Fibrolamellar Carcinoma with DNAJB1-PRKACA Fusion in a 16-Year-Old: Case Report and Review of Literature
Main Article Content
Keywords
DNAJB1-PRKACA fusion, fibrolamellar carcinoma, hepatocellular carcinoma, mixed fibrolamellar hepatocellular carcinoma, PRKACA rearrangement
Abstract
Fibrolamellar hepatocellular carcinoma (FLC) is a unique primary liver malignancy arising in noncirrhotic livers of young adults with an incidence of 0.02 per 100,000 in the USA (1). In the 5th edition of the WHO classification of the digestive system tumors published in 2019, fibrolamellar carcinoma is categorized as a subset of hepatocellular carcinoma (HCC). In 2014, the unique DNAJB1-PRKACA chimeric fusion protein was identified. Later studies proved this chimeric fusion protein as the main pathological driver in the disease manifestation of fibrolamellar carcinoma. Despite the invention of specific molecular genetic alteration in FLC, its oncogenic role and implication in FLC treatment remain an enigma. Surgical resection remains the primary therapeutic option, and the recurrence rate is extremely high (1). We present a case of fibrolamellar carcinoma in a pediatric patient with the PRKACA rearrangement resulting in DNAJB1-PRKACA fusion.
References
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14. Vyas M, Hechtman JF, Zhang Y, et al. DNAJB1-PRKACA fusions occur in oncocytic pancreatic and biliary neoplasms and are not specific for fibrolamellar hepatocellular carcinoma. Mod Pathol. 2020;33:648–56. 10.1038/s41379-019-0398-2
15. Graham RP, Lackner C, Terracciano L, González-Cantú Y, Maleszewski JJ, Greipp PT, et al. Fibrolamellar carcinoma in the Carney complex: PRKAR1A loss instead of the classic DNAJB1-PRKACA fusion. Hepatology. 2018 Oct;68(4):1441–7. 10.1002/hep.29719
16. Kakar S, Chen X, Ho C, Burgart LJ, Sahai V, Dachrut S, et al. Chromosomal changes in fibrolamellar hepatocellular carcinoma detected by array comparative genomic hybridization. Mod Pathol. 2009 Jan;22(1):134–41. 10.1038/modpathol.2008.178
17. Lee JH, Choi MS, Gwak GY, et al. Clinicopathologic characteristics and long-term prognosis of scirrhous hepatocellular carcinoma. Dig Dis Sci. 2012;57:1698–707. 10.1007/s10620-012-2075-x
18. Kim YJ, Rhee H, Yoo JE, et al. Tumour epithelial and stromal characteristics of hepatocellular carcinomas with abundant fibrous stroma: Fibrolamellar versus scirrhous hepatocellular carcinoma. Histopathology. 2017;71:217–26. 10.1111/his.13219
19. Matsuura S, Aishima S, Taguchi K, et al. “Scirrhous” type hepatocellular carcinomas: A special reference to expression of cytokeratin 7 and hepatocyte paraffin 1. Histopathology. 2005;47:382–90. 10.1111/j.1365-2559.2005.02230.x
20. Limaiem F, Bouraoui S. Mixed fibrolamellar hepatocellular carcinoma. Clin Case Rep. 2021 Jun 24;9(6):e04318. 10.1002/ccr3.4318
21. Hirsch TZ, Negulescu A, Gupta B, Caruso S, Noblet B, Couchy G, et al. BAP1 mutations define a homogeneous subgroup of hepatocellular carcinoma with fibrolamellar-like features and activated PKA. J Hepatol. 2020 May;72(5):924–36. 10.1016/j.jhep.2019.12.006. Erratum In: J Hepatol. 2020 Jul;73(1):225–226.
22. Uka K, Aikata H, Takaki S, Shirakawa H, Jeong SC, Yamashina K, et al. Clinical feature and prognosis of patients with extrahepatic metastases from hepatocellular carcinoma. World J Gastroenterol. 2007;13:414–20. 10.3748/wjg.v13.i3.414
23. Liu S, Chan KW, Wang B, Qiao L. Fibrolamellar hepatocellular carcinoma. Am J Gastroenterol. 2009;104(10):2617–24. 10.1038/ajg.2009.440
24. Polychronidis G, Feng J, Murtha-Lemekhova A, Heger U, Mehrabi A, Hoffmann K. Factors influencing overall survival for patients with fibrolamellar hepatocellular carcinoma: Analysis of the surveillance, epidemiology, and end results database. Int J Gen Med. 2022 Jan 8;15:393–406. 10.2147/IJGM.S338066
25. Mroz RM, Korniluk M, Swidzinska E, Dzieciol J, Czaban J, Panek B, et al. Lung mass in a 28-year-old male: A case report of a rare tumor. Eur J Med Res. 2010 Nov 4;15(Suppl 2):95–7. 10.1186/2047-783x-15-s2-95
2. Edmondson HA. Differential diagnosis of tumors and tumor-like lesions of the liver in infancy and childhood. AMA J Dis Child. 1956 Feb;91(2):168–86. 10.1001/archpedi.1956.02060020170015
3. 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 Dec;215(6):820–30. 10.1016/j.jamcollsurg.2012.08.001
4. Graham RP, Jin L, Knutson DL, Kloft-Nelson SM, Greipp PT, Waldburger N, et al. DNAJB1-PRKACA is specific for fibrolamellar carcinoma. Mod Pathol. 2015 Jun;28(6):822–9. 10.1038/modpathol.2015.4
5. Torbenson M. Review of the clinicopathologic features of fibrolamellar carcinoma. Adv Anat Pathol. 2007 May;14(3):217–23. 10.1097/PAP.0b013e3180504913
6. El-Serag HB, Davila JA. Is fibrolamellar carcinoma different from hepatocellular carcinoma? A US population-based study. Hepatology. 2004 Mar;39(3):798–803. 10.1002/hep.20096
7. Smith M, Tomboc PJ, Markovich B. Fibrolamellar hepatocellular carcinoma. StatPearls. Treasure Island, FL: StatPearls Publishing; 2022.
8. Polavarapu AD, Ahmed M, Samaha G, Weerasinghe CK, Deeb L, Sokoloff A. Spontaneous rupture of fibrolamellar variant hepatocellular carcinoma. Gastroenterology Res. 2019 Jun;12(3):166–70. 10.14740/gr1148
9. Graham RP. Fibrolamellar carcinoma: What is new and why it matters. Surg Pathol Clin. 2018 Jun;11(2):377–87. 10.1016/j.path.2018.02.006
10. Ichikawa T, Federle MP, Grazioli L, et al. Fibrolamellar hepatocellular carcinoma: Imaging and pathologic findings in 31 recent cases. Radiology. 1999;213:352–61. 10.1148/radiology.213.2.r99nv31352
11. Craig JR, Peters RL, Edmondson HA, Omata M. Fibrolamellar carcinoma of the liver: A tumor of adolescents and young adults with distinctive clinicopathologic features. Cancer. 1980 Jul 15;46(2):372–9. 10.1002/1097-0142(19800715)46:2<372:aid-cncr2820460227>3.0.co;2-s
12. O’Neill AF, Church AJ, Perez-Atayde AR, Shaikh R, Marcus KJ, Vakili K. Fibrolamellar carcinoma: An entity all its own. Curr Probl Cancer. 2021 Aug;45(4):100770. 10.1016/j.currproblcancer.2021.100770
13. Honeyman JN, Simon EP, Robine N, et al. Detection of a recurrent DNAJB1–PRKACA chimeric transcript in fibrolamellar hepatocellular carcinoma. Science. 2014;343:1010–14. 10.1126/science.1249484
14. Vyas M, Hechtman JF, Zhang Y, et al. DNAJB1-PRKACA fusions occur in oncocytic pancreatic and biliary neoplasms and are not specific for fibrolamellar hepatocellular carcinoma. Mod Pathol. 2020;33:648–56. 10.1038/s41379-019-0398-2
15. Graham RP, Lackner C, Terracciano L, González-Cantú Y, Maleszewski JJ, Greipp PT, et al. Fibrolamellar carcinoma in the Carney complex: PRKAR1A loss instead of the classic DNAJB1-PRKACA fusion. Hepatology. 2018 Oct;68(4):1441–7. 10.1002/hep.29719
16. Kakar S, Chen X, Ho C, Burgart LJ, Sahai V, Dachrut S, et al. Chromosomal changes in fibrolamellar hepatocellular carcinoma detected by array comparative genomic hybridization. Mod Pathol. 2009 Jan;22(1):134–41. 10.1038/modpathol.2008.178
17. Lee JH, Choi MS, Gwak GY, et al. Clinicopathologic characteristics and long-term prognosis of scirrhous hepatocellular carcinoma. Dig Dis Sci. 2012;57:1698–707. 10.1007/s10620-012-2075-x
18. Kim YJ, Rhee H, Yoo JE, et al. Tumour epithelial and stromal characteristics of hepatocellular carcinomas with abundant fibrous stroma: Fibrolamellar versus scirrhous hepatocellular carcinoma. Histopathology. 2017;71:217–26. 10.1111/his.13219
19. Matsuura S, Aishima S, Taguchi K, et al. “Scirrhous” type hepatocellular carcinomas: A special reference to expression of cytokeratin 7 and hepatocyte paraffin 1. Histopathology. 2005;47:382–90. 10.1111/j.1365-2559.2005.02230.x
20. Limaiem F, Bouraoui S. Mixed fibrolamellar hepatocellular carcinoma. Clin Case Rep. 2021 Jun 24;9(6):e04318. 10.1002/ccr3.4318
21. Hirsch TZ, Negulescu A, Gupta B, Caruso S, Noblet B, Couchy G, et al. BAP1 mutations define a homogeneous subgroup of hepatocellular carcinoma with fibrolamellar-like features and activated PKA. J Hepatol. 2020 May;72(5):924–36. 10.1016/j.jhep.2019.12.006. Erratum In: J Hepatol. 2020 Jul;73(1):225–226.
22. Uka K, Aikata H, Takaki S, Shirakawa H, Jeong SC, Yamashina K, et al. Clinical feature and prognosis of patients with extrahepatic metastases from hepatocellular carcinoma. World J Gastroenterol. 2007;13:414–20. 10.3748/wjg.v13.i3.414
23. Liu S, Chan KW, Wang B, Qiao L. Fibrolamellar hepatocellular carcinoma. Am J Gastroenterol. 2009;104(10):2617–24. 10.1038/ajg.2009.440
24. Polychronidis G, Feng J, Murtha-Lemekhova A, Heger U, Mehrabi A, Hoffmann K. Factors influencing overall survival for patients with fibrolamellar hepatocellular carcinoma: Analysis of the surveillance, epidemiology, and end results database. Int J Gen Med. 2022 Jan 8;15:393–406. 10.2147/IJGM.S338066
25. Mroz RM, Korniluk M, Swidzinska E, Dzieciol J, Czaban J, Panek B, et al. Lung mass in a 28-year-old male: A case report of a rare tumor. Eur J Med Res. 2010 Nov 4;15(Suppl 2):95–7. 10.1186/2047-783x-15-s2-95
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Jul 19, 2022
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How to Cite
Fibrolamellar Carcinoma with DNAJB1-PRKACA Fusion in a 16-Year-Old: Case Report and Review of Literature. (2022). Journal of Renal and Hepatic Disorders, 6(2), 1-7. https://doi.org/10.15586/jrenhep.v6i2.147
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Case Reports Hepatology
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