Diagnostic value of HepPar1, pCEA, CD10, and CD34 expression in separating hepatocellular carcinoma from metastatic carcinoma in fine‐needle aspiration cytology

Differentiating primary and metastatic hepatic malignancies can be diagnostically challenging in fine‐needle aspiration cytology (FNAC). We compared four immunohistochemical (IHC) markers, pCEA, CD10, HepPar1, and CD34, in differentiating hepatocellular carcinoma (HCC) from metastatic carcinoma (MC) in FNAC specimens. Sixty cases of liver FNAC with their corresponding cell blocks were retrieved from the hospital computer system, including 30 HCC and 30 MC (15 colon, 10 breast, and 5 pancreas). The diagnoses were confirmed by clinical follow‐up and surgical resection or core needle biopsy. The direct cytologic smears were air‐dried and Diff‐Quik‐stained, and alcohol‐fixed and Papanicolaou‐stained. Cell block sections from the aspirates were immunostained for pCEA, CD10, HepPar1, and CD34. IHC on cytologic smears for HCC was performed on 10 cases and compared with the cell block results. In HCC, CD10, and pCEA demonstrated the characteristic canalicular staining in 23/30 (77%) and 24/30 (80%) of the cases, respectively; however, none of the MC showed a canalicular staining pattern. HepPar1 was positive in 26/30 (87%) of the HCC cases and one MC. CD34 stained sinusoidal endothelial cells in 27/30 (90%) cases of HCC and six MC. Our results demonstrate that the canalicular staining pattern for CD10 and sinusoidal staining pattern of CD34 are very specific, in addition to the high specificity and sensitivity of HepPar1 for HCC. Cell blocks were more informative in demonstrating the characteristic architecture and immunostaining pattern of the malignancy than the cytologic smears. An IHC panel consisting of pCEA, CD10, HepPar1, and CD34 is useful for confirming HCC in FNAC of the liver. Diagn. Cytopathol. 2004;30:1–6. © 2004 Wiley‐Liss, Inc.

[1]  W. Coleman,et al.  Hepatocyte paraffin 1: a monoclonal antibody that reacts with hepatocytes and can be used for differential diagnosis of hepatic tumors. , 1993, The American journal of pathology.

[2]  N. Ron,et al.  Use of CD34 and Factor VIII To Diagnose Hepatocellular Carcinoma on Fine Needle Aspirates , 1998, Acta Cytologica.

[3]  D. Gardiol,et al.  Immunohistochemistry in the Differential Diagnosis of Liver Carcinomas , 1991, The American journal of surgical pathology.

[4]  M. Bibbo,et al.  Diagnostic utility of Glut‐1 and CA 15‐3 in discriminating adenocarcinoma from hepatocellular carcinoma in liver tumors biopsied by fine‐needle aspiration , 2002, Cancer.

[5]  M. Bibbo,et al.  Diagnostic value of hepatocyte paraffin 1 antibody to discriminate hepatocellular carcinoma from metastatic carcinoma in fine‐needle aspiration biopsies of the liver , 2001, Cancer.

[6]  P. Scheuer,et al.  An immunohistochemical study of the blood vessels within primary hepatocellular tumours. , 2008, Liver.

[7]  H. Honda,et al.  CD34 expression in endothelial cells of small hepatocellular carcinoma: Its correlation with tumour progression and angiographic findings , 1995, Journal of gastroenterology and hepatology.

[8]  P. Ruck,et al.  Immunoreactivity of sinusoids in hepatocellular carcinoma. An immunohistochemical study using lectin UEA-1 and antibodies against endothelial markers, including CD34. , 1995, Archives of pathology & laboratory medicine.

[9]  H. Hano,et al.  Enhanced CD34 expression of sinusaid‐like vascular endothelial cells in hepatocellular carcinoma , 1996, Pathology international.

[10]  A. Roessner,et al.  Canalicular Immunostaining of Neprilysin (CD10) as a Diagnostic Marker for Hepatocellular Carcinomas , 2001, The American journal of surgical pathology.

[11]  G. Sterrett,et al.  Can CD34 discriminate between benign and malignant hepatocytic lesions in fine‐needle aspirates and thin core biopsies? , 2000, Cancer.

[12]  F. Tan,et al.  Increased expression of neprilysin (neutral endopeptidase 24.11) in rat and human hepatocellular carcinomas. , 1994, Laboratory investigation; a journal of technical methods and pathology.

[13]  J. Rodríguez-Peralto,et al.  Fine Needle Aspiration Cytology of Metastatic Hepatic Adrenocortical Carcinoma Mimicking Hepatocellular Carcinoma , 2001, Acta Cytologica.

[14]  L. Ma,et al.  Localisation of CD10 to biliary canaliculi by immunoelectron microscopical examination. , 1990, Journal of clinical pathology.

[15]  L. Terracciano,et al.  Hepatoid Adenocarcinoma With Liver Metastasis Mimicking Hepatocellular Carcinoma: An Immunohistochemical and Molecular Study of Eight Cases , 2003, The American journal of surgical pathology.

[16]  R. Sormunen,et al.  Hep Par 1 and selected antibodies in the immunohistological distinction of hepatocellular carcinoma from cholangiocarcinoma, combined tumours and metastatic carcinoma , 1998, Histopathology.

[17]  J. Boitnott,et al.  Immunoperoxidase staining as a diagnostic aid for hepatocellular carcinoma. , 1989, Modern pathology : an official journal of the United States and Canadian Academy of Pathology, Inc.

[18]  R. Ashfaq,et al.  Diagnostic utility of the HepPar1 antibody to differentiate hepatocellular carcinoma from metastatic carcinoma in fine‐needle aspiration samples , 2002, Cancer.

[19]  Prabodh K. Gupta,et al.  Differential diagnostic dilemmas in malignant fine‐needle aspirates of liver: A practical approach to final diagnosis , 1995, Diagnostic cytopathology.

[20]  M. Rijn,et al.  Hep Par 1 Antibody Stain for the Differential Diagnosis of Hepatocellular Carcinoma: 676 Tumors Tested Using Tissue Microarrays and Conventional Tissue Sections , 2003, Modern Pathology.

[21]  K. Shiraki,et al.  High expression of CD34-positive sinusoidal endothelial cells is a risk factor for hepatocellular carcinoma in patients with HCV-associated chronic liver diseases. , 2001, Human pathology.

[22]  Randall G. Lee,et al.  Utilization of hepatocyte-specific antibody in the immunocytochemical evaluation of liver tumors. , 1997, Modern pathology : an official journal of the United States and Canadian Academy of Pathology, Inc.

[23]  C. Morrison,et al.  A Comparison of CD10 to pCEA, MOC-31, and Hepatocyte for the Distinction of Malignant Tumors in the Liver , 2002, Modern Pathology.

[24]  L. Hersh,et al.  Common acute lymphoblastic leukemia antigen (CALLA) is active neutral endopeptidase 24.11 ("enkephalinase"): direct evidence by cDNA transfection analysis. , 1989, Proceedings of the National Academy of Sciences of the United States of America.

[25]  T. Yoshiki,et al.  Gastrointestinal hepatoid adenocarcinoma: venous permeation and mimicry of hepatocellular carcinoma, a report of four cases , 1997, Histopathology.

[26]  R. Bhan,et al.  Spindling artefact of urothelial cells , 1995, Diagnostic cytopathology.

[27]  P. Watson,et al.  NCL-CD10-270: a new monoclonal antibody recognizing CD10 in paraffin-embedded tissue. , 1999, The American journal of pathology.

[28]  P. Chu,et al.  Paraffin-section detection of CD10 in 505 nonhematopoietic neoplasms. Frequent expression in renal cell carcinoma and endometrial stromal sarcoma. , 2000, American journal of clinical pathology.

[29]  K. Ishak,et al.  Clear Cell Carcinoma of the Liver: A Comparative Immunohistochemical Study with Renal Clear Cell Carcinoma , 2000, Modern Pathology.

[30]  R. P. Becker,et al.  Detection of neutral endopeptidase 24.11 (neprilysin) in human hepatocellular carcinomas by immunocytochemistry. , 1997, Anticancer research.

[31]  S. Xiao,et al.  cDNA arrays and immunohistochemistry identification of CD10/CALLA expression in hepatocellular carcinoma. , 2001, The American journal of pathology.

[32]  M. Fiorentino,et al.  Histogenesis of primary liver carcinomas: strengths and weaknesses of cytokeratin profile and albumin mRNA detection. , 1996, Human pathology.

[33]  Y. N. Park,et al.  Neoangiogenesis and sinusoidal "capillarization" in dysplastic nodules of the liver. , 1998, The American journal of surgical pathology.

[34]  A. Maitra,et al.  Immunoreactivity for hepatocyte paraffin 1 antibody in hepatoid adenocarcinomas of the gastrointestinal tract. , 2001, American journal of clinical pathology.

[35]  H. Frierson,et al.  Comparative immunohistochemical study of primary and metastatic carcinomas of the liver. , 1993, American journal of clinical pathology.

[36]  H. Lazarus,et al.  A monoclonal antibody to human acute lymphoblastic leukaemia antigen , 1980, Nature.

[37]  S. Kakar,et al.  Immunoreactivity of Hep Par 1 in hepatic and extrahepatic tumors and its correlation with albumin in situ hybridization in hepatocellular carcinoma. , 2003, American journal of clinical pathology.

[38]  P. Chu,et al.  Hepatocyte Antigen as a Marker of Hepatocellular Carcinoma: An Immunohistochemical Comparison to Carcinoembryonic Antigen, CD10, and Alpha-Fetoprotein , 2002, The American journal of surgical pathology.