Malignant mesothelioma in situ: morphologic features and clinical outcome

Our plain-English summary of Malignant mesothelioma in situ: morphologic features and clinical outcome, by A. Churg, F. Galateau-Salle, A.C. Roden, et al (Modern Pathology, 2020).

The study

• Authors: A. Churg, F. Galateau-Salle, A.C. Roden, R. Attanoos, J.H. von der Thusen, M.S. Tsao, N. Chang, M. De Perrot, S. Dacic
• Journal: Modern Pathology
• Published: 2020;33(2):297-302
• Cited by: 89 articles, as counted by NIH iCite
• Read it: PubMed · Publisher

Abstract

The existence of an in situ phase of malignant mesothelioma has long been postulated but until recently has been impossible to prove. Here we describe ten patients with mesothelioma in situ, defined by a single layer of surface mesothelial cells showing loss of BAP1 nuclear immunostaining, no evidence of tumor by imaging and/or by direct examination of the pleura/peritoneum, and no invasive mesothelioma developing for at least 1 year. Nine cases were pleural and one peritoneal. Most patients were biopsied for repeated effusions of unknown etiology; in two patients mesothelioma in situ was found incidentally in lung cancer resections. In addition to surface mesothelium with BAP1 loss, one case had a surface papillary proliferation with BAP1 loss, and two cases had a small (few millimeter) nodule with BAP1 loss. CDKN2A was deleted by FISH in one of eight cases. Methylthioadenosine phosphorylase showed partial loss in the surface mesothelium by immunohistochemistry in three cases. Invasive malignant mesothelioma developed in seven patients with time between biopsy and invasive disease from 12 to 92 (median 60) months. Invasive mesothelioma has not developed in the other three patients at 12, 57, and 120 months, but the latter patient, who has pleural plaques, still has repeated pleural effusions, probably representing a so-called "benign asbestos effusion." We conclude that mesothelioma in situ, as diagnosed using the criteria outlined above, is associated with a high risk of developing invasive mesothelioma, but typically over a relatively protracted time, so that curable interventions maybe possible.

In plain English

This case series described ten patients with what the authors called malignant mesothelioma in situ. The authors defined it as a single layer of lining cells that had lost a protein called BAP1, with no tumor seen on imaging or direct inspection and no invasive mesothelioma for at least one year. The patients were six men and four women aged 53 to 79. Nine cases were pleural and one peritoneal. Most had repeated fluid build-up of unknown cause, and two were found by chance during lung cancer surgery. The abnormal cells usually looked bland under the microscope. Invasive mesothelioma developed in seven patients (six pleural, one peritoneal), 12 to 92 months after biopsy (median 60 months). Three had not developed it at 12, 57 and 120 months. The last of these, who had pleural plaques, still had repeated pleural effusions. The article did not report asbestos exposure histories. The authors concluded that BAP1 loss in the surface lining carries a very high risk of invasive mesothelioma, usually over a long period, possibly allowing treatment beforehand. They noted that their one-year entry rule may have biased the median time upwards.

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: Case series of ten patients collected from pathologists at several centers, with clinical follow-up
• Who was studied: Ten patients (six men, four women; average age 69, range 53 to 79). Nine had pleural disease and one presented with ascites (peritoneal). Most had repeated effusions of unknown cause, and two were incidental findings in lung cancer resections. The article does not give the years in which the cases occurred.
• Exposure: The article does not report asbestos exposure histories or fiber types. One patient (case 8) had pleural plaques and recurrent effusions that the authors thought best fit a so-called benign asbestos effusion.
• Main results:
  • Invasive malignant mesothelioma developed in seven of the ten patients (six pleural, one peritoneal). The time from biopsy to invasive tumor was 12 to 92 months, with a median of 60 months.
  • Three patients had not developed invasive disease at 12, 57 and 120 months of follow-up. Case 9 had developed recurrent effusions at 57 months, and case 8 had persisting pleural effusions and pleural plaques at 120 months, both without overt tumor.
  • In most cases the in situ mesothelial cells showed little or no cytologic atypia. Only one case (case 7) showed significant atypia.
  • CDKN2A homozygous deletion by FISH was found in only one of eight cases tested (case 1).
  • MTAP staining was run on the flat mesothelium in seven cases: four showed no loss and three showed patchy loss.
  • Data were available for four of the invasive tumors that developed. All four showed BAP1 loss and none showed CDKN2A deletion.
• The authors' conclusion: The authors concluded that BAP1 loss in flat surface mesothelium confers a very high risk of later invasive mesothelioma. They also concluded that progression is usually slow, which potentially allows a therapeutic intervention before invasive disease occurs.
• Limitations the authors state:
  • The median time to progression may be biased upwards, because cases progressing in under one year were excluded by design.
  • Most cases were consultation referrals, so the authors could not obtain tissue for a comprehensive molecular comparison of in situ and matched invasive mesothelioma.
  • The small nodule in case 9 could be argued to be an early tiny clone of invasive mesothelioma. The authors stated that a molecular marker separating invasive from in situ disease is needed.

Topics

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

Medical terms in this study, explained in our Lexicon: Malignant Mesothelioma, Mesothelioma in Situ, Mesothelial Cells, BAP1, Pleura, Peritoneum, Mesothelioma, Etiology.

Related studies

• Utility of Methylthioadenosine Phosphorylase Compared With BAP1 Immunohistochemistry, and CDKN2A and NF2 Fluorescence In Situ Hybridization in Separating Reactive Mesothelial Proliferations From Epithelioid Malignant Mesotheliomas — K.B. Berg, S. Dacic, et al. (2018)
• Fluorescence in situ hybridization (FISH) provides estimates of minute and interstitial BAP1, CDKN2A, and NF2 gene deletions in peritoneal mesothelioma — S. Brich, F. Bozzi, et al. (2020)
• MTAP immunohistochemistry is an accurate and reproducible surrogate for CDKN2A fluorescence in situ hybridization in diagnosis of malignant pleural mesothelioma — D.B. Chapel, J.J. Schulte, et al. (2020)
• Usefulness of methylthioadenosine phosphorylase and BRCA-associated protein 1 immunohistochemistry in the diagnosis of malignant mesothelioma in effusion cytology specimens — K.B. Berg, A.M. Churg, et al. (2020)
• New Markers for Separating Benign From Malignant Mesothelial Proliferations: Are We There Yet? — A. Churg, B.S. Sheffield, et al. (2016)
• BAP1 immunohistochemistry has limited prognostic utility as a complement of CDKN2A (p16) fluorescence in situ hybridization in malignant pleural mesothelioma — S.M. McGregor, J. McElherne, et al. (2017)

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