Usefulness of malignant pleural effusion for early cytological diagnosis of mesothelioma in situ: A case report

Our plain-English summary of Usefulness of malignant pleural effusion for early cytological diagnosis of mesothelioma in situ: A case report, by Y. Yabuuchi, K. Hiroshima, H. Oshima, et al (Oncology Letters, 2022).

The study

• Authors: Y. Yabuuchi, K. Hiroshima, H. Oshima, J. Kanazawa, K. Hayashihara, T. Nakagawa, M. Shimanouchi, S. Usui, S. Oh-Ishi, T. Saito, N. Hizawa, Y. Minami
• Journal: Oncology Letters
• Published: 2022;24(6):440
• Cited by: 3 articles, as counted by NIH iCite
• Read it: PubMed · Publisher · Free full text

Abstract

Mesothelioma in situ (MIS) is defined as a preinvasive mesothelioma that forms a single layer of mild atypical mesothelial cells lining on the serosa surface of pleura. The atypical mesothelial cells present loss of BRCA-1 associated protein-1 (BAP-1) and/or methylthioadenosine phosphorylase as examined by immunohistochemistry (IHC) and/or homozygous deletion of cyclin-dependent kinase inhibitor 2A/p16 as examined by fluorescence in situ hybridization. It is difficult to diagnose because of the unremarkable clinical findings except for pleural effusion. The present report describes a case in which MIS was diagnosed at the time of sampling due to the presence of clearly malignant mesothelial cells in the pleural fluid. In 2016, a 74-year-old man with a history of past exposure to asbestos was admitted to Ibaraki Higashi National Hospital (Tokai-mura, Japan) with dyspnea. Chest CT indicated only right pleural effusion. Malignant mesothelial cells were suspected in a cell block made using pleural effusion; therefore, right pleural biopsy was performed. Pathologically, there was proliferation of mesothelial cells with mild atypia that formed a single-flat layer on the pleural surface; however, there was no invasion. Furthermore, IHC revealed loss of BAP-1 in cells from the biopsied pleura and pleural effusion. MIS was suspected at the time; however, the patient arbitrarily quit his medical check-ups. After 44 months, the patient was readmitted to our hospital complaining of dyspnea. CT indicated a large right pleural mass. A specimen of the mass obtained via CT-guided needle biopsy revealed malignant mesothelioma. The patient continued to deteriorate and eventually died. This case indicated that pleural effusion could be used to demonstrate overtly malignant mesothelial cells and diagnose MIS at the time of sampling. To the best of our knowledge, this is first report of MIS with overtly malignant mesothelial cells in pleural effusion. Pleural effusion may serve an important role in MIS diagnosis.

Copyright: © Yabuuchi et al.

In plain English

This case report described a 74-year-old man in Japan, an ex-smoker who worked as a mason from age 23 to 60, exposed without a dust respirator to cement particles containing asbestos and hexavalent chromium. In 2016 he was hospitalized with shortness of breath. Imaging showed only fluid around the right lung (pleural effusion). Its cytology was overtly malignant, with BAP-1 loss in the fluid cells. A pleural biopsy showed a non-invasive single layer of mildly atypical mesothelial cells with BAP-1 loss. MTAP was retained and homozygous deletion of CDKN2A/p16 was not found. Early, non-invasive mesothelioma in situ (MIS) was suspected. The patient declined surgery and stopped check-ups. Forty-four months later a large right pleural mass was diagnosed as mesothelioma. After five courses of carboplatin with pemetrexed the tumor progressed; he did not respond to nivolumab and died 52 months after MIS diagnosis. The authors concluded that pleural fluid cytology may play an important role in diagnosing MIS at presentation. To their knowledge, it was the first reported MIS case with overtly malignant cells in the first pleural fluid.

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 (single patient), with a comparison table of previously published MIS cases
• Who was studied: One 74-year-old man, an ex-smoker, admitted to Ibaraki Higashi National Hospital (Tokai-mura, Japan) in 2016 with dyspnea and right pleural effusion
• Exposure: Worked as a mason from age 23 to 60, exposed to particles of cement containing asbestos and hexavalent chromium, without a dust respirator; fiber type not stated
• Main results:
  • At first presentation, pleural effusion cytology was classified as class V (overtly malignant) on the Papanicolaou classification
  • Cells in the cell block made from the pleural effusion showed loss of BAP-1 on immunohistochemistry
  • Surgery showed no obvious nodule and no pleural thickening. The right pleural biopsy showed mildly atypical cells derived from mesothelial cells, forming a single layer in places.
  • In the biopsy, BAP-1 loss was confirmed, MTAP was retained, and CDKN2A/p16 homozygous deletion was not identified
  • The case retrospectively met the 2021 WHO criteria for MIS
  • The patient declined an operation and stopped attending check-ups 4 months after the MIS diagnosis
  • Forty-four months later he returned with dyspnea and worsening right pleural effusion. CT showed a large mass originating from the right pleura, and progression to mesothelioma was confirmed. The serum marker CYFRA was 19.4 ng/ml.
  • He received five courses of carboplatin with pemetrexed, after which the tumor progressed. He was then switched to nivolumab, to which he did not respond.
  • The patient died 52 months after the initial MIS diagnosis
  • The authors suggested that the relatively slow progression might have been related to BAP-1 loss with retained CDKN2A and MTAP
• The authors' conclusion: The authors concluded that cytology of pleural fluid may play an important role in diagnosing MIS at the time of presentation. As far as they knew, this was the first report of MIS with overtly malignant mesothelial cells in the initially obtained pleural fluid.
• Limitations the authors state:
  • The original Papanicolaou smears had been borrowed from a previous hospital and returned, so their images could not be shown

Topics

Medical terms in this study, explained in our Lexicon: Pleural Effusion, Mesothelioma in Situ, Mesothelioma, Mesothelial Cells, Pleura, Immunohistochemistry, Homozygous Deletion, Fluorescence In Situ Hybridization (FISH).

Related studies

• Usefulness of Claudin 4 in the cytological diagnosis of serosal effusions — S. Lonardi, C. Manera, et al. (2011)
• Usefulness of p16/CDKN2A fluorescence in situ hybridization and BAP1 immunohistochemistry for the diagnosis of biphasic mesothelioma — D. Wu, K. Hiroshima, et al. (2017)
• Cytological diagnosis of mesothelioma in situ versus invasive mesothelioma — A. Churg, F. Galateau-Salle, et al. (2022)
• Cytological differential diagnosis among adenocarcinoma, epithelial mesothelioma, and reactive mesothelial cells in serous effusions by immunocytochemistry — X.Y. Su, G.D. Li, et al. (2011)
• 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)
• Fluorescence in situ hybridization in the definitive diagnosis of malignant mesothelioma in effusion cytology — S. Savic, N. Franco, et al. (2010)

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