Fibrolamellar hepatocellular carcinoma is a rare primary malignant liver neoplasm. Benefits from liver transplant for patients with fibrolamellar hepa­tocellular carcinoma have not yet been reported. Here, we report a 19-year-old female patient who presented with abdominal pain. A computed tomography scan revealed bilobar and multiple solid lesions with the largest measuring 15 cm in diameter on the right lobe of her liver. Her blood alpha-fetoprotein level and viral hepatitis markers were normal. A fine-needle biopsy of the largest lesion detected fibrolamellar hepto­cellular carcinoma. Because no distant metastasis was evident and the carcinoma was unresectable, a right lobe living-donor liver transplant with hilar lymph node dissection was performed. A pathology report revealed poorly differentiated fibrolamellar hepato­cellular carcinoma, and further testing indi­cated microvascular invasion and hilar lymph node metastasis. The largest tumor measured 12 cm. She was discharged on postoperative day 14. During postoperative month 22, multiple vertebral meta­stases were detected, and she died with diffuse metastasis during postoperative month 26. Our patient, with poor prognostic criteria such as hilar lymph node metastasis, microvascular invasion, and poor differentiation, had 22 months of tumor-free survival and 26 months of overall survival after having undergone living-donor liver transplant.

Key words : Liver neoplasm, Microvascular invasion, Unresectable metastasis

Introduction

Fibrolamellar hepatocellular carcinoma (FL-HCC) is a rare primary malignant liver neoplasm that occurs predominantly in adolescents and young adults, with no predisposing liver disease. Although hepatic resection is the best treatment option for this disease, patients with tumors in cirrhotic livers or unresectable tumors in noncirrhotic livers are good candidates for liver transplant. Although liver transplant has been reported for some such case presentations, identifying patients who could benefit from this treatment modality has not been accomplished. Liver transplant for patients with hilar lymph node metastasis has also not been reported. Here, we report a patient who was treated with liver transplant after being diagnosed with both FL-HCC and hilar lymph node metastasis.

Case Report

A 19-year-old female patient presented with abdominal pain and was discovered, by computed tomography scanning, to have bilobar and multiple solid liver lesions, with the largest measuring 15 cm in diameter on the right lobe. Her blood alpha-fetoprotein level (1.9 IU/mL) and viral hepatitis markers were within normal ranges. A fine-needle biopsy of the largest lesion detected FL-HCC tumor cells containing fibrous septa with large eosinophilic cytoplasm and pleomorphic nuclei. She was found to have unresectable FL-HCC with no distant metastasis, and so a living-donor liver transplant (LDLT) was planned for her treatment. The patient's cousin was determined to be donor-recipient compatible and provided the donor liver.

A hilar lymph node, measuring 5 cm in diameter, was explored during surgery. Right lobe LDLT with hilar lymph node dissection was performed. The pathology report revealed poorly differentiated multiple FL-HCC, with the largest tumor measuring 12 cm. Microvascular invasion and 7 metastatic hilar lymph nodes, with the largest measuring 5 cm, were present. The recipient and the donor were discharged on postoperative day 14 and day 7, respectively.

Multiple vertebral metastases were diagnosed during postoperative month 22. Sorafenib treatment was planned, but the patient refused further treatment. Retroperitoneal metastatic mass and splenic metastasis were detected in the patient during postoperative month 24, and the patient died 26 months after LDLT.

Discussion

Unlike hepatocellular carcinoma, FL-HCC is a rare condition, with not well-known causes. At our center during 2006 to 2016, we performed 260 liver transplant procedures for hepatocellular carcinoma patients, and only 1 patient (0.4% of this group) was diagnosed with FL-HCC. Generally, FL-HCC progresses slowly with nonspecific symptoms and is not associated with underlying liver disease. Surveying our FL-HCC patients, only 3% had a cirrhotic liver, just 1% to 2% were infected with hepatitis B virus or hepatitis C virus, and merely 10% had abnormal alpha-fetoprotein levels. The FL-HCC tumors are visualized as hypervascular, well-circumscribed masses with a central scar visible on contrast-enhanced computed tomography scanning or magnetic resonance imaging. All of the aforementioned typical findings were also present in our patient, as well as hilar lymph node metastasis. Lymph node metastasis is a poor prognostic marker for FL-HCC patients receiving either resection or liver transplant.^1,2

The most effective treatment for FL-HCC is hepatic resection together with hilar lymph node dissection. Surgical resection is the most effective choice of treatment for FL-HCC, and this is true even for such cases with recurrent disease.2-4 One-, 3-, and 5-year overall survival rates after liver transplant were reported to be 86% to 96%, 42% to 80%, and 34% to 48%, respectively.^1,5,6 Liver transplant is the recommended treatment option for unresectable tumors. Liver transplant can be performed to increase the survival rate of these typically young patients without underlying liver disease for cases that present with chemotherapy-resistant tumors, involving either portal vein or lymph node metastasis.^5,6

Most studies regarding FL-HCC have excluded cases with co-occurring hilar lymph node metastasis. In a similar study that reported the survival outcomes of 3 FL-HCC patients with hilar lymph node metastasis, 2 patients developed recurrence after an average of 8 months, and these patients had a median survival of 26 months.6 Similarly, our patient, with hilar lymph node metastasis, had an overall survival of 26 months after LDLT.

Median survival for unresectable FL-HCC is reported to be 12 months, whereas, for FL-HCC with lymph node metastasis, 26 months of median survival can be achieved by liver transplant.²

Conclusions

A 19-year-old FL-HCC patient with poor prognostic markers, including hilar lymph node metastasis, microvascular invasion, and poor differentiation, survived for 22 months tumor free and for 26 months overall after LDLT.

References:

1. Mavros MN, Mayo SC, Hyder O, Pawlik TM. A systematic review: treatment and prognosis of patients with fibrolamellar hepatocellular carcinoma. J Am Coll Surg. 2012;215(6):820-830.
   CrossRef - PubMed
   
2. Stipa F, Yoon SS, Liau KH, et al. Outcome of patients with fibrolamellar hepatocellular carcinoma. Cancer. 2006;106(6):1331-1338.
   CrossRef - PubMed
   
3. Nguyen BD. Education and imaging. Hepatobiliary and Pancreatic: Post-transplant recurrence of fibrolamellar hepatocellular carcinoma in lung and pancreas.. J Gastroenterol Hepatol. 2016;31(2):286.
   CrossRef - PubMed
   
4. Wojcicki M, Lubikowski J, Post M, Chmurowicz T, Wiechowska-Kozlowska A, Krawczyk M. Aggressive surgical management of recurrent lymph node and pancreatic head metastases of resected fibrolamellar hepatocellular carcinoma: a case report. JOP. 2012;13(5):529-532.
   CrossRef - PubMed
   
5. Atienza LG, Berger J, Mei X, et al. Liver transplantation for fibrolamellar hepatocellular carcinoma: A national perspective. J Surg Oncol. 2017;115(3):319-323.
   CrossRef - PubMed
   
6. El-Gazzaz G, Wong W, El-Hadary MK, et al. Outcome of liver resection and transplantation for fibrolamellar hepatocellular carcinoma. Transpl Int. 2000;13(Suppl 1):S406-S409.
   CrossRef - PubMed