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Liver Cytopathology

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Practical Cytopathology

Part of the book series: Practical Anatomic Pathology ((PAP))

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Abstract

Fine needle aspiration (FNA) has become one of the most popular diagnostic approaches for focal liver lesions, not only for primary hepatocellular carcinoma (HCC) and cholangiocarcinoma but also for various metastatic tumors. For practicing cytopathologists, recognition of normal cellular components of liver, pigments, and FNA-carried contaminating cells is important for accurate diagnosis of different types of tumors. One particular diagnostic challenge of liver FNA is well-differentiated HCC, because the tumor cells are very similar to its normal counterparts. Identification of endothelium, either wrapping around tumor cell groups or traversing tumor cell sheets, is a highly specific and sensitive indicator for HCCs. Separation of more poorly differentiated HCCs from cholangiocarcinoma, metastatic carcinomas, angiosarcoma, and hepatoblastoma may require not only characteristic cytomorphological features but also immunohistochemical or even molecular markers. This chapter covers most of the common diagnostic dilemmas encountered in daily cytopathological practice.

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References

  1. Conrad R, Castelino-Prabhu S, Cobb C, Raza A. Cytopathologic diagnosis of liver mass lesions. J Gastrointest Oncol. 2013;4:53–61.

    PubMed  PubMed Central  Google Scholar 

  2. Butnor KJ. My approach to the diagnosis of mesothelial lesions. J Clin Pathol. 2006;59:564–74.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  3. Niels T, Torben S, Kjeld W. Correlation between pathological and clinical findings in 195 consecutive liver biopsies showing brown pigment. Gut. 1965;6:194–200.

    Article  Google Scholar 

  4. Bassett ML, Halliday JW, Powell LW. Value of hepatic iron measurements in early hemochromatosis and determination of the critical iron level associated with fibrosis. Hepatology. 1986;6:24–9.

    Article  CAS  PubMed  Google Scholar 

  5. Harman D. Lipofuscin and ceroid formation: the cellular recycling system. Adv Exp Med Biol. 1989;266:3–15.

    CAS  PubMed  Google Scholar 

  6. Russack V1, Vass L, Gupta PK. Comparison of morphologic features of benign hepatocytes associated with nonmalignant and malignant liver lesions. Acta Cytol. 1993;37:153–7.

    CAS  PubMed  Google Scholar 

  7. Swamy MC, Arathi C, Kodandaswamy C. Value of ultrasonography-guided fine needle aspiration cytology in the investigative sequence of hepatic lesions with an emphasis on hepatocellular carcinoma. J Cytol. 2011;28:178–84.

    Article  PubMed  PubMed Central  Google Scholar 

  8. Wee A. Fine needle aspiration biopsy of the liver: algorithmic approach and current issues in the diagnosis of hepatocellular carcinoma. CytoJournal. 2005;2:7–12.

    Article  PubMed  PubMed Central  Google Scholar 

  9. Zhu ZW, Friess H, Wang L, Abou-Shady M, Zimmermann A, Lander AD, Korc M, Kleeff J, Büchler MW. Enhanced glypican-3 expression differentiates the majority of hepatocellular carcinomas from benign hepatic disorders. Gut. 2001;48:558–64.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  10. Yamauchi N, Watanabe A, Hishinuma M, Ohashi K, Midorikawa Y, Morishita Y, Niki T, Shibahara J, Mori M, Makuuchi M, Hippo Y, Kodama T, Iwanari H, Aburatani H, Fukayama M. Glypican 3 oncofetal protein is a promising diagnostic marker for hepatocellular carcinoma. Mod Pathol. 2005;18:1591–8.

    Article  CAS  PubMed  Google Scholar 

  11. Shafizadeh N, Ferrell LD, Kakar S. Utility and limitations of glypican-3 expression for the diagnosis of hepatocellular carcinoma at both ends of the differentiation spectrum. Mod Pathol. 2008;21:1011–8.

    Article  CAS  PubMed  Google Scholar 

  12. Libbrecht L, Severi T, Cassiman D, Vander Borght S, Pirenne J, Nevens F, Verslype C, van Pelt J, Roskams T. Glypican-3 expression distinguishes small hepatocellular carcinomas from cirrhosis, dysplastic nodules, and focal nodular hyperplasia-like nodules. Am J Surg Pathol. 2006;30:1405–11.

    Article  PubMed  Google Scholar 

  13. Coston WM, Loera S, Lau SK, Ishizawa S, Jiang Z, Wu CL, Yen Y, Weiss LM, Chu PG. Distinction of hepatocellular carcinoma from benign hepatic mimickers using Glypican-3 and CD34 immunohistochemistry. Am J Surg Pathol. 2008;32:433–44.

    Article  PubMed  Google Scholar 

  14. Huang H, Fujii H, Sankila A, Mahler-Araujo BM, Matsuda M, Cathomas G, Ohgaki H. Beta-catenin mutations are frequent in human hepatocellular carcinomas associated with hepatitis C virus infection. Am J Pathol. 1999;155:1795–801.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  15. Nasarek A, Werner M, Nolte M, Klempnauer J, Georgii A. Trisomy 1 and 8 occur frequently in hepatocellular carcinoma but not in liver cell adenoma and focal nodular hyperplasia. A fluorescence in situ hybridization study. Virchows Arch. 1995;427:373–8.

    Article  CAS  PubMed  Google Scholar 

  16. Wilkens L, Bredt M, Flemming P, Schwarze Y, Becker T, Mengel M, von Wasielewski R, Klempnauer J, Kreipe H. Diagnostic impact of fluorescence in situ hybridization in the differentiation of hepatocellular adenoma and well-differentiated hepatocellular carcinoma. J Mol Diagn. 2001;3:68–73.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  17. Saleh HA, Aulicino M, Zaidi SY, et al. 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.

    Article  PubMed  Google Scholar 

  18. Canberk S, Onenerk M, Sayman E, Goret CC, Erkan M, Atasoy T, Kilicoglu GZ. Is DOG1 really useful in the diagnosis of salivary gland acinic cell carcinoma? A DOG1 (clone K9) analysis in fine needle aspiration cell blocks and the review of the literature. Cytojournal. 2015;12:18–24.

    Article  PubMed  PubMed Central  Google Scholar 

  19. Gokce A, Vikram D, Olca B. Expression of markers of hepatocellular differentiation in pancreatic acinar cell neoplasms; a potential diagnostic pitfall. Am J Clin Pathol. 2016;146:163–9.

    Article  CAS  Google Scholar 

  20. Pérez-Guillermo M, Masgrau NA, García-Solano J, Sola-Pérez J, de Agustín y de Agustín P. Cytologic aspect of fibrolamellar hepatocellular carcinoma in fine-needle aspirates. Diagn Cytopathol. 1999;21:180–7.

    Article  PubMed  Google Scholar 

  21. Rondell PG. Fibrolamellar carcinoma. Surg Pathol Clin. 2018;11(2):377–87.

    Article  Google Scholar 

  22. Riehle KJ, Yeh MM, Yu JJ, Kenerson HL, Harris WP, Park JO, Yeung RS. mTORC1 and FGFR1 signaling in fibrolamellar hepatocellular carcinoma. Mod Pathol. 2015;28:103–10.

    Article  CAS  PubMed  Google Scholar 

  23. Singh HK, Silverman JF, Geisinger KR. Fine-needle aspiration cytomorphology of clear-cell hepatocellular carcinoma. Diagn Cytopathol. 1997;17:306–10.

    Article  CAS  PubMed  Google Scholar 

  24. de Gonzalez AKK, Salomao MA, Lagana SM. Current concepts in the immunohistochemical evaluation of liver tumors. World J Hepatol. 2015;7:1403–11.

    Article  Google Scholar 

  25. Fu LY, Mitchell KA, Cai G. Clear cell hepatocellular carcinoma diagnosed by bile duct brushing cytology. Diagn Cytopathol. 2016;44:147–51.

    Article  PubMed  Google Scholar 

  26. Chen L, Huang K, Himmelfarb EA, Zhai J, Lai JP, Lin F, Wang HL. Diagnostic value of maspin in distinguishing adenocarcinoma from benign biliary epithelium on endoscopic bile duct biopsy. Hum Pathol. 2015;46:1647–54.

    Article  CAS  PubMed  Google Scholar 

  27. Kanzawa M, Sanuki T, Onodera M, Fujikura K, Itoh T, Zen Y. Double immunostaining for maspin and p53 on cell blocks increases the diagnostic value of biliary brushing cytology. Pathol Int. 2017;67:91–8.

    Article  CAS  PubMed  Google Scholar 

  28. Katabi N. Neoplasia of gallbladder and biliary epithelium. Arch Pathol Lab Med. 2010;134:1621–7.

    PubMed  Google Scholar 

  29. Brooks C, Gausman V, Kokoy-Mondragon C, Munot K, Amin SP, Desai A, Kipp C, Poneros J, Sethi A, Gress FG, Kahaleh M, Murty VV, Sharaiha R, Gonda TA. Role of fluorescent in situ hybridization, cholangioscopic biopsies, and EUS-FNA in the evaluation of biliary strictures. Dig Dis Sci. 2018;63:636–44.

    Article  CAS  PubMed  Google Scholar 

  30. Meara RS, Jhala D, Eloubeidi MA, Eltoum I, Chhieng DC, Crowe DR, Varadarajulu S, Jhala N. Endoscopic ultrasound-guided FNA biopsy of bile duct and gallbladder: analysis of 53 cases. Cytopathology. 2006;17:42–9.

    Article  CAS  PubMed  Google Scholar 

  31. 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.

    Article  PubMed  PubMed Central  Google Scholar 

  32. Chaudhary HB, Bhanot P, Logroño R. Phenotypic diversity of intrahepatic and extrahepatic cholangiocarcinoma on aspiration cytology and core needle biopsy: case series and review of the literature. Cancer. 2005;105:220–8.

    Article  PubMed  Google Scholar 

  33. Hertz G, Reddy VB, Green L, Spitz D, Massarani-Wafai R, Selvaggi SM, Kluskens L, Gattuso P. Fine-needle aspiration biopsy of the liver: a multicenter study of 602 radiologically guided FNA. Diagn Cytopathol. 2000;23:326–8.

    Article  CAS  PubMed  Google Scholar 

  34. Curcio G, Traina M, Mocciaro F, Liotta R, Gentile R, Tarantino I, Barresi L, Granata A, Tuzzolino F, Gridelli B. Intraductal aspiration: a promising new tissue-sampling technique for the diagnosis of suspected malignant biliary strictures. Gastrointest Endosc. 2012;75:798–804.

    Article  PubMed  Google Scholar 

  35. Pitman MB, Centeno BA, Ali SZ, Genevay M, Stelow E, Mino-Kenudson M, Castillo CF, Schmidt CM, Brugge WR, Layfield LJ. Standardized terminology and nomenclature for pancreatobiliary cytology: the Papanicolaou Society of Cytopathology Guidelines. Cytojournal. 2014;11(Suppl 1):3–16.

    PubMed  PubMed Central  Google Scholar 

  36. Kipp BR, Stadheim LM, Halling SA, Pochron NL, Harmsen S, Nagorney DM, et al. A comparison of routine cytology and fluorescence in situ hybridization for the detection of malignant bile duct strictures. Am J Gastroenterol. 2004;99:1675–81.

    Article  PubMed  Google Scholar 

  37. Bertram S, Padden J, Kälsch J, Ahrens M, Pott L, Canbay A, Weber F, Fingas C, Hoffmann AC, Vietor A, Schlaak JF, Eisenacher M, Reis H, Sitek B, Baba HA. Novel immunohistochemical markers differentiate intrahepatic cholangiocarcinoma from benign bile duct lesions. J Clin Pathol. 2016;69:619–26.

    Article  CAS  PubMed  Google Scholar 

  38. Liew ZH, Loh TJ, Lim TKH, Lim TH, Khor CJL, Mesenas SJ, Kong CSC, Ong WC, Tan DMY. Role of fluorescence in situ hybridization in diagnosing cholangiocarcinoma in indeterminate biliary strictures. J Gastroenterol Hepatol. 2018;33:315–9.

    Article  PubMed  Google Scholar 

  39. Lagana SM, Moreira RK, Remotti HE, Bao F. Immunohistochemical distinction between intrahepatic cholangiocarcinoma and pancreatic ductal adenocarcinoma. Hum Pathol. 2014;45:394–400.

    Article  CAS  Google Scholar 

  40. Wee A. Fine needle aspiration biopsy of hepatocellular carcinoma and hepatocellular nodular lesions: role, controversies and approach to diagnosis. Cytopathology. 2011;22:287–305.

    Article  CAS  PubMed  Google Scholar 

  41. 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. 2007;111:259–68.

    Article  PubMed  CAS  Google Scholar 

  42. Sampatanukul P, Leong AS, Kosolbhand P, Tangkijvanich P. Proliferating ductules are a diagnostic discriminator for intrahepatic cholangiocarcinoma in FNA biopsies. Diagn Cytopathol. 2000;22:359–63.

    Article  CAS  PubMed  Google Scholar 

  43. Lok T, et al. Immunohistochemical distinction between intrahepatic cholangiocarcinoma and pancreatic ductal adenocarcinoma. Hum Pathol. 2014;45:394–400.

    Article  CAS  PubMed  Google Scholar 

  44. Lagana SM, Moreira RK, Remotti HE, Bao F. Glutamine synthetase, heat shock protein-70, and glypican-3 in intrahepatic cholangiocarcinoma and tumors metastatic to liver. Appl Immunohistochem Mol Morphol. 2013;21:254–7.

    CAS  PubMed  Google Scholar 

  45. Ma CK, Zarbo RJ, Frierson HF Jr, Lee MW. Comparative immunohistochemical study of primary and metastatic carcinomas of the liver. Am J Clin Pathol. 1993;99(5):551–7.

    Article  CAS  PubMed  Google Scholar 

  46. 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.

    Article  PubMed  Google Scholar 

  47. Shin E, Lee KB, Park SY, Kim SH, Ryu HS, Park YN, Yu E, Jang JJ. Gene expression profiling of human hepatoblastoma using archived formalin-fixed and paraffin-embedded tissues. Virchows Arch. 2011;458:453–65.

    Article  CAS  PubMed  Google Scholar 

  48. Gupta R, Mathur SR, Gupta SD, Durgapal P, Iyer VK, Das CJ, Shalimar, Acharya SK. Hepatic epithelioid hemangioendothelioma: a diagnostic pitfall in aspiration cytology. Cytojournal. 2009;6:25–30.

    Article  Google Scholar 

  49. den Bakker MA, Marx A, Mukai K, Ströbel P. Mesenchymal tumours of the mediastinum–part II. Virchows Arch. 2015;467:501–17.

    Article  CAS  Google Scholar 

  50. Jung MJ, Kim YO. A case of metastatic angiosarcoma diagnosed by liquid-based preparation: peculiar cytoplasmic changes. Korean J Pathol. 2014;48:241–7.

    Article  PubMed  PubMed Central  Google Scholar 

  51. Dusenbery D. Combined hepatocellular-cholangiocarcinoma. Cytologic findings in four cases. Acta Cytol. 1997;41:903–9.

    Article  CAS  PubMed  Google Scholar 

  52. Gibbons D, de las Morenas A. Fine needle aspiration diagnosis of combined hepatocellular carcinoma and cholangiocarcinoma. A case report. Acta Cytol. 1997;4:1269–72.

    Article  Google Scholar 

  53. Wee A, Nilsson B. Combined hepatocellular-cholangiocarcinoma. Diagnostic challenge in hepatic fine needle aspiration biopsy. Acta Cytol. 1999;43:131–8.

    Article  CAS  PubMed  Google Scholar 

  54. Gu Q, Yu X, Chen H, Chen G. Clinicopathological features of combined hepatocellular-cholangiocarcinoma with sarcomatous change: case report and literature review. Medicine (Baltimore). 2018;97:e9640. https://doi.org/10.1097/MD.9640.

    Article  Google Scholar 

  55. Brunt E, Aishima S, Clavien PA, Fowler K, Goodman Z, Gores G, Gouw A, Kagen A, Klimstra D, Komuta M, Kondo F, Miksad R, Nakano M, Nakanuma Y, Ng I, Paradis V, Nyun Park Y, Quaglia A, Roncalli M, Roskams T, Sakamoto M, Saxena R, Sempoux C, Sirlin C, Stueck A, Thung S, Tsui WMS, Wang XW, Wee A, Yano H, Yeh M, Zen Y, Zucman-Rossi J, Theise N. cHCC-CCA: consensus terminology for primary liver carcinomas with both hepatocytic and cholangiocytic differentation. Hepatology. 2018;68:113–26.

    Article  PubMed  Google Scholar 

  56. Gera S, Ettel M, Acosta-Gonzalez G, Xu R. Clinical features, histology, and histogenesis of combined hepatocellular-cholangiocarcinoma. World J Hepatol. 2017;9:300–9.

    Article  PubMed  PubMed Central  Google Scholar 

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Author information

Authors and Affiliations

  1. Department of Pathology, University of New Mexico Hospital, Albuquerque, NM, USA

    Jain Zhou

  2. Department of Pathology and Laboratory Medicine, Robert Wood Johnson Medical School, Rutgers University, New Brunswick, NJ, USA

    He Wang

  3. Pathology and Laboratory Medicine, Temple University Hospital, Philadelphia, PA, USA

    Nirag Jhala

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  1. Jain Zhou
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  2. He Wang
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  3. Nirag Jhala
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Correspondence to Jain Zhou .

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Editors and Affiliations

  1. VA Boston Healthcare System, Boston, MA, USA

    Huihong Xu

  2. Brigham and Women’s Hospital, Boston, MA, USA

    Xiaohua Qian

  3. Robert Wood Johnson University Hospital, New Brunswick, NJ, USA

    He Wang

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Zhou, J., Wang, H., Jhala, N. (2020). Liver Cytopathology. In: Xu, H., Qian, X., Wang, H. (eds) Practical Cytopathology . Practical Anatomic Pathology. Springer, Cham. https://doi.org/10.1007/978-3-030-24059-2_16

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  • DOI: https://doi.org/10.1007/978-3-030-24059-2_16

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