Immunohistochemical pitfalls and the importance of glypican 3 and arginase in the diagnosis of scirrhous hepatocellular carcinoma

Gregor Krings, Rageshree Ramachandran, Dhanpat Jain, Tsung-Teh Wu, Matthew M. Yeh, Michael Torbenson, Sanjay Kakar

Research output: Contribution to journalArticle

41 Citations (Scopus)

Abstract

Scirrhous hepatocellular carcinoma is a rare ill-defined morphological subtype of hepatocellular carcinoma characterized by marked stromal fibrosis. This variant can be difficult to distinguish from intrahepatic cholangiocarcinoma and metastatic adenocarcinoma, especially on needle biopsies. We performed immunohistochemistry for hepatocellular and adenocarcinoma- associated markers on 20 scirrhous hepatocellular carcinoma cases and compared the results with classical hepatocellular carcinoma and intrahepatic cholangiocarcinoma. Scirrhous hepatocellular carcinomas were significantly less likely to be HepPar-1 positive than classical hepatocellular carcinomas (26% and 74%, respectively; P<0.001) and were significantly more likely to express adenocarcinoma-associated markers such as epithelial cell adhesion molecule (63 vs 11%; P<0.001), cytokeratin 19 (26 vs 2%; P<0.001), and cytokeratin 7 (53 vs 2%; P<0.001). At least one of these adenocarcinoma-related markers was positive in 80% of scirrhous hepatocellular carcinoma cases. Glypican 3 and arginase were positive in 79% and 85% of cases of scirrhous hepatocellular carcinoma, respectively; the combined use of these two markers yielded 100% sensitivity for scirrhous hepatocellular carcinoma. In conclusion, the scirrhous morphology, absence of HepPar-1 staining, and frequent positivity with adenocarcinoma-related markers in scirrhous hepatocellular carcinoma can lead to an erroneous diagnosis of adenocarcinoma. Glypican 3 and arginase are the most reliable markers for identifying hepatocellular differentiation in this setting.

Original languageEnglish (US)
Pages (from-to)782-791
Number of pages10
JournalModern Pathology
Volume26
Issue number6
DOIs
StatePublished - Jun 2013

Fingerprint

Scirrhous Adenocarcinoma
Glypicans
Arginase
Hepatocellular Carcinoma
Adenocarcinoma
Cholangiocarcinoma
Keratin-7
Keratin-19
Needle Biopsy
Fibrosis

Keywords

  • Arginase
  • cholangiocarcinoma
  • glypican 3
  • scirrhous hepatocellular carcinoma

ASJC Scopus subject areas

  • Pathology and Forensic Medicine

Cite this

Immunohistochemical pitfalls and the importance of glypican 3 and arginase in the diagnosis of scirrhous hepatocellular carcinoma. / Krings, Gregor; Ramachandran, Rageshree; Jain, Dhanpat; Wu, Tsung-Teh; Yeh, Matthew M.; Torbenson, Michael; Kakar, Sanjay.

In: Modern Pathology, Vol. 26, No. 6, 06.2013, p. 782-791.

Research output: Contribution to journalArticle

Krings, Gregor ; Ramachandran, Rageshree ; Jain, Dhanpat ; Wu, Tsung-Teh ; Yeh, Matthew M. ; Torbenson, Michael ; Kakar, Sanjay. / Immunohistochemical pitfalls and the importance of glypican 3 and arginase in the diagnosis of scirrhous hepatocellular carcinoma. In: Modern Pathology. 2013 ; Vol. 26, No. 6. pp. 782-791.
@article{b19ba0180718402cbbc71400992f6c1b,
title = "Immunohistochemical pitfalls and the importance of glypican 3 and arginase in the diagnosis of scirrhous hepatocellular carcinoma",
abstract = "Scirrhous hepatocellular carcinoma is a rare ill-defined morphological subtype of hepatocellular carcinoma characterized by marked stromal fibrosis. This variant can be difficult to distinguish from intrahepatic cholangiocarcinoma and metastatic adenocarcinoma, especially on needle biopsies. We performed immunohistochemistry for hepatocellular and adenocarcinoma- associated markers on 20 scirrhous hepatocellular carcinoma cases and compared the results with classical hepatocellular carcinoma and intrahepatic cholangiocarcinoma. Scirrhous hepatocellular carcinomas were significantly less likely to be HepPar-1 positive than classical hepatocellular carcinomas (26{\%} and 74{\%}, respectively; P<0.001) and were significantly more likely to express adenocarcinoma-associated markers such as epithelial cell adhesion molecule (63 vs 11{\%}; P<0.001), cytokeratin 19 (26 vs 2{\%}; P<0.001), and cytokeratin 7 (53 vs 2{\%}; P<0.001). At least one of these adenocarcinoma-related markers was positive in 80{\%} of scirrhous hepatocellular carcinoma cases. Glypican 3 and arginase were positive in 79{\%} and 85{\%} of cases of scirrhous hepatocellular carcinoma, respectively; the combined use of these two markers yielded 100{\%} sensitivity for scirrhous hepatocellular carcinoma. In conclusion, the scirrhous morphology, absence of HepPar-1 staining, and frequent positivity with adenocarcinoma-related markers in scirrhous hepatocellular carcinoma can lead to an erroneous diagnosis of adenocarcinoma. Glypican 3 and arginase are the most reliable markers for identifying hepatocellular differentiation in this setting.",
keywords = "Arginase, cholangiocarcinoma, glypican 3, scirrhous hepatocellular carcinoma",
author = "Gregor Krings and Rageshree Ramachandran and Dhanpat Jain and Tsung-Teh Wu and Yeh, {Matthew M.} and Michael Torbenson and Sanjay Kakar",
year = "2013",
month = "6",
doi = "10.1038/modpathol.2012.243",
language = "English (US)",
volume = "26",
pages = "782--791",
journal = "Modern Pathology",
issn = "0893-3952",
publisher = "Nature Publishing Group",
number = "6",

}

TY - JOUR

T1 - Immunohistochemical pitfalls and the importance of glypican 3 and arginase in the diagnosis of scirrhous hepatocellular carcinoma

AU - Krings, Gregor

AU - Ramachandran, Rageshree

AU - Jain, Dhanpat

AU - Wu, Tsung-Teh

AU - Yeh, Matthew M.

AU - Torbenson, Michael

AU - Kakar, Sanjay

PY - 2013/6

Y1 - 2013/6

N2 - Scirrhous hepatocellular carcinoma is a rare ill-defined morphological subtype of hepatocellular carcinoma characterized by marked stromal fibrosis. This variant can be difficult to distinguish from intrahepatic cholangiocarcinoma and metastatic adenocarcinoma, especially on needle biopsies. We performed immunohistochemistry for hepatocellular and adenocarcinoma- associated markers on 20 scirrhous hepatocellular carcinoma cases and compared the results with classical hepatocellular carcinoma and intrahepatic cholangiocarcinoma. Scirrhous hepatocellular carcinomas were significantly less likely to be HepPar-1 positive than classical hepatocellular carcinomas (26% and 74%, respectively; P<0.001) and were significantly more likely to express adenocarcinoma-associated markers such as epithelial cell adhesion molecule (63 vs 11%; P<0.001), cytokeratin 19 (26 vs 2%; P<0.001), and cytokeratin 7 (53 vs 2%; P<0.001). At least one of these adenocarcinoma-related markers was positive in 80% of scirrhous hepatocellular carcinoma cases. Glypican 3 and arginase were positive in 79% and 85% of cases of scirrhous hepatocellular carcinoma, respectively; the combined use of these two markers yielded 100% sensitivity for scirrhous hepatocellular carcinoma. In conclusion, the scirrhous morphology, absence of HepPar-1 staining, and frequent positivity with adenocarcinoma-related markers in scirrhous hepatocellular carcinoma can lead to an erroneous diagnosis of adenocarcinoma. Glypican 3 and arginase are the most reliable markers for identifying hepatocellular differentiation in this setting.

AB - Scirrhous hepatocellular carcinoma is a rare ill-defined morphological subtype of hepatocellular carcinoma characterized by marked stromal fibrosis. This variant can be difficult to distinguish from intrahepatic cholangiocarcinoma and metastatic adenocarcinoma, especially on needle biopsies. We performed immunohistochemistry for hepatocellular and adenocarcinoma- associated markers on 20 scirrhous hepatocellular carcinoma cases and compared the results with classical hepatocellular carcinoma and intrahepatic cholangiocarcinoma. Scirrhous hepatocellular carcinomas were significantly less likely to be HepPar-1 positive than classical hepatocellular carcinomas (26% and 74%, respectively; P<0.001) and were significantly more likely to express adenocarcinoma-associated markers such as epithelial cell adhesion molecule (63 vs 11%; P<0.001), cytokeratin 19 (26 vs 2%; P<0.001), and cytokeratin 7 (53 vs 2%; P<0.001). At least one of these adenocarcinoma-related markers was positive in 80% of scirrhous hepatocellular carcinoma cases. Glypican 3 and arginase were positive in 79% and 85% of cases of scirrhous hepatocellular carcinoma, respectively; the combined use of these two markers yielded 100% sensitivity for scirrhous hepatocellular carcinoma. In conclusion, the scirrhous morphology, absence of HepPar-1 staining, and frequent positivity with adenocarcinoma-related markers in scirrhous hepatocellular carcinoma can lead to an erroneous diagnosis of adenocarcinoma. Glypican 3 and arginase are the most reliable markers for identifying hepatocellular differentiation in this setting.

KW - Arginase

KW - cholangiocarcinoma

KW - glypican 3

KW - scirrhous hepatocellular carcinoma

UR - http://www.scopus.com/inward/record.url?scp=84878620058&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=84878620058&partnerID=8YFLogxK

U2 - 10.1038/modpathol.2012.243

DO - 10.1038/modpathol.2012.243

M3 - Article

C2 - 23348905

AN - SCOPUS:84878620058

VL - 26

SP - 782

EP - 791

JO - Modern Pathology

JF - Modern Pathology

SN - 0893-3952

IS - 6

ER -