The histopathological diagnosis of malignant mesothelioma v. pulmonary adenocarcinoma: reproducibility of the histopathological diagnosis

Our plain-English summary of The histopathological diagnosis of malignant mesothelioma v. pulmonary adenocarcinoma: reproducibility of the histopathological diagnosis, by B.G. Skov, A.F. Lauritzen, F. Hirsch, et al (Histopathology, 1994).

The study

• Authors: B.G. Skov, A.F. Lauritzen, F. Hirsch, H.W. Nielsen
• Journal: Histopathology
• Published: 1994;24(6):553-7
• Cited by: 27 articles, as counted by NIH iCite
• Read it: PubMed · Publisher

Abstract

In a randomized design we examined the interobserver variation in the histopathological diagnosis of adenocarcinoma of the lung and malignant mesothelioma. In three rounds, three pathologists assessed slides from 42 tumours originally diagnosed as adenocarcinomas, malignant mesotheliomas or benign lesions in the pleura. In the first round the assessments were made on haematoxylin and eosin (H & E) stained sections; in the second, on H & E sections plus sections stained with histochemical mucin stains; and in the final round, the diagnoses were made on H & E sections and sections stained with a panel of antibodies against various antigens (cytokeratin, EMA, CEA, Ber-EP4, B72.3, Leu-M1, vimentin and S-100 protein) said to be of value in the differential diagnosis. The overall interobserver agreements for the three rounds were 0.659, 0.802 and 0.817; the kappa values were 0.461, 0.681 and 0.690. It is concluded that differentiation between adenocarcinoma of the lung and malignant mesothelioma should be made on sections stained with H & E and mucin and/or immunohistochemical staining reactions, including antibodies against B72.3, Ber-EP4 and CEA.

In plain English

This Danish study tested how often pathologists agree when telling malignant mesothelioma apart from lung adenocarcinoma. It did not study asbestos exposure. Tissue came from 42 cases from a Copenhagen hospital register covering 1981 to 1991. The cases had originally been diagnosed as lung adenocarcinoma, malignant mesothelioma or a benign pleural lesion. Three pathologists, who did not know the original diagnoses, classified every case in three rounds. Round one used routine H and E stained slides only. Round two used H and E slides plus mucin stains. Round three used H and E slides plus antibody stains instead, and the mucin and antibody stains were judged separately. Overall agreement was 0.659, 0.802 and 0.817 across the three rounds. The chance-corrected kappa values were 0.461 (95% confidence interval 0.340 to 0.581), 0.681 (0.561 to 0.801) and 0.690 (0.563 to 0.817). The authors concluded that H and E slides alone should not be used for this distinction. They recommended adding mucin and/or antibody stains, including B72.3, Ber-EP4 and CEA. They noted that each pathologist had only one slide per tumour and no clinical information.

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: Randomized, blinded study of agreement between pathologists (interobserver variation) in diagnosis, using cases identified retrospectively from a pathology register
• Who was studied: 45 cases were selected from the pathology register at Rigshospitalet, Copenhagen, covering 1 January 1981 to 1 January 1991: 20 consecutive cases originally diagnosed as pulmonary adenocarcinoma, 20 as malignant mesothelioma and 5 as benign lesions of the pleura. Three blocks lacked material, leaving 42 tumours. These were assessed by three pathologists.
• Exposure: No asbestos or other exposure was studied. The comparison was between diagnostic methods: H and E stained sections alone, H and E plus histochemical mucin stains, and H and E plus a panel of antibody stains (cytokeratin, EMA, CEA, Ber-EP4, B72.3, Leu-M1, vimentin and S-100 protein). The mucin stains and the antibody stains were evaluated separately, not one after the other.
• Main results:
  • Among the three pathologists, overall agreement was 0.659 with H and E alone, 0.802 with H and E plus mucin stains, and 0.817 with H and E plus antibody stains. The matching kappa values were 0.461, 0.681 and 0.690.
  • Table 2 gives 95% confidence intervals for the kappa values of 0.340 to 0.581 (H and E alone, kappa 0.461), 0.561 to 0.801 (H and E plus mucin stains, kappa 0.681) and 0.563 to 0.817 (H and E plus antibody stains, kappa 0.690).
  • When one pathologist called a case malignant mesothelioma on the H and E slide, the chance that a second pathologist made the same diagnosis was 58.5%. The chance of a diagnosis of pulmonary adenocarcinoma was 24.4%, and of a benign lesion 17.1%. With mucin stains added, these figures became 80.6%, 9.7% and 9.7%.
  • For 30% of the pulmonary adenocarcinoma cases, the three pathologists did not agree on the diagnosis using H and E sections.
  • With antibody stains, the three pathologists disagreed in only one pulmonary adenocarcinoma case and in five malignant mesothelioma cases.
• The authors' conclusion: The authors concluded that reproducibility increased significantly when mucin and antibody stains were added to H and E sections, and that the diagnosis should not be made on H and E sections alone. They recommended making the distinction on H and E sections plus mucin and/or antibody stains, including antibodies against B72.3, Ber-EP4 and CEA.
• Limitations the authors state:
  • The setting differed from daily routine: the pathologists had only one slide per tumour.
  • The authors did not examine whether diagnosis would improve if the pathologists had information on the gross (macroscopic) appearance or the clinical course.
  • The kappa value reflects reproducibility only. It gives no indication of how many cases are affected by disagreement, or of the consequences for patients' treatment.

Topics

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

Medical terms in this study, explained in our Lexicon: Malignant Mesothelioma, Adenocarcinoma, Pleura, Ber-EP4, B72.3 (TAG-72), S-100, Differential Diagnosis, Immunohistochemistry.

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