Evidence‐based guidelines to optimize the selection of antibody panels in cytopathology: Pleural effusions with malignant epithelioid cells

Abstract

There is no established methodology to help select cost effective antibody panels. We used Bayesian statistics and an evidence-based pathology (EBP) approach to retrospectively review the use of immunohistochemistry (IHC) in 153 consecutive pleural effusions evaluated in our laboratory from 2005-2007 for the differential diagnosis of malignant mesothelial cells versus carcinoma cells and to estimate the likely site of origin of a carcinoma. The results in this "training" set were used to design antibody panels and test their clinical applicability on a "test set" of 44 pleural effusions collected in early 2008. Cytopathologists had used 6 +/- 4.5 IHC tests per case for the diagnosis of malignant mesothelioma (n = 9) and carcinomas of lung (n = 60), breast (n = 47), Müllerian (n = 25), and other origins in the "training set". The sensitivity and specificity of pleural cytology using all these IHC tests were 32% and 95%, respectively. Sensitivity, specificity and post-test odds (PTO) of a positive IHC result were calculated for each antibody and by the following classes: malignant mesothelial cells and carcinoma cells by primary site of origin. The antibodies that provided the best PTO to diagnose the most prevalent tumors in our population were included in diagnostic panels for male (calretinin, TTF-1, PSA and CDX-2) and female (calretinin, TTF-1, ER and CA125) patients. These panels provided 100% specificity and 77% and 50% sensitivity, respectively, for the pleural effusions from female and male patients in the "test set." The use of an EBP approach for test selection in cytopathology is discussed.

Advances in the diagnosis of pleural disease in lung cancer

“…The future spells interest in sensitive technologies and techniques for imaging the pleura such as MRI, PET-CT, autofluorescence thoracoscopy and NBI as well as novel biomarkers which can translate to improved clinical diagnostic and staging accuracy. Strategies incorporating biomarkers combined with Bayesian statistics [Westfall et al 2010] or clinical characteristics [Sales et al 2009] are being developed to improve biomarker specificity in the diagnosis of malignant pleural effusions [Huang et al 2010;Li et al 2010;Pu et al 2008aPu et al , 2008b, and validation studies are eagerly awaited before recommendation for use in diagnostic algorithms of pleural diseases.…”

Evidence-Based Pathology: Systematic Literature Reviews as the Basis for Guidelines and Best Practices

“…A computerized query of the literature would yield multiple articles showing the sensitivity and specificity of antibodies, such as calretinin, podoplanin, CK5/6, Wilms tumor antigen-1 (WT-1), and many others, for the diagnosis of mesothelioma, and other tumors that need to be considered in a differential diagnosis. 21,24 However, the information collected from this literature search may be overwhelming and may actually provide the surgical pathologist with limited help for the diagnosis of the particular biopsy under consideration. For example, the patient may have a previous clinical history of another malignancy and/or the pleural tumor could appear as an epithelioid, sarcomatoid, or undifferentiated neoplasm; these considerations would introduce different variables to be considered during a differential diagnosis.…”

“…4,5 Evidence-based medicine took academic medicine and its various specialties by storm, resulting in more than 60 000 publications, multiple books, various educational medical school and graduate education courses, and a large number of guidelines published by various specialty societies. 6,11,[13][14][15][16][17][18][19][20][21][22][23][24][25][26][27] These evidence-based guidelines have been used extensively in the United Kingdom, Canada, and other countries to determine which diagnostic and therapeutic methods should be used by physicians in their daily practice, and as a guidance for the compensation of professional services. Multiple American medical societies and federal agencies have also published a large number of guidelines that in the past few years have been increasingly used by various specialists as the standards of quality practice, or ''best practices'' for the diagnosis and treatment of their patients.…”

Diagnostic Value of Interleukin 21 and Carcinoembryonic Antigen Levels in Malignant Pleural Effusions

“…In negative cytology samples, although detection of tumour markers like carcinoembryonic antigen (CEA), adenosine dehydrogenase (ADA) and lactate dehydrogenase (LDH) by immunohistochemistry can be performed, sensitivity and specificity remain limited (Radjenovik-Petrovic et al, 2009;Gupta et al, 2010;Hackbarth et al, 2010). Moreover, the sensitivity and specificity of immunohistochemistry are affected by the levels of expression of the protein being evaluated, antibody specificity and the quality of the pleural fluid sample provided to the laboratory (Pomjanski et al, 2005;Westfall et al, 2010). When cytology in conjuncture with immunohistochemistry does not provide a definitive diagnosis, more invasive procedures are indicated.…”