Liver, Bile Ducts, and Gallbladder

  • Jeffrey Prichard
  • Fan Lin


The liver is a common site for metastatic tumors, so differentiation of primary from metastatic lesions and identification of site of origin of metastatic tumors are frequent questions faced by pathologists. This chapter focuses on the application of immunohistochemical markers to these questions of hepatic and biliary tumor pathology. Staining profiles are presented for differentiating primary hepatocellular carcinomas, adenoma, and dysplastic nodules. Prognostic markers of hepatocellular adenoma subtypes are described. Challenges of distinguishing intrahepatic cholangiocarcinoma from metastatic mimics are addressed. A unique combination of complimentary markers useful in discriminating reactive from neoplastic epithelium in the gallbladder is shown. A process is defined utilizing an initial screening panel and subsequent confirmatory markers for unknown primary tumors in liver. Photomicrographs illustrate characteristic staining patterns.


Liver Gallbladder Hepatocellular Canalicular Biliary Cholangiocarcinoma HepPar-1 AFP Glypican-3 Alpha-1antitrypsin pVHL Maspin IMP3 (KOC) 


  1. 1.
    Chu PG, Weiss LM. Modern immunohistochemistry. New York, NY: Cambridge University Press; 2009.Google Scholar
  2. 2.
    Dabbs DJ. Diagnostic immunohistochemistry. 3rd ed. Philadelphia, PA: Churchill Livingstone Elsevier; 2010.Google Scholar
  3. 3.
    Taylor C, Cote R. Immunomicroscopy a diagnostic tool for the surgical pathologist, Major problems in pathology. 3rd ed. Philadelphia, PA: Saunders Elsevier; 2006.Google Scholar
  4. 4.
    Geller SA, Dhall D, Alsabeh R. Application of immunohistochemistry to liver and gastrointestinal neoplasms: liver, stomach, colon, and pancreas. Arch Pathol Lab Med. 2008;132(3):490–9.PubMedGoogle Scholar
  5. 5.
    Mills SE. Histology for pathologists. 3rd ed. Philadelphia: Lippincott Williams & Wilkins; 2007. p. 696–7.Google Scholar
  6. 6.
    Burt AD, Portmann BC, Ferrell LD. MacSween’s pathology of the liver. 5th ed. Philadelphia: Churchill Livingstone Elsevier; 2007. p. 20–45.Google Scholar
  7. 7.
    De Young BR, Frierson Jr HF, Ly MN, Smith D, Swanson PE. CD31 immunoreactivity in carcinomas and mesotheliomas. Am J Clin Pathol. 1998;110(3):374–7.PubMedGoogle Scholar
  8. 8.
    de Boer WB, Segal A, Frost FA, Sterrett GF. Can CD34 discriminate between benign and malignant hepatocytic lesions in fine-needle aspirates and thin core biopsies? Cancer. 2000;90(5):273–8.PubMedCrossRefGoogle Scholar
  9. 9.
    Gottschalk-Sabag S, Ron N, Glick T. Use of CD34 and factor VIII to diagnose hepatocellular carcinoma on fine needle aspirates. Acta Cytol. 1998;42(3):691–6.PubMedCrossRefGoogle Scholar
  10. 10.
    Coston WM, Loera S, Lau SK, Ishizawa S, Jiang Z, Wu CL, et al. Distinction of hepatocellular carcinoma from benign hepatic mimickers using Glypican-3 and CD34 immunohistochemistry. Am J Surg Pathol. 2008;32(3):433–44.PubMedCrossRefGoogle Scholar
  11. 11.
    Lin F, Shi J, Liu H, et al. Immunohistochemical detection of the von Hippel–Lindau gene product (pVHL) in human tissues and tumors: a useful marker for metastatic renal cell carcinoma and clear cell carcinoma of the ovary and uterus. Am J Clin Pathol. 2008;129(4):592–605.PubMedCrossRefGoogle Scholar
  12. 12.
    Shah S, Gupta S, Shet T, Maheshwari A, Wuntkal R, Mohandas KM. Metastatic clear cell variant of hepatocellular carcinoma with an occult hepatic primary. Hepatobiliary Pancreat Dis Int. 2005;4(2):306–7.PubMedGoogle Scholar
  13. 13.
    Maeda T, Kajiyama K, Adachi E, Takenaka K, Sugimachi K, Tsuneyoshi M. The expression of cytokeratins 7, 19, and 20 in primary and metastatic carcinomas of the liver. Mod Pathol. 1996;9(9):901–9.PubMedGoogle Scholar
  14. 14.
    Rullier A, Le Bail B, Fawaz R, Blanc JF, Saric J, Bioulac-Sage P. Cytokeratin 7 and 20 expression in cholangiocarcinomas varies along the biliary tract but still differs from that in colorectal carcinoma metastasis. Am J Surg Pathol. 2000;24(6):870–6.PubMedCrossRefGoogle Scholar
  15. 15.
    Harder J, Waiz O, Otto F, Geissler M, Olschewski M, Weinhold B, et al. EGFR and HER2 expression in advanced biliary tract cancer. World J Gastroenterol. 2009;15(36):4511–7.PubMedCrossRefGoogle Scholar
  16. 16.
    Kandil DH, Cooper K. Glypican-3: a novel diagnostic marker for hepatocellular carcinoma and more. Adv Anat Pathol. 2009;16(2):125–9.PubMedCrossRefGoogle Scholar
  17. 17.
    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(8):1011–8. Epub 6 Jun 2008.PubMedCrossRefGoogle Scholar
  18. 18.
    Wang HL, Anatelli F, Zhai QJ, Adley B, Chuang ST, Yang XJ. Glypican-3 as a useful diagnostic marker that distinguishes hepatocellular carcinoma from benign hepatocellular mass lesions. Arch Pathol Lab Med. 2008;132(11):1723–8.PubMedGoogle Scholar
  19. 19.
    Yamauchi N, Watanabe A, Hishinuma M, Ohashi K, Midorikawa Y, Morishita Y, et al. The glypican 3 oncofetal protein is a promising diagnostic marker for hepatocellular carcinoma. Mod Pathol. 2005;18(12):1591–8.PubMedGoogle Scholar
  20. 20.
    Christensen WN, Boitnott JK, Kuhajda FP. Immunoperoxidase staining as a diagnostic aid for hepatocellular carcinoma. Mod Pathol. 1989;2(1):8–12.PubMedGoogle Scholar
  21. 21.
    Varma V, Cohen C. Immunohistochemical and molecular markers in the diagnosis of hepatocellular carcinoma. Adv Anat Pathol. 2004;11(5):239–49.PubMedCrossRefGoogle Scholar
  22. 22.
    Haratake J, Hashimoto H. An immunohistochemical analysis of 13 cases with combined hepatocellular and cholangiocellular carcinoma. Liver. 1995;15(1):9–15.PubMedGoogle Scholar
  23. 23.
    Fanni D, Nemolato S, Ganga R, Senes G, Gerosa C, Van Eyken P, et al. Cytokeratin 20-positive hepatocellular carcinoma. Eur J Histochem. 2009;53(4):269–73.PubMedGoogle Scholar
  24. 24.
    Kakar S, Gown AM, Goodman ZD, Ferrell LD. Best practices in diagnostic immunohistochemistry: hepatocellular carcinoma versus metastatic neoplasms. Arch Pathol Lab Med. 2007;131(11):1648–54.PubMedGoogle Scholar
  25. 25.
    Krishna M. Diagnosis of metastatic neoplasms: an immunohistochemical approach. Arch Pathol Lab Med. 2010;134(2):207–15.PubMedGoogle Scholar
  26. 26.
    Lau SK, Prakash S, Geller SA, Alsabeh R. Comparative immunohistochemical profile of hepatocellular carcinoma, cholangiocarcinoma, and metastatic adenocarcinoma. Hum Pathol. 2002;33(12):1175–81.PubMedCrossRefGoogle Scholar
  27. 27.
    Wieczorek TJ, Pinkus JL, Glickman JN, Pinkus GS. Comparison of thyroid transcription factor-1 and hepatocyte antigen immunohistochemical analysis in the differential diagnosis of hepatocellular carcinoma, metastatic adenocarcinoma, renal cell carcinoma, and adrenal cortical carcinoma. Am J Clin Pathol. 2002;118:911–21.PubMedCrossRefGoogle Scholar
  28. 28.
    Van Eyken P. Cytokeratin immunohistochemistry in liver histopatology. Adv Clin Pathol. 2000;4(4):201–11.Google Scholar
  29. 29.
    Zatloukal K, Stumptner C, Fuchsbichler A, Fickert P, Lackner C, Trauner M, et al. The keratin cytoskeleton in liver diseases. J Pathol. 2004;204(4):367–76.PubMedCrossRefGoogle Scholar
  30. 30.
    Yang XR, Xu Y, Shi GM, Fan J, Zhou J, Ji Y, et al. Cytokeratin 10 and cytokeratin 19: predictive markers for poor prognosis in hepatocellular carcinoma patients after curative resection. Clin Cancer Res. 2008;14(12):3850–9.PubMedCrossRefGoogle Scholar
  31. 31.
    Yong X-R, Xu Y, Shi G-M, Fan J, Zhou J, Ji Y, et al. Cytokeratin 10 and cytokeratin 19: predictive markers for poor prognosis in hepatocellular carcinoma patients after curative resection. Clin Cancer Res. 2008;14(12):3850–9.CrossRefGoogle Scholar
  32. 32.
    Lackner C, Gogg-Kamerer M, Zatloukal K, Stumptner C, Brunt EM, Denk H. Ballooned hepatocytes in steatohepatitis: the value of keratin immunohistochemistry for diagnosis. J Hepatol. 2008;48(5):821–8. Epub 22 Feb 2008.PubMedCrossRefGoogle Scholar
  33. 33.
    Lee MJ, Lee HS, Kim WH, Choi Y, Yang M. Expression of mucins and cytokeratins in primary carcinomas of the digestive system. Mod Pathol. 2003;16(5):403–10.PubMedCrossRefGoogle Scholar
  34. 34.
    Listrom MB, Dalton LW. Comparison of keratin monoclonal antibodies MAK-6, AE1:AE3, and CAM-5.2. Am J Clin Pathol. 1987;88(3):297–301.PubMedGoogle Scholar
  35. 35.
    Jain R, Fischer S, Serra S, Chetty R. The use of cytokeratin 19 (CK19) immunohistochemistry in lesions of the pancreas, gastrointestinal tract, and liver. Appl Immunohistochem Mol Morphol. 2010;18(1):9–15.PubMedCrossRefGoogle Scholar
  36. 36.
    Lefkowitch JH. Special stains in diagnostic liver pathology. Semin Diagn Pathol. 2006;23(3–4):190–8.PubMedCrossRefGoogle Scholar
  37. 37.
    Fan Z, van de Rijn M, Montgomery K, Rouse RV. Hep par 1 antibody stain for the differential diagnosis of hepatocellular carcinoma: 676 tumors tested using tissue microarrays and conventional tissue sections. Mod Pathol. 2003;16(2):137–44.PubMedCrossRefGoogle Scholar
  38. 38.
    Roskams T. The role of immunohistochemistry in diagnosis. Clin Liver Dis. 2002;6(2):571–89.PubMedCrossRefGoogle Scholar
  39. 39.
    Morrison C, Marsh Jr W, Frankel WL. A comparison of CD10 to pCEA, MOC-31, and hepatocyte for the distinction of malignant tumors in the liver. Mod Pathol. 2002;15(12):1279–87.PubMedCrossRefGoogle Scholar
  40. 40.
    Porcell AI, De Young BR, Proca DM, Frankel WL. Immunohistochemical analysis of hepatocellular and adenocarcinoma in the liver: MOC31 compares favorably with other putative markers. Mod Pathol. 2000;13(7):773–8.PubMedCrossRefGoogle Scholar
  41. 41.
    Weinreb I, Cunningham KS, Perez-Ordoñez B, Hwang DM. CD10 is expressed in most epithelioid hemangioendotheliomas: a potential diagnostic pitfall. Arch Pathol Lab Med. 2009;133(12):1965–8.PubMedGoogle Scholar
  42. 42.
    Gu K, Shah V, Ma C, Zhang L, Yang M. Cytoplasmic immunoreactivity of thyroid transcription factor-1 (clone 8G7G3/1) in hepatocytes: true positivity or cross-reaction? Am J Clin Pathol. 2007;128(3):382–8.PubMedCrossRefGoogle Scholar
  43. 43.
    Pan C-C, Chen PC-H, Tsay S-H, Chiang H. Cytoplasmic immunoreactivity for thyroid transcription factor-1 in hepatocellular ­carcinoma. A comparative immunohistochemical analysis of four commercial antibodies using a tissue array technique. Am J Clin Pathol. 2004;121:343–9.PubMedCrossRefGoogle Scholar
  44. 44.
    Batheja N, Suriawinata A, Saxena R, Ionescu G, Schwartz M, Thung SN. Expression of p53 and PCNA in cholangiocarcinoma and primary sclerosing cholangitis. Mod Pathol. 2000;13(12):1265–8.PubMedCrossRefGoogle Scholar
  45. 45.
    Kanamoto M, Yoshizumi T, Ikegami T, Imura S, Morine Y, Ikemoto T, et al. Cholangiolocellular carcinoma containing hepatocellular carcinoma and cholangiocellular carcinoma, extremely rare tumor of the liver: a case report. J Med Invest. 2008;55(1–2):161–5.PubMedCrossRefGoogle Scholar
  46. 46.
    Kang YK, Kim WH, Jang JJ. Expression of G1-S modulators (p53, p16, p27, cyclin D1, Rb) and Smad4/Dpc4 in intrahepatic cholangiocarcinoma. Hum Pathol. 2002;33(9):877–83.PubMedCrossRefGoogle Scholar
  47. 47.
    Mosnier JF, Kandel C, Cazals-Hatem D, Bou-Hanna C, Gournay J, Jarry A, et al. N-cadherin serves as diagnostic biomarker in intrahepatic and perihilar cholangiocarcinomas. Mod Pathol. 2009;22(2):182–90. Epub 11 Jul 2008.PubMedCrossRefGoogle Scholar
  48. 48.
    Nakanuma Y, Harada K, Ishikawa A, Zen Y, Sasaki M. Anatomic and molecular pathology of intrahepatic cholangiocarcinoma. J Hepatobiliary Pancreat Surg. 2003;10(4):265–81.PubMedCrossRefGoogle Scholar
  49. 49.
    Rizzi PM, Ryder SD, Portmann B, Ramage JK, Naoumov NV, Williams R. p53 Protein overexpression in cholangiocarcinoma arising in primary sclerosing cholangitis. Gut. 1996;38(2):265–8.PubMedCrossRefGoogle Scholar
  50. 50.
    Röcken C, Pross M, Brucks U, Ridwelski K, Roessner A. Cholangiocarcinoma occurring in a liver with multiple bile duct hamartomas (von Meyenburg complexes). Arch Pathol Lab Med. 2000;124(11):1704–6.PubMedGoogle Scholar
  51. 51.
    Nash JW, Morrison C, Frankel WL. The utility of estrogen receptor and progesterone receptor immunohistochemistry in the distinction of metastatic breast carcinoma from other tumors in the liver. Arch Pathol Lab Med. 2003;127(12):1591–5.PubMedGoogle Scholar
  52. 52.
    Esheba GE, Longacre TA, Atkins KA, Higgins JP. Expression of the urothelial differentiation markers GATA3 and placental S100 (S100P) in female genital tract transitional cell proliferations. Am J Surg Pathol. 2009;33(3):347–53.PubMedCrossRefGoogle Scholar
  53. 53.
    Findeis-Hosey JJ, Yang Q, Spaulding BO, Wang HL, Xu H. IMP3 expression is correlated with histologic grade of lung adenocarcinoma. Human Pathol. 2010;41(4):477–84. Epub 11 Dec 2009.CrossRefGoogle Scholar
  54. 54.
    Lu D, Vohra P, Chu PG, Woda B, Rock KL, Jiang Z. An oncofetal protein IMP3: a new molecular marker for the detection of esophageal adenocarcinoma and high-grade dysplasia. Am J Surg Pathol. 2009;33(4):521–5.PubMedCrossRefGoogle Scholar
  55. 55.
    Werling RW, Yaziji H, Bacchi CE, Gown AM. CDX2, a highly sensitive and specific marker of adenocarcinomas of intestinal origin: an immunohistochemical survey of 476 primary and metastatic carcinomas. Am J Surg Pathol. 2003;27(3):303–10.PubMedCrossRefGoogle Scholar
  56. 56.
    Jarmay K, Gallai M, Karacsony G, et al. Decorin and actin expression and distribution in patients with chronic hepatitis C following interferon-alpha-2b-treatment. J Hepatol. 2000;32:993–1002.PubMedCrossRefGoogle Scholar
  57. 57.
    Knittel T, Kobold D, Saile B, et al. Rat liver myofibroblasts and hepatic stellate cells: different cell populations of the fibroblast lineage with fibrogenic potential. Gastroenterology. 1999;117:1205–21.PubMedCrossRefGoogle Scholar
  58. 58.
    Moreira RK. Hepatic stellate cells and liver fibrosis. Arch Pathol Lab Med. 2007;131(11):1728–34.PubMedGoogle Scholar
  59. 59.
    Okabe H, Beppu T, Hayashi H, Horino K, Masuda T, Komori H, et al. Hepatic stellate cells may relate to progression of intrahepatic cholangiocarcinoma. Ann Surg Oncol. 2009;16(9):2555–64. Epub 23 Jun 2009.PubMedCrossRefGoogle Scholar
  60. 60.
    Snover D. Immunohistochemical analysis in steatohepatitis: does it have a role in diagnosis and management? Am J Clin Pathol. 2005;123(4):491–3.PubMedCrossRefGoogle Scholar
  61. 61.
    Svegliati Baroni G, D’Ambrosio L, Ferretti G, et al. Fibrogenic effect of oxidative stress on rat hepatic stellate cells. J Hepatol. 1999;30:868–75.PubMedCrossRefGoogle Scholar
  62. 62.
    Tomanovic NR, Boricic IV, Brasanac DC, Stojsic ZM, Delic DS, Brmbolic BJ. Activated liver stellate cells in chronic viral C hepatitis: histopathological and immunohistochemical study. J Gastrointestin Liver Dis. 2009;18(2):163–7.PubMedGoogle Scholar
  63. 63.
    Bioulac-Sage P, Balabaud C, Bedossa P, et al. Pathological diagnosis of liver cell adenoma and focal nodular hyperplasia: Bordeaux update. J Hepatol. 2007;46:521–7.PubMedCrossRefGoogle Scholar
  64. 64.
    Bioulac-Sage P, Balabaud C, Zucman-Rossi J. Subtype classification of hepatocellular adenoma. Dig Surg. 2010;27(1):39–45. Epub 1 Apr 2010.PubMedCrossRefGoogle Scholar
  65. 65.
    Bioulac-Sage P, Blanc JF, Rebouissou S, Balabaud C, Zucman-Rossi J. Genotype phenotype classification of hepatocellular adenoma. World J Gastroenterol. 2007;13(19):2649–54.PubMedGoogle Scholar
  66. 66.
    Bioulac-Sage P, Laumonier H, Couchy G, Le Bail B, Sa Cunha A, Rullier A, et al. Hepatocellular adenoma management and phenotypic classification: the Bordeaux experience. Hepatology. 2009;50(2):481–9.PubMedCrossRefGoogle Scholar
  67. 67.
    Bioulac-Sage P, Laumonier H, Laurent C, Zucman-Rossi J, Balabaud C. Hepatocellular adenoma: what is new in 2008. Hepatol Int. 2008;2(3):316–21. Epub 1 May 2008.PubMedCrossRefGoogle Scholar
  68. 68.
    Chen ZM, Crone KG, Watson MA, Pfeifer JD, Wang HL. Identification of a unique gene expression signature that differentiates hepatocellular adenoma from well-differentiated hepatocellular carcinoma. Am J Surg Pathol. 2005;29:1600–8.PubMedCrossRefGoogle Scholar
  69. 69.
    Cohen C, Lawson D, DeRose PB. Sex and androgenic steroid receptor expression in hepatic adenomas. Human Pathology. 1998;29(12):1428–32.PubMedCrossRefGoogle Scholar
  70. 70.
    Micchelli ST, Vivekanandan P, Boitnott JK, Pawlik TM, Choti MA, Torbenson M. Malignant transformation of hepatic adenomas. Mod Pathol. 2008;21:491–7.PubMedCrossRefGoogle Scholar
  71. 71.
    Torbenson M, Lee JH, Choti M, et al. Hepatic adenomas: analysis of sex steroid receptor status and the Wnt signaling pathway. Mod Pathol. 2002;15(3):189–96.PubMedCrossRefGoogle Scholar
  72. 72.
    Zucman-Rossi J, Jeannot E, Tran Van Nhieu J, et al. Genotype–phenotype correlation in hepatocellular adenoma: new classification and relationship with HCC. Hepatology. 2006;43:515–24.PubMedCrossRefGoogle Scholar
  73. 73.
    Ahmad I, Iyer A, Marginean CE, Yeh MM, Ferrell L, Qin L, et al. Diagnostic use of cytokeratins, CD34, and neuronal cell adhesion molecule staining in focal nodular hyperplasia and hepatic adenoma. Hum Pathol. 2009;40(5):726–34. Epub 20 Jan 2009.PubMedCrossRefGoogle Scholar
  74. 74.
    Rebouissou S, Bioulac-Sage P, Zucman-Rossi J. Molecular pathogenesis of focal nodular hyperplasia and hepatocellular adenoma. J Hepatol. 2008;48(1):163–70.PubMedCrossRefGoogle Scholar
  75. 75.
    Masood S, West AB, Barwick KW. Expression of steroid hormone receptors in benign hepatic tumors. An immunocytochemical study. Arch Pathol Lab Med. 1992;116(12):1355–9.PubMedGoogle Scholar
  76. 76.
    Yamamoto M, Nakajo S, Tahara E. Immunohistochemical analysis of estrogen receptors in human gallbladder. Acta Pathol Jpn. 1990;40(1):14–21.PubMedGoogle Scholar
  77. 77.
    Chen Ban K, Singh H, Krishnan R, Fong Seow H. Comparison of the expression of beta-catenin in hepatocellular carcinoma in areas with high and low levels of exposure to aflatoxin B1. J Surg Oncol. 2004;86(3):157–63.PubMedCrossRefGoogle Scholar
  78. 78.
    Torbenson M, Kannangai R, Abraham S, Sahin F, Choti M, Wang J. Concurrent evaluation of p53, beta-catenin, and alpha-fetoprotein expression in human hepatocellular carcinoma. Am J Clin Pathol. 2004;122:377–82.PubMedCrossRefGoogle Scholar
  79. 79.
    Peroukides S, Bravou V, Alexopoulos A, Varakis J, Kalofonos H, Papadaki H. Survivin overexpression in HCC and liver cirrhosis differentially correlates with p-STAT3 and E-cadherin. Histol Histopathol. 2010;25(3):299–307.PubMedGoogle Scholar
  80. 80.
    Malouf G, Falissard B, Azoulay D, Callea F, Ferrell LD, Goodman ZD, et al. Is histological diagnosis of primary liver carcinomas with fibrous stroma reproducible among experts? J Clin Pathol. 2009;62(6):519–24. Epub 20 Jan 2009.PubMedCrossRefGoogle Scholar
  81. 81.
    Lau SK, Weiss LM, Chu PG. Differential expression of MUC1, MUC2, and MUC5AC in carcinomas of various sites: an immunohistochemical study. Am J Clin Pathol. 2004;122(1):61–9.PubMedCrossRefGoogle Scholar
  82. 82.
    Cho MS, Lee SN, Sung SH, Han WS. Sarcomatoid hepatocellular carcinoma with hepatoblastoma-like features in an adult. Pathol Int. 2004;54(6):446–50.PubMedCrossRefGoogle Scholar
  83. 83.
    Fu Y, Kobayashi S, Kushida Y, Saoo K, Haba R, Mori S, et al. Sarcomatoid hepatocellular carcinoma with chondroid variant: case report with immunohistochemical findings. Pathol Int. 2000;50(11):919–22.PubMedCrossRefGoogle Scholar
  84. 84.
    Górnicka B, Ziarkiewicz-Wróblewska B, Wróblewski T, Wilczynski GM, Koperski L, Krawczyk M, et al. Carcinoma, a fibrolamellar variant–immunohistochemical analysis of 4 cases. Hepatogastroenterology. 2005;52(62):519–23.PubMedGoogle Scholar
  85. 85.
    Ward SC, Huang J, Tickoo SK, Thung SN, Ladanyi M, Klimstra DS. Fibrolamellar carcinoma of the liver exhibits immunohistochemical evidence of both hepatocyte and bile duct differentiation. Mod Pathol. 2010;23(9):1180–90.PubMedCrossRefGoogle Scholar
  86. 86.
    Abenoza P, Manivel JC, Wick MR, Hagen K, Dehner LP. Hepatoblastoma: an immunohistochemical and ultrastructural study. Hum Pathol. 1987;18(10):1025–35.PubMedCrossRefGoogle Scholar
  87. 87.
    Cajaiba MM, Neves JI, Casarotti FF, de Camargo B, ChapChap P, Sredni ST, et al. Hepatoblastomas and liver development: a study of cytokeratin immunoexpression in twenty-nine hepatoblastomas. Pediatr Dev Pathol. 2006;9(3):196–202.PubMedCrossRefGoogle Scholar
  88. 88.
    López-Terrada D, Gunaratne PH, Adesina AM, Pulliam J, Hoang DM, Nguyen Y, et al. Histologic subtypes of hepatoblastoma are characterized by differential canonical Wnt and Notch pathway activation in DLK+ precursors. Hum Pathol. 2009;40(6):783–94. Epub 5 Feb 2009.PubMedCrossRefGoogle Scholar
  89. 89.
    Stocker JT. Hepatoblastoma. Semin Diagn Pathol. 1994;11(2):136–43.PubMedGoogle Scholar
  90. 90.
    Warfel KA, Hull MT. Hepatoblastomas: an ultrastructural and immunohistochemical study. Ultrastruct Pathol. 1992;16(4):451–61.PubMedCrossRefGoogle Scholar
  91. 91.
    Ushiku T, Shinozaki A, Shibhara J, et al. SALL4 represents fetal gut differentiation of gastric cancer, and is diagnostically useful in distinguishing hepatoid gastric carcinoma from hepatocellular carcinoma. Am J Surg Pathol. 2010;34:533–40.PubMedCrossRefGoogle Scholar
  92. 92.
    Machado I, Noguera R, Santonja N, Donat J, Fernandez-Delgado R, Acevedo A, et al. Immunohistochemical study as a tool in differential diagnosis of pediatric malignant rhabdoid tumor. Appl Immunohistochem Mol Morphol. 2010;18(2):150–8.PubMedCrossRefGoogle Scholar
  93. 93.
    Lin F, Liu H, Shi J, Xu Y, Zhang J, Wang HL. Diagnostic utility of von Hipple–Lindau gene product (pVHL) and S100P in adenocarcinoma and dysplasia of the gallbladder. Abstract presentation in CAP 2009.Google Scholar
  94. 94.
    Lin F, Shi J, Wang HL, Liu H. Diagnostic utility of von Hipple–Lindau gene product (pVHL), maspin, KOC, and S100P in adenocarcinoma of the gallbladder. Accepted for poster presentation in the coming USCAP meeting, 2010 in Washington, DC.Google Scholar
  95. 95.
    Nagata S et al. Co-expression of gastric and biliary. Oncol Rep. 2007;17:721–9.PubMedGoogle Scholar
  96. 96.
    Shibahara H et al. Pathologic features of mucin. Am J Surg Pathol. 2004;28:327–38.PubMedCrossRefGoogle Scholar
  97. 97.
    Yang GC, Yang GY, Tao LC. Distinguishing well-differentiated hepatocellular carcinoma from benign liver by the physical features of fine-needle aspirates. Mod Pathol. 2004;17(7):798–802.PubMedCrossRefGoogle Scholar
  98. 98.
    Terracciano LM, Glatz K, Mhawech P, et al. Hepatoid adenocarcinoma with liver metastasis mimicking hepatocellular carcinoma. Am J Surg Pathol. 2003;27:1302–12.PubMedCrossRefGoogle Scholar
  99. 99.
    Di Tommaso L, Destro A, Seok JY, Balladore E, Terracciano L, Sangiovanni A, et al. The application of markers (HSP70 GPC3 and GS) in liver biopsies is useful for detection of hepatocellular carcinoma. J Hepatol. 2009;50(4):746–54. Epub 25 Dec 2008.PubMedCrossRefGoogle Scholar
  100. 100.
    Di Tommaso L, Franchi G, Park YN, Fiamengo B, Destro A, Morenghi E, et al. Diagnostic value of HSP70, glypican 3, and glutamine synthetase in hepatocellular nodules in cirrhosis. Hepatology. 2007;45(3):725–34.PubMedCrossRefGoogle Scholar
  101. 101.
    Hytiroglou P, Theise ND. Differential diagnosis of hepatocellular nodular lesions. Semin Diagn Pathol. 1998;15(4):285–99.PubMedGoogle Scholar
  102. 102.
    Libbrecht L, Severi T, Cassiman D, et al. Glycipan-3 expression distinguishes small hepatocellular carcinomas from cirrhosis, dysplastic nodules, and focal nodular hyperplasia-like nodules. Am J Surg Pathol. 2006;30:1405–11.PubMedCrossRefGoogle Scholar
  103. 103.
    Roskams T, Kojiro M. Pathology of early hepatocellular carcinoma: conventional and molecular diagnosis. Semin Liver Dis. 2010;30(1):17–25. Epub 19 Feb 2010.PubMedCrossRefGoogle Scholar
  104. 104.
    Hornick JL, Fletcher CD. PEComa: what do we know so far? Histopathology. 2006;48(1):75–82.PubMedCrossRefGoogle Scholar
  105. 105.
    Tryggvason G, Blöndal S, Goldin RD, Albrechtsen J, Björnsson J, Jónasson JG. Epithelioid angiomyolipoma of the liver: case report and review of the literature. APMIS. 2004;112(9):612–6.PubMedCrossRefGoogle Scholar
  106. 106.
    Chu PG, Schwarz RE, Lau SK, Yen Y, Weiss LM. Immunohistochemical staining in the diagnosis of pancreatobiliary and ampulla of Vater adenocarcinoma: application of CDX2, CK17, MUC1, and MUC2. Am J Surg Pathol. 2005;29(3):359–67.PubMedCrossRefGoogle Scholar
  107. 107.
    Hruban RH, Pitman MB, Klimstra DS. AFIP Atlast of Tumor Pathology, Tumors of the Pancreas, vol. 4. 6th ed. Washington, DC: American Registry of Pathology; 2007.Google Scholar
  108. 108.
    Levy M, Lin F, Xu H, Dhall D, Spaulding BO, Wang HL. S100P, von Hippel-Lindau gene product, and IMP3 serve as a useful immunohistochemical panel in the diagnosis of adenocarcinoma on endoscopic bile duct biopsy. Hum Pathol. 2010;41(9):1210–9.PubMedCrossRefGoogle Scholar
  109. 109.
    Lin F, Shi J, Liu H, et al. Diagnostic utility of S100P and von Hippel–Lindau gene product (pVHL) in pancreatic adenocarcinoma – with implication of their roles in early tumorigenesis. Am J Surg Pathol. 2008;32(1):78–91.PubMedCrossRefGoogle Scholar
  110. 110.
    Zhou H, Schaefer N, Wolff M, Fischer HP. Carcinoma of the ampulla of Vater: comparative histologic/immunohistochemical classification and follow-up. Am J Surg Pathol. 2004;28(7):875–82.PubMedCrossRefGoogle Scholar
  111. 111.
    Yesim G, Gupse T, Zafer U, Ahmet A. Mesenchymal hamartoma of the liver in adulthood: immunohistochemical profiles, clinical and histopathological features in two patients. J Hepatobiliary Pancreat Surg. 2005;12(6):502–7.PubMedCrossRefGoogle Scholar
  112. 112.
    Doi H, Horiike N, Hiraoka A, Koizumi Y, Yamamoto Y, Hasebe A, et al. Primary hepatic marginal zone B cell lymphoma of mucosa-associated lymphoma of mucosa-associated lymphoid tissue type: case report and review of the literature. Int J Hematol. 2008;88:418–23. Epub 23 Sep 2008.PubMedCrossRefGoogle Scholar
  113. 113.
    Anagnostopoulos G, Sakorafas GH, Grigoriadis K, Kostopoulos P. Malignant fibrous histiocytoma of the liver: a case report and review of the literature. Mt Sinai J Med. 2005;72(1):50–2.PubMedGoogle Scholar
  114. 114.
    Fujita S, Lauwers GY. Primary hepatic malignant fibrous histiocytoma: report of a case and review of the literature. Pathol Int. 1998;48(3):225–9.PubMedCrossRefGoogle Scholar
  115. 115.
    Yuri T, Danbara N, Shikata N, Fujimoto S, Nakano T, Sakaida N, et al. Malignant rhabdoid tumor of the liver: case report and literature review. Pathol Int. 2004;54(8):623–9.PubMedCrossRefGoogle Scholar
  116. 116.
    Guglielmi A, Frameglia M, Iuzzolino P, Martignoni G, De Manzoni G, Laterza E, et al. Solitary fibrous tumor of the liver with CD 34 positivity and hypoglycemia. J Hepatobiliary Pancreat Surg. 1998;5(2):212–6.PubMedCrossRefGoogle Scholar
  117. 117.
    Zhang MF, Zhang ZY, Fu J, Yang YF, Yun JP. Correlation between expression of p53, p21/WAF1, and MDM2 proteins and their prognostic significance in primary hepatocellular carcinoma. J Transl Med. 2009;22(7):110.CrossRefGoogle Scholar

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© Springer Science+Business Media, LLC 2011

Authors and Affiliations

  1. 1.Department of Pathology and Laboratory MedicineGeisinger Medical CenterDanvilleUSA

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