Histopathology of Hepatocellular Carcinoma

  • Valérie Paradis
Part of the Recent Results in Cancer Research book series (RECENTCANCER, volume 190)


Hepatocellular Carcinoma (HCC) is the most frequent primary liver malignancy, mostly occurring in the context of chronic liver diseases leading to cirrhosis. Epidemiological data demonstrate the increasing incidence of HCC worldwide, mainly related to viral hepatitis and metabolic syndrome. Pathological analysis recognizes several types of HCC according to macroscopic and microscopic features. A subset of HCC can develop on normal liver and usually corresponds to specific variants, including fibrolamellar carcinoma mostly encountered in young population. Prognosis of HCC remains poor, depending on delayed tumor diagnosis, the clinical status of the patient but also tumor behavior with a great propensity for angioinvasion.


Chronic Liver Disease Vascular Invasion Dysplastic Nodule Satellite Nodule Hepatocellular Adenoma 
These keywords were added by machine and not by the authors. This process is experimental and the keywords may be updated as the learning algorithm improves.


  1. 1.
    El-Serag HB (2007) Epidemiology of hepatocellular carcinoma in USA. Hepatol Res 37:S88–S94PubMedCrossRefGoogle Scholar
  2. 2.
    Nordenstedt H, White DL, El-Serag HB (2010) The changing pattern of epidemiology in hepatocellular carcinoma. Dig Liver Dis 42:S206–S214PubMedCrossRefGoogle Scholar
  3. 3.
    Sherman M (2005) Hepatocellular carcinoma: epidemiology, risk factors, and screening. Semin Liver Dis 25:143–154PubMedCrossRefGoogle Scholar
  4. 4.
    Bosman FT, Carneiro F, Hruban RH et al (2010) WHO classification of tumours of the Digestive System 4th edn. IARC Press, Lyon, pp 322–326Google Scholar
  5. 5.
    Colombo M, de Franchis R, Del Ninno E et al (1991) Hepatocellular carcinoma in Italian patients with cirrhosis. N Engl J Med 325:675–680PubMedCrossRefGoogle Scholar
  6. 6.
    International Working Party (1995) Terminology of nodular hepatocellular lesions. Hepatology 22:983–993Google Scholar
  7. 7.
    Okuda K, Peters RL, Simson IW (1984) Gross anatomic features of hepatocellular carcinoma from three disparate geographic areas: proposal of new classification. Cancer 54:2165–2173PubMedCrossRefGoogle Scholar
  8. 8.
    International Consensus Group for Hepatocellular Carcinoma (2009) Pathologic diagnosis of early hepatocellular carcinoma: a report of the international consensus group for hepatocellular neoplasia. Hepatology 49:658–664CrossRefGoogle Scholar
  9. 9.
    Hytiroglou P, Park YN, Krinsky G et al (2007) Hepatic precancerous lesions and small hepatocellular carcinoma. Gastroenterol Clin North Am 36:867–887PubMedCrossRefGoogle Scholar
  10. 10.
    Anthony PP (1973) Primary carcinoma of the liver: a study of 282 cases in Ugandan Africans. J Pathol 110:37–48PubMedCrossRefGoogle Scholar
  11. 11.
    Omata M, Peters RL, Tatter D (1981) Sclerosing hepatic carcinoma: relationship to hypercalcemia. Liver 1:33–49PubMedCrossRefGoogle Scholar
  12. 12.
    Kojiro M, Sugihara S, Kakizoe S et al (1989) Hepatocellular carcinoma with sarcomatous change: a special reference to the relationship with anticancer therapy. Cancer Chemother Pharmacol 23:4–8CrossRefGoogle Scholar
  13. 13.
    Shafizadeh N et al (2008) Utility and limitations of glypican-3 expression for the diagnosis of hepatocellular carcinoma at both ends of the differentiation spectrum. Modern Pathol 21:1011–1018CrossRefGoogle Scholar
  14. 14.
    Wang XY, Degos F, Dubois S et al (2006) Glypican-3 expression in hepatocellular tumors: diagnostic value for preneoplastic lesions and hepatocellular carcinomas. Human Pathol 37:1435–1441CrossRefGoogle Scholar
  15. 15.
    Di Tommaso L, Franchi G, Park YN et al (2007) Diagnostic value of HSP70, Glypican 3 and Glutamine synthetase i hepatocellular nodules in cirrhosis. Hepatology 45:725–737PubMedCrossRefGoogle Scholar
  16. 16.
    Libbrecht L, Severi T, Cassiman D et al (2006) Glypican-3 expression distinguishes small hepatocellular carcinomas from cirrhosis, dysplastic nodules, and focal nodular hyperplasia-like nodules. Am J Surg Pathol 30:1405–1411PubMedCrossRefGoogle Scholar
  17. 17.
    Chuma M, Sakamoto M, Yamazaki K et al (2003) Expression profiling in multistage hepatocarcinogenesis: identification of HSP70 as a molecular marker of early hepatocellular carcinoma. Hepatology 37:198–207PubMedCrossRefGoogle Scholar
  18. 18.
    Villanueva A, Newell P, Chiang DY et al (2007) Genomics and signaling pathways in hepatocellular carcinoma. Semin Liver Dis 27:55–76PubMedCrossRefGoogle Scholar
  19. 19.
    Boyault S, Rickman DS, de Reynies A et al (2007) Transcriptome classification of HCC is related to gene alterations and to new therapeutic targets. Hepatology 45:42–52PubMedCrossRefGoogle Scholar
  20. 20.
    Ladeiro Y, Couchy G, Balabaud C et al (2008) MicroRNA profiling in hepatocellular tumors is associated with clinical features and oncogene/tumor suppressor gene mutations. Hepatology 47:1955–1963PubMedCrossRefGoogle Scholar
  21. 21.
    Villanueva A, Chiang DY, Newell P et al (2008) Pivotal role of mTOR signaling in hepatocellular carcinoma. Gastroenterology 135:1972–1983PubMedCrossRefGoogle Scholar
  22. 22.
    de La Coste A, Romagnolo B, Billuart P et al (1998) Somatic mutations of the beta-catenin gene are frequent in mouse and human hepatocellular carcinomas. Proc Natl Acad Sci U S A 95:8847–8851CrossRefGoogle Scholar
  23. 23.
    Edmondson HA, Steiner PE (1954) Primary carcinoma of the liver: a study of 100 cases among 48,900 necropsies. Cancer 7:462–503PubMedCrossRefGoogle Scholar
  24. 24.
    Pawlik TM, Gleisner AL, Anders RA et al (2007) Preoperative assessment of hepatocellular carcinoma tumor grade using needle biopsy: implications for transplant eligibility. Ann Surg 245:435–442PubMedCrossRefGoogle Scholar
  25. 25.
    Chuong JJ, Livstone EM, Barwick KW (1982) The histopathologic and clinical indicators of prognosis in hepatoma. J Clin Gastroenterol 4:547–552PubMedCrossRefGoogle Scholar
  26. 26.
    Lai CL, Wu PC, Lam KC et al (1979) Histologic prognostic indicators in hepatocellular carcinoma. Cancer 44:1677–1683PubMedCrossRefGoogle Scholar
  27. 27.
    Nathan H, Schulick RD, Choti MA et al (2009) Predictors of survival after resection of early hepatocellular carcinoma. Ann Surg 249:799–805PubMedCrossRefGoogle Scholar
  28. 28.
    Pawlik TM, Delman KA, Vauthey JN et al (2005) Tumor size predicts vascular invasion and histologic grade: implications for selection of surgical treatment for hepatocellular carcinoma. Liver Transpl 11:1086–1092PubMedCrossRefGoogle Scholar
  29. 29.
    Lee J-S, Chu I-S, Heo J et al (2004) Classification and prediction of survival in hepatocellular carcinoma by gene expression profiling. Hepatology 40:667–676PubMedCrossRefGoogle Scholar
  30. 30.
    Ferrell L, Wright T, Lake J et al (1992) Incidence and diagnostic features of macroregenerative nodules vs. small hepatocellular carcinoma in cirrhotic livers. Hepatology 16:1372–1381PubMedCrossRefGoogle Scholar
  31. 31.
    Mion F, Grozel L, Boillot O et al (1996) Adult cirrhotic liver explants: precancerous lesions and undetected small hepatocellular carcinomas. Gastroenterology 111:1587–1592PubMedCrossRefGoogle Scholar
  32. 32.
    Takayama T, Makuuchi M, Hirohashi S et al (1990) Malignant transformation of adenomatous hyperplasia to hepatocellular carcinoma. Lancet 336:1150–1153PubMedCrossRefGoogle Scholar
  33. 33.
    Theise ND, Schwartz M, Miller C et al (1992) Macroregenerative nodules and hepatocellular carcinoma in forty-four sequential adult liver explants with cirrhosis. Hepatology 16:949–955PubMedCrossRefGoogle Scholar
  34. 34.
    Kojiro M, Roskams T (2005) Early hepatocellular carcinoma and dysplastic nodules. Semin Liver Dis 25:133–142PubMedCrossRefGoogle Scholar
  35. 35.
    Theise ND, Park YN, Kojiro M (2002) Dysplastic nodules and hepatocarcinogenesis. Clin Liver Dis 6:497–512PubMedCrossRefGoogle Scholar
  36. 36.
    Park YN, Kojiro M, Di Tommaso L et al (2007) Ductular reaction is helpful in defining early stromal invasion, small hepatocellular carcinoma, and dysplastic nodules. Cancer 109:915–923PubMedCrossRefGoogle Scholar
  37. 37.
    Borzio M, Bruno S, Roncalli M et al (1995) Liver cell dysplasia is a major risk factor for hepatocellular carcinoma in cirrhosis: a prospective study. Gastroenterology 108:812–817PubMedCrossRefGoogle Scholar
  38. 38.
    Lee RG, Tsamandas AC, Demetris AJ (1997) Large cell change (liver cell dysplasia) and hepatocellular carcinoma in cirrhosis: matched case-control study, pathological analysis, and pathogenetic hypothesis. Hepatology 26:1415–1422PubMedCrossRefGoogle Scholar
  39. 39.
    Lam CM, Chan AO, Ho P et al (2004) Different presentation of hepatitis B-related hepatocellular carcinoma in a cohort of 1863 young and old patients: implications for screening. Aliment Pharmacol Ther 19:771–777PubMedCrossRefGoogle Scholar
  40. 40.
    Marrero JA, Fontana RJ, Su GL et al (2002) NAFLD may be a common underlying liver disease in patients with hepatocellular carcinoma in the United States. Hepatology 36:1349–1354PubMedGoogle Scholar
  41. 41.
    Paradis V, Zalinski S, Chelbi E et al (2009) Hepatocellular carcinomas in patients with metabolic syndrome often develop without significant liver fibrosis: a pathological analysis. Hepatology 49:851–859PubMedCrossRefGoogle Scholar
  42. 42.
    Adams LA, Lymp JF, Sauver JS et al (2005) The natural history of nonalcoholic fatty liver disease: a population-based cohort study. Gastroenterology 129:113–121PubMedCrossRefGoogle Scholar
  43. 43.
    Angulo P (2002) Non alcoloholic fatty liver diseases. New Engl J Med 346:1221–1231PubMedCrossRefGoogle Scholar
  44. 44.
    Farrell GC, Larter CZ (2006) Nonalcoholic fatty liver disease: from steatosis to cirrhosis. Hepatology 43:S99–S112PubMedCrossRefGoogle Scholar
  45. 45.
    El-Serag HB, Tran T, Everhart JE (2004) Diabetes increases the risk of chronic liver disease and hepatocellular carcinoma. Gastroenterology 126:460–468PubMedCrossRefGoogle Scholar
  46. 46.
    Nair S, Mason A, Eason J et al (2002) Is obesity an independent risk factor for hepatocellular carcinoma in cirrhosis? Hepatology 36:150–155PubMedCrossRefGoogle Scholar
  47. 47.
    Cuadrado A, Orive A, García-Suárez C et al (2005) Non-alcoholic steatohepatitis (Nash) and hepatocellular carcinoma. Obes Surg 15:442–446PubMedCrossRefGoogle Scholar
  48. 48.
    Guzman G, Brunt EM, Petrovic LM et al (2008) Does nonalcoholic fatty liver disease predispose patients to hepatocellular carcinoma in the absence of cirrhosis? Ach Pathol Lab Med 132:1761–1766Google Scholar
  49. 49.
    Kawada N, Imanaka K, Kawaguchi T et al (2009) Hepatocellular carcinoma arising from non-cirrhotic nonalcoholic steatohepatitis. J Gastroenterol 44:1190–1194PubMedCrossRefGoogle Scholar
  50. 50.
    Farges O, Ferreira N, Dokmak S et al (2011) Changing trends in malignant transformation of hepatocellular adenoma. Gut 60:85–89PubMedCrossRefGoogle Scholar
  51. 51.
    Craig JR, Peters RL, Edmondson HA et al (1980) Fibrolamellar carcinoma of the liver: a tumor of adolescents and young adults with distinctive clinico-pathologic features. Cancer 46:372–379PubMedCrossRefGoogle Scholar
  52. 52.
    El-Serag HB, Davila JA (2004) Is fibrolamellar carcinoma different from hepatocellular carcinoma? A US population-based study. Hepatology 39:798–803PubMedCrossRefGoogle Scholar
  53. 53.
    Van Eyken P, Sciot R, Brock P et al (1990) Abundant expression of cytokeratin 7 in fibrolamellar carcinoma of the liver. Histopathology 17:101–107PubMedCrossRefGoogle Scholar
  54. 54.
    Rosenberg L (1991) The risk of liver neoplasia in relation to combined oral contraceptive use. Contraception 43:643–652PubMedCrossRefGoogle Scholar
  55. 55.
    Socas L, Zumbado M, Pérez-Luzardo O et al (2005) Hepatocellular adenomas associated with anabolic androgenic steroid abuse in bodybuilders: a report of two cases and a review of the literature. Br J Sports Med 39:e27PubMedCrossRefGoogle Scholar
  56. 56.
    Dokmak S, Paradis V, Vilgrain V et al (2009) A single-center surgical experience of 122 patients with single and multiple hepatocellular adenomas. Gastroenterology 137:1698–1705PubMedCrossRefGoogle Scholar
  57. 57.
    Paradis V, Champault A, Ronot M et al (2007) Telangiectatic adenomas: an entity associated with increased body mass index and inflammation. Hepatology 46:140–146PubMedCrossRefGoogle Scholar
  58. 58.
    Bioulac-Sage P, Laumonier H, Couchy G et al (2009) Hepatocellular adenoma management and phenotypic classification: the Bordeaux experience. Hepatology 50:481–489PubMedCrossRefGoogle Scholar
  59. 59.
    Deneve JL, Pawlik TM, Cunningham S et al (2009) Liver cell adenoma: a multicenter analysis of risk factors for rupture and malignancy. Ann Surg Oncol 16:640–648PubMedCrossRefGoogle Scholar

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© Springer-Verlag Berlin Heidelberg 2013

Authors and Affiliations

  1. 1.Departement of PathologyBeaujon Hospital—Assistance Publique—Hôpitaux de ParisClichyFrance

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