Fibrolamellar hepatocellular carcinoma (FL-HCC) is a liver cancer that is different in its clinical features from conventional hepatocellular carcinoma (HCC). A nearly negligible amount of liver cancers are attributed to FL-HCC. FL-HCC affects patients from a different and lower demographic age than HCC. Prompt initiation of treatment is of utmost importance since it can have a positive impact on patient outcomes. This article aims at reviewing the salient clinical and imaging features of FL-HCC, in contrast to HCC.
Patients most commonly present in their second or third decade. In contrast, patients with HCC are often in their sixth decade. Fibrolamellar hepatocellular carcinoma is approximately 100 times less common than conventional HCC and demonstrates no gender preference like HCC, which is more common in men. More than 80% of patients affected by FL-HCC are White.
These tumors are often large at presentation, measuring greater than 10 cm. On histopathological examination, these tumors demonstrate vascular invasion and have a positive surgical margin in about one-third of patients. Almost half of these patients demonstrate locoregional disease in the abdomen outside the liver. These tumors are usually large and single, with well-demarcated borders and features of rapid growth outgrowing their blood supply. These masses can also have a central scar.
On microscopic examination, these tumors have large cells with eosinophilic cytoplasm, large nuclei and features of lamellated fibrous tissue distributed between sheets of malignant cells.
Patients with fibrolamellar hepatocellular carcinoma present with nonspecific signs and symptoms. These may vary from a patient with no symptoms with an abdominal mass detected during the evaluation of some other clinical condition to a patient who presents with abdominal discomfort or a palpable mass. Cachectic symptoms seen with other liver malignancies are not seen often.
Serum tumor markers are not commonly elevated in these patients when evaluating patients with FL-HCC. In contrast to conventional HCC, serum alpha-fetoprotein is elevated in less than one-tenth of the patients.
Due to the uncommon nature of fibrolamellar hepatocellular carcinoma and varied presentation, radiological evaluation plays an important role in the management of these patients and can include ultrasonography (US), Computed Tomography (CT) and magnetic resonance imaging (MRI).
Sonographic features include a single, large, lobulated tumor of varied echogenicity. The central scar described above is not readily demonstrated on ultrasound but, if seen, can demonstrate increased echogenicity.
On CT, these masses are seen as a single, large tumor with well-demarcated margins in more than two-thirds of the patients. These tumors, more often than not, demonstrate decreased attenuation characteristics in reference to the surrounding liver parenchyma, with more than two-thirds of patients showing a calcified central stellate scar. Liver protocol CT examinations are usually acquired in 3 distinct phases performed in specific time intervals to highlight tumor and liver parenchymal characteristics in the early arterial, portal venous, and delayed phases. In the arterial phase, most of these tumors enhance more than the surrounding liver with attenuation characteristics similar to the liver on portal venous and delayed phases reflecting the vascular nature of this tumor. If present, the central scar shows delayed enhancement secondary to the fibrous nature of the tissue.
On magnetic resonance imaging, these masses demonstrate decreased signal on T1 weighted sequences more commonly in contrast to the surrounding liver parenchymal signal characteristics with increased T2-signal and restricted diffusion. The central scar of these tumors demonstrates a signal in keeping with the fibrous tissue described above with hypointense T1 and T2 signal and delayed enhancement. The enhancement characteristics following contrast administration follow the pattern described above with increased arterial enhancement.
Radiological evaluation is crucial in detecting additional locoregional and distant disease, which is not apparent clinically.
The goal of primary treatment in fibrolamellar hepatocellular carcinoma is a cure, which can significantly impact the outcome, especially in patients who have surgical treatment with complete removal of the tumor. A good portion of these patients have locoregional disease at diagnosis, and surgical treatment of these disease sites is often undertaken along with primary tumor resection, which has been shown to improve the outcome in these patients. Since these tumors grow rapidly and tend to spread to adjacent disease sites, the chances of incomplete resection, second surgical intervention, and liver transplant are high, which in turn increases the associated mortality and morbidity.
Chemotherapy before and/or after definitive treatment improves outcomes. Treatment with agents like gemcitabine, cisplatin, fluorouracil, and oxaliplatin can be utilized with good treatment response. There is an improved overall prognosis and outcome with a combined treatment approach involving surgery, chemotherapy, and radiation. Decreasing the size of the tumor prior to surgical resection through radioembolization has been achieved.
Focal nodular hyperplasia, large cavernous hemangioma, and conventional HCC are diagnoses that have to be considered when evaluating a tumor with characteristics described above. Focal nodular hyperplasia follows attenuation characteristics of the surrounding liver on portal venous and delayed phase imaging with increased contrast enhancement on the arterial phase. The central scar in these tumors do not show calcification and have hyperintense T2-signal attributed to biliary ductules when imaged with MRI.
Although cavernous hemangiomas can have similar imaging features, they have distinctive enhancement features, which are early peripheral and nodular enhancement with subsequent central filling.
Conventional HCC, on the other hand, demonstrates early arterial phase enhancement with subsequent washout. Background liver fibrotic changes are often demonstrated.
The surgical treatment of this condition includes preoperative radioembolization, wedge resection, anatomic liver resection, or total hepatectomy with orthotopic liver transplantation.
Complete surgical removal of fibrolamellar hepatocellular carcinoma is associated with a higher survival rate. As expected, microvascular invasion and positive locoregional or distant disease have a negative impact on the outcome. Rarely patients can have a combined FL-HCC and conventional HCC pattern of disease, which has a poor outcome. Overall, patients with FL-HCC do better than those with conventional HCC. There is a statistically significant better prognosis in patients with FL-HCC than patients with conventional HCC in cirrhotic patients as opposed to patients with noncirrhotic livers and conventional HCC. Patients with localized disease did better than patients with extrahepatic disease. Surgical resection of metastases and combined treatment using different modalities have a positive impact on treatment.
Considering the patient demographics, the aggressive behavior of the disease and technically difficult surgical management of these patients, complications and associated comorbidities are very common and should be anticipated for prompt care.
Patient education on the risks of this disease is essential as there is a high rate of recurrence.
Studies have shown a statistically significant better outcome if patients are managed by an interprofessional team well versed in managing complicated oncology patients with an evidence-based approach in a higher level care center with facilities and resources that can handle prompt and timely management of these patients.
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