eMedicine Specialties > Radiology > Gastrointestinal
Hepatocellular Carcinoma, Fibrolamellar
Updated: Aug 22, 2007
Introduction
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). Fibrolamellar carcinoma occurs in a younger population than does HCC, and it is typically not associated with underlying liver disease or elevated serum levels of alpha-fetoprotein tumor markers.1 Also, fibrolamellar carcinoma may have a slightly better prognosis than HCC.
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, of metastatic disease, and even of recurrent disease can extend patient survival. Radiographic evaluation of patients with fibrolamellar carcinoma may be used for the initial diagnosis of the tumor, for the preoperative staging of the disease, and for follow-up surveillance to detect recurrent or metastatic disease.
Pathophysiology
Gross findings
Fibrolamellar carcinoma most commonly presents as a large, solitary intrahepatic mass with well-defined margins and a lobulated contour. The tumors are typically large at the time of diagnosis, with a 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. Hemorrhage and necrosis are uncommon.
Central calcification is present in 35-60% of tumors and thus can be a useful diagnostic feature. However, fibrolamellar carcinomas are not the only liver tumors in which calcifications appear; calcifications may also be found in a minority of HCCs, as well as in some metastatic tumors, such as those arising from mucinous colon or ovarian carcinomas.
Microscopic findings
Microscopically, 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 containing granular cytoplasm, large nuclei, and prominent nucleoli.
Metastatic lesions appear to be 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 follows2 :
- In grade 1 tumors, 75-100% of the tumor cells are well differentiated.
- In grade 2 tumors, 50-75% of the tumor cells are well differentiated.
- In grade 3 tumors, 25-50% of the tumor cells are well differentiated.
- In grade 4 tumors, 0-25% of the tumor cells are well differentiated.
See also Clinical Details, Staging .
Frequency
United States
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 it accounts for approximately 35% of all cases of HCC in patients younger than 50 years who do not also have cirrhosis.
International
The more common form of HCC has a greater prevalence in Asia than in it does in the United States, accounting for as many as 40% of all cancer cases in endemic areas. However, the prevalence of fibrolamellar carcinoma in Asia is lower than it is in the United States.
Mortality/Morbidity
- In patients with fibrolamellar carcinoma, the 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 has been reported.
- Although the postoperative recurrence of fibrolamellar carcinoma is high, ranging from 42-100% in reported series, aggressive surgical management, including the resection of recurrent and metastatic disease, has been reported to improve survival rates and disease-free intervals.
Race
No racial predilection has been reported in fibrolamellar carcinoma.
Sex
No clear sex predilection has been reported in fibrolamellar carcinoma.
Age
Fibrolamellar carcinoma occurs primarily in young adults. Reported series indicate a patient age range of 5-69 years, with a mean age of 23 years at the time of initial diagnosis.
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 have been reported.
Presentation
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. Computed tomography (CT) scan findings usually suggest the diagnosis.
StagingFibrolamellar carcinoma is usually advanced at the time of initial diagnosis. Primary tumors are large, with a 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 in most patients progresses to recurrent liver masses and metastatic lymph node metastases. 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.
Preferred Examination
Abdominal CT scanning is the preferred examination for the detection, diagnosis, staging, and postoperative follow-up evaluation of fibrolamellar carcinoma.
Magnetic resonance imaging (MRI) of the liver can be useful in detecting and characterizing primary tumors, and MRI may be slightly more sensitive than CT scanning in detecting multiple intrahepatic recurrent lesions. However, MRI is less sensitive than CT scanning in the detection of extrahepatic disease.
Ultrasonography has been used in the surveillance of the progression of known intrahepatic lesions. Radionuclide sulfur-colloid scans or scans obtained with labeled red blood cells are occasionally useful in the differentiation of fibrolamellar carcinomas from other types of hepatic tumors. Percutaneous biopsy with CT scanning or ultrasonographic guidance may be necessary for a definitive preoperative diagnosis of fibrolamellar carcinoma.
Limitations of Techniques
For the best evaluation of the liver and liver tumors with CT scanning, the intravenous administration of iodinated contrast material is necessary. Therefore, the use of CT scanning is limited in patients who cannot have iodinated contrast material because of an allergy or renal insufficiency. In these patients, MRI is preferred. In addition, CT scanning uses ionizing radiation; therefore, it can be relatively contraindicated in children or in women of childbearing age, in whom radiation doses should be limited as much as possible.
The imaging time with MRI examinations tends to be longer than with CT scanning or ultrasonography. In patients who are unwilling or unable to remain still during the imaging period, poor-quality images can result because of motion artifact; these artifacts can limit the usefulness of the MRI examination. Some patients may become claustrophobic while they are in the MRI machine; patients may require sedation, or they may not be able to complete the examination. Because of the high magnetic field strength, MRI is contraindicated in patients with a cardiac pacemaker or some internal metallic object, such as an aneurysm clip or metal shrapnel or filings in a critical location.
Ultrasonography is more operator dependent than is CT scanning or MRI, and poor technique in scanning can limit its diagnostic usefulness. Ultrasonography may be limited by the patient's anatomy. Hepatic imaging may be difficult in obese patients or in patients whose liver is located high under the ribs. Overlying bowel gas may obscure portions of the liver in some patients.
Differential Diagnoses
Focal Nodular Hyperplasia
Hepatic Adenoma
Hepatocellular Carcinoma
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Further Reading
Keywords
HCC, fibrolamellar carcinoma, fibrolamellar hepatoma, oncocytic hepatocellular carcinoma
