Differential Diagnosis of Reactive Mesothelial Cells and Adenocarcinoma Cells Using Immunocytochemical markers (Ber-EP 4, MOC-31, Calretinin and HBME-1) in Serous Effusions

The inability to undisputedly distinguish reactive mesothelial cells from metastatic adenocarcinoma cells exfoliated in serous effusions is the most common difficulty encountered by pathologists. Ancillary studies are being useful in improving the accuracy of cytological diagnosis. From all the available methods, Immunochemical stains have excelled in the diagnosis of effusion cytology.A combination of epithelial and mesothelial markers is recommended, as use of a single marker alone can’t establish the diagnosis.In present study, we aimed to distinguish adenocarcinoma cells from reactive mesothelial cells with the help of a panel of immunomarkers including; two epithelial cell markers; Ber-EP 4 and MOC 31, and two mesothelial markers; Calretinin and HBME1. Objective: To differentiate reactive mesothelial cells and adenocarcinoma cells by using immunocytochemical markers (Ber-EP 4, MOC-31, Calretinin and HBME-1) in serous effusions. Subjects and Methods: A total 75 fluid samples containing either reactive mesothelial cells or adenocarcinoma were included in the study.Cytospin smears were made and subjected to immunocytochemistry for Ber-EP 4, MOC-31,Calretinin and HBME-1 staining. Results: Ber- EP 4, an epithelial marker, showed positive membranous/cytoplasmic expression in 100% of the effusions which were cytologically diagnosed as positive for adenocarcinoma. MOC 31 expressed diffuse membranous staining in 93% of the total cases of adenocarcinoma.HBME-1 was positively stained in 100% of cases of reactive mesothelial effusions. 100% effusions containing reactive mesothelial cells showed both cytoplasmic and nuclear staining with Calretinin. Conclusion: The immunomarkersBer-EP 4 and Calretinin are more effective in distinguishing reactive mesothelial cells and adenocarcinoma, and they should be included in immunocytochemical (ICC) panel.

[1]  N. Cha,et al.  Expression and significance of MOC‐31 and calretinin in pleural fluid of patients with lung cancer , 2015, Diagnostic cytopathology.

[2]  M. Zaghloul Cytokeratin 19 (CK19) as a Tumor Marker in Pleural Effusion , 2014 .

[3]  Z. Borbényi,et al.  Monoclonal antibody HBME-1 reacts with a minor subset of B cells with villous surface and can be useful in the diagnosis of hairy cell leukemia and other indolent lymphoproliferations of villous B lymphocytes , 2013, Virchows Archiv.

[4]  N. McElvaney,et al.  Pleural Fluid Analysis: Standstill or a Work in Progress? , 2012, Pulmonary medicine.

[5]  N. Hafez,et al.  Diagnostic value of p53 and ki67 immunostaining for distinguishing benign from malignant serous effusions. , 2011, Journal of the Egyptian National Cancer Institute.

[6]  M. Aron,et al.  Utility of a limited panel of calretinin and Ber-EP4 immunocytochemistry on cytospin preparation of serous effusions: A cost-effective measure in resource-limited settings , 2011, CytoJournal.

[7]  F. Demirağ,et al.  A review of uncommon cytopathologic diagnoses of pleural effusions from a chest diseases center in Turkey , 2011, CytoJournal.

[8]  Alireza Rahmani,et al.  HBME-1 immunostaining in reactive mesothelial versus metastatic adenocarcinoma cells in serous fluid. , 2011, Indian journal of pathology & microbiology.

[9]  M. Jordá,et al.  Effusion Cytology: A Practical Guide to Cancer Diagnosis , 2011 .

[10]  A. Algeciras-Schimnich,et al.  Performance of CEA and CA19-9 in identifying pleural effusions caused by specific malignancies. , 2010, Clinical biochemistry.

[11]  R. Morice,et al.  Does pleural fluid appearance really matter? The relationship between fluid appearance and cytology, cell counts, and chemical laboratory measurements in pleural effusions of patients with cancer , 2010, Journal of Cardiothoracic Surgery.

[12]  S. Masood,et al.  Differentiating reactive mesothelial cells from metastatic adenocarcinoma in serous effusions: The utility of immunocytochemical panel in the differential diagnosis , 2009, Diagnostic cytopathology.

[13]  R. West,et al.  MOC-31 Exhibits Superior Reactivity Compared With Ber-EP4 in Invasive Lobular and Ductal Carcinoma of the Breast: A Tissue Microarray Study , 2009, Applied immunohistochemistry & molecular morphology : AIMM.

[14]  S. Habeebullah,et al.  Immunohistochemical distinction between mesothelial and adenocarcinoma cells in serous effusions: a combination panel-based approach with a brief review of the literature. , 2009, Indian journal of pathology & microbiology.

[15]  D. Coffey,et al.  Cytologic malignancy versus benignancy: how useful are the "newer" markers in body fluid cytology? , 2009, Archives of pathology & laboratory medicine.

[16]  S. Sahn Diagnosis and management of parapneumonic effusions and empyema. , 2007, Clinical infectious diseases : an official publication of the Infectious Diseases Society of America.

[17]  K. Kostikas,et al.  Acute phase markers for the differentiation of infectious and malignant pleural effusions. , 2007, Respiratory medicine.

[18]  J. Silverman,et al.  The Diagnosis of Malignancy in Effusion Cytology: A Pattern Recognition Approach , 2006, Advances in anatomic pathology.

[19]  K. Butnor My approach to the diagnosis of mesothelial lesions , 2006, Journal of Clinical Pathology.

[20]  Mutsuo Takahashi,et al.  Comparison of three cytologic preparation methods and immunocytochemistries to distinguish adenocarcinoma cells from reactive mesothelial cells in serous effusion , 2006, Diagnostic cytopathology.

[21]  G. Pinkus,et al.  Monoclonal antibody MOC‐31 reactivity as a marker for adenocarcinoma in cytologic preparations , 2005, Cancer.

[22]  N. Ordóñez The diagnostic utility of immunohistochemistry and electron microscopy in distinguishing between peritoneal mesotheliomas and serous carcinomas: a comparative study , 2006, Modern Pathology.

[23]  R. Zimmerman Effusion cytology: Keeping researchers and journals in business for the past 20 years—and it is not over yet , 2005 .

[24]  C. Kandaraki,et al.  Immunocytochemical panel for distinguishing between carcinoma and reactive mesothelial cells in body cavity fluids , 2005, Diagnostic cytopathology.

[25]  N. Jhala,et al.  Use of a panel of markers in the differential diagnosis of adenocarcinoma and reactive mesothelial cells in fluid cytology. , 2001, American journal of clinical pathology.

[26]  M. Lozano,et al.  Immunocytochemistry in the differential diagnosis of serous effusions , 2001, Cancer.