Abstract
The distinction of hepatocellular carcinoma (HCC), neuroendocrine tumor (NET) metastatic to the liver, and cholangiocarcinoma (CC) can sometimes be challenging on small biopsies. Tissue microarrays were constructed from HCCs, NETs, and CCs. The immunoprofile was evaluated using HepPar1, glypican-3 (GPC3), synaptophysin (SYN), chromogranin A (CHR), CD56, MOC-31, and pCEA. One hundred thirteen HCCs, 48 NETs, and 44 CCs were included. Of HCCs, 107 (95 %) expressed HepPar1 and/or GPC3, 52 (46 %) both, and 97 (88 %) marked with pCEA (canalicular pattern). Seven (6 %) expressed CD56, of which 3 (3 %) expressed SYN. All 7 HCCs that expressed CD56 and/or SYN also expressed HepPar1 and/or GPC3, and none of the HCCs expressed CHR. Fourteen (13 %) expressed MOC-31. All 48 NETs expressed at least one neuroendocrine marker: 47 (98 %) positive for SYN, 40 (83 %) for CHR, 39 (81 %) for CD56, and 34 (71 %) for all three markers. None expressed HepPar1 or GPC3. All 44 CCs showed at least focal reactivity with MOC-31 and pCEA (membranous/cytoplasmic). One (2 %) was positive for HepPar1, 4 (9 %) for GPC3, 1 (2 %) for SYN and CHR, and 7 (16 %) for CD56. HCCs rarely express CD56 and SYN, while all express either HepPar1 or GPC3. NETs do not express HepPar1 or GPC3 and almost always express SYN, while CHR and CD56 are seen in most cases. Rare CCs focally express HepPar1 and GPC3. Utilizing a limited staining panel can efficiently distinguish HCCs, NETs, and CCs and help avoid diagnostic pitfalls on small biopsies.
Similar content being viewed by others
References
Al-Muhannadi N, Ansari N, Brahmi U, Satir AA: Differential diagnosis of malignant epithelial tumours in the liver: an immunohistochemical study on liver biopsy material. Ann Hepatol, 10(4):508–515,2011.
Chen H, Hardacre JM, Uzar A, Cameron JL, Choti MA: Isolated liver metastases from neuroendocrine tumors: does resection prolong survival? J Am Coll Surg, 187(1):88–92,1998
Arista-Nasr J, Fernandez-Amador JA, Martinez-Benitez B, de Anda-Gonzalez J, Bornstein-Quevedo L: Neuroendocrine metastatic tumors of the liver resembling hepatocellular carcinoma. Ann Hepatol, 9(2):186–191,2010.
Chu PG, Ishizawa S, Wu E, Weiss LM: Hepatocyte antigen as a marker of hepatocellular carcinoma: an immunohistochemical comparison to carcinoembryonic antigen, CD10, and alpha-fetoprotein. Am J Surg Pathol, 26(8):978–988, 2002.
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, 143(4):1050–1054, 1993.
Yamauchi N, Watanabe A, Hishinuma M, Ohashi K, Midorikawa Y, Morishita Y, Niki T, Shibahara J, Mori M, Makuuchi M et al.: The glypican 3 oncofetal protein is a promising diagnostic marker for hepatocellular carcinoma. Mod Pathol, 18(12):1591–1598, 2005.
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, 16(2):137–144, 2003.
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, 30(11):1405–1411, 2006.
Wang XY, Degos F, Dubois S, Tessiore S, Allegretta M, Guttmann RD, Jothy S, Belghiti J, Bedossa P, Paradis V: Glypican-3 expression in hepatocellular tumors: diagnostic value for preneoplastic lesions and hepatocellular carcinomas. Hum Pathol, 37(11):1435–1441, 2006.
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, 32(3):433–444, 2008.
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, 21(8):1011–1018, 2008.
Yan B, Wei JJ, Qian YM, Zhao XL, Zhang WW, Xu AM, Zhang SH: Expression and clinicopathologic significance of glypican 3 in hepatocellular carcinoma. Ann Diagn Pathol, 15(3):162–169, 2011.
Machinami R, Oono Y: Carcinoembryonic antigen and lectin binding in the bile canalicular structures of hepatocellular carcinoma. Virchows Arch A Pathol Anat Histopathol, 412(2):111–118, 1987.
Morrison C, Marsh W, Jr., Frankel WL: A comparison of CD10 to pCEA, MOC-31, and hepatocyte for the distinction of malignant tumors in the liver. Mod Pathol, 15(12):1279–1287, 2002.
Kakar S, Gown AM, Goodman ZD, Ferrell LD: Best practices in diagnostic immunohistochemistry: hepatocellular carcinoma versus metastatic neoplasms. Arch Pathol Lab Med, 131(11):1648–1654, 2007.
Wang JH, Dhillon AP, Sankey EA, Wightman AK, Lewin JF, Scheuer PJ: 'Neuroendocrine' differentiation in primary neoplasms of the liver. J Pathol, 163(1):61–67, 1991.
Garcia de Davila MT, Gonzalez-Crussi F, Mangkornkanok M: Fibrolamellar carcinoma of the liver in a child: ultrastructural and immunohistologic aspects. Pediatr Pathol, 7(3):319–331, 1987.
Gornicka B, Ziarkiewicz-Wroblewska B, Wroblewski T, Wilczynski GM, Koperski L, Krawczyk M, Wasiutynski A: Carcinoma, a fibrolamellar variant--immunohistochemical analysis of 4 cases. Hepatogastroenterology, 52(62):519–523, 2005.
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, 23(9):1180–1190, 2010.
Mounajjed T, Zhang L, Wu TT: Glypican-3 expression in gastrointestinal and pancreatic epithelial neoplasms. Hum Pathol, 44(4):542–550; 2013.
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, 13(7):773–778, 2000.
Roskams T, van den Oord JJ, De Vos R, Desmet VJ: Neuroendocrine features of reactive bile ductules in cholestatic liver disease. Am J Pathol, 137(5):1019–1025, 1990.
Akiba J1, Nakashima O, Hattori S, Tanikawa K, Takenaka M, Nakayama M, Kondo R, Nomura Y, Koura K, Ueda K, Sanada S, Naito Y, Yamaguchi R, Yano H. Clinicopathologic analysis of combined hepatocellular-cholangiocarcinoma according to the latest WHO classification. Am J Surg Pathol. 37(4):496–505, 2013.
Ikeda H, Sato Y, Yoneda N, Harada K, Sasaki M, Kitamura S, Sudo Y, Ooi A, Nakanuma Y: alpha-Fetoprotein-producing gastric carcinoma and combined hepatocellular and cholangiocarcinoma show similar morphology but different histogenesis with respect to SALL4 expression. Hum Pathol, 43(11):1955–1963, 2012.
Author information
Authors and Affiliations
Corresponding author
Rights and permissions
About this article
Cite this article
Jin, M., Zhou, X., Yearsley, M. et al. Liver Metastases of Neuroendocrine Tumors Rarely Show Overlapping Immunoprofile with Hepatocellular Carcinomas. Endocr Pathol 27, 253–258 (2016). https://doi.org/10.1007/s12022-016-9442-7
Published:
Issue Date:
DOI: https://doi.org/10.1007/s12022-016-9442-7