The malignancy grading method is not a reliable assessment of malignancy in mesothelioma

Our plain-English summary of The malignancy grading method is not a reliable assessment of malignancy in mesothelioma, by G. Tierney, M.J. Wilkinson, J.S. Jones (The Journal of Pathology, 1990).

The study

• Authors: G. Tierney, M.J. Wilkinson, J.S. Jones
• Journal: The Journal of Pathology
• Published: 1990;160(3):209-11
• Cited by: 5 articles, as counted by NIH iCite
• Read it: PubMed · Publisher
• In J-M's library: Johns-Manville's company medical library held a copy (J-M no. 003823).

Abstract

The ploidy of a series of pleural lesions--reactive proliferations, malignant mesotheliomas and metastatic tumours--was measured on a Leitz Miamed DNA image analyser using Feulgen-stained slides. The technique successfully recognized all the metastatic tumours as malignant; this corresponds to previous work. However, it was not successful in classifying mesothelial lesions as benign or malignant, resulting in a very high false-negative rate and a moderately high false-positive rate. Mesothelial lesions appear to have a wide range of ploidy values irrespective of their biological behaviour. Thus, for primary mesothelial tumours, the ploidy value cannot be used as a reliable diagnostic index.

In plain English

This laboratory study from Nottingham, U.K., tested whether measuring nuclear DNA content (ploidy) could distinguish malignant mesothelioma from benign reactive growths of the mesothelium. Tissue came from 56 cases submitted to the Commission of the European Communities Mesothelioma Panel. The authors measured 100 nuclei per case before seeing clinical data. Definite mesothelioma required a panel diagnosis of mesothelioma, death within a year of diagnosis, and known asbestos exposure. There were 36 primary mesothelial lesions: 11 benign proliferations and 25 malignant mesotheliomas. The test classed 14 as benign and 22 as malignant. It wrongly called eight of the 25 mesotheliomas benign and five of the 11 benign lesions malignant. The authors reported a false-positive rate of 23 per cent and a false-negative rate of 57 per cent. These figures match five of the 22 lesions classed malignant and eight of the 14 classed benign. All 20 other malignancies, the control group, were classified correctly. The authors suggested false negatives might reflect sampling error or too few nuclei. They concluded that the technique has little value in diagnosing mesothelial lesions.

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: Laboratory study of a diagnostic test. The authors used DNA image cytometry on archived tissue sections, measured without knowing the clinical data, and compared the results with a reference diagnosis. The test measured ploidy and the 5c exceeding rate, which is the percentage of aneuploid cells with a DNA content above 5c (a normal diploid cell is 2c).
• Who was studied: Tissue blocks from 56 cases submitted to the Commission of the European Communities Mesothelioma Panel, studied in Nottingham, U.K. Of these, 36 were primary mesothelial lesions: 11 benign proliferations and 25 malignant mesotheliomas. The other 20 were other malignancies, used as a control group: adenocarcinoma or large cell carcinoma of the bronchus, or various metastatic tumours.
• Exposure: Asbestos exposure was not measured. A known history of asbestos exposure was one of three criteria the authors used to judge a case a definite mesothelioma. The other two were a panel diagnosis of mesothelioma and death within 1 year of diagnosis. No fiber types are named.
• Main results:
  • The reference diagnoses for the 36 primary mesothelial lesions were 11 benign proliferations and 25 malignant mesotheliomas.
  • Of the 36 mesothelial lesions, the measurement classified 14 as benign. Eight of these were false negatives, meaning eight of the 25 mesotheliomas were classed as benign.
  • Of the 36 mesothelial lesions, the measurement classified 22 as malignant. Five of these were false positives, meaning five of the 11 benign proliferations were classed as malignant.
  • For the mesothelial lesions, the authors reported a false-positive rate of 23 per cent and a false-negative rate of 57 per cent. These figures correspond to five of the 22 lesions the test classed as malignant and eight of the 14 it classed as benign.
  • For the 20 malignancies other than mesotheliomas, the machine diagnosis matched the reference diagnosis in every case, with no false negatives or false positives.
  • The cells with high DNA content in the false-positive cases did not appear to be dividing cells. The authors took this to mean that benign mesothelial proliferations vary in ploidy as well as in their appearance under the microscope.
• The authors' conclusion: The authors concluded that measuring ploidy by static morphometry has little value in diagnosing mesothelial lesions.
• Limitations the authors state:
  • The authors suggested the false negatives could be due to sampling error: only the benign reactive tissue surrounding a malignant area might have been measured.
  • The authors suggested mesotheliomas may have few aneuploid cells, so measuring 100 nuclei may not be sensitive enough to detect them.
  • The authors suggested the false positives could be due to overlapping nuclei, which would give an incorrect 5c exceeding rate. Nuclei that overlapped could not be measured.

Topics

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

Medical terms in this study, explained in our Lexicon: Mesothelioma, Malignant Mesothelioma.

Related studies

• A novel method for accurate collagen and biochemical assessment of pulmonary tissue utilizing one animal — C.R. Kliment, J.M. Englert, et al. (2011)
• Comparison of exposure assessment methods for occupational carcinogens in a multi-centre lung cancer case-control study — S. Peters, R. Vermeulen, et al. (2011)
• Patterns of histopathological change determined by the point counting method and its application for the hazard assessment of respirable dust — A. Ogami, Y. Morimoto, et al. (2004)
• Comparison of exposure assessment methods in a lung cancer case-control study: performance of a lifelong task-based questionnaire for asbestos and PAHs — E. Bourgkard, P. Wild, et al. (2013)
• Retrospective Exposure Assessment Methods Used in Occupational Human Health Risk Assessment: A Systematic Review — F. Borghi, L.A. Mazzucchelli, et al. (2020)
• Assessments of lung digestion methods for recovery of fibers — D.B. Warheit, H.C. Hwang, et al. (1991)

Browse more research in The Journal of Pathology, or return to medical research.