Liver Cytology

  • Derek B. Allison
  • David Borzik
  • Qing Kay LiEmail author
Part of the Atlas of Anatomic Pathology book series (AAP)


Although there have been many advancements in imaging techniques for the diagnosis of benign and malignant liver lesions, obtaining tissue for morphologic and molecular characterization is critical for diagnosis and treatment. Fine needle aspiration (FNA) and needle core biopsy are the most commonly used procedures for the morphological evaluation of liver lesions because of their decreased rates of procedural complications compared with open and more invasive approaches. These procedures are usually performed in an outpatient setting under the guidance of ultrasound or CT. This chapter summarizes the key findings for the accurate morphological diagnosis of benign, malignant, and metastatic lesions of the liver.


Liver cytology Benign liver lesions Malignant liver tumors Metastatic tumors to the liver Ultrasound-guided fine needle aspiration CT-guided fine needle aspiration FNA 


  1. 1.
    Xue Y, Farris AB, Quigley B, Krasinskas A. The impact of new technologic and molecular advances in the daily practice of gastrointestinal and hepatobiliary pathology. Arch Pathol Lab Med. 2017;141:517–27.CrossRefPubMedGoogle Scholar
  2. 2.
    Srinivasan I, Tang SJ, Vilmann AS, Menachery J, Vilmann P. Hepatic applications of endoscopic ultrasound: Current status and future directions. World J Gastroenterol. 2015;21:12544–57.CrossRefPubMedPubMedCentralGoogle Scholar
  3. 3.
    Sadeghi A, Mohamadnejad M, Islami F, Keshtkar A, Biglari M, Malekzadeh R, Eloubeidi MA. Diagnostic yield of EUS-guided FNA for malignant biliary stricture: a systematic review and meta-analysis. Gastrointest Endosc. 2016;83:290–8.CrossRefPubMedGoogle Scholar
  4. 4.
    Koduru P, Suzuki R, Lakhtakia S, Ramchandani M, Makmun D, Bhutani MS. Role of endoscopic ultrasound in diagnosis and management of hepatocellular carcinoma. J Hepatocell Carcinoma. 2015;2:143–9.PubMedPubMedCentralGoogle Scholar
  5. 5.
    Crowe DR, Eloubeidi MA, Chhieng DC, Jhala NC, Jhala D, Eltoum IA. Fine-needle aspiration biopsy of hepatic lesions: computerized tomographic-guided versus endoscopic ultrasound-guided FNA. Cancer. 2006;108:180–5.CrossRefPubMedGoogle Scholar
  6. 6.
    Onofre AS, Pomjanski N, Buckstegge B, Böcking A. Immunocytochemical diagnosis of hepatocellular carcinoma and identification of carcinomas of unknown primary metastatic to the liver on fine-needle aspiration cytologies. Cancer Cytopathol. 2007;111:259–68.CrossRefGoogle Scholar
  7. 7.
    Cibas ES. Peritoneal washings. In: Cibas ES, Ducatman BS, editors. Cytology: diagnostic principles and clinical correlates. Philadelphia: Saunders/Elsevier; 2014. p. 155–70.Google Scholar
  8. 8.
    Dodd LG, Mooney EE, Layfield LJ, Nelson RC. Fine-needle aspiration of the liver and pancreas: a cytology primer for radiologists. Radiology. 1997;203:1–9.CrossRefPubMedGoogle Scholar
  9. 9.
    Ljung BM, Ferrell LD. Fine-needle aspiration biopsy of the liver: diagnostic problems. Pathology (Phila). 1996;4:365–88.Google Scholar
  10. 10.
    Hammoud GM, Almashhrawi A, Ibdah JA. Usefulness of endoscopic ultrasound-guided fine needle aspiration in the diagnosis of hepatic, gallbladder and biliary tract Lesions. World J Gastrointest Oncol. 2014;6:420–9.CrossRefPubMedPubMedCentralGoogle Scholar
  11. 11.
    Jones K, Biederman L, Draganova-Tacheva R, Solomides C, Bibbo M. Diagnostic yield of endoscopic ultrasound-guided fine-needle aspiration cytology of porta hepatis lesions: a retrospective study. Acta Cytol. 2016;60:154–60.CrossRefPubMedGoogle Scholar
  12. 12.
    Wee A. Fine needle aspiration biopsy of hepatocellular carcinoma and hepatocellular nodular lesions: role, controversies and approach to diagnosis. Cytopathology. 2011;22:287–305.CrossRefPubMedGoogle Scholar
  13. 13.
    Chaudhary HB, Bhanot P, Logroño R. Phenotypic diversity of intrahepatic and extrahepatic cholangiocarcinoma on aspiration cytology and core needle biopsy. Cancer Cytopathol. 2005;105:220–8.CrossRefGoogle Scholar
  14. 14.
    VandenBussche C, Gocke CD, Li QK. Fine needle aspiration of metastatic papillary thyroid carcinoma found in the liver. Diagn Cytopathol. 2013;41:418–24.CrossRefPubMedGoogle Scholar
  15. 15.
    Balani S, Malik R, Malik R, Kapoor N. Cytomorphological variables of hepatic malignancies in fine needle aspiration smears with special reference to grading of hepatocellular carcinoma. J Cytol. 2013;30:116–20.CrossRefPubMedPubMedCentralGoogle Scholar
  16. 16.
    Geramizadeh B, Asadi N, Tabei SZ. Cytologic comparison between malignant and regenerative nodules in the background of cirrhosis. Hepat Mon. 2012;12:448–52.CrossRefPubMedPubMedCentralGoogle Scholar
  17. 17.
    Bibbo M, Wood MD, Fitzpatrick BT. Peritoneal washings and ovary. In: Bibbo M, Wilbur D, editors. Comprehensive cytopathology. 3rd ed. Philadelphia: Saunders/Elsevier; 2008. p. 291–302.CrossRefGoogle Scholar
  18. 18.
    DeMay RM. The art and science of cytopathology, exfoliative cytology, vol. 1. 2nd ed. Chicago: ASCP Press; 2012.Google Scholar
  19. 19.
    Lev-Toaff AS, Bach AM, Wechsler RJ, Hilpert PL, Gatalica Z, Rubin R. The radiologic and pathologic spectrum of biliary hamartomas. AJR Am J Roentgenol. 1995;165:309–13.CrossRefPubMedGoogle Scholar
  20. 20.
    Mortele KJ, Ros PR. Benign liver neoplasms. Clin Liver Dis. 2002;6:119–45.CrossRefPubMedGoogle Scholar
  21. 21.
    Salles VJ, Marotta A, Netto JM, Speranzini MB, Martins MR. Bile duct hamartomas—the von Meyenburg complex. Hepatobiliary Pancreat Dis Int. 2007;6:108–9.PubMedGoogle Scholar
  22. 22.
    Ghouri YA, Mian I, Rowe JH. Review of hepatocellular carcinoma: Epidemiology, etiology, and carcinogenesis. J Carcinog. 2017;16:1. Scholar
  23. 23.
    Ma C, Zhang Q, Greten TF. Nonalcoholic fatty liver disease promotes hepatocellular carcinoma through direct and indirect effects on hepatocytes. FEBS J. 2017;285:752–62. Scholar
  24. 24.
    Sheikh U, Rodic N, Maleki Z. Extramedullary hematopoiesis: cytomorphologic, histologic, and radiologic findings in sixteen cases. Acta Cytol. 2015;59:144–8.CrossRefPubMedGoogle Scholar
  25. 25.
    Naganuma H, Ishida H, Ogawa M, Watanabe Y, Watanabe D, Ohyama Y, Watanabe T. Focal nodular hyperplasia: our experience of 53 Japanese cases. J Med Ultrason (2001). 2017;44:79–88.CrossRefGoogle Scholar
  26. 26.
    Burgio MD, Ronot M, Salvaggio G, Vilgrain V, Brancatelli G. Imaging of hepatic focal nodular hyperplasia: pictorial review and diagnostic strategy. Semin Ultrasound CT MR. 2016;37:511–24.CrossRefGoogle Scholar
  27. 27.
    Doolittle DA, Atwell TD, Sanchez W, Mounajjed T, Hough DM, Schmit GD, Kurup AN. Safety and outcomes of percutaneous biopsy of 61 hepatic adenomas. AJR Am J Roentgenol. 2016;206:871–6.CrossRefPubMedGoogle Scholar
  28. 28.
    Bioulac-Sage P, Sempoux C, Balabaud C. Hepatocellular adenomas: morphology and genomics. Gastroenterol Clin North Am. 2017;46:253–72.CrossRefPubMedGoogle Scholar
  29. 29.
    Nault JC, Couchy G, Balabaud C, Morcrette G, Caruso S, Blanc JF, et al.; GENTHEP Investigators. Molecular classification of hepatocellular adenoma associates with risk factors, bleeding, and malignant transformation. Gastroenterology. 2017;152:880–94.CrossRefPubMedGoogle Scholar
  30. 30.
    VandenBussche CJ, Wakely PE Jr, Siddiqui MT, Maleki Z, Ali SZ. Cytopathologic characteristics of epithelioid vascular malignancies. Acta Cytol. 2014;58:356–66.CrossRefPubMedGoogle Scholar
  31. 31.
    Harman M, Nart D, Acar T, Elmas N. Primary mesenchymal liver tumors: radiological spectrum, differential diagnosis, and pathologic correlation. Abdom Imaging. 2015;40:1316–30.CrossRefPubMedGoogle Scholar
  32. 32.
    Ahrens WA, Ridenour RV III, Caron BL, Miller DV, Folpe AL. GLUT-1 expression in mesenchymal tumors: an immunohistochemical study of 247 soft tissue and bone neoplasms. Hum Pathol. 2008;39:1519–26.CrossRefPubMedGoogle Scholar
  33. 33.
    Das DK, Bhambhani S, Pant CS. Ultrasound guided fine-needle aspiration cytology: diagnosis of hydatid disease of the abdomen and thorax. Diagn Cytopathol. 1995;12:173–6.CrossRefPubMedGoogle Scholar
  34. 34.
    Babu KS, Goel D, Prayaga A, Rao IS, Kumar A. Intraabdominal hydatid cyst: a case report. Acta Cytol. 2008;52:464–6.CrossRefPubMedGoogle Scholar
  35. 35.
    Siegel RL, Miller KD, Jemal A. Cancer statistics, 2017. CA Cancer J Clin. 2017;67:7–30.CrossRefGoogle Scholar
  36. 36.
    Islami F, Miller KD, Siegel RL, Fedewa SA, Ward EM, Jemal A. Disparities in liver cancer occurrence in the United States by race/ethnicity and state. CA Cancer J Clin. 2017;67:273–89.CrossRefPubMedGoogle Scholar
  37. 37.
    Nault JC. Pathogenesis of hepatocellular carcinoma according to aetiology. Best Pract Res Clin Gastroenterol. 2014;28:937–47.CrossRefPubMedGoogle Scholar
  38. 38.
    Charrez B, Qiao L, Hebbard L. Hepatocellular carcinoma and non-alcoholic steatohepatitis: the state of play. World J Gastroenterol. 2016;22:2494–502.CrossRefPubMedPubMedCentralGoogle Scholar
  39. 39.
    Nishida N, Kudo M. Clinical significance of epigenetic alterations in human hepatocellular carcinoma and its association with genetic mutations. Dig Dis. 2016;34:708–13.CrossRefPubMedGoogle Scholar
  40. 40.
    Jain D. Tissue diagnosis of hepatocellular carcinoma. J Clin Exp Hepatol. 2014;4(Suppl 3):S67–73.CrossRefPubMedPubMedCentralGoogle Scholar
  41. 41.
    Soudah B, Schirakowski A, Gebel M, Potthoff A, Braubach P, Schlue J, et al. Overview and evaluation of the value of fine needle aspiration cytology in determining the histogenesis of liver nodules: 14 years of experience at Hannover Medical School. Oncol Rep. 2015;33:81–7.CrossRefPubMedGoogle Scholar
  42. 42.
    Wee A. Fine-needle aspiration biopsy of hepatocellular carcinoma and related hepatocellular nodular lesions in cirrhosis: controversies, challenges, and expectations. Patholog Res Int. 2011;2011:587936.PubMedPubMedCentralGoogle Scholar
  43. 43.
    Saleh HA, Aulicino M, Zaidi SY, Khan AZ, Masood S. Discriminating hepatocellular carcinoma from metastatic carcinoma on fine-needle aspiration biopsy of the liver: the utility of immunocytochemical panel. Diagn Cytopathol. 2009;37:184–90.CrossRefPubMedGoogle Scholar
  44. 44.
    Khurana U, Handa U, Mohan H, Sachdev A. Evaluation of aspiration cytology of the liver space occupying lesions by simultaneous examination of smears and cell blocks. Diagn Cytopathol. 2009;37:557–63.CrossRefPubMedGoogle Scholar
  45. 45.
    Yan BC, Gong C, Song J, Krausz T, Tretiakova M, Hyjek E, et al. Arginase-1: a new immunohistochemical marker of hepatocytes and hepatocellular neoplasms. Am J Surg Pathol. 2010;34:1147–54.CrossRefPubMedPubMedCentralGoogle Scholar
  46. 46.
    Lau SK, Prakash S, Geller SA, Alsabeh R. Comparative immunohistochemical profile of hepatocellular carcinoma, cholangiocarcinoma, and metastatic adenocarcinoma. Hum Pathol. 2002;33:1175–81.CrossRefPubMedGoogle Scholar
  47. 47.
    Wang HL, Kim CJ, Koo J, Zhou W, Choi EK, Arcega R, et al. Practical immunohistochemistry in neoplastic pathology of the gastrointestinal tract, liver, biliary tract, and pancreas. Arch Pathol Lab Med. 2017;141:1155–80.CrossRefPubMedGoogle Scholar
  48. 48.
    Wennerberg AE, Nalesnik MA, Coleman WB. Hepatocyte paraffin 1: a monoclonal antibody that reacts with hepatocytes and can be used for differential diagnosis of hepatic tumors. Am J Pathol. 1993;143:1050–4.PubMedPubMedCentralGoogle Scholar
  49. 49.
    Nautsch F, Ludwig JM, Xing M, Johnson KM, Kim HS. Racial disparities and sociodemographic differences in incidence and survival among pediatric patients in the United States with primary liver cancer: a surveillance, epidemiology, and end results (SEER) population study. J Clin Gastroenterol. 2017;52(3):262–7. Scholar
  50. 50.
    Vlajnic T, Brisse HJ, Aerts I, Fréneaux P, Cellier C, Fabre M, Klijanienko J. Fine needle aspiration in the diagnosis and classification of hepatoblastoma: analysis of 21 new cases. Diagn Cytopathol. 2017;45:91–100.CrossRefPubMedGoogle Scholar
  51. 51.
    Fiegel HC, Glüer S, Roth B, Rischewski J, von Schweinitz D, Ure B, et al. Stem-like cells in human hepatoblastoma. J Histochem Cytochem. 2004;52:1495–501.CrossRefPubMedPubMedCentralGoogle Scholar
  52. 52.
    Razumilava N, Gores GJ. Cholangiocarcinoma. Lancet. 2014;383:2168–79.CrossRefPubMedPubMedCentralGoogle Scholar
  53. 53.
    Nakanuma Y, Sato Y, Harada K, Sasaki M, Xu J, Ikeda H. Pathological classification of intrahepatic cholangiocarcinoma based on a new concept. World J Hepatol. 2010;2:419–27.CrossRefPubMedPubMedCentralGoogle Scholar
  54. 54.
    El-Fattah MA. Non-Hodgkin lymphoma of the liver: a US population-based analysis. J Clin Transl Hepatol. 2017;5:83–91.PubMedPubMedCentralGoogle Scholar
  55. 55.
    Padhan RK, Das P, Shalimar. Primary hepatic lymphoma. Trop Gastroenterol. 2015;36:14–20.CrossRefPubMedGoogle Scholar
  56. 56.
    Moriarty AT, Banks ER, Bloch T. Cytologic criteria for subclassification of Hodgkin’s disease using fine-needle aspiration. Diagn Cytopathol. 1989;5:122–5.CrossRefPubMedGoogle Scholar
  57. 57.
    Campione S, Cozzolino I, Mainenti P, D’Alessandro V, Vetrani A, D’Armiento M. Hepatic epithelioid hemangioendothelioma: Pitfalls in the diagnosis on fine needle cytology and “small biopsy” and review of the literature. Pathol Res Pract. 2015;211:702–5.CrossRefPubMedGoogle Scholar
  58. 58.
    Mitra V, Nayar MK, Leeds JS, Wadehra V, Haugk B, Scott J, et al. Diagnostic performance of endoscopic ultrasound (EUS)/endoscopic ultrasound—fine needle aspiration (EUS-FNA) cytology in solid and cystic pancreatic neuroendocrine tumours. J Gastrointestin Liver Dis. 2015;24:69–75.PubMedGoogle Scholar

Copyright information

© Springer International Publishing AG, part of Springer Nature 2018

Authors and Affiliations

  1. 1.Department of PathologyThe Johns Hopkins Medical InstitutionsBaltimoreUSA
  2. 2.Department of Pathology and OncologyThe Johns Hopkins Medical InstitutionsBaltimoreUSA

Personalised recommendations