Improving the Accuracy of Mesothelioma Diagnosis in China

Our plain-English summary of Improving the Accuracy of Mesothelioma Diagnosis in China, by Z. Guo, M. Carbone, X. Zhang, et al (Journal of Thoracic Oncology, 2017).

The study

• Authors: Z. Guo, M. Carbone, X. Zhang, D. Su, W. Sun, J. Lou, Z. Gao, D. Shao, J. Chen, G. Zhang, J. Hu, K. Chen, F. Wang, H.I. Pass, H. Yu, A. Napolitano, H. Yang, W. Mao
• Journal: Journal of Thoracic Oncology
• Published: 2017;12(4):714-723
• Cited by: 49 articles, as counted by NIH iCite
• Read it: PubMed · Publisher · Free full text

Abstract

Introduction: In the Western world, malignant mesothelioma (MM) is most prevalent in the pleura of older males who have been professionally exposed to asbestos. Information about MM from rapidly industrializing countries such as China is minimal. There is concern that a proportion of MM diagnoses in China may be incorrect because most Chinese physicians do not have experience diagnosing this rare cancer. We recently reported an unusually high incidence of peritoneal MM among eastern Chinese female patients. Here, we review the accuracy of MM diagnoses in China and provide suggestions to improve the accuracy of diagnosis.

Methods: We reviewed 92 pathological diagnosis of MM in 2002-2015 from two reference centers in the province of Zhejiang in eastern China. We performed a large set of immunohistochemistry analyses to increase the reliability of the diagnosis.

Results: We confirmed the MM diagnosis in 12 of 34 of the pleural tumors (35.3%), in 38 of 56 of the peritoneal tumors (67.9%), and in two of two of the MMs of the tunica vaginalis (100%). MMs were characterized by tumor cells showing nuclear Wilms tumor 1 and calretinin staining and by strong membranous staining for cytokeratin CAM5.2. The results of staining for the epithelial markers carcinoembryonic antigen, thyroid transcription factor-1, MOC31, BerEP4, p63, p40, paired box 8, ER and PR were negative. BRCA1 associated protein 1 nuclear staining was lost in percentages similar to what has been reported for samples from Western countries.

Conclusions: Our findings suggest that MM-especially in its pleural localization-is often misdiagnosed in eastern China. Identifying pitfalls and possible solutions in the pathological diagnosis of MM will affect both the standard of care and research in China.

Copyright © 2016 International Association for the Study of Lung Cancer. Published by Elsevier Inc. All rights reserved.

In plain English

This retrospective study re-examined tissue slides from 92 tumors diagnosed as malignant mesothelioma between 2002 and 2015 at two hospitals in Zhejiang province, eastern China. One hospital is in Yuyao, a town with an asbestos textile industry. Pathologists from China and Hawaii reviewed each case and ran extra stains where tissue was available. They confirmed mesothelioma in 12 of 34 pleural tumors (35.3%), 38 of 56 peritoneal tumors (67.9%) and both tumors of the tunica vaginalis. Overall, 52 of 92 were confirmed, 16 were ruled out and 24 were left uncertain. Tumors mistaken for pleural mesothelioma were most often poorly differentiated metastatic carcinomas, including from the lung and kidney. In the peritoneum, metastatic ovarian carcinoma was most common. One case was chronic pleuritis, a benign condition. Confirmed mesotheliomas stained more often than other tumors for CAM5.2, calretinin and WT-1. The authors concluded that mesothelioma, especially pleural, is often misdiagnosed in eastern China, and they recommended a minimum stain panel. They noted they could not tell how many mesotheliomas had been misdiagnosed as other cancers, and that two hospitals may not represent all of China.

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: Retrospective pathology review of earlier mesothelioma diagnoses, with additional immunohistochemistry (IHC) staining
• Who was studied: 92 tumors originally diagnosed as malignant mesothelioma (34 pleural, 56 peritoneal, 2 tunica vaginalis), 2002-2015, at Zhejiang Cancer Hospital (Hangzhou) and Yuyao People's Hospital (Yuyao), Zhejiang province, eastern China. Control tumors were also stained: 10 lung adenocarcinomas, 10 lung squamous cell carcinomas and 15 carcinosarcomas.
• Exposure: Asbestos exposure was not analysed in this study, which is about diagnostic accuracy. The two hospitals were chosen because one sees mostly patients without asbestos exposure and the other is in a town with an asbestos textile industry; the authors describe that industry as using chrysotile asbestos. Exposure details for these patients were reported in the authors' earlier publication.
• Main results:
  • Mesothelioma was confirmed in 12/34 (35.3%) pleural tumors (10 women, 2 men), 38/56 (67.9%) peritoneal tumors (32 women, 6 men) and 2/2 (100%) tunica vaginalis tumors.
  • Confirmation was statistically more common for peritoneal than for pleural tumors (P less than 0.01).
  • Across all 92 cases, the diagnosis was confirmed in 52/92 (56.5%), ruled out in 16/92 (17.4%) and left uncertain in 24/92 (26%).
  • In 18 cases the diagnosis could not be confirmed because the specimens were inadequate: tiny needle biopsies without identifiable invasion and/or conflicting stains, with no block available for further testing.
  • Among tumors wrongly identified as pleural mesothelioma, the most common were poorly differentiated metastatic carcinomas from the lung, kidney and other organs. In the peritoneum, the most common mimic was metastatic ovarian carcinoma. One case was chronic pleuritis.
  • Compared with non-mesothelioma tumors, mesotheliomas stained more often for CAM5.2 (34/36, 94% vs 26/40, 65%; P less than 0.01), calretinin (47/52, 90% vs 14/40, 35%; P less than 0.0001) and WT-1 (40/49, 82% vs 4/40, 10%; P less than 0.0001), per Table 2.
  • D2-40 was not specific for mesothelioma. It stained 88% of mesotheliomas, but also 80% of carcinosarcomas and lung squamous cell carcinomas, and 40% of lung adenocarcinomas.
  • Loss of BAP1 nuclear staining was associated with mesothelioma (P less than 0.0001). Of 17 epithelial-type mesotheliomas, 14 were BAP1-negative. All 35 control carcinomas and carcinosarcomas stained positive for BAP1.
  • The authors stated that regular use of the three positive markers CAM5.2, calretinin and WT-1 would significantly improve diagnostic accuracy in China.
  • The authors attributed the misdiagnoses mainly to incomplete stain panels and/or incorrect interpretation of the stains.
• The authors' conclusion: The authors concluded that mesothelioma, especially in the pleura, is often misdiagnosed in eastern China. They proposed that a routine minimum immunostain panel, and requiring evidence of tissue invasion, would improve accuracy.
• Limitations the authors state:
  • Because the study started from cases already diagnosed as mesothelioma, the authors could not tell what percentage of mesotheliomas were misdiagnosed as other cancers.
  • Only two hospitals in eastern China were studied, so the results may not represent all of China.

Topics

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

Medical terms in this study, explained in our Lexicon: Mesothelioma, Pleura, Immunohistochemistry, Tunica Vaginalis, Wilms Tumor 1 (WT-1), Calretinin, CAM5.2, Carcinoembryonic Antigen (CEA).

Related studies

• Asbestos textile production linked to malignant peritoneal and pleural mesothelioma in women: Analysis of 28 cases in Southeast China — Z. Gao, K. Hiroshima, et al. (2015)
• Improving the cytological diagnosis of high-grade serous carcinoma in ascites with a panel of complementary biomarkers in cell blocks — X. Zhang, L. Chen, et al. (2018)
• Overexpression of fibulin-3 in tumor tissue predicts poor survival of malignant mesothelioma patients from hand-spinning asbestos exposed area in eastern China — Z. Jiang, W. Shen, et al. (2020)
• Yale Cancer Center Precision Medicine Tumor Board: molecular findings alter a diagnosis and treatment plan — J.A. Gibson, K.E. Finberg, et al. (2021)
• Influence of age at death on accuracy of death certificate disease diagnosis: findings in 475 consecutive deaths of mesothelioma among asbestos insulation workers and asbestos factory workers — I.J. Selikoff (1992)
• Hand-spinning chrysotile exposure and risk of malignant mesothelioma: A case-control study in Southeastern China — Z. Jiang, T. Chen, et al. (2018)

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