Pathology analysis for mesothelioma study in the United Kingdom: Current practice and historical development

Our plain-English summary of Pathology analysis for mesothelioma study in the United Kingdom: Current practice and historical development, by B.W. Case (Journal of Toxicology and Environmental Health. Part B, Critical Reviews, 2016).

The study

• Author: B.W. Case
• Journal: Journal of Toxicology and Environmental Health. Part B, Critical Reviews
• Published: 2016;19(5-6):201-212
• Type of article: Historical article
• Cited by: 6 articles, as counted by NIH iCite
• Read it: PubMed · Publisher

Abstract

Following up on the largest case-control study of malignant mesothelioma yet performed, investigators at the London School of Hygiene and Tropical Medicine assessed 1732 male and 670 female cases as of May 2013. Epidemiological findings of a subset of these were published previously, excluding patients who died or who refused to be interviewed. Pathology reports were collected for subjects, including those both eligible and ineligible for epidemiology study based on vital status. The current investigation examined 860 cases having pathology reports available. Sixty-one cases were diagnosed using cytology only, often with equivocal diagnoses, while 799 reported at least a biopsy of the tumor. Of these, 748 had pathology sufficiently detailed for evaluation. These reports were examined for basis of diagnosis, differences between study cases and ineligible cases, pathology characteristics, and immunohistochemical and other tests used. The most prominent subtype was epithelioid (64% of study cases but only 49% of ineligible cases). Biphasic subtype was present in 10% of study cases and 16% of those ineligible. Sarcomatoid subtype was present in 7% of study cases and 19% of ineligible cases, most of whom died. Twelve percent of study cases displayed no specified subtype, versus 7% of ineligible cases. Of recorded immunohistochemical stains specific for mesothelial cell origin, calretinin (95%) and CK 5/6 or CK5 alone (84%) were by far the most common. Calretinin and CK 5/6 or CK 5 alone were also most sensitive and positive in 92% of cases presenting with surgical pathology report. Ninety percent of cases had at least one immunohistochemical marker for possible lung carcinoma applied, with BER-Ep4 and TTF-1 the most frequent at 68% and CEA at 58%. TTF-1 and CEA were positive in 1% or less of cases. Patterns of use and positive and negative results for each of these as well as other immunohistochemical stains are presented and discussed, along with a brief historical description of their development and use. Possible effects of the pathologic analysis on the results of previously published and future epidemiological studies are discussed.

In plain English

This article described pathology reports for mesothelioma cases collected by the London School of Hygiene and Tropical Medicine for a UK case-control study (MALCS-II). The author was blind to asbestos exposure information. A two-thirds sample of 860 cases was drawn from the available reports. Of these, 61 had been included on cytology alone, and the 799 with a surgical pathology report were evaluated. Where the site was indicated, 97% were pleural. Of 706 reports with histology detail, 503 (71.3%) were epithelioid, 85 (12%) biphasic and 75 (10.6%) sarcomatoid or desmoplastic. Cases known to have died were less often epithelioid (45 of 78, 58%) than living cases eligible for interview (458 of 601, 76%). Among 748 cases with immunohistochemistry results, calretinin was used in 710 (95%) and was positive in 654 of the 710 tested (92%). The lung cancer marker TTF-1 was positive in 3 of 506 cases tested. No case reported electron microscopy. Overall, 92 of 860 cases (over 10%) had equivocal or negative diagnoses in the available reports. The author wrote that including incorrect diagnoses might affect attributable risk calculations, and noted the sample was not fully representative.

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: Descriptive analysis of pathology reports from cases in an ongoing case-control study, with a historical discussion of how mesothelioma is diagnosed
• Who was studied: Mesothelioma cases in the United Kingdom ascertained by London School of Hygiene and Tropical Medicine investigators for the MALCS-II study. As of May 2013 there were 1732 male and 670 female cases, diagnosed 2005 to 2013 (elsewhere stated as 2006 to 2012). Pathology reports were available for 953 male and 357 female cases. A two-thirds sample of 860 cases was drawn; 61 were cytology-only, and 799 cases with a surgical pathology report were evaluated (566 male, 233 female).
• Exposure: Asbestos exposure was not studied. The author reviewed pathology reports while blind to interview results and asbestos exposure information.
• Main results:
  • Where the site of the tumor was indicated, 97% of cases were pleural.
  • Of the 706 surgical pathology reports with histology detail, 503 (71.3%) were epithelioid, 85 (12%) were biphasic or mixed, and 75 (10.6%) were sarcomatoid, sarcomatous or desmoplastic.
  • Among cases clearly described as one of four subtypes, those known to have died were less often epithelioid (45 of 78, 58%) than living cases eligible for interview (458 of 601, 76%).
  • Cases that had died were more often biphasic (18%) or sarcomatoid/desmoplastic (23%) than living cases (12% biphasic, 10% sarcomatoid/desmoplastic).
  • Among 748 cases with immunohistochemistry results, at least one mesothelial cell marker was performed in 734 cases (98%).
  • Calretinin was the most used mesothelial cell marker. It was applied in 710 of the 748 cases (95%) and was positive in 654 of the 710 tested (92%).
  • CK 5/6 or CK5 was applied in 625 of the 748 cases (84%) and was positive in 572 of 625 (92%).
  • The lung epithelial marker TTF-1 was applied in 506 cases (68%) and was positive in 3 of 506 (less than 1%).
  • The lung epithelial marker CEA was applied in 435 cases (58%) and was positive in 5 of 435 (1%).
  • The lung epithelial marker BER-Ep4 was applied in 511 cases (68%) and was positive in 67 of 511 (13%).
  • In cases with sarcomatoid, desmoplastic or poorly differentiated histology, calretinin was positive in 35 of 71 tested (49%).
  • In the same sarcomatoid, desmoplastic or poorly differentiated group, WT-1 was positive in 22 of 36 tested (61%).
  • Electron microscopy was not reported in any case.
  • Classical special stains (PAS, PAS diastase or mucicarmine) were reported in 40 (5.3%) of the 748 cases.
  • Counting 61 cytology-only cases, 13 reports giving a different diagnosis, and 18 reports giving more than one diagnosis, 92 of 860 cases (over 10%) were equivocal to negative in the available diagnostic reports.
• The authors' conclusion: The author concluded that including a large proportion of incorrect diagnoses in the epidemiological study might affect attributable risk calculations.
• Limitations the authors state:
  • Many cases had no available pathology report, and only a two-thirds sample of those with reports was used, so the cases are not entirely representative of all UK cases.
  • Almost all cases were pleural, so the data mainly reflect pleural mesothelioma.
  • The apparent differences between men and women in age at diagnosis, age at death and year of diagnosis may be artifacts of how cases were sampled.
  • Because all cases were assumed to be mesothelioma, the specificity of the markers could not be assessed.
  • Recording results simply as positive or negative may oversimplify immunohistochemistry findings.
  • The cases did not overlap with those in the 2009 published study, so these findings do not necessarily apply to that published work.

Topics

The National Library of Medicine indexes this study under subjects our site covers: Mesothelioma.

Medical terms in this study, explained in our Lexicon: Pathology, Mesothelioma, Case-Control Study, Malignant Mesothelioma, Pathology Report, Epidemiology, Cytology, Biopsy.

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