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Fibrolamellar Hepatocellular Carcinoma: A Population-Based Observational Study

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Abstract

Background

In the USA, fibrolamellar hepatocellular carcinoma (FLC) accounts for 1–2% of all cases of hepatocellular carcinoma. FLC remains poorly understood.

Aim

We aim to investigate the incidence, demographics, tumor characteristics, treatment, and prognosis of patients with FLC.

Methods

Data on FLC between 2000 and 2016 were extracted from the SEER database and analyzed.

Results

A total of 300 patients with FLC were identified where 126 were male. Median age at diagnosis was 27 ± 22 years. The overall age-adjusted incidence of FLC between 2000 and 2016 was 0.02 per 100,000 per year. A bimodal distribution was observed where the highest incidences occurred between 15–19 years and 70–74 years. Most tumors on presentation were moderately differentiated (20.7%), while the most common stage at presentation was stage 1 (21.7%) followed by stages 3 and 4 (20.0% and 20.3%, respectively); 50.3% of these tumors were surgically resected, while 8.0% received radiation and 45.3% received chemotherapy. One- and 5-year cause-specific survival for FLC was 72.0% and 32.9%, respectively, with a median survival of 32.9 months. HCC had a median survival time of 11.7 months. Patients who were not treated with surgical intervention had about 3 times increased risk for death (HR 2.8, 95% CI 1.68–4.72, P = 0.000). Radiation and chemotherapy did not significantly affect outcomes.

Conclusion

FLC presents with a bimodal distribution in both early and elderly individuals. Compared to HCC, FLC has a higher recurrence rate but better survival outcome. Surgical intervention is superior to chemotherapy and radiation.

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References

  1. El-Serag HB, Davila JA. Is fibrolamellar carcinoma different from hepatocellular carcinoma? A US population-based study. Hepatology. 2004;39:798–803.

    Article  Google Scholar 

  2. Ross HM, Daniel HDJ, Vivekanandan P, et al. Fibrolamellar carcinomas are positive for CD68. Mod Pathol. 2011;24:390–395.

    Article  CAS  Google Scholar 

  3. Farber BA, Lalazar G, Simon EP, et al. Non coding RNA analysis in fibrolamellar hepatocellular carcinoma. Oncotarget. 2018;9:10211–10227.

    Article  Google Scholar 

  4. Lim I, Farber B, LaQuaglia M. Advances in Fibrolamellar Hepatocellular Carcinoma: A Review. Eur J Pediatr Surg. 2014;24:461–466.

    Article  Google Scholar 

  5. Graham RP, Yeh MM, Lam-Himlin D, et al. Molecular testing for the clinical diagnosis of fibrolamellar carcinoma. Mod Pathol. 2018;31:141–149.

    Article  CAS  Google Scholar 

  6. Graham RP, Jin L, Knutson DL, et al. DNAJB1-PRKACA is specific for fibrolamellar carcinoma. Mod Pathol. 2015;28:822–829.

    Article  CAS  Google Scholar 

  7. Stipa F, Yoon SS, Liau KH, et al. Outcome of patients with fibrolamellar hepatocellular carcinoma. Cancer. 2006;106:1331–1338.

    Article  Google Scholar 

  8. Maniaci V, Davidson BR, Rolles K, et al. Fibrolamellar hepatocellular carcinoma—prolonged survival with multimodality therapy. Eur J Surg Oncol. 2009;35:617–621.

    Article  CAS  Google Scholar 

  9. Yamashita S, Vauthey J-N, Kaseb AO, et al. Prognosis of fibrolamellar carcinoma compared to non-cirrhotic conventional hepatocellular carcinoma. J Gastrointest Surg. 2016;20:1725–1731.

    Article  Google Scholar 

  10. Chakrabarti S, Tella SH, Kommalapati A, et al. Clinicopathological features and outcomes of fibrolamellar hepatocellular carcinoma. J Gastrointest Oncol. 2019;10:554–561.

    Article  Google Scholar 

  11. Eggert T, McGlynn KA, Duffy A, et al. Fibrolamellar hepatocellular carcinoma in the USA, 2000-2010: A detailed report on frequency, treatment and outcome based on the surveillance, epidemiology, and end results database. United Eur Gastroenterol J. 2013;1:351–357.

    Article  Google Scholar 

  12. Jernigan PL, Wima K, Hanseman DJ, et al. Natural history and treatment trends in hepatocellular carcinoma subtypes: Insights from a national cancer registry. J Surg Oncol. 2015;112:872–876.

    Article  Google Scholar 

  13. Mayo SC, Mavros MN, Nathan H, et al. Treatment and prognosis of patients with fibrolamellar hepatocellular carcinoma: A national perspective. J Am Coll Surg. 2014;218:196–205.

    Article  Google Scholar 

  14. Malouf GG, Brugières L, Le Deley M-C, et al. Pure and mixed fibrolamellar hepatocellular carcinomas differ in natural history and prognosis after complete surgical resection. Cancer. 2012;118:4981–4990.

    Article  Google Scholar 

  15. Katzenstein HM, Krailo MD, Malogolowkin MH, et al. Fibrolamellar hepatocellular carcinoma in children and adolescents. Cancer. 2003;97(8):2006–2012.

    Article  Google Scholar 

  16. SEER Registries - About SEER [Internet]. [cited 2019 Mar 8] Available from: https://seer.cancer.gov/registries/index.html.

  17. Glossary of Statistical Terms [Internet]. [cited 2019 Mar 8] Available from: https://seer.cancer.gov/cgi-bin/glossary/glossary.pl.

  18. Wahab MA, El Hanafy E, El Nakeeb A, et al. Clinicopathological features and surgical outcome of patients with fibrolamellar hepatocellular carcinoma (experience with 22 patients over a 15-year period). World J Gastrointest Surg. 2017;9:61.

    Article  Google Scholar 

  19. Herman P, Chagas AL, Perini MV, et al. Surgical treatment of fibrolamellar hepatocellular carcinoma: An underestimated malignant tumor? Hepatobiliary Pancreat. Dis. Int. 2014;13:618–621.

    Article  Google Scholar 

  20. Kakar S, Burgart LJ, Batts KP, et al. Clinicopathologic features and survival in fibrolamellar carcinoma: Comparison with conventional hepatocellular carcinoma with and without cirrhosis. Mod Pathol. 2005;18:1417–1423.

    Article  Google Scholar 

  21. El–Serag HB, Rudolph KL. Hepatocellular carcinoma: Epidemiology and molecular carcinogenesis. Gastroenterology. 2007;132:2557–2576.

    Article  Google Scholar 

  22. Llovet JM, Burroughs A, Bruix J. Hepatocellular carcinoma. Lancet. 2003;362:1907–1917.

    Article  Google Scholar 

  23. Kassahun WT. Contemporary management of fibrolamellar hepatocellular carcinoma: Diagnosis, treatment, outcome, prognostic factors, and recent developments. World J Surg Oncol. 2016;14:151.

    Article  Google Scholar 

  24. Moreno-Luna LE, Arrieta O, García-Leiva J, et al. Clinical and pathologic factors associated with survival in young adult patients with fibrolamellar hepatocarcinoma. BMC Cancer. 2005;5:142.

    Article  Google Scholar 

  25. Berman MA, Burnham JA, Sheahan DG. Fibrolamellar carcinoma of the liver: An immunohistochemical study of nineteen cases and a review of the literature. Hum Pathol. 1988;19:784–794.

    Article  CAS  Google Scholar 

  26. Khan AS, Hussain HK, Johnson TD, et al. Value of delayed hypointensity and delayed enhancing rim in magnetic resonance imaging diagnosis of small hepatocellular carcinoma in the cirrhotic liver. J Magn Reson Imaging. 2010;32:360–366.

    Article  Google Scholar 

  27. Lo EC, Rucker AN, Federle MP. Hepatocellular carcinoma and intrahepatic cholangiocarcinoma: Imaging for diagnosis, tumor response to treatment and liver response to radiation. Semin Radiat Oncol. 2018;28:267–276.

    Article  Google Scholar 

  28. Do RKG, McErlean A, Ang CS, et al. CT and MRI of primary and metastatic fibrolamellar carcinoma: a case series of 37 patients. Br J Radiol. 2014;87:20140024.

    Article  CAS  Google Scholar 

  29. Kaseb AO, Shama M, Sahin IH, et al. Prognostic indicators and treatment outcome in 94 cases of fibrolamellar hepatocellular carcinoma. Oncology. 2013;85:197–203.

    Article  CAS  Google Scholar 

  30. Njei B, Rotman Y, Ditah I, et al. Emerging trends in hepatocellular carcinoma incidence and mortality. Hepatology. 2015;61:191–199.

    Article  Google Scholar 

  31. Njei B, Konjeti VR, Ditah I. Prognosis of patients with fibrolamellar hepatocellular carcinoma versus conventional hepatocellular carcinoma: A systematic review and meta-analysis. Gastrointest Cancer Res. 2014;7:49–54.

    PubMed  PubMed Central  Google Scholar 

  32. Grandhi MS, Pawlik TM. Managing fibrolamellar hepatocellular carcinoma. Expert Opin Orphan Drugs. 2017;5:143–152.

    Article  CAS  Google Scholar 

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Authors and Affiliations

  1. Department of Medicine, The Brooklyn Hospital Center, Clinical Affiliate of The Mount Sinai Hospital, Brooklyn, NY, 11201, USA

    Daryl Ramai

  2. Division of Gastroenterology and Hepatology, The Brooklyn Hospital Center, Clinical Affiliate of The Mount Sinai Hospital, Brooklyn, NY, 11201, USA

    Andrew Ofosu

  3. Department of Pathology, McGill University, Montreal, QC, Canada

    Jonathan K. Lai & Zu-Hua Gao

  4. Division of Gastroenterology and Hepatology, Huntsman Cancer Center, University of Utah School of Medicine, Salt Lake City, UT, USA

    Douglas G. Adler

Authors
  1. Daryl Ramai
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  2. Andrew Ofosu
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  4. Zu-Hua Gao
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Contributions

DR conceived the study and conducted data analysis; DR, JL, and AO interpreted the data and drafted the manuscript. ZHG provided histology. DA and ZHG revised the manuscript for intellectual content. All authors approved the final version of the manuscript.

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Correspondence to Douglas G. Adler.

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Ramai, D., Ofosu, A., Lai, J.K. et al. Fibrolamellar Hepatocellular Carcinoma: A Population-Based Observational Study. Dig Dis Sci 66, 308–314 (2021). https://doi.org/10.1007/s10620-020-06135-3

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  • DOI: https://doi.org/10.1007/s10620-020-06135-3

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