Malignant mesothelioma in situ

Our plain-English summary of Malignant mesothelioma in situ, by A. Churg, H. Hwang, L. Tan, et al (Histopathology, 2018).

The study

• Authors: A. Churg, H. Hwang, L. Tan, G. Qing, A. Taher, A. Tong, A.M. Bilawich, S. Dacic
• Journal: Histopathology
• Published: 2018;72(6):1033-1038
• Type of article: Case report
• Cited by: 52 articles, as counted by NIH iCite
• Read it: PubMed · Publisher

Abstract

Aims: The existence of malignant mesothelioma in situ (MIS) is often postulated, but there are no accepted morphological criteria for making such a diagnosis.

Methods And Results: Here we report two cases that appear to be true MIS on the basis of in-situ genomic analysis. In one case the patient had repeated unexplained pleural unilateral effusions. Two thoracoscopies 9 months apart revealed only visually normal pleura. Biopsies from both thoracoscopies showed only a single layer of mildly reactive mesothelial cells. However, these cells had lost BRCA1-associated protein 1 (BAP1) and showed loss of cyclin-dependent kinase inhibitor 2 (CDKN2A) (p16) by fluorescence in-situ hybridisation (FISH). NF2 was not deleted by FISH but 28% of the mesothelial cells showed hyperploidy. Six months after the second biopsy the patient has persisting effusions but no evidence of pleural malignancy on imaging. The second patient presented with ascites and minimal omental thickening on imaging, but no visual evidence of tumour at laparoscopy. Omental biopsy showed a single layer of minimally atypical mesothelial cells with rare tiny foci of superficial invasion of fat. BAP1 immunostain showed loss of nuclear BAP1 in all the surface mesothelial cells and the invasive cells. There was CDKN2A deletion, but no deletion of NF2 by FISH.

Conclusions: These cases show that morphologically bland single-layered surface mesothelial proliferations with molecular alterations seen previously only in invasive malignant mesotheliomas exist, and presumably represent malignant MIS. More cases are need to understand the frequency of such changes and the time-course over which invasive tumour develops.

© 2018 John Wiley & Sons Ltd.

In plain English

This report described two patients whose biopsies, the authors argued, showed malignant mesothelioma in situ (MIS): an early, surface-only stage of mesothelioma that has no accepted microscopic criteria. The article does not report any asbestos exposure for either patient. The first patient was a 70-year-old woman with repeated, unexplained right pleural effusions (fluid around the lung). Two random pleural biopsies taken 9 months apart showed only a single layer of bland mesothelial cells. Those cells had lost BAP1 staining and showed CDKN2A deletion by FISH. NF2 was not deleted, but 28% of cells showed hyperploidy. Six months after the second biopsy, imaging still showed no pleural malignancy. The second patient was a 60-year-old woman with ascites (abdominal fluid). An omental biopsy showed a single cell layer with a few tiny foci of shallow invasion into fat, with BAP1 loss and CDKN2A deletion. She died 27 months later, and no autopsy was done. The authors concluded that these cases presumably represent malignant MIS. They cautioned that it is unknown whether such lesions always become invasive, or how fast.

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 report (two cases)
• Who was studied: Two patients from the consultation files of one author: a 70-year-old woman with recurrent right pleural effusions, and a 60-year-old woman with a past history of breast cancer who presented with abdominal bloating and ascites
• Main results:
  • Patient 1, first and second pleural biopsies: BAP1 immunostain showed loss of normal nuclear staining in all the mesothelial cells
  • Patient 1, first biopsy: CDKN2A FISH showed homozygous deletion in 3.8% of cells and hemizygous deletion in 22.5% of cells
  • Patient 1, second biopsy: CDKN2A FISH showed homozygous loss in 10% of cells and hemizygous loss in 23.0% of cells (normal range 0 to 20%)
  • Patient 1: NF2 FISH showed no hemizygous or homozygous loss, but 28% of cells showed hyperploidy
  • Patient 1: over the 6 months after the second biopsy, effusions kept recurring, but imaging showed no evidence of pleural malignancy
  • Patient 2, omental biopsy: in a few scattered tiny foci, the mesothelial cells formed glands that shallowly invaded the underlying fat
  • Patient 2: BAP1 nuclear staining was lost in all the surface mesothelial cells and in the minute invasive foci
  • Patient 2: CDKN2A FISH showed homozygous loss in 10% of cells and hemizygous loss in 30% of cells (normal range 0 to 20%)
  • Patient 2: NF2 FISH showed homozygous loss in 3.6% of cells and hemizygous loss in 3.6% of cells (normal range 0 to 20%), and 6.0% of cells showed hyperploidy; the authors described neither case as showing NF2 deletion
  • Patient 2 was tentatively diagnosed with idiopathic sclerosing peritonitis, treated with tamoxifen, and died 27 months later; no autopsy was performed
• The authors' conclusion: The authors concluded that bland, single-layered surface mesothelial proliferations carrying molecular changes previously seen only in invasive malignant mesothelioma do exist, and presumably represent malignant MIS
• Limitations the authors state:
  • The authors stated that it is not yet known whether surface processes with this appearance always become invasive, or how long that takes
  • The authors acknowledged that in case 2 the surface cells could be spread from an invasive mesothelioma, although they judged true MIS with very early invasion more likely
  • The authors stated that more cases are needed

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, Pleura, Reactive Mesothelial Cells, BAP1, CDKN2A, Fluorescence In Situ Hybridization (FISH), Mesothelial Cells, Biopsy.

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• Germline BAP1-positive patients: the dilemmas of cancer surveillance and a proposed interdisciplinary consensus monitoring strategy — P. Star, A. Goodwin, et al. (2018)
• Mesothelioma Biomarkers: A Review Highlighting Contributions from the Early Detection Research Network — H.I. Pass, M. Alimi, et al. (2020)

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