Prevalence of benign focal liver lesions and non-hepatocellular carcinoma malignant lesions in liver cirrhosis

Abstract

Liver cirrhosis is associated with an increased risk of developing hepatocellular carcinoma (HCC). However, other benign and malignant liver lesions may co-exist or may be the only focal liver lesion (FLL) detected. Compared to HCC, comparatively little is known about the frequency and natural history of benign FLL in patients with established liver cirrhosis.

This review analyses the prevalence and frequency of benign and malignant FLL others than hepatocellular carcinoma (HCC) in liver cirrhosis including imaging and autopsy studies. Understanding these data should be helpful in avoiding misdiagnoses.

Zusammenfassung

Die Leberzirrhose ist mit einem erhöhten Risiko verbunden, ein hepatozelluläres Karzinom (HCC) zu entwickeln. Es können jedoch auch andere benigne und maligne Leberläsionen koexistieren oder die einzige nachgewiesene fokale Leberläsion (FLL) sein. Im Vergleich zum HCC ist über die Häufigkeit und den Verlauf benigner FLL bei Patienten mit bestehender Leberzirrhose vergleichsweise wenig bekannt.

Dieser Review analysiert die Prävalenz und Häufigkeit von benignen und malignen FLL außer dem hepatozellulären Karzinom (HCC) bei Leberzirrhose, einschließlich Bildgebungs- und Autopsiestudien. Das Verständnis dieser Daten sollte hilfreich sein, um Fehldiagnosen zu vermeiden.

Schlüsselwörter

Hämangiom - Fokal Noduläre Hyperplasie - Adenom - Leberzirrhose - HCC

Keywords

hemangioma - focal nodular hyperplasia - adenoma - Liver cirrhosis - HCC

Publication History

Received: 15 December 2021

Accepted after revision: 13 June 2022

Article published online:
22 November 2022

• References

• 1 Yu MW, Hsu FC, Sheen IS. et al. Prospective study of hepatocellular carcinoma and liver cirrhosis in asymptomatic chronic hepatitis B virus carriers. Am J Epidemiol 1997; 145: 1039-1047 DOI: 10.1093/oxfordjournals.aje.a009060. (PMID: 9169913)
• 2 Pocha C, Xie C. Hepatocellular carcinoma in alcoholic and non-alcoholic fatty liver disease-one of a kind or two different enemies?. Transl Gastroenterol Hepatol 2019; 4: 72 DOI: 10.21037/tgh.2019.09.01. (PMID: 31728429)
• 3 Caraiani C, Boca B, Bura V. et al. CT/MRI LI-RADS v2018 vs. CEUS LI-RADS v2017-Can Things Be Put Together?. Biology (Basel) 2021; 10 DOI: 10.3390/biology10050412. (PMID: 34066607)
• 4 Dietrich CF, Dong Y, Kono Y. et al. LI-RADS ancillary features on contrast-enhanced ultrasonography. Ultrasonography 2020; 39: 221-228 DOI: 10.14366/usg.19052. (PMID: 32475089)
• 5 Dietrich CF, Potthoff A, Helmberger T. et al. Group CL-RW. [Contrast-enhanced ultrasound: Liver Imaging Reporting and Data System (CEUS LI-RADS)]. Z Gastroenterol 2018; 56: 499-506 DOI: 10.1055/s-0043-124874. (PMID: 29734449)
• 6 Lyshchik A, Kono Y, Dietrich CF. et al. Contrast-enhanced ultrasound of the liver: technical and lexicon recommendations from the ACR CEUS LI-RADS working group. NY: Abdom Radiol; 2017
• 7 Piscaglia F, Wilson SR, Lyshchik A. et al. American College of Radiology Contrast Enhanced Ultrasound Liver Imaging Reporting and Data System (CEUS LI-RADS) for the diagnosis of Hepatocellular Carcinoma: a pictorial essay. Ultraschall Med 2017; 38: 320-324 DOI: 10.1055/s-0042-124661. (PMID: 28329875)
• 8 Renzulli M, Brocchi S, Ierardi AM. et al. Imaging-based diagnosis of benign lesions and pseudolesions in the cirrhotic liver. Magn Reson Imaging 2021; 75: 9-20 DOI: 10.1016/j.mri.2020.09.008. (PMID: 32926993)
• 9 Ignee A, Weiper D, Schuessler G. et al. Sonographic characterisation of hepatocellular carcinoma at time of diagnosis. Z. Gastroenterol 2005; 43: 289-294 DOI: 10.1055/s-2004-813815. (PMID: 15765302)
• 10 Dodd GD, Baron RL, Oliver JH. et al. Spectrum of imaging findings of the liver in end-stage cirrhosis: Part II, focal abnormalities. AJR Am J Roentgenol 1999; 173: 1185-1192 DOI: 10.2214/ajr.173.5.10541086. (PMID: 10541086)
• 11 Ruiz Guinaldo A, Martin Herrera L, Roldan Cuadra R. Hepatic tumors in patients with cirrhosis: an autopsy study. Rev Esp Enferm Dig 1997; 89: 771-780 (PMID: 9401434)
• 12 Galvao B, Torres LR, Cardia PP. et al. Prevalence of simple liver cysts and hemangiomas in cirrhotic and non-cirrhotic patients submitted to magnetic resonance imaging. J Radiologia Brasileira 2013; 46: 203-208
• 13 Karhunen PJ. Benign hepatic tumours and tumour like conditions in men. J Clin Pathol 1986; 39: 183-188 DOI: 10.1136/jcp.39.2.183. (PMID: 3950039)
• 14 Karhunen PJ, Penttila A, Liesto K. et al. Benign bile duct tumours, non-parasitic liver cysts and liver damage in males. J Hepatol 1986; 2: 89-99 DOI: 10.1016/s0168-8278(86)80012-5. (PMID: 3950364)
• 15 Brancatelli G, Federle MP, Blachar A. et al. Hemangioma in the cirrhotic liver: diagnosis and natural history. Radiology 2001; 219: 69-74 DOI: 10.1148/radiology.219.1.r01ap3269. (PMID: 11274536)
• 16 Duran R, Ronot M, Di Renzo S. et al. Is magnetic resonance imaging of hepatic hemangioma any different in liver fibrosis and cirrhosis compared to normal liver?. Eur J Radiol 2015; 84: 816-822 DOI: 10.1016/j.ejrad.2015.01.016. (PMID: 25703650)
• 17 Mastropasqua M, Kanematsu M, Leonardou P. et al. Cavernous hemangiomas in patients with chronic liver disease: MR imaging findings. Magn Reson Imaging 2004; 22: 15-18 DOI: 10.1016/j.mri.2003.02.001. (PMID: 14972389)
• 18 Dietrich CF, Mertens JC, Braden B. et al. Contrast-enhanced ultrasound of histologically proven liver hemangiomas. Hepatology 2007; 45: 1139-1145 DOI: 10.1002/hep.21615. (PMID: 17464990)
• 19 Dietrich CF, Ignee A, Trojan J. et al. Improved characterisation of histologically proven liver tumours by contrast enhanced ultrasonography during the portal venous and specific late phase of SHU 508A. Gut 2004; 53: 401-405 DOI: 10.1136/gut.2003.026260. (PMID: 14960524)
• 20 Vernuccio F, Cannella R, Porrello G. et al. Uncommon imaging evolutions of focal liver lesions in cirrhosis. Abdom Radiol (NY) 2019; 44: 3069-3077 DOI: 10.1007/s00261-019-02101-4. (PMID: 31222462)
• 21 Ren Y, Yuan G, Zhou Y. et al. Incidence and characteristics of benign liver space-occupying mass in 17 721 patients with chronic hepatitis B: a color Doppler ultrasound-based case-control study. Nan Fang Yi Ke Da Xue Xue Bao 2019; 39: 1149-1154 DOI: 10.12122/j.issn.1673-4254.2019.10.03. (PMID: 31801719)
• 22 Libbrecht L, Cassiman D, Verslype C. et al. Clinicopathological features of focal nodular hyperplasia-like nodules in 130 cirrhotic explant livers. Am J Gastroenterol 2006; 101: 2341-2346 DOI: 10.1111/j.1572-0241.2006.00783.x. (PMID: 17032200)
• 23 Seitz K, Greis C, Schuler A. et al. Frequency of tumor entities among liver tumors of unclear etiology initially detected by sonography in the noncirrhotic or cirrhotic livers of 1349 patients. Results of the DEGUM multicenter study. Ultraschall Med 2011; 32: 598-603 DOI: 10.1055/s-0031-1281858. (PMID: 22161557)
• 24 Dietrich CF, Shi L, Lowe A. et al. Conventional ultrasound for diagnosis of hepatic steatosis is better than believed. Z Gastroenterol 2021; DOI: 10.1055/a-1491-1771. (PMID: 34171931)
• 25 Chiorean L, Caraiani C, Radzina M. et al. Vascular phases in imaging and their role in focal liver lesions assessment. Clin Hemorheol Microcirc 2015; 62: 299-326 DOI: 10.3233/CH-151971. (PMID: 26444602)
• 26 Hirche TO, Ignee A, Hirche H. et al. Evaluation of hepatic steatosis by ultrasound in patients with chronic hepatitis C virus infection. Liver Int 2007; 27: 748-757 DOI: 10.1111/j.1478-3231.2007.01491.x. (PMID: 17617117)
• 27 Dietrich CF, Schall H, Kirchner J. et al. Sonographic detection of focal changes in the liver hilus in patients receiving corticosteroid therapy. Z. Gastroenterol 1997; 35: 1051-1057 (PMID: 9487637)
• 28 Kaltenbach TE, Engler P, Kratzer W. et al. Prevalence of benign focal liver lesions: ultrasound investigation of 45,319 hospital patients. Abdom Radiol (NY) 2016; 41: 25-32 DOI: 10.1007/s00261-015-0605-7. (PMID: 26830608)
• 29 Seguchi T, Akiyama Y, Itoh H. et al. Multiple hepatic peribiliary cysts with cirrhosis. J Gastroenterol 2004; 39: 384-390 DOI: 10.1007/s00535-003-1307-4. (PMID: 15168252)
• 30 Nakanuma Y, Kurumaya H, Ohta G. Multiple cysts in the hepatic hilum and their pathogenesis. A suggestion of periductal gland origin. Virchows Arch A Pathol Anat Histopathol 1984; 404: 341-350 DOI: 10.1007/BF00695218. (PMID: 6093347)
• 31 Bazerbachi F, Haffar S, Sugihara T. et al. Peribiliary cysts: a systematic review and proposal of a classification framework. BMJ Open Gastroenterol 2018; 5: e000204 DOI: 10.1136/bmjgast-2018-000204. (PMID: 29915665)
• 32 Ronot M, Dioguardi Burgio M, Purcell Y. et al. Focal lesions in cirrhosis: Not always HCC. Eur J Radiol 2017; 93: 157-168
• 33 Pedica F, Heaton N, Quaglia A. Peribiliary glands pathology in a large series of end-stage alcohol-related liver disease. Virchows Arch 2020; 477: 817-823 DOI: 10.1007/s00428-020-02851-3. (PMID: 32506156)
• 34 Nakanuma Y, Uesaka K, Kakuda Y. et al. Intraductal Papillary Neoplasm of Bile Duct: Updated Clinicopathological Characteristics and Molecular and Genetic Alterations. J Clin Med 2020; 9 DOI: 10.3390/jcm9123991. (PMID: 33317146)
• 35 Goldstein MJ. Metastases in the cirrhotic liver. N Engl J Med 1969; 281: 221 DOI: 10.1056/NEJM196907242810421. (PMID: 5790511)
• 36 Hamaya K, Hashimoto H, Maeda Y. Metastatic carcinoma in cirrhotic liver--Statistical survey of autopsies in Japan. Acta Pathol Jpn 1975; 25: 153-159 DOI: 10.1111/j.1440-1827.1975.tb00854.x. (PMID: 1166800)
• 37 Pereira-Lima JE, Lichtenfels E, Barbosa FS. et al. Prevalence study of metastases in cirrhotic livers. Hepatogastroenterology 2003; 50: 1490-1495 (PMID: 14571771)
• 38 Vanbockrijck M, Kloppel G. Incidence and morphology of liver metastasis from extrahepatic malignancies to cirrhotic livers. Zentralbl Pathol 1992; 138: 91-96 (PMID: 1610770)
• 39 Melato M, Laurino L, Mucli E. et al. Relationship between cirrhosis, liver cancer, and hepatic metastases. An autopsy study. Cancer 1989; 64: 455-459 DOI: 10.1002/1097-0142(19890715)64:23.0.co;2-c. (PMID: 2736492)
• 40 Seymour K, Charnley RM. Evidence that metastasis is less common in cirrhotic than normal liver: a systematic review of post-mortem case-control studies. Br J Surg 1999; 86: 1237-1242 DOI: 10.1046/j.1365-2168.1999.01228.x. (PMID: 10540123)
• 41 Mahdi Z, Ettel MG, Gonzalez RS. et al. Metastases can occur in cirrhotic livers with patent portal veins. Diagn Pathol 2021; 16: 18 DOI: 10.1186/s13000-021-01076-5. (PMID: 33639984)
• 42 Seitz G. Why are metastases in cirrhotic livers so rare?. Ultraschall Med 1989; 10: 123-126 DOI: 10.1055/s-2007-1005976. (PMID: 2672314)
• 43 Ramia JM, Lopez-Andujar R, Torras J. et al. Multicentre study of liver metastases from colorectal cancer in pathological livers. HPB (Oxford) 2011; 13: 320-323 DOI: 10.1111/j.1477-2574.2010.00287.x. (PMID: 21492331)
• 44 Liu Q, Zhang H, Jiang X. et al. Factors involved in cancer metastasis: a better understanding to “seed and soil” hypothesis. Mol Cancer 2017; 16: 176 DOI: 10.1186/s12943-017-0742-4. (PMID: 29197379)
• 45 Iwakiri Y, Shah V, Rockey DC. Vascular pathobiology in chronic liver disease and cirrhosis – current status and future directions. J Hepatol 2014; 61: 912-924 DOI: 10.1016/j.jhep.2014.05.047. (PMID: 24911462)
• 46 Cai B, Liao K, Song XQ. et al. Patients with chronically diseased livers have lower incidence of colorectal liver metastases: a meta-analysis. PLoS One 2014; 9: e108618 DOI: 10.1371/journal.pone.0108618. (PMID: 25265536)
• 47 Song E, Chen J, Ouyang N. et al. Kupffer cells of cirrhotic rat livers sensitize colon cancer cells to Fas-mediated apoptosis. Br J Cancer 2001; 84: 1265-1271 DOI: 10.1054/bjoc.2000.1737. (PMID: 11336480)
• 48 Cheng L, Geng L, Dai B. et al. Repression of let-7a cluster prevents adhesion of colorectal cancer cells by enforcing a mesenchymal phenotype in presence of liver inflammation. Cell Death Dis 2018; 9: 489 DOI: 10.1038/s41419-018-0477-1. (PMID: 29695839)
• 49 Beuth J, Ko HL, Pulverer G. et al. Importance of lectins for the prevention of bacterial infections and cancer metastases. Glycoconj J 1995; 12: 1-6 DOI: 10.1007/BF00731862. (PMID: 7795408)
• 50 Uhlenbruck G, Beuth J, Weidtman V. Liver lectins: mediators for metastases?. Experientia 1983; 39: 1314-1315 DOI: 10.1007/BF01990389. (PMID: 6641914)
• 51 Lieber MM. The rare occurrence of metastatic carcinoma in the cirrhotic liver. Am J Med Sci 1957; 233: 145-152 DOI: 10.1097/00000441-195702000-00005. (PMID: 13394591)
• 52 Ruebner BH, Green R, Miyai K. et al. The rarity of intrahepatic metastasis in cirrhosis of the liver. A statistical explanation with some comments on the interpretation of necropsy data. Am J Pathol 1961; 39: 739-746 (PMID: 14495098)
• 53 Han EC, Ryoo SB, Park JW. et al. Oncologic and surgical outcomes in colorectal cancer patients with liver cirrhosis: A propensity-matched study. PLoS One 2017; 12: e0178920 DOI: 10.1371/journal.pone.0178920. (PMID: 28586376)
• 54 Chiou WY, Chang CM, Tseng KC. et al. Effect of liver cirrhosis on metastasis in colorectal cancer patients: a nationwide population-based cohort study. Jpn J Clin Oncol 2015; 45: 160-168 DOI: 10.1093/jjco/hyu178. (PMID: 25378650)
• 55 Kondo T, Okabayashi K, Hasegawa H. et al. The impact of hepatic fibrosis on the incidence of liver metastasis from colorectal cancer. Br J Cancer 2016; 115: 34-39 DOI: 10.1038/bjc.2016.155. (PMID: 27280634)
• 56 Terzi E, Iavarone M, Pompili M. et al. Contrast ultrasound LI-RADS LR-5 identifies hepatocellular carcinoma in cirrhosis in a multicenter restropective study of 1,006 nodules. J Hepatol 2018; 68: 485-492 DOI: 10.1016/j.jhep.2017.11.007. (PMID: 29133247)
• 57 Mork H, Ignee A, Schuessler G. et al. Analysis of neuroendocrine tumour metastases in the liver using contrast enhanced ultrasonography. Scand.J. Gastroenterol 2007; 42: 652-662 DOI: 10.1080/00365520601021765. (PMID: 17454888)
• 58 Dong Y, Teufel A, Trojan J. et al. Contrast enhanced ultrasound in mixed hepatocellular cholangiocarcinoma: Case series and review of the literature. Dig Liver Dis 2018; 50: 401-407 DOI: 10.1016/j.dld.2017.11.003. (PMID: 29233685)
• 59 Dantas E, Santos J, Coelho M. et al. Primary hepatic lymphoma in a patient with cirrhosis: a case report. J Med Case Rep 2020; 14: 168 DOI: 10.1186/s13256-020-02471-0. (PMID: 32977834)
• 60 Imrani K, Znati K, Amouri W. et al. Primary hepatic lymphoma in liver cirrhosis: A rare case report. Radiol Case Rep 2021; 16: 2179-2183 DOI: 10.1016/j.radcr.2021.05.028. (PMID: 34188736)
• 61 European Association for the Study of the Liver. Electronic address: [e-mail], European Association for the Study of the L. EASL Clinical Practice Guidelines: Management of hepatocellular carcinoma. J Hepatol 2018; 69: 182-236
• 62 Heimbach JK, Kulik LM, Finn RS. et al. AASLD guidelines for the treatment of hepatocellular carcinoma. Hepatology 2018; 67: 358-380 DOI: 10.1002/hep.29086. (PMID: 28130846)
• 63 Forner A, Vilana R, Ayuso C. et al. Diagnosis of hepatic nodules 20 mm or smaller in cirrhosis: Prospective validation of the noninvasive diagnostic criteria for hepatocellular carcinoma. Hepatology 2008; 47: 97-104 DOI: 10.1002/hep.21966. (PMID: 18069697)
• 64 Mullhaupt B, Durand F, Roskams T. et al. Is tumor biopsy necessary?. Liver Transpl 2011; 17: S14-25 DOI: 10.1002/lt.22374. (PMID: 21744470)
• 65 Khalili K, Kim TK, Jang HJ. et al. Indeterminate 1–2-cm nodules found on hepatocellular carcinoma surveillance: biopsy for all, some, or none?. Hepatology 2011; 54: 2048-2054 DOI: 10.1002/hep.24638. (PMID: 22057624)
• 66 Bru C, Maroto A, Bruix J. et al. Diagnostic accuracy of fine-needle aspiration biopsy in patients with hepatocellular carcinoma. Dig Dis Sci 1989; 34: 1765-1769 DOI: 10.1007/BF01540056. (PMID: 2555123)
• 67 Choi JY, Lee HC, Yim JH. et al. Focal nodular hyperplasia or focal nodular hyperplasia-like lesions of the liver: a special emphasis on diagnosis. J Gastroenterol Hepatol 2011; 26: 1004-1009 DOI: 10.1111/j.1440-1746.2011.06659.x. (PMID: 21251063)
• 68 Lee H, Yoon JH, Kim H. et al. False Positive Diagnosis of Hepatocellular Carcinoma in Liver Resection Patients. J Korean Med Sci 2017; 32: 315-320 DOI: 10.3346/jkms.2017.32.2.315. (PMID: 28049244)
• 69 Kim MJ, Lee S, An C. Problematic lesions in cirrhotic liver mimicking hepatocellular carcinoma. Eur Radiol 2019; 29: 5101-5110 DOI: 10.1007/s00330-019-06030-0. (PMID: 30788586)
• 70 Lee YH, Kim SH, Cho MY. et al. Focal nodular hyperplasia-like nodules in alcoholic liver cirrhosis: radiologic-pathologic correlation. AJR Am J Roentgenol 2007; 188: W459-463 DOI: 10.2214/AJR.05.1998. (PMID: 17449744)
• 71 Marin D, Galluzzo A, Plessier A. et al. Focal nodular hyperplasia-like lesions in patients with cavernous transformation of the portal vein: prevalence, MR findings and natural history. Eur Radiol 2011; 21: 2074-2082 DOI: 10.1007/s00330-011-2161-z. (PMID: 21710271)
• 72 Seo JM, Lee SJ, Kim SH. et al. Hepatocellular carcinoma arising from hepatocellular adenoma in a hepatitis B virus-associated cirrhotic liver. Clin Radiol 2012; 67: 329-333
• 73 Alshak NS, Cocjin J, Podesta L. et al. Hepatocellular adenoma in glycogen storage disease type IV. Arch Pathol Lab Med 1994; 118: 88-91 (PMID: 8285839)