Development of mesothelioma in situ and its progression to invasive disease observed in a patient with uncontrolled pleural effusions for 15 years

Our plain-English summary of Development of mesothelioma in situ and its progression to invasive disease observed in a patient with uncontrolled pleural effusions for 15 years, by K. Hidaka, T. Takeda, Y. Kinoshita, et al (Pathology International, 2020).

The study

• Authors: K. Hidaka, T. Takeda, Y. Kinoshita, K. Nabeshima, S. Tamiya, Y. Yoshikawa, T. Tsujimura
• Journal: Pathology International
• Published: 2020;70(12):1009-1014
• Type of article: Case report
• Cited by: 14 articles, as counted by NIH iCite
• Read it: PubMed · Publisher

Abstract

Mesothelioma in situ (MIS) has recently been investigated as a distinct phase of mesothelioma carcinogenesis. The diagnostic criteria proposed for MIS include a loss of BRCA1-associated protein 1 (BAP1) expression detected by immunohistochemistry (IHC). However, the length of time that MIS typically remains an in situ lesion before progression to invasive disease is still unclear. Herein, we report a case of a Japanese woman in her early seventies who had suffered from recurrent pleural effusions for 15 years, during which MIS developed and progressed to invasive mesothelioma. Retrospective diagnosis of partial MIS, fully developed MIS, and invasive disease was made using BAP1 IHC on three biopsy specimens and via clinical observations with radiological images. MIS and invasive lesions revealed BAP1 loss. The interval from partial or full MIS to invasive disease was 14 and 7 years, respectively. These results support a diagnostic strategy combining histomorphology with genomic-based assays including BAP1 IHC in biopsy tissues from a patient with recurrent pleural effusions.

© 2020 Japanese Society of Pathology and John Wiley & Sons Australia, Ltd.

In plain English

This case report described one Japanese woman who had recurring fluid around her right lung (pleural effusions) for 15 years. When first referred, in her 50s, she had a history of 5 years of asbestos exposure at an electrical factory in her 40s. The article does not name a fiber type. Two thoracoscopic biopsies of her pleura did not lead to a diagnosis at the time. When the authors later re-examined them with BAP1 staining, the first biopsy showed partial BAP1 loss in the lining cells. The second showed BAP1 loss in all lining cells in all six samples, which they classed as mesothelioma in situ, an early non-invasive stage. A CT scan 5 years after the second biopsy showed no new lesions. Seven years after that biopsy, a neck lymph node biopsy showed metastatic mesothelioma with BAP1 loss, and she later died of malignant mesothelioma. No inherited BAP1 mutation was found in her blood. The authors concluded that mesothelioma in situ, including partial, could stay non-invasive for more than 10 years. They said more cases are needed to confirm this.

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 of a single patient, with retrospective re-examination of earlier biopsy tissue
• Who was studied: one Japanese woman, first referred in her 50s with cough and chest tightness, followed over about 15 years of right-sided pleural effusions
• Exposure: 5 years of asbestos exposure at an electrical factory while in her 40s; no fiber type or dose given
• Main results:
  • First thoracoscopic (VATS) biopsy, 14 years before death: focal loss of BAP1 in the pleural lining cells, with other parts retaining BAP1
  • First biopsy: MTAP retained and 9p21 and NF2 FISH tests normal
  • Second VATS biopsy: BAP1 loss in all lining cells in all six samples from the right parietal pleura
  • Second biopsy: no MTAP loss, 9p21 homozygous deletion or NF2 hemizygous loss
  • CT 5 years after the second biopsy showed no additional lesions
  • Pleural thickening and other signs of invasive disease appeared 14 years after the effusions began, 7 years after the second biopsy
  • Lymph node biopsy: mesothelioma cells with BAP1 loss, MTAP retained, and normal 9p21 and NF2 FISH
  • The patient died of malignant mesothelioma after one course of carboplatin and pemetrexed chemotherapy
  • No germline (inherited) BAP1 mutation was found in blood DNA
  • The authors counted 7 years from full mesothelioma in situ (second biopsy) to invasive disease
  • The authors counted 14 years from partial mesothelioma in situ (first biopsy) to invasive disease
  • The authors stated that the diagnosis could not have been made by microscopy alone without the genomic-based tests
• The authors' conclusion: The authors concluded that in this case mesothelioma in situ, including partial mesothelioma in situ, could remain non-invasive for more than 10 years before progressing to invasive disease
• Limitations the authors state:
  • The small size of the first biopsy may have affected the proportion of cells showing BAP1 loss
  • It is not known what number or proportion of cells with BAP1 loss is needed to diagnose mesothelioma
  • The authors could not review cytology preparations from the first or second biopsy
  • Further cases are needed to validate the findings

Topics

The National Library of Medicine indexes this study under subjects our site covers: Mesothelioma, Pleural plaques and thickening.

Medical terms in this study, explained in our Lexicon: Mesothelioma in Situ, Pleural Effusion, Mesothelioma, Carcinogenesis, BAP1, Immunohistochemistry, Biopsy.

Related studies

• A combination of MTAP and BAP1 immunohistochemistry in pleural effusion cytology for the diagnosis of mesothelioma — Y. Kinoshita, T. Hida, et al. (2018)
• Cytological diagnosis of mesothelioma in situ versus invasive mesothelioma — A. Churg, F. Galateau-Salle, et al. (2022)
• Usefulness of p16/CDKN2A fluorescence in situ hybridization and BAP1 immunohistochemistry for the diagnosis of biphasic mesothelioma — D. Wu, K. Hiroshima, et al. (2017)
• Fluorescence in situ hybridization detection of chromosome 22 monosomy in pleural effusion cytology for the diagnosis of mesothelioma — Y. Kinoshita, M. Hamasaki, et al. (2021)
• Malignant mesothelioma in situ: diagnostic and clinical considerations — E. Pulford, D.W. Henderson, et al. (2020)
• BAP1 protein is a progression factor in malignant pleural mesothelioma — L. Arzt, F. Quehenberger, et al. (2014)

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