How to assess the best immunohistochemical panel in the diagnosis of malignant pleural mesothelioma in a pathology lab

Our plain-English summary of How to assess the best immunohistochemical panel in the diagnosis of malignant pleural mesothelioma in a pathology lab, by M. Mlika, O. Lamzibri, S. Bacha, et al (Journal of Immunoassay & Immunochemistry, 2018).

The study

• Authors: M. Mlika, O. Lamzibri, S. Bacha, S. Laabidi, C. Haddouchi, F.E. Mezni
• Journal: Journal of Immunoassay & Immunochemistry
• Published: 2018;39(3):263-273
• Cited by: 1 article, as counted by NIH iCite
• Read it: PubMed · Publisher

Abstract

Background: malignant pleural mesothelioma (MPM) is a rare tumor with a challenging diagnosis. Even if, clinical data are mandatory to suspect the diagnosis, the positive diagnosis is based on microscopic features. Morphologic features are still the port of call of the diagnosis but their non specific character and the multiplicity of differential diagnoses made the immunohistochemical markers mandatory for the diagnosis. Many antibodies with a positive diagnostic value including claretinin, mesothelin, WT1 and antibodies with a negative diagnostic value including TTF1, EMA, CD15 are recommended by the scientific societies. This is due to the diagnostic limits of every antibody which necessitate the association of multiple antibodies. In the diagnostic demarch, pathologists deal with different antibodies and clones. Even if many recommendations are available, every pathology lab has to experiment its own antibodies in order to optimize the routine diagnostic demarch especially in low-income country. Our aim was to assess the diagnostic value of different antibodies available in our lab and to recommend a decisional flowchart.

Patients And Methods: we conducted a retrospective study about 30 MPM diagnosed over a 20-year-period. The different techniques were realized manually. The different antibodies used were anti-calretinin, anti-Epithelial Membrane Antigen (EMA), anti-mesothelin, anti-Thyroid Transcription Factor 1 (TTF1), anti-ACE, anti-cytokeratin, anti-vimentin, anti-CD15, anti-cytokeratin 5/6, anti-bcl2, and anti-CD99 and anti-CD34 antibodies. The sensitivity and specificity of these antibodies were assessed.

Results: the microscopic exam concluded to an epithelioid mesothelioma (EM) in 17 cases, sarcomatoid mesothelioma (SM) in four cases and biphasic mesothelioma (BM) in nine cases. The immunohistochemical study was performed in all cases. A mean of eight antibodies was used in every case, average 4 to 20 antibodies. The immunohistochemical study was repeated from 2 to 5 times in 15 cases and concerned a mean of 3 antibodies per case. In EM and BM, the antibodies with positive predictive value and highest sensitivity were calretinin, EMA, cytokeratin, and vimentin reaching respectively a sensitivity of 86.2%, 89.7%, 92.9% and 89.3%. The most valuable antibodies with negative predictive value were TTF1, CD15 and ACE that presented a specificity reaching respectively 100%. In sarcomatoid mesothelima, the most sensitive antibody was the cytokeratin antibody.

Conclusion: these results yielded to a diagnostic flowchart that we can use in routine practice and that is in accordance with the literature findings. Many diagnostic and technical pitfalls have to be known by pathologists when dealing with MPM.

In plain English

This retrospective study from the pathology department of Abderrahman Mami Hospital in Tunis reviewed 30 cases of malignant pleural mesothelioma diagnosed between 1995 and 2015. It looked at how well the lab's own antibody stains (immunohistochemistry) helped confirm the diagnosis. The patients' mean age was 61 years, most were men, and asbestos exposure was reported in 21 cases. Under the microscope, 17 tumors were epithelioid, four sarcomatoid and nine biphasic. The authors gave these sensitivities for epithelioid and biphasic tumors: calretinin 86.2%, EMA 89.7%, cytokeratin 92.9% and vimentin 89.3%. The article's own case counts do not fit that label: three figures match counts that also include the sarcomatoid tumors, and the EMA figure does not match the number of cases actually stained. TTF1, CD15 and ACE were negative in every mesothelioma case tested. The authors called this 100% specificity, but no non-mesothelioma tumors were tested. In the four sarcomatoid tumors, cytokeratin was positive in all cases and calretinin in two. The authors concluded that these results produced a diagnostic flowchart for routine use that agrees with published findings. They cautioned that the results depend on the antibody clones used, which manufacturers change periodically.

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 study of diagnosed cases (single pathology department), assessing the diagnostic value of immunohistochemical antibodies
• Who was studied: 30 patients with malignant pleural mesothelioma diagnosed 1995 to 2015 at the Department of Pathology, Abderrahman Mami Hospital, Tunis, Tunisia. Only patients with complete records were included. Mean age was 61 years (range 22 to 80). The sex ratio of men to women was 6.5 (26 men, 4 women).
• Exposure: The study evaluated a panel of antibody stains: calretinin, EMA, mesothelin, TTF1, ACE, cytokeratin, vimentin, CD15, cytokeratin 5/6, bcl2, CD99 and CD34. HBME1 and cytokeratin 20 were also used in a few cases. Asbestos exposure was reported in 21 of the 30 patients; no fiber type or job is given.
• Main results:
  • Microscopic subtypes among the 30 cases: 17 epithelioid, 4 sarcomatoid, 9 biphasic.
  • The authors reported sensitivities of 86.2% for calretinin, 89.7% for EMA, 92.9% for cytokeratin and 89.3% for vimentin, labeled as epithelioid and biphasic results. Pooling the article's per-subtype counts tells a different story for each figure. The calretinin, cytokeratin and vimentin figures match only when the sarcomatoid cases are included. The EMA figure does not match the number of cases actually stained.
  • TTF1, CD15 and ACE were negative in all mesothelioma cases in which they were used, and the authors reported this as 100% specificity. No non-mesothelioma tumors were tested.
  • In epithelioid mesothelioma, calretinin was used in 16 of 17 cases and was positive in 14 (sensitivity 87.5%).
  • In epithelioid mesothelioma, cytokeratin 5/6 was used in 11 of 17 cases and was positive in 6 (sensitivity 54.5%).
  • Mesothelin was used in only 2 epithelioid cases and was positive in both.
  • In the 4 sarcomatoid cases, cytokeratin was positive in all cases (sensitivity 100%).
  • In the 4 sarcomatoid cases, calretinin was positive in 2 (sensitivity 50%).
  • Staining was repeated 2 to 5 times in 15 cases, with a mean of three antibodies per case. The authors attributed this to overfixation in one case and to signal quality in the others.
• The authors' conclusion: The authors concluded that their results produced a diagnostic flowchart they can use in routine practice, and that it agrees with findings in the published literature.
• Limitations the authors state:
  • The results must be interpreted with caution because they depend on the antibody clones used, and manufacturers periodically change clones and dilutions.
  • Clinical history data were frequently missing.

Topics

Medical terms in this study, explained in our Lexicon: Pleural Mesothelioma, Pathology, Mesothelin, Calretinin, Epithelial Membrane Antigen (EMA), Cytokeratin 5/6, CD34, Epithelioid.

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