Reactive mesothelial hyperplasia vs mesothelioma, including mesothelioma in situ: a brief review

Our plain-English summary of Reactive mesothelial hyperplasia vs mesothelioma, including mesothelioma in situ: a brief review, by D.W. Henderson, K.B. Shilkin, D. Whitaker (American Journal of Clinical Pathology, 1998).

The study

• Authors: D.W. Henderson, K.B. Shilkin, D. Whitaker
• Journal: American Journal of Clinical Pathology
• Published: 1998;110(3):397-404
• Type of article: Review
• Cited by: 81 articles, as counted by NIH iCite
• Read it: PubMed · Publisher

Abstract

In biopsy tissue, discrimination between reactive mesothelial hyperplasia and epithelial mesothelioma can pose a major problem for the surgical pathologist. Confidence in the diagnosis is often proportional to the amount of tissue available for study and depends largely on findings of invasion and the extent and cytologic atypia of the lesion, because there is no marker specific for the mesothelium and that discriminates consistently among normal, hyperplastic, and neoplastic mesothelial tissue. Therefore, mesothelioma in situ is diagnosable only when invasive epithelial mesothelioma is demonstrable in the same specimen, in a follow-up biopsy specimen, or at autopsy. Comparison of 22 cases of mesothelioma in situ that fulfill these requirements for diagnosis with 141 invasive mesotheliomas and 78 reactive mesothelioses indicates that strong linear membrane-related labeling for epithelial membrane antigen and silver-labeled nucleolar organizer region-positive material that occupies 0.6677 microm2 or more of the nucleus in an atypical in situ mesothelial lesion of the pleura are found consistently in neoplastic mesothelial cells. Although these findings may engender suspicion of mesothelioma in situ in high-risk persons, the criteria for diagnosis of pure mesothelial lesions of this type are still under study. Mesothelioma in situ should be considered proved only when unequivocal invasion is identified in a different area of the pleura or at a different time; a diagnosis of pure mesothelioma in situ should not be made in patients not exposed to asbestos.

In plain English

This article was a review of how to tell reactive mesothelial hyperplasia, a benign reaction of the lining cells, from epithelial mesothelioma in biopsy tissue, and of the idea of mesothelioma in situ. It summarized the authors' experience with more than 1,500 mesotheliomas from Australian hospital archives, a national surveillance program and consultation cases. The authors wrote that invasion was arguably the most decisive sign of mesothelioma. In their series, 103 (73.0%) of 141 invasive mesotheliomas and 17 (77%) of 22 mesotheliomas in situ were positive for epithelial membrane antigen (EMA), while 3 (4%) of 73 reactive lesions showed equivocal positive labeling. A silver-staining nuclear measure (AgNOR) reached their threshold in 64% of mesotheliomas but in only 3 of 15 in situ cases. All in situ cases were pleural. All but one were confirmed by invasive mesothelioma in the same specimen, a later biopsy or at autopsy. The authors concluded that strong EMA labeling was evidence against a reactive process. They stated that criteria for diagnosing mesothelioma in situ on biopsy were still being worked out.

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: Review summarizing the authors' combined diagnostic experience, including a comparison of in situ mesotheliomas with invasive mesotheliomas and reactive mesothelial lesions
• Who was studied: More than 1,500 mesotheliomas from the archives of Flinders Medical Centre (Adelaide) and Sir Charles Gairdner Hospital (Perth), cases from the Australian Mesothelioma Surveillance Program (1979-1985), and consultation cases, including medicolegal cases. A subset of 22 minimal-bulk mesotheliomas with an in situ component was compared with 141 invasive mesotheliomas and 78 reactive mesothelial lesions.
• Exposure: Asbestos exposure was not measured; the article concerns tissue diagnosis. Among clinical features that raise the probability of mesothelioma, the authors listed a history of asbestos exposure and a lag time usually more than 20 years. They also mentioned a mother and daughter in their series with mesotheliomas after household contact exposure to asbestos.
• Main results:
  • The authors described invasion as arguably the most decisive indicator of mesothelioma, as opposed to reactive hyperplasia.
  • EMA positivity in archival biopsy tissue: 103 (73.0%) of 141 invasive mesotheliomas and 17 (77%) of 22 mesotheliomas in situ. Only 3 (4%) of 73 reactive mesothelial proliferations showed equivocal positive labeling.
  • The AgNOR threshold of 0.6677 square micrometres was the upper limit seen in all their reactive cases. In a series of 80 mesotheliomas, 63 (79%) were EMA-positive and 51 (64%) were AgNOR-positive. Combining the two tests raised the detection rate to 95%.
  • Among in situ mesotheliomas, only 3 of 15 cases reached the AgNOR threshold, whereas 17 of 22 showed thick linear labeling for EMA.
  • All in situ cases were pleural. In all but 1 case the diagnosis was supported by invasive mesothelioma in the same biopsy specimen, a follow-up biopsy, or at autopsy.
  • Minimal or in situ mesothelioma made up less than 3% of the authors' combined series of mesotheliomas presenting with effusion. Some patients with in situ disease had prolonged survival.
• The authors' conclusion: The authors concluded that a weak or negative EMA reaction does not weigh against mesothelioma. In their experience, extensive or strong linear membrane-related EMA labeling is evidence against a reactive mesotheliosis.
• Limitations the authors state:
  • The authors stated that criteria for a biopsy diagnosis of mesothelioma in situ were still being worked out.
  • The authors reported that their own experience with p53 labeling had been largely unrewarding.

Topics

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

Medical terms in this study, explained in our Lexicon: Reactive Mesothelial Hyperplasia, Mesothelioma, Mesothelioma in Situ, Biopsy, Mesothelium, Autopsy, Epithelial Membrane Antigen (EMA), Pleura.

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