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Focal nodular hyperplasia of the liver: Controversy over etiology

2000; Wiley; Volume: 15; Issue: 11 Linguagem: Inglês

10.1046/j.1440-1746.2000.2374.x

1440-1746

Fukuo Kondo,

Liver Disease and Transplantation

Journal of Gastroenterology and HepatologyVolume 15, Issue 11 p. 1229-1231 Free Access Focal nodular hyperplasia of the liver: Controversy over etiology Fukuo Kondo, Fukuo Kondo Departments of Pathology at Chiba University School of Medicine, Chiba and Funabashi Central Hospital, Funabashi, JapanSearch for more papers by this author Fukuo Kondo, Fukuo Kondo Departments of Pathology at Chiba University School of Medicine, Chiba and Funabashi Central Hospital, Funabashi, JapanSearch for more papers by this author First published: 09 October 2008 https://doi.org/10.1046/j.1440-1746.2000.2374.xCitations: 4 Correspondence: Dr F Kondo Funabashi Central Hospital, Department of Pathology, 6-13-10 Kaijin, Funabashi 273-8556, Chiba, Japan. Email: funabb12@pmet.or.jp AboutSectionsPDF ToolsRequest permissionExport citationAdd to favoritesTrack citation ShareShare Give accessShare full text accessShare full-text accessPlease review our Terms and Conditions of Use and check box below to share full-text version of article.I have read and accept the Wiley Online Library Terms and Conditions of UseShareable LinkUse the link below to share a full-text version of this article with your friends and colleagues. Learn more.Copy URL Share a linkShare onFacebookTwitterLinkedInRedditWechat See article on page 1344 Kumagai et al. described a 2-year-old girl who had been operated on for Wilm's tumor and who, 10 months subsequent to chemotherapy, developed focal nodular hyperplasia (FNH) in the liver.1 Within the lesion, there were organized portal vein thrombi, organized and recanalized arterial thrombi and a necrotic area. The etiology of FNH has long been an enigma. The authors provided direct evidence for thrombosis and circulatory disturbances, with a suggestion that FNH, rather than a congenital lesion, is acquired. With advanced imaging techniques, various benign nodular lesions are now frequently detected and FNH is one of the most commonly found lesions. Some of these lesions are seen in combination with other nodular lesions.2,3 ETIOLOGY The suggested etiologies of FNH in the literature include oral contraceptives,4 hamartoma,5 and vascular abnormalities. Several recent studies support the hypothesis that it is a hyperplastic reaction resulting from arterial malformation that causes FNH.3,6,7 In the report by Kumagai et al., the authors speculate that thrombosis of the hepatic artery and portal vein results in ischemic necrosis that subsequently gives rise to nodule formation following a hepatic arterial recanalization and tissue reperfusion.1 A large artery with a thick muscular wall described in the 2-year-old girl more likely represents a congenital malformation rather than a secondary reaction to thrombosis. Vascular anomalies seen in various other organs in multiple FNH syndrome also suggest a congenital malformation,7 while regenerative nodules are formed by a compensatory regeneration reaction that follows liver cell damage. Regenerative nodules in Budd–Chiari syndrome, which are morphologically similar to FNH,8 are thought to form via such a process. At the same time, it is also possible that FNH or various FNH-like nodular lesions are produced by different causes. It is necessary, however, to determine what is the real cause of abnormal vasculature in FNH: thrombosis, congenital anomaly or both? It is to be noted that an area in the liver where portal blood flow has been interrupted or reduced undergoes atrophy.9 Therefore, simple recanalization of thrombosis may not explain the nodule formation because blood flow within a recanalized artery is less than normal. Additional hyperplastic stimuli are perhaps required. SOME FOCAL NODULAR HYPERPLASIA IS COEXISTENT WITH NODULAR REGENERATIVE HYPERPLASIA Recently, FNH nodules that are in coexistence with nodular regenerative hyperplasia (NRH) have been described.3 Nodules with intermediate features between FNH and NRH also exist as shown in Fig. 1. Focal nodular hyperplasia and NRH are conceptually two different entities. Nonetheless, we sometimes encounter such intermediate types, but their etiology remains obscure. Wanless et al. hypothesized, based on hematologically-induced NRH cases, that NRH results from obliterative portal venopathy.10 Others describe arterial changes that occur in NRH.11,12 Kondo et al. speculated that the congenital anomaly of arteries, as well as portal veins can explain the nodule formation of both FNH and NRH.12 Kumagai et al. also described the role of arteries in the etiology of FNH, but the cause of hyperperfusion is attributed to the recanalization of thrombi.1 Figure 1Open in figure viewerPowerPoint Various nodular lesions with intermediate features between focal nodular hyperplasia (FNH) and nodular regenerative hyperplasia (NRH) in the same patient. This case also demonstrates a typical FNH nodule and typical NRH areas. (A) This lesion was typical NRH in another cross-section. It was also accompanied by portal hypertension. (a) Central scar-like tissues are seen, showing the macroscopic feature of FNH, (b) no scar-like tissue is present so that the lesion is considered to be a large nodule of NRH. In this cross-section and in some other parts of the background liver, no nodule formation is recognized histologically. (B) This is the same case as (A). (a,b) Indiscrete scar-like tissues are present in the nodules, (c) lacks scar-like tissue and is considered to be a large nodule of NRH, (d) is a small nodule and is almost typical of NRH. COEXISTING DISEASES AND CAUSE OF THROMBOSIS In the patient Kumagai et al. presented, chemotherapy with the use of actinomycin D and vincristine was thought to have caused thrombosis.1 Nodular regenerative hyperplasia is known to occur in various diseases. It is notably associated with hematologic disorders,10 immunologic abnormalities and vasculitis.13 They could also induce thrombosis, subsequent liver cell damage and hyperplasia or nodule formation. However, such coexistent diseases are not always able to be demonstrated. CONCLUSION It is generally postulated that circulatory disturbances underlie FNH, NRH and other benign nodular lesions, but precise mechanisms are yet to be elucidated. The following problems remain unresolved: 1 Is the cause of abnormal hepatic circulation ‘thrombosis’ or ‘congenital anomaly’? 2 Is thrombosis a cause or a result? 3 Does the primary damage to vessels occur in the portal or the arterial system? 4 How are FNH, NRH and other nodular lesions related to the reported coexistent disorders? 5 How should various intermediate cases be interpreted? ACKNOWLEDGMENTS The author wishes to express his sincere gratitude to Prof Y Nakanuma from Kanazawa University; Prof. IR Wanless from the University of Toronto and Prof. Emeritus K Okuda from Chiba University, Japan for offering this opportunity to publish this article. REFERENCES 1 Kumagai H, Masuda T & Oikawa H et al. Focal nodular hyperplasia of the liver: Direct evidence of circulatory disturbances. J. Gastroenterol. Hepatol. 2000; 15: 1344– 7. 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– 54. 3 Portmann B, Stewart S, Higenbottam TW, Clayton PT, Lloyd JK & Williams R. Nodular transformation of the liver associated with portal and pulmonary arterial hypertension. Gastroenterology 1993; 104: 616– 21. 4 Baum JK, Holtz F, Bookstein JJ & Klein EW. Possible association between benign hepatomas and oral contraceptives. Lancet 1973; 2: 926– 9. 5 Benz EJ & Baggenstoss AH. Focal cirrhosis of the liver: Its relation to the so-called hamartoma (Adenoma, benign hepatoma). Cancer 1953; 4: 743– 55. 6 Wanless IR, Maudsley C & Adams R. On the pathogenesis of focal nodular hyperplasia of the liver. Hepatology 1985; 6: 1194– 200. 7 Wanless IR, Albrech S & Bilbao J et al. Multiple focal nodular hyperplasia of the liver associated with vascular malformations of various organs and neoplasia of the brain: A new syndrome. Mod. Pathol 1989; 2: 456– 62. 8 International Working Party. Terminology of nodular hepatocellular lesions. Hepatology 1995; 22: 983– 93. 9 Harada H, Imamura H, Miyagawa S & Kawasaki S. Fate of human liver after hemihepatic portal vein embolization: Cell kinetic and morphometric study. Hepatology 1997; 26: 1162– 70. 10 Wanless IR, Godwin TA, Allen F & Feder A. Nodular regenerative hyperplasia of the liver in hematologic disorders: A possible response to obliterative portal venopathy. A morphometric study of nine cases with an hypothesis on the pathogenesis. Medicine (Baltimore) 1980; 59: 367– 79. 11 Stromeyer FW & Ishak KG. Nodular transformation (nodular ‘regenerative’ hyperplasia) of the liver. A clinicopathologic study of 30 cases. Hum. Pathol. 1981; 12: 60– 71. 12 Kondo F, Kondo Y & Nagao T et al. Etiological analysis of focal nodular hyperplasia of the liver, with emphasis on similar abnormal vasculatures to nodular regenerative hyperplasia and idiopathic portal hypertension. Pathol. Res. Pract. 1998; 194: 487– 95. 13 Reynolds WJ & Wanless IR. Nodular regenerative hyperplasia of the liver in a patient with rheumatoid vasculitis; a morphometric study suggesting a role for hepatic arteries in the pathogenesis. J. Rheumatol 1984; 11: 838– 42. Citing Literature Volume15, Issue11November 2000Pages 1229-1231 FiguresReferencesRelatedInformation