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

Our plain-English summary of Evidence-based guidelines to optimize the selection of antibody panels in cytopathology: pleural effusions with malignant epithelioid cells, by D.E. Westfall, X. Fan, A.M. Marchevsky (Diagnostic Cytopathology, 2010).

The study

• Authors: D.E. Westfall, X. Fan, A.M. Marchevsky
• Journal: Diagnostic Cytopathology
• Published: 2010;38(1):9-14
• Cited by: 16 articles, as counted by NIH iCite
• Read it: PubMed · Publisher

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.

(c) 2009 Wiley-Liss, Inc.

In plain English

This study from the Cedars-Sinai Medical Center cytopathology laboratory in Los Angeles looked back at pleural fluid samples containing malignant epithelioid cells. Its aim was to design smaller sets of antibody stains for telling malignant mesothelioma apart from spread carcinoma, and for estimating where a carcinoma began. It did not study asbestos exposure. The training set was 153 samples from 2005 to 2007: 9 malignant mesotheliomas, all in men, plus carcinomas of lung (60), breast (47), Müllerian (25) and other origins. Cytopathologists had used 1 to 22 stains per sample. Using a measure called post-test odds, the authors chose a panel for men (TTF-1, PSA, CDX-2, calretinin) and one for women (calretinin, TTF-1, ER, CA125). Calretinin gave the best odds for mesothelioma. In 44 samples from early 2008, the panels correctly diagnosed 77% (20/26) of samples from women and 50% (9/18) from men, with no false positives. The authors concluded the panels gave a cost-effective, sensitive initial work-up. They said their convenience samples need confirming in a larger prospective study. Some figures are reported inconsistently within the article.

We wrote this plain-English summary from the full article with the help of AI, and a second AI model checked each sentence against the article. It is not the authors' wording; the abstract and the article are their own account.

What the study did and found

• Design: Retrospective review of laboratory records (training set), with the resulting antibody panels tested on a separate later set of cases (test set), using Bayesian statistics within an evidence-based pathology approach
• Who was studied: Pleural effusion cytology specimens at Cedars-Sinai Medical Center, Los Angeles. Of 1,360 specimens from 2005 to 2007, 181 had malignant epithelioid cells, and 153 with an established diagnosis formed the training set. The test set was 44 specimens from the first six months of 2008 (18 male and 26 female patients), of which 21 had malignant epithelioid cells.
• Exposure: No asbestos or other fiber exposure was studied. What was examined was the use of immunohistochemistry (antibody stain) tests on pleural fluid, up to 31 different antibodies.
• Main results:
  • In the 153 training-set specimens there were 9 malignant mesotheliomas (about 6%), all in male patients. There were carcinomas of lung (60, 40%), breast (47, 31%), Müllerian (25, 16%), stomach (5), colon (5) and prostate (2) origin.
  • Cytopathologists had used from 1 to 22 antibody tests per specimen in the training set, with an average of 6 (plus or minus 4.5).
  • Of the antibodies, calretinin gave the best post-test odds for mesothelioma (4). TTF-1 gave the best post-test odds for lung carcinoma (infinity).
  • The panel proposed for female patients was calretinin, TTF-1, ER and CA125. No malignant mesotheliomas were found in pleural effusions from female patients in this study.
  • The panel proposed for male patients was TTF-1, PSA, CDX-2 and calretinin.
  • In the 2008 test set, the panels correctly diagnosed 77% (20/26) of specimens from female patients and 50% (9/18) from male patients, with no false-positive results. This was reported as 100% specificity.
• The authors' conclusion: The authors concluded that two gender-specific antibody panels, optimized for the frequency of tumors in their hospital population, provided a cost-effective and sensitive method for the initial work-up of pleural effusions with malignant epithelioid cells. They said other antibodies can be added according to clinical information.
• Limitations the authors state:
  • The results are based on convenience samples of different sizes and need confirmation in a prospective study of more specimens.
  • The panels may under-diagnose infrequent metastatic prostatic, thyroid and pancreatic carcinoma.
  • The approach is not designed to address all diagnostic possibilities, and the panels need updating as experience accrues.
  • A larger future study may show the panels need to be modified.

Topics

The National Library of Medicine indexes this study under subjects our site covers: Pleural plaques and thickening.

Medical terms in this study, explained in our Lexicon: Cytopathology, Pleural Effusion, Epithelioid, Pathology, Immunohistochemistry, Differential Diagnosis, Mesothelial Cells, Carcinoma.

Related studies

• Current controversies regarding the role of asbestos exposure in the causation of malignant mesothelioma: the need for an evidence-based approach to develop medicolegal guidelines — A.M. Marchevsky, M.R. Wick (2003)
• Guidelines for the cytopathologic diagnosis of epithelioid and mixed-type malignant mesothelioma: Complementary statement from the international mesothelioma interest group, also endorsed by the international academy of cytology and the papanicolaou society of cytopathology. A proposal to be applauded and promoted but which requires updating — M. Sheaff (2020)
• The differential diagnosis between pleural sarcomatoid mesothelioma and spindle cell/pleomorphic (sarcomatoid) carcinomas of the lung: evidence-based guidelines from the International Mesothelioma Panel and the MESOPATH National Reference Center — A.M. Marchevsky, N. LeStang, et al. (2017)
• Guidelines for the cytopathologic diagnosis of epithelioid and mixed-type malignant mesothelioma: Complementary Statement from the International Mesothelioma Interest Group, Also Endorsed by the International Academy of Cytology and the Papanicolaou Society of Cytopathology — A. Hjerpe, V. Ascoli, et al. (2015)
• Guidelines for the cytopathologic diagnosis of epithelioid and mixed-type malignant mesothelioma. Complementary statement from the International Mesothelioma Interest Group, also endorsed by the International Academy of Cytology and the Papanicolaou Society of Cytopathology — A. Hjerpe, V. Ascoli, et al. (2015)
• V-domain Ig-containing suppressor of T-cell activation (VISTA), a potentially targetable immune checkpoint molecule, is highly expressed in epithelioid malignant pleural mesothelioma — S. Muller, W. Victoria Lai, et al. (2020)

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