Sarcomatoid mesothelioma diagnosed in a patient with mesothelioma in situ: a case report on morphologic differences after 9-month interval with details analysis of cytology in early-stage mesothelioma

Our plain-English summary of Sarcomatoid mesothelioma diagnosed in a patient with mesothelioma in situ: a case report on morphologic differences after 9-month interval with details analysis of cytology in early-stage mesothelioma, by M. Yoshida, N. Jimbo, R. Tsukamoto, et al (Diagnostic Pathology, 2023).

The study

• Authors: M. Yoshida, N. Jimbo, R. Tsukamoto, T. Itoh, K. Kawahara, S. Mitsui, Y. Tanaka, Y. Maniwa
• Journal: Diagnostic Pathology
• Published: 2023;18(1):126
• Type of article: Case report
• Cited by: 3 articles, as counted by NIH iCite
• Read it: PubMed · Publisher · Free full text

Abstract

Background: Overlapping morphological features of mesothelial cells have been rendered it difficult to distinguish between reactive and malignant conditions. The development of methods based on detecting genomic abnormalities using immunohistochemistry and fluorescence in situ hybridization have contributed markedly to solving this problem. It is important to identify bland mesothelioma cells on cytological screening, perform efficient genomic-based testing, and diagnose mesothelioma, because the first clinical manifestation of pleural mesothelioma is pleural effusion, which is the first sample available for pathological diagnosis. However, certain diagnostic aspects remain challenging even for experts.

Case Presentation: This report describes a case of a 72-year-old man with a history of asbestos exposure who presented with pleural effusion as the first symptom and was eventually diagnosed as mesothelioma. Mesothelioma was suspected owing to prominent cell-in-cell engulfment in mesothelial cells on the first cytological sample, and the diagnosis of mesothelioma in situ was confirmed by histology. Unexpectedly, sarcomatoid morphology of mesothelioma was found in the second pathology samples 9 months after the first pathological examination. Both the mesothelioma in situ and invasive lesion showed immunohistochemical loss of methylthioadenosine phosphorylase (MTAP) and homozygous deletion of cyclin dependent kinase inhibitor 2A (CDKN2A) on fluorescence in situ hybridization. The patient received medication therapy but died of disease progression 12 months after the diagnosis of the sarcomatoid morphology of mesothelioma.

Conclusion: Our case suggests that cell-in-cell engulfment can be conspicuous in early-stage mesothelioma with inconspicuous nuclear atypia and few multinucleated cells. In addition, the presence of MTAP loss and CDKN2A homozygous deletion are suspected to be involved in early formation to invasive lesions and/or sarcomatoid morphology. We believe that it is important to consider genetic abnormalities when deciding on individual patient management. Furthermore, cases of mesothelioma, even those of an in situ lesion, with MTAP loss and/or CDKN2A deletion should be carefully followed up or subjected to early treatment.

© 2023. The Author(s).

In plain English

This case report described a 72-year-old man, a heavy smoker with past occupational asbestos exposure as a welder (no fiber type named), whose first symptom was fluid around the right lung. In the first fluid sample, the mesothelial cells looked only mildly abnormal, but 7.3% of evaluated cells showed cell-in-cell engulfment, meaning one cell enclosed within another. A pleural biopsy was diagnosed as mesothelioma in situ, an early form with a single layer of abnormal surface cells. In areas lacking the MTAP protein, 61.5% (115/187) of mesothelial cells showed homozygous CDKN2A gene deletion. A solid nodule appeared nine months after the biopsy. A second biopsy showed invasive spindle cells consistent with sarcomatoid mesothelioma, again with MTAP loss and homozygous CDKN2A deletion in at least 31% (31/100) of mesothelial cells. Despite immunotherapy and chemotherapy, the patient died 12 months after the second biopsy. The authors noted biphasic mesothelioma could not be fully ruled out. Based on this case and an earlier one from their group, they concluded that MTAP loss and/or homozygous CDKN2A deletion in mesothelioma in situ may indicate aggressive features.

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)
• Who was studied: One 72-year-old man, a heavy smoker (50 pack-years), referred to the authors' hospital (Kobe University, Japan) with recurrent right pleural effusion; dates of care not stated
• Exposure: History of occupational asbestos exposure as a welder; fiber type and dose not given
• Main results:
  • First pleural fluid cytology: 1,201 mesothelial cells per smear, much lower than the more than 10,000 cells on average seen in 3 cases of overt mesothelioma in the authors' department
  • First cytology: binucleated and multinucleated mesothelial cells were scarce (4.0% and 1.2%, respectively)
  • First cytology: cell-in-cell engulfment was conspicuous in 7.3% of the evaluated cells
  • First biopsy (diagnosed as mesothelioma in situ): all mesothelial cells retained BAP1 expression
  • First biopsy: in areas with MTAP loss, 61.5% (115/187) of mesothelial cells showed homozygous deletion of CDKN2A on FISH
  • A solid nodule appeared in the right parietal pleura 9 months after the first biopsy
  • Second biopsy (CT-guided) showed spindle cells without epithelioid atypical cells, with clear invasion
  • Second biopsy: most atypical cells lost MTAP expression, and at least 31% (31/100) of mesothelial cells showed homozygous deletion of CDKN2A on FISH
  • The authors judged the second sample highly suggestive of sarcomatoid mesothelioma
  • Disease progressed during treatment with ipilimumab and nivolumab followed by carboplatin and pemetrexed
  • The patient died 33 months after the first symptoms: 21 months after the first biopsy and 12 months after the second biopsy
• The authors' conclusion: The authors concluded that MTAP loss and/or CDKN2A homozygous deletion in mesothelioma in situ may indicate aggressive features, based on their two such cases that later showed invasive sarcomatoid mesothelioma. They also concluded that when many mesothelial cells show cell-in-cell engulfment, mesothelioma should be considered even without overt atypia.
• Limitations the authors state:
  • Sampling may not have been representative, especially in the second biopsy, so biphasic mesothelioma cannot be completely ruled out. No autopsy was performed.
  • Whether the mesothelioma in situ actually progressed into the sarcomatoid tumor could only be proven by clonal-evolution genomic analysis, which was not done

Topics

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

Medical terms in this study, explained in our Lexicon: Sarcomatoid, Mesothelioma, Mesothelioma in Situ, Cytology, Mesothelial Cells, Immunohistochemistry, Fluorescence In Situ Hybridization (FISH), Pleural Mesothelioma.

Related studies

• 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 diagnosed by methylthioadenosine phosphorylase loss and homozygous deletion of CDKN2A: a case report — K. Minami, N. Jimbo, et al. (2020)
• Sarcomatoid Mesothelioma: A CDKN2A molecular analysis of 53 cases with immunohistochemical correlation with BAP1 — M. Zaleski, N. Kalhor, et al. (2020)
• Diagnostic mesothelioma biomarkers in effusion cytology — A. Eccher, I. Girolami, et al. (2021)
• A combination of MTAP and BAP1 immunohistochemistry in pleural effusion cytology for the diagnosis of mesothelioma — Y. Kinoshita, T. Hida, et al. (2018)
• Pleural irregularities and mediastinal pleural involvement in early stages of malignant pleural mesothelioma and benign asbestos pleural effusion — K. Kato, K. Gemba, et al. (2016)

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