Diagnosis and treatment of focal nodular hyperplasia

  • David L. Bartlett
  • Lawrence H. Schwartz
  • David Klimstra
  • Leslie H. Blumgart


Focal nodular hyperplasia is an uncommon, benign lesion of the liver of minimal clinical significance. Its importance lies in differentiating it from clinically significant lesions such as liver cell adenoma and hepatocellular carcinoma. The purpose of this review is to provide a background on the pathogenesis of focal nodular hyperplasia, discuss current imaging modalities which provide the most specificity in diagnosis, and provide an update on the accepted management of these lesions. While debate still exists, most current authors believe that focal nodular hyperplasia represents a local response of the liver to injury. The source of that injury seems to be vascular malformations. Magnetic resonance imaging (MRI) provides the most specificity in diagnosis, although the characteristics are still being described. Classically, the lesions will be isointense on T2-weighted images with rapid homogenous contrast enhancement and delayed enhancing central stellate scar. Surgical resection is limited to symptomatic lesions or lesions with atypical imaging characteristics suggesting the possibility of a malignant diagnosis. Percutaneous biopsy can be helpful in those lesions where there is an overall high suspicion of focal nodular hyperplasia, but some of the clinical aspects or imaging characteristics are atypical for the diagnosis. The use of embolization as first line therapy for symptomatic lesions deserves further investigation.

Key words

liver tumor benign focal nodular hyperplasia pathogenesis 


Unable to display preview. Download preview PDF.

Unable to display preview. Download preview PDF.


  1. 1.
    Benz EJ, Baggenstoss AH (1953) Focal cirrhosis of the liver: Its relation to the so-called hamartoma (adenoma, benign hepatoma). Cancer 6:743–755PubMedGoogle Scholar
  2. 2.
    Simmonds M (1988) Die knotige hyperplasie und das adenom der leber. Deutsches Arch F Klin Med 34:388–408Google Scholar
  3. 3.
    Shaw AFB (1923) Primary liver cell adenoma (hepatoma). J Path Bact 26:475–484CrossRefGoogle Scholar
  4. 4.
    Albrecht (1904) Ueber hamartome. Verh Dtsch Ges Pathol 7:153–157Google Scholar
  5. 5.
    Benson CD, Penberthy GC (1942) Surgical excision of primary tumor of liver (hamartoma) in infant 7 months old with recovery. Surgery 12:881–886Google Scholar
  6. 6.
    Warvi WN (1944) Primary neoplasms of the liver. Arch Pathol 37:367–382Google Scholar
  7. 7.
    McBurney RP, Woolner LB, Laeger EE (1950) Solitary hyperplastic nodule of the liver simulating a neoplasm: Report of case. Proc Staff Meet Mayo Clin 25:606–611Google Scholar
  8. 8.
    Edmondson HA (1958) Tumors of the liver and intrahepatic bile ducts. In: Armed Forces Institute of Pathology (ed) Atlas of tumor pathology fascicle 25. Washington DCGoogle Scholar
  9. 9.
    Gold JH, Guzman IJ, Rosai J (1978) Benign tumors of the liver. Pathologic examination of 45 cases. Am J Clin Pathol 70:6–17PubMedGoogle Scholar
  10. 10.
    Fischer HP, Lankes G (1991) Morphologic correlation between liver epithelium and mesenchyme allows insight into histogenesis of focal nodular hyperplasia (FNH) of the liver. Virchows Arch [Cell Pathol] 60:373–380Google Scholar
  11. 11.
    Kienzle GD, Stern J (1985) Pedunculated focal nodular hyperplasia. Clin Nucl Med 10:524PubMedGoogle Scholar
  12. 12.
    Knowles DM, Wolff M (1976) Focal nodular hyperplasia of the liver: A clinicopathologic study and review of the literature. Hum Pathol 7:533–545PubMedGoogle Scholar
  13. 13.
    Wetzel WJ, Alexander RW (1979) Focal nodular hyperplasia of the liver with alcoholic hyalin bodies and cytologic atypia. Cancer 51:1947–1952Google Scholar
  14. 14.
    Burton Vila MM, Haot, J, Desmet VJ (1984) Cholestatic feature in focal nodular hyperplasia. Liver 4:387–395Google Scholar
  15. 15.
    Lee RG (1994) Neoplasms and other masses. In: Lee RG (ed) Diagnostic liver pathology. Mosby, St Louis, pp 421–489Google Scholar
  16. 16.
    Lough J, Spicer, P, Kinch R (1980) Focal nodular hyperplasia of the liver. An electron microscopic study of the vascular lesions. Hum Pathol 11:181–186PubMedGoogle Scholar
  17. 17.
    Wessely Z, Shapiro SH, Scherer JD (1982) Focal nodular hyperplasia of the liver: Ultrastructural observations. Ann Clin Lab Sci 12:119–125PubMedGoogle Scholar
  18. 18.
    Koelma IA, Nap M, Huitema S, Krom RA, Houthoff HJ (1986) Hepatocellular carcinoma, adenoma, and focal nodular hyperplasia. Comparative histopathologic study with immunohistochemical parameters. Arch Pathol Lab Med 110:1035–1040PubMedGoogle Scholar
  19. 19.
    Phillips MJ, Langer B, Stone R, Fisher MM, Ritchie S (1973) Bening liver cell tumors. Classification and ultrastructural pathology. Cancer 32:463–470PubMedGoogle Scholar
  20. 20.
    Wanless IR, Mawdsley C, Adams R (1985) On the pathogenesis of focal nodular hyperplasia of the liver. Hepatology 5:1194–1200PubMedGoogle Scholar
  21. 21.
    Wanless IR, Albrecht S, Bilbao J, et al. (1989) Multiple focal nodular hyperplasia of the liver associated with vascular malformations of various organs and neoplasia of the brain: A new syndromo. Mod Pathol 2:456–462PubMedGoogle Scholar
  22. 22.
    Mathieu D, Zafrani ES, Anglade MC, Dhumeaux D (1989) Association of focal nodular hyperplasia and hepatic hemangiona. Gastroenterology 97:154–157PubMedGoogle Scholar
  23. 23.
    Whelan TJ Jr, Baugh JH, Chandor S (1973) Focal nodular hyperplasia of the liver. Ann, Surg 177:150–158Google Scholar
  24. 24.
    Ndimbie OK, Goodman ZD, Chase RL, Ma CK, Lee MW (1990) Hemangiomas with localized nodular proliferation of the liver. A suggestion on the pathogenesis of focal nodular hyperplasia. Am J Surg Pathol 14:142–150PubMedGoogle Scholar
  25. 25.
    Strain AJ, McGowan JA, Bucher NL (1984) Biological properties of a hepatocyte growth factor from rat platelets. J Cell Physiol 119:193–197Google Scholar
  26. 26.
    Schilling JA, McKee FW (1953) Late follow-up on experimental hepatic-portal arteriovenous fistulae. Surg Forum 4:392–393PubMedGoogle Scholar
  27. 27.
    Schwartz SI, Morton JH, McGovern GR (1961) Experimental hepatic-portal arteriovenous fistulae. Surgery 49:611–615PubMedGoogle Scholar
  28. 28.
    Zuidema GD, Gaisford WD, Abell MR (1963) Segmental portal arterialization of canine liver. Surgery 53:689–694PubMedGoogle Scholar
  29. 29.
    Klatskin G (1977) Hepatic tumors. Possible relationship to use of oral contraceptives. Gastroenterology 73:386–394PubMedGoogle Scholar
  30. 30.
    Brady MS, Coit DG (1990) Focal nodular hyperplasia of the liver. Surg Gynecol Obstet 171:377–381PubMedGoogle Scholar
  31. 31.
    Pain JA, Gimson AE, Williams R, Howard ER (1991) Focal nodular hyperplasia of the liver: Results of treatment and options in management. Gut 32:542–527Google Scholar
  32. 32.
    Ross D, Pina J, Mirza M, Galvan A, Ponce L (1976) Letter: Regression of focal nodular hyperplasia after discontinuation of oral contraceptives. Ann Intern Med 85:203–204PubMedGoogle Scholar
  33. 33.
    Kerlin P, Davis GL, McGill DB, Weiland LH, Adson MA, Sheedy PF (1983) Hepatic adenoma and focal nodular hyperplasia: Clinical, pathologic, and radiologic features. Gastroenterology 84:994–1002PubMedGoogle Scholar
  34. 34.
    Ishak KG (1979) Hepatic neoplasms associated with contraceptive and anabolic steroids. Recent Results in Cancer Res 69:73–124Google Scholar
  35. 35.
    Farrell GC (1994) Hepatic tumours. In: Farrell GC (ed) Druginduced liver disease. Churchill Livingstone, Melbourne, pp 489–495Google Scholar
  36. 36.
    Shortell CK, Schwartz SI (1991) Hepatic adenoma and focal nodular hyperplasia (review). Surg Gynecol Obstet 173:426–431PubMedGoogle Scholar
  37. 37.
    Nime F, Pickren JW, Vana J, Aronoff BL, Baker HW, Murphy GP (1979) The histology of liver tumors in oral contraceptive users observed during a national survey by the American College of Surgeons Commission on Cancer. Cancer 44:1481–1489PubMedGoogle Scholar
  38. 38.
    Rogers JV, Mack LA, Freeny PC, Johnson ML, Sones PJ (1987) Hepatic focal nodular hyperplasia: Angiography, CT, sonography, and scintigraphy AJR 137:983–990Google Scholar
  39. 39.
    Catalano PW, Early ME, Topolosky HW, Martin EW, Jr, Carey LC (1977) Focal nodular hyperplasia of the liver: Report of six patients. Concepts of surgical management. Cancer 39:587–591PubMedGoogle Scholar
  40. 40.
    Stauffer JQ, Lapinski MW, Honold DJ, Myers JK (1975) Focal nodular hyperplasia of the liver and intrahepatic hemorrhage in young women on oral contraceptives. Ann Intern Med 83:301–306PubMedGoogle Scholar
  41. 41.
    Becker YT, Raiford DS, Webb L, Wright JK, Chapman WC, Pinson CW (1995) Rupture and hemorrhage of hepatic focal nodular hyperplasia. Am Surg 61:210–214PubMedGoogle Scholar
  42. 42.
    Luks FI, Yazbeck S, Brandt ML, Bensoussan AL, Brochu P, Blanchard H (1991) Benign liver tumors in children: A 25-year experience. J Pediatr Surg 26:1326–1330PubMedGoogle Scholar
  43. 43.
    Evans JE, Dick R, Sherlock S (1980) Focal nodular hyperplasia of the liver. Br J Surg 67:175–177PubMedGoogle Scholar
  44. 44.
    Petrikovsky BM, Cohen HL, Scimeca P, Bellucci E (1994) Prenatal diagnosis of focal nodular hyperplasia of the liver. Prenat Diagn 14:406–409PubMedGoogle Scholar
  45. 45.
    Ishak KG, Rabin L (1975) Benign tumors of the liver. Med Clin North Am 59:995–1013PubMedGoogle Scholar
  46. 46.
    Stocker JT, Ishak KG (1981) Focal nodular hyperplasia of the liver: A study of 21 pediatric cases. Cancer 48:336–345PubMedGoogle Scholar
  47. 47.
    Belghiti J, Pateron D, Panis Y, Vilgrain V, Flejou JF, Benhamou JP, Fekete F (1993) Resection of presumed benign liver tumours. Br J Surg 80:380–383PubMedGoogle Scholar
  48. 48.
    Iwatsuki S, Todo S, Starzl TE (1990) Excisional therapy for benign hepatic lesions. Surg Gynecol Obstet 171:240–246PubMedGoogle Scholar
  49. 49.
    Berman MN, Libbey NP, Foster JH (1980) Hepatocellular carcinoma. Polygonal cell type with fibrous stroma—an atypical variant with a favorable prognosis. Cancer 46:1448–1455PubMedGoogle Scholar
  50. 50.
    Vecchio FM, Fabiano A, Ghirlanda G, Manna R, Massi G (1984) Fibrolamellar carcinoma of the liver: The malignant counterpart of focal nodular hyperplasia with oncocytic change. Am J Clin Pathol 81:521–526PubMedGoogle Scholar
  51. 51.
    Saul SH, Titelbaum DS, Gansler TS, Vareilo M, Burke DR, Atkinson BF, Rosato EF (1987) The fibrolamellar variant of hepatocellular carcinoma. Its association with focal nodular hyperplasia (review). Cancer 60:3049–3055PubMedGoogle Scholar
  52. 52.
    Welch TJ, Sheedy PF, Johnson CM, Stephens DH, Charboneau JW, Brown ML, May GR, Adson MA, McGill DB (1985) Focal nodular hyperplasia and hepatic adenoma: Comparison of angiography, CT, US, and scintigraphy. Radiology 156:593–595PubMedGoogle Scholar
  53. 53.
    Sandler MA, Petrocelli RD, Marks DS, Lopez R (1980) Ultrasonic features and radionuclide correlation in liver cell adenoma and focal nodular hyperplasia. Radiology 135:393–397PubMedGoogle Scholar
  54. 54.
    Mathieu D, Bruneton JN, Drouillard J (1986) Hepatic adenoma and focal nodular hyperplasia: Dynamic CT study. Radiology 160:53–58PubMedGoogle Scholar
  55. 55.
    Takayasu K, Muramatsu Y, Moriyama N, Yamazaki S, Takayama T, Hirohashi S, Shimamura Y, Takahashi A (1992) Focal nodular hyperplasia of the liver: Arterial angio-CT and microangiography. J Comput Assist Tomogr 16:212–215PubMedGoogle Scholar
  56. 56.
    Fechner RE, Roehm JO (1977) Angiographic and pathologic corelations of hepatic focal nodular hyperplasia. Am J Surg Pathol 1:217–224PubMedGoogle Scholar
  57. 57.
    Park CH, Kim SM, Intenzo C, McEwan J, Zhang J (1993) Focal nodular hyperplasia of the liver. Diagnosis by danamic and SPECT scintigraphy. Clin Nucl Med 18:701–703PubMedGoogle Scholar
  58. 58.
    Lee MJ, Saini S, Hamma B (1991) Focal nodular hyperplasia of the liver: MR findings in 35 proved cases. AJR 156:317–320PubMedGoogle Scholar
  59. 59.
    Mahfouz AE, Hamm B, Taupitz M, Wolf KJ (1993) Hypervascular liver lesions: Differentiation of focal nodular hyperplasia from malignant tumors with dynamic gadolinium-enhanced MR imaging. Radiology 186:133–138PubMedGoogle Scholar
  60. 60.
    Hamrick-Turner JE, Shipkey FH, Cranston PE (1994) Fibrolamellar hepatocellular carcinoma: MR appearance mimicking focal nodular hyperplasia. J Comput Assist Tomogr 18:301–304PubMedGoogle Scholar
  61. 61.
    Rummeny E, Weissleder R, Sironi S, Stark DD, Comptom CC, Hahn PF, Saini S, Wittenberg J, Ferrucci JT (1989) Central scars in primary liver tumors: MR features, specificity, and pathologic correlation. Radiology 171:323–326PubMedGoogle Scholar
  62. 62.
    Mathieu D, Rahmouni A, Anglade MC, Falise B, Beges C, Gheung P, Mollet JJ, Vasile N (1991) Focal nodular hyperplasia of the liver: Assessment with contrast-enhanced TurboFLASH MR imaging. Radiology 180:25–30PubMedGoogle Scholar
  63. 63.
    Carney CN (1974) Clinical cytology of the liver. Acta Cytol 19:244–250Google Scholar
  64. 64.
    Nosher JL, Plafker J (1980) Fine needle aspiration of the liver with ultrasound guidance. Radiology 136:177–180PubMedGoogle Scholar
  65. 65.
    Rosenblatt R, Kutscher R, Moussouris F, Schrieber K, Koss LG (1982) Sonographically guided fine-needle aspiration of liver lesions. JAMA 248:1639–1641CrossRefPubMedGoogle Scholar
  66. 66.
    Ruschenburg I, Droese M (1989) Fine needle aspiration cytology of focal nodular hyperplasia of the liver. Acta Cytol 33:857–860PubMedGoogle Scholar
  67. 67.
    Bottles K, Cohen MB (1991) An approach to fine-needle aspiration biopsy diagnosis of hepatic masses (review). Diagn Cytopathol 7:204–210PubMedGoogle Scholar
  68. 68.
    Foster JH (1994) Benign liver tumors. In: Blumgart LH (ed) Surgery of the liver and biliary tract, 2nd edn. Churchill Livingstone, Edinburgh, pp 1331–1336Google Scholar
  69. 69.
    Blumgart LH (1994) Liver resection. In: Blumgart LH (ed) Surgery of the liver and biliary tract, 2nd edn. Churchill Livingstone, Edinburgh, pp 1495–1538Google Scholar
  70. 70.
    Tepetes K, Selby R, Webb M, Madariaga JR, Iwatsuki S, Starzl TE (1995) Orthotopic liver transplantation for benign hepatic neoplasms. Arch Surg 130:153–156PubMedGoogle Scholar
  71. 71.
    Mowat AP, Gutjahr P, Protmann B, Dawson, JL, Williams R (1976) Focal nodular hyperplasia of the liver: A rational approach to treatment. Gut 17:492–494PubMedGoogle Scholar
  72. 72.
    Nichols FC, van Heerden JA, Weiland LH (1989) Benign liver tumors (review). Surg Clin North Am 69:297–314PubMedGoogle Scholar

Copyright information

© Springer-Verlag 1996

Authors and Affiliations

  • David L. Bartlett
    • 1
  • Lawrence H. Schwartz
    • 2
  • David Klimstra
    • 3
  • Leslie H. Blumgart
    • 1
  1. 1.Department of SurgeryMemorial Sloan-Kettering Cancer CenterNew York
  2. 2.Department of RadiologyMemorial Sloan-Kettering Cancer CenterNew York
  3. 3.Department of PathologyMemorial Sloan-Kettering Cancer CenterNew York

Personalised recommendations