Journal of Gastrointestinal Surgery

, Volume 15, Issue 12, pp 2275–2283

Focal Nodular Hyperplasia—A Review of Myths and Truths

  • Christopher B. Nahm
  • Kevin Ng
  • Philip Lockie
  • Jaswinder S. Samra
  • Thomas J. Hugh
Review Article

Abstract

Background

Focal nodular hyperplasia (FNH) is a benign hyperplastic lesion of the liver with no known malignant potential. It has generated much interest due to the frequency with which it presents with atypical features on radiological imaging. Often resulting in misdiagnosis. Moreover, the understanding of particular subtypes of this lesion at a molecular level has changed in recent years. This may have implications on how certain subtypes should be managed.

Purpose

This review aims to analyse current literature pertaining to FNH and to provide clinically relevant advice regarding diagnosis and management.

Keywords

Diagnosis Focal nodular hyperplasia Liver Neoplasms Treatment 

References

  1. 1.
    Wanless IR, Mawdsley C, Adams R. On the pathogenesis of focal nodular hyperplasia of the liver. Hepatology 1985;5:1194–1200.PubMedCrossRefGoogle Scholar
  2. 2.
    Nguyen BN, Flejou JF, Terris B, Belghiti J, Degott C. Focal nodular hyperplasia of the liver: a comprehensive pathologic study of 305 lesions and recognition of new histologic forms. Am J Surg Pathol 1999;23:1441–1454.PubMedCrossRefGoogle Scholar
  3. 3.
    Luciani A, Kobeiter H, Maison P, Cherqui D, Zafrani ES, Dhumeaux D, Mathieu D. Focal nodular hyperplasia of the liver in men: is presentation the same in men and women? Gut 2002;50:877–880.PubMedCrossRefGoogle Scholar
  4. 4.
    Stocker JT, Ishak KG. Focal nodular hyperplasia of the liver: a study of 21 pediatric cases. Cancer 1981;48:336–345.PubMedCrossRefGoogle Scholar
  5. 5.
    Buetow PC, Pantongrag-Brown L, Buck JL, Ros PR, Goodman ZD. Focal nodular hyperplasia of the liver: radiologic–pathologic correlation. Radiographics 1996;16:369–388.PubMedGoogle Scholar
  6. 6.
    Shen YH, Fan J, Wu ZQ, Ma ZC, Zhou XD, Zhou J, Qiu SJ, Qin LX, Ye QH, Sun HC, Huang XW, Tang ZY. Focal nodular hyperplasia of the liver in 86 patients. Hepatobiliary Pancreat Dis Int 2007;6:52–57.PubMedGoogle Scholar
  7. 7.
    Mathieu D, Kobeiter H, Maison P, Rahmouni A, Cherqui D, Zafrani ES, Dhumeaux D. Oral contraceptive use and focal nodular hyperplasia of the liver. Gastroenterology 2000;118:560–564.PubMedCrossRefGoogle Scholar
  8. 8.
    Becker YT, Raiford DS, Webb L, Wright JK, Chapman WC, Pinson CW. Rupture and hemorrhage of hepatic focal nodular hyperplasia. Am Surg 1995;61:210–214.PubMedGoogle Scholar
  9. 9.
    Hardwigsen J, Pons J, Veit V, Garcia S, Le Treut YP. A life-threatening complication of focal nodular hyperplasia. J Hepatol 2001;35:310–312.PubMedCrossRefGoogle Scholar
  10. 10.
    Demarco MP, Shen P, Bradley RF, Levine EA. Intraperitoneal hemorrhage in a patient with hepatic focal nodular hyperplasia. Am Surg 2006;72:555–559.PubMedGoogle Scholar
  11. 11.
    Uggowitzer M, Kugler C, Groll R, Mischinger HJ, Stacher R, Fickert P, Weiglein A. Sonographic evaluation of focal nodular hyperplasias (FNH) of the liver with a transpulmonary galactose-based contrast agent (Levovist). Br J Radiol 1998;71:1026–1032.PubMedGoogle Scholar
  12. 12.
    Ishak KG, Rabin L. Benign tumors of the liver. Med Clin North Am 1975;59:995–1013.PubMedGoogle Scholar
  13. 13.
    Sato Y, Harada K, Ikeda H, Fijii T, Sasaki M, Zen Y, Nakanuma Y. Hepatic stellate cells are activated around central scars of focal nodular hyperplasia of the liver—a potential mechanism of central scar formation. Hum Pathol 2009;40:181–188.PubMedCrossRefGoogle Scholar
  14. 14.
    Scalori A, Tavani A, Gallus S, La Vecchia C, Colombo M. Oral contraceptives and the risk of focal nodular hyperplasia of the liver: a case-control study. Am J Obstet Gynecol 2002;186:195–197.PubMedCrossRefGoogle Scholar
  15. 15.
    Klatskin G. Hepatic tumors: possible relationship to use of oral contraceptives. Gastroenterology 1977;73:386–394.PubMedGoogle Scholar
  16. 16.
    Heinemann LA, Weimann A, Gerken G, Thiel C, Schlaud M, DoMinh T. Modern oral contraceptive use and benign liver tumors: the German Benign Liver Tumor Case-Control Study. Eur J Contracept Reprod Health Care 1998;3:194–200.PubMedCrossRefGoogle Scholar
  17. 17.
    Mathieu D, Kobeiter H, Cherqui D, Rahmouni A, Dhumeaux D. Oral contraceptive intake in women with focal nodular hyperplasia of the liver. Lancet 1998;352:1679–1680.PubMedCrossRefGoogle Scholar
  18. 18.
    Kapp N, Curtis KM. Hormonal contraceptive use among women with liver tumors: a systematic review. Contraception 2009;80:387–390.PubMedCrossRefGoogle Scholar
  19. 19.
    Weimann A, Mossinger M, Fronhoff K, Nadalin S, Raab R. Pregnancy in women with observed focal nodular hyperplasia of the liver. Lancet 1998;351:1251–1252.PubMedCrossRefGoogle Scholar
  20. 20.
    Paradis V, Laurent A, Flejou JF, Vidaud M, Bedossa P. Evidence for the polyclonal nature of focal nodular hyperplasia of the liver by the study of X-chromosome inactivation. Hepatology 1997;26:891–895.PubMedCrossRefGoogle Scholar
  21. 21.
    Bioulac-Sage P, Rebouissou S, Sa Cunha A, Jeannot E, Lepreux S, Blanc JF, Blanche H, Le Bail B, Saric J, Laurent-Puig P, Balabaud C, Zucman-Rossi J. Clinical, morphologic, and molecular features defining so-called telangiectatic focal nodular hyperplasias of the liver. Gastroenterology 2005;128:1211–1218.PubMedCrossRefGoogle Scholar
  22. 22.
    Chen YW, Jeng YM, Yeh SH, Chen PJ. P53 gene and Wnt signaling in benign neoplasms: beta-catenin mutations in hepatic adenoma but not in focal nodular hyperplasia. Hepatology 2002;36:927–935.PubMedGoogle Scholar
  23. 23.
    Gaffey MJ, Iezzoni JC, Weiss LM. Clonal analysis of focal nodular hyperplasia of the liver. Am J Pathol 1996;148:1089–1096.PubMedGoogle Scholar
  24. 24.
    Chen YJ, Chen PJ, Lee MC, Yeh SH, Hsu MT, Lin CH. Chromosomal analysis of hepatic adenoma and focal nodular hyperplasia by comparative genomic hybridization. Genes Chromosomes Cancer 2002;35:138–143.PubMedCrossRefGoogle Scholar
  25. 25.
    Cai YR, Gong L, Teng XY, Zhang HT, Wang CF, Wei GL, Guo L, Ding F, Liu ZH, Pan QJ, Su Q. Clonality and allelotype analyses of focal nodular hyperplasia compared with hepatocellular adenoma and carcinoma. World J Gastroenterol 2009;15:4695–4708.PubMedCrossRefGoogle Scholar
  26. 26.
    Gong L, Li YH, Su Q, Li G, Zhang WD, Zhang W. Use of X-chromosome inactivation pattern and laser microdissection to determine the clonal origin of focal nodular hyperplasia of the liver. Pathology 2009;41:348–355.PubMedCrossRefGoogle Scholar
  27. 27.
    Paradis V, Benzekri A, Dargere D, Bieche I, Laurendeau I, Vilgrain V, Belghiti J, Vidaud M, Degott C, Bedossa P. Telangiectatic focal nodular hyperplasia: a variant of hepatocellular adenoma. Gastroenterology 2004;126:1323–1329.PubMedCrossRefGoogle Scholar
  28. 28.
    Saul SH, Titelbaum DS, Gansler TS, Varello M, Burke DR, Atkinson BF, Rosato EF. The fibrolamellar variant of hepatocellular carcinoma. Its association with focal nodular hyperplasia. Cancer 1987;60:3049–3055.PubMedCrossRefGoogle Scholar
  29. 29.
    Petsas T, Tsamandas A, Tsota I, Karavias D, Karatza C, Vassiliou V, Kardamakis D. A case of hepatocellular carcinoma arising within large focal nodular hyperplasia with review of the literature. World J Gastroenterol 2006;12:6567–6571.PubMedGoogle Scholar
  30. 30.
    Pain JA, Gimson AE, Williams R, Howard ER. Focal nodular hyperplasia of the liver: results of treatment and options in management. Gut 1991;32:524–527.PubMedCrossRefGoogle Scholar
  31. 31.
    Kerlin P, Davis GL, McGill DB, Weiland LH, Adson MA, Sheedy PF, 2nd. Hepatic adenoma and focal nodular hyperplasia: clinical, pathologic, and radiologic features. Gastroenterology 1983;84:994–1002.PubMedGoogle Scholar
  32. 32.
    Weimann A, Ringe B, Klempnauer J, Lamesch P, Gratz KF, Prokop M, Maschek H, Tusch G, Pichlmayr R. Benign liver tumors: differential diagnosis and indications for surgery. World J Surg 1997;21:983–990; discussion 990–981.PubMedCrossRefGoogle Scholar
  33. 33.
    Kuo YH, Wang JH, Lu SN, Hung CH, Wei YC, Hu TH, Chen CH, Yen YH, Lee CM, Eng HL. Natural course of hepatic focal nodular hyperplasia: a long-term follow-up study with sonography. J Clin Ultrasound 2009;37:132–137.PubMedCrossRefGoogle Scholar
  34. 34.
    Vilgrain V, Flejou JF, Arrive L, Belghiti J, Najmark D, Menu Y, Zins M, Vullierme MP, Nahum H. Focal nodular hyperplasia of the liver: MR imaging and pathologic correlation in 37 patients. Radiology 1992;184:699–703.PubMedGoogle Scholar
  35. 35.
    Caseiro-Alves F, Zins M, Mahfouz AE, Rahmouni A, Vilgrain V, Menu Y, Mathieu D. Calcification in focal nodular hyperplasia: a new problem for differentiation from fibrolamellar hepatocellular carcinoma. Radiology 1996;198:889–892.PubMedGoogle Scholar
  36. 36.
    Shamsi K, De Schepper A, Degryse H, Deckers F. Focal nodular hyperplasia of the liver: radiologic findings. Abdom Imaging 1993;18:32–38.PubMedCrossRefGoogle Scholar
  37. 37.
    Golli M, Mathieu D, Anglade MC, Cherqui D, Vasile N, Rahmouni A. Focal nodular hyperplasia of the liver: value of color Doppler US in association with MR imaging. Radiology 1993;187:113–117.PubMedGoogle Scholar
  38. 38.
    Wang LY, Wang JH, Lin ZY, Yu ML, Lu SN, Chuang WL, Chen SC, Hseih MY, Tsai JF, Chang WY. Hepatic focal nodular hyperplasia: findings on color Doppler ultrasound. Abdom Imaging 1997;22:178–181.PubMedCrossRefGoogle Scholar
  39. 39.
    Rogers JV, Mack LA, Freeny PC, Johnson ML, Sones PJ. Hepatic focal nodular hyperplasia: angiography, CT, sonography, and scintigraphy. AJR Am J Roentgenol 1981;137:983–990.PubMedGoogle Scholar
  40. 40.
    Procacci C, Fugazzola C, Cinquino M, Mangiante G, Zonta L, Andreis IA, Nicoli N, Pistolesi GF. Contribution of CT to characterization of focal nodular hyperplasia of the liver. Gastrointest Radiol 1992;17:63–73.PubMedCrossRefGoogle Scholar
  41. 41.
    Shirkhoda A, Farah MC, Bernacki E, Madrazo B, Roberts J. Hepatic focal nodular hyperplasia: CT and sonographic spectrum. Abdom Imaging 1994;19:34–38.PubMedCrossRefGoogle Scholar
  42. 42.
    Carlson SK, Johnson CD, Bender CE, Welch TJ. CT of focal nodular hyperplasia of the liver. AJR Am J Roentgenol 2000;174:705–712.PubMedGoogle Scholar
  43. 43.
    Choi CS, Freeny PC. Triphasic helical CT of hepatic focal nodular hyperplasia: incidence of atypical findings. AJR Am J Roentgenol 1998;170:391–395.PubMedGoogle Scholar
  44. 44.
    Attal P, Vilgrain V, Brancatelli G, Paradis V, Terris B, Belghiti J, Taouli B, Menu Y. Telangiectatic focal nodular hyperplasia: US, CT, and MR imaging findings with histopathologic correlation in 13 cases. Radiology 2003;228:465–472.PubMedCrossRefGoogle Scholar
  45. 45.
    Ruppert-Kohlmayr AJ, Uggowitzer MM, Kugler C, Zebedin D, Schaffler G, Ruppert GS. Focal nodular hyperplasia and hepatocellular adenoma of the liver: differentiation with multiphasic helical CT. AJR Am J Roentgenol 2001;176:1493–1498.PubMedGoogle Scholar
  46. 46.
    Friedman AC, Lichtenstein JE, Goodman Z, Fishman EK, Siegelman SS, Dachman AH. Fibrolamellar hepatocellular carcinoma. Radiology 1985;157:583–587.PubMedGoogle Scholar
  47. 47.
    Teefey SA, Stephens DH, Weiland LH. Calcification in hepatocellular carcinoma: not always an indication of fibrolamellar histology. AJR Am J Roentgenol 1987;149:1173–1174.PubMedGoogle Scholar
  48. 48.
    Scatarige JC, Fishman EK, Saksouk FA, Siegelman SS. Computed tomography of calcified liver masses. J Comput Assist Tomogr 1983;7:83–89.PubMedCrossRefGoogle Scholar
  49. 49.
    Mathieu D, Vilgrain V, Mahfouz AE, Anglade MC, Vullierme MP, Denys A. Benign liver tumors. Magn Reson Imaging Clin N Am 1997;5:255–288.PubMedGoogle Scholar
  50. 50.
    Lee MJ, Saini S, Hamm B, Taupitz M, Hahn PF, Seneterre E, Ferrucci JT. Focal nodular hyperplasia of the liver: MR findings in 35 proved cases. AJR Am J Roentgenol 1991;156:317–320.PubMedGoogle Scholar
  51. 51.
    Cherqui D, Rahmouni A, Charlotte F, Boulahdour H, Metreau JM, Meignan M, Fagniez PL, Zafrani ES, Mathieu D, Dhumeaux D. Management of focal nodular hyperplasia and hepatocellular adenoma in young women: a series of 41 patients with clinical, radiological, and pathological correlations. Hepatology 1995;22:1674–1681.PubMedCrossRefGoogle Scholar
  52. 52.
    Grazioli L, Morana G, Kirchin MA, Schneider G. Accurate differentiation of focal nodular hyperplasia from hepatic adenoma at gadobenate dimeglumine-enhanced MR imaging: prospective study. Radiology 2005;236:166–177.PubMedCrossRefGoogle Scholar
  53. 53.
    Boulahdour H, Cherqui D, Charlotte F, Rahmouni A, Dhumeaux D, Zafrani ES, Meignan M. The hot spot hepatobiliary scan in focal nodular hyperplasia. J Nucl Med 1993;34:2105–2110.PubMedGoogle Scholar
  54. 54.
    Davis LP, McCarroll K. Correlative imaging of the liver and hepatobiliary system. Semin Nucl Med 1994;24:208–218.PubMedCrossRefGoogle Scholar
  55. 55.
    Kurtaran A, Muller C, Novacek G, Kaserer K, Mentes M, Raderer M, Pidlich J, Eibenberger K, Angelberger P, Virgolini I. Distinction between hepatic focal nodular hyperplasia and malignant liver lesions using technetium-99m-galactosyl-neoglycoalbumin. J Nucl Med 1997;38:1912–1915.PubMedGoogle Scholar
  56. 56.
    Fabre A, Audet P, Vilgrain V, Nguyen BN, Valla D, Belghiti J, Degott C. Histologic scoring of liver biopsy in focal nodular hyperplasia with atypical presentation. Hepatology 2002;35:414–420.PubMedCrossRefGoogle Scholar
  57. 57.
    Charny CK, Jarnagin WR, Schwartz LH, Frommeyer HS, DeMatteo RP, Fong Y, Blumgart LH. Management of 155 patients with benign liver tumours. Br J Surg 2001;88:808–813.PubMedCrossRefGoogle Scholar
  58. 58.
    Reddy KR, Kligerman S, Levi J, Livingstone A, Molina E, Franceschi D, Badalamenti S, Jeffers L, Tzakis A, Schiff ER. Benign and solid tumors of the liver: relationship to sex, age, size of tumors, and outcome. Am Surg 2001;67:173–178.PubMedGoogle Scholar
  59. 59.
    Colli A, Fraquelli M, Massironi S, Colucci A, Paggi S, Conte D. Elective surgery for benign liver tumours. Cochrane Database Syst Rev 2007:CD005164.Google Scholar
  60. 60.
    Bonney GK, Gomez D, Al-Mukhtar A, Toogood GJ, Lodge JP, Prasad R. Indication for treatment and long-term outcome of focal nodular hyperplasia. HPB (Oxford) 2007;9:368–372.Google Scholar
  61. 61.
    Hsee LC, McCall JL, Koea JB. Focal nodular hyperplasia: what are the indications for resection? HPB (Oxford) 2005;7:298–302.Google Scholar
  62. 62.
    Descottes B, Glineur D, Lachachi F, Valleix D, Paineau J, Hamy A, Morino M, Bismuth H, Castaing D, Savier E, Honore P, Detry O, Legrand M, Azagra JS, Goergen M, Ceuterick M, Marescaux J, Mutter D, de Hemptinne B, Troisi R, Weerts J, Dallemagne B, Jehaes C, Gelin M, Donckier V, Aerts R, Topal B, Bertrand C, Mansvelt B, Van Krunckelsven L, Herman D, Kint M, Totte E, Schockmel R, Gigot JF. Laparoscopic liver resection of benign liver tumors. Surg Endosc 2003;17:23–30.PubMedCrossRefGoogle Scholar
  63. 63.
    Amesur N, Hammond JS, Zajko AB, Geller DA, Gamblin TC. Management of unresectable symptomatic focal nodular hyperplasia with arterial embolization. J Vasc Interv Radiol 2009;20:543–547.PubMedCrossRefGoogle Scholar

Copyright information

© The Society for Surgery of the Alimentary Tract 2011

Authors and Affiliations

  • Christopher B. Nahm
    • 1
  • Kevin Ng
    • 2
  • Philip Lockie
    • 1
  • Jaswinder S. Samra
    • 1
  • Thomas J. Hugh
    • 1
    • 3
  1. 1.Upper Gastrointestinal Surgical UnitRoyal North Shore HospitalSt LeonardsAustralia
  2. 2.Department of Radiology, Westmead HospitalUniversity of SydneyWestmeadAustralia
  3. 3.North Shore Private HospitalUniversity of SydneySt LeonardsAustralia

Personalised recommendations