Fibrolamellar hepatocellular carcinoma

Diagnosis

Fibrolamellar hepatocellular carcinoma

History

13 year-old girl with abdominal mass, inappetence and weight loss

Findings

Large liver mass located in the right lobe and measuring 10,8 x 8.4 x 9.5 cm. SUV max of 2.4. SUVmax in 1.9 in the left lobe of the liver. Multiples lymph nodes in the hepatic hilum, retroperitoneal region and cardiophrenic region with SUVmax ranging from 1.6 to 2.6.

DDx

Hepatoblastoma

Focal Nodular Hyperplasia

Adenoma

Hepatocellular  carcinoma

Mesenchymal hamartoma

Discussion

In children, 1 to 2% of tumors  involve the liver. Half of them are hepatoblastoma and a quarter hepatocellular carcinoma (HCC). Fibrolamellar hepatocellular carcinoma (FLHCC)  is a rare subtype of hepatocarcinoma occuring in young patients without preexisting liver disease. The vast majority of patients with FLHCC are 35 year-old and younger. Initially thought to be mostly in females, it is equally frequent in both sexes.

α-fetoprotein is usually normal with abnormal levels in only 7-11% of patients. Differential diagnosis includes benign lesions of the liver and fibrosis producing metastases ( breast, thyroid) and in children hepatoblastoma and mesenchymal hamartoma.

Cytogenetic characters of FLHCC are also different from the classical hepatocarcinoma (CHCC) . It presents itself as a large mass, with a central scar and abundant fibrous tissue. Lamellar denomination is due to the presence of thin layers of fibrous stroma around regions of polygonal tumor cells. FLHCC tumor cells are 3 times the size of a normal hepatocyte with large nucleoli and eosinophilic cytoplasm. Cells are positive for Hepar and CD99.Overexpression of the potential oncogene anterior gradient-2 has been found in 75% of FLHCC but is  extremely rare in CHCC

Clinical findings are abdominal pain and mass, weight loss and rarely jaundice. Nodal metastases are present in 50-65% of cases and distant metastases mostly to lung in 20-30%. Metastatic localisations include the lung, ovaries, pericardium and bone. FLHCC can be associated with amyloid depositions in organs.

Treatment is surgical resection with lymph node dissection. Following surgery, survival at 5 years is 70% versus < 40% for classical hepatocellular carcinoma. No effective chemotherapy is avalaible.Some patients may respond to the combination of 5-fluorouracil and α-2b interferon or intra-arterial lipiodolized doxorubicin.

It has been shown that F18-FDG uptake in all forms of hepatocellular carcinoma is proportional to grade. As well- differentiated tumor exhibits characteristics similar to normal hepatocytes, low F18-FDG activity in  those  lesions is secondary to  lower Glut-1 and  hexokinase II activity  levels  and the presence of Glu-6-phosphatase. Furthermore, SUVmax do not increase significantly with time in HCC in opposition with metastases.

Sensitivity  for primary HCC varies between 30 and 70% and is size dependant ( 27% pour lesions 1 to 2 cm, 48% for lesions 2 to 5 cm and 93% for lesions more than 5 cm). Global sensitivity for the detection of HCC metastases is around 85%  and FDG PET/CT is more effective for the detection of bone lesions than lung lesions. In some patients, uptake by metastasis is higher than the one of the primary tumor but the exact mechanism of this discordance has not yet  been  clarified.

Upon revising the litterature, only eight  FLHCC patients imaged with F18-FDG were found, with the majority demonstrating mild to moderate uptake in the primary lesion and metastasis. In only one or two, management seemed to have affected by PET/CT findings.

References

Bassan et al : A review of 218 pediatric cases of hepatocellular carcinoma. J Ped Surg 2014;49:166-171

Okazumie et al : Evaluation of Liver Tumors Using fluorine- 18- Fluorodeoxyglucose PET: Characterization of Tumor and Assessment of Effect of Treatment . J Nucl Med 1992;33:333-339

Blechacz et al:  Positron Emission Tomography Scan for a Hepatic Mass. Hepatology 2010;56:2186-2191

Tsurusaki et al: Clinical application of 18F-fluorodeoxyglucose positron emission tomography for assessment and evaluation after therapy for malignant hepatic tumor. J Gastroenterol 2014;49:46-59

Lee et al: Primary Cancer of the Liver and Biliary Duct. PET Clinics 2008;3:169-186

Zhao et al: Biologic Correlates of Intratumoral Heterogeneity in 18F-FDG Distribution with Regional Expression of Glucose Transporters and Hexokinase-II in Experimental Tumor.  J Nucl Med 2005;46:675-682

Imaging Techniques for the Diagnosis and Staging of Hepatocellular Carcinoma. Effective Health Care Program. Comparative review number 143. Agency for Healthcare Research and Quality 2014

Lee et al: Diagnostic value for extrahepatic metastases of hepatocellular carcinoma in positron emission tomography/computed tomography scan. World J Gastroenterol 2012; 18: 2979-2987

Ganeshan et al: Imaging Features of Fibrolamellar Hepatocellular Carcinoma. AJR 2014;202:544-552

Liu et al: Fibrolamellar Hepatocellular Carcinoma.Am J Gastroenterol 2009;104:2617-2624 

Von Falck et al: F-18 FDG PET Imaging of Fibrolamellar Hepatocellular. Clin Nucl Med 2008;33:633-634

Maniaci et al: Fibrolamellar hepatocellular carcinoma: Prolonged survival with multimodality therapy. ESJO Journal of Cancer Surgery 2009;35:617-621

Liu et al: PET–CT scan is a valuable modality in the diagnosis of fibro lamellar hepatocellular carcinoma: a case report and a summary of recent literature. S Liu, K Wah Chan, T Tong, J Tong, Y Wang, B Wang, L Qia Q J Med 2011;104:477-483

Butte et al: Carcinoma hepatocelular variedad fibrolamelar metastásico en menores de 20 años. Reporte de 2 casos tratados con intención curativa y revisión de la literatura. Rev Med Chile 2009;137:394-400