background: Fibrolamellar hepatocellular carcinoma, or fibrolamellar carcinoma, is an uncommon malignant neoplasm of the liver. Fibrolamellar carcinoma has distinctive clinical, histologic, and radiographic features that distinguish it from the relatively more common hepatocellular carcinoma (HCC). Compared with HCC, fibrolamellar carcinoma occurs in a younger population, and it is typically not associated with underlying liver disease or elevated serum levels of alpha-fetoprotein tumor markers. Also, fibrolamellar carcinoma may have a slightly better prognosis. 

Perhaps because of the younger ages of the patients and the lack of coexisting cirrhosis, patients with fibrolamellar carcinoma are often treated aggressively. Resection of large tumor masses, metastatic disease, and even recurrent disease can extend patient survival. Radiographic evaluation of patients with fibrolamellar carcinoma may be used for the initial diagnosis of the tumor, the preoperative staging of disease, and the follow-up surveillance to detect recurrent or metastatic disease. 
  
Gross findings: Fibrolamellar carcinoma most commonly presents as a solitary large intrahepatic mass with well-defined margins and a lobulated contour. The tumors are typically large at the time of diagnosis, with mean diameter of 10-20 cm. Regional lymph node metastases are found in 50-70% of patients at the time of initial diagnosis. Portal or hepatic venous invasion is not typical. Grossly, the primary tumor appears as a well-demarcated, lobular, bile-stained, white or tan mass with a central stellate scar or fibrotic bands. Central calcification is present in 35-60% of tumors. Hemorrhage and necrosis are uncommon.

Microscopic findings: Microscropically, fibrolamellar carcinomas have a characteristic pattern of nests, sheets, or cords of malignant cells, which are separated by lamellar bands of dense, hypocellular, collagen connective tissue. The fibrotic connective tissue coalesces into the central scar. The malignant cells are usually well-differentiated polygonal cells with granular cytoplasm, large nuclei, and prominent nucleoli. 

Metastatic lesions appear histopathologically similar to the primary tumors. The internal architecture of fibrolamellar carcinomas may be heterogeneous, and foci of focal nodular hyperplasia (FNH) may occur in the liver adjacent to the tumors. For accurate diagnosis at percutaneous biopsy, the acquisition of multiple core specimens is recommended to avoid misdiagnosis resulting from sampling error.

Staging:  Tumors may be graded histologically according to the Broders method, as follows:
                               In grade 1 tumors, 75-100% of the tumor cells are well differentiated. 
                               In grade 2 tumors, 50-75% are well differentiated.
                               In grade 3 tumors, 25-50% are well differentiated. 
                               In grade 4 tumors, 0-25% of the tumor cells are well differentiated.
See also Staging.

Frequency: In the US: HCC is the most common primary malignancy of the liver and accounts for
approximately 2-3% of all cancers in the United States. Fibrolamellar carcinoma accounts for fewer than 10% of all cases of HCC but approximately 35% of the cases of HCC in patients younger than 50 years without cirrhosis. Internationally: Usual HCC is more common in Asia than in the United States, and it accounts for as many as 40% of all cancer cases in endemic areas. However, the prevalence of fibrolamellar carcinoma in Asia is lower than that in the United States.
 
Mortality/Morbidity: In patients with fibrolamellar carcinoma, reported 5-year survival rates are approximately 25-30% if all patients are included. However, the rates increase to as high as 63% in patients in whom tumors are resected.

Long-term survival as long as 14 years is reported.

Although the postoperative recurrence of fibrolamellar carcinoma is high, ranging from 42-100% in reported series, aggressive surgical management, including resection of recurrent and metastatic disease, is reported to improve survival rates and disease-free intervals.

Anatomy: Fibrolamellar carcinoma may occur anywhere in the liver. Anatomically, the liver is composed of right, left, and caudate lobes. It can be further divided into 8 surgical subsegments based on the locations of the major portal and hepatic venous structures. Attention to the location and extent of fibrolamellar tumors with respect to the surgical anatomy is important, because tumor resection is recommended in most patients. Metastatic tumoral involvement is most common in the regional lymph nodes of the porta hepatis or celiac axis. Distant metastases to the lungs, paraspinal tissues, and supraclavicular lymph nodes are reported. Clinical

Details: Presentation Patients with fibrolamellar carcinoma may present with abdominal pain, a palpable abdominal mass, hepatomegaly, or cachexia. Jaundice is not common. Serum alpha-fetoprotein levels are within the reference range or mildly elevated. Liver function test results may be elevated. Patients typically do not have hepatitis or cirrhosis. CT findings usually suggest the diagnosis.

Staging: Fibrolamellar carcinoma is usually advanced at the time of initial diagnosis. Primary tumors are large, with reported mean diameter of 10-20 cm. Extrahepatic disease, most often in regional lymph nodes, is present in as many as 80% of patients at the time of initial diagnosis. Portal or hepatic venous invasion may occur, but it is not common. Diffuse intraperitoneal carcinomatosis has been reported. Distant metastases are typically not found at the time of presentation.

Recurrence and follow-up: Fibrolamellar carcinoma is an aggressive tumor that progresses to recurrent liver masses and metastatic lymph node metastases in most patients. Recurrent lesions often develop 6-18 months after attempted curative resection and may progress rapidly; therefore, follow-up imaging is recommended at 2- to 4-month intervals for at least 12-18 months after resection of the primary tumor. The early detection of metastatic disease is important because surgical resection of metastases improves patient survival rates.