Discriminant analysis between malignant mesothelioma and reactive mesothelium using nuclear three-dimensional analysis is useful for morphologically suspicious cases

Our plain-English summary of Discriminant analysis between malignant mesothelioma and reactive mesothelium using nuclear three-dimensional analysis is useful for morphologically suspicious cases, by K. Washiya, Y. Mizuki, M. Nakamura, et al (Acta Cytologica, 2013).

The study

• Authors: K. Washiya, Y. Mizuki, M. Nakamura, H. Kakinuma, M. Saegusa, Y. Satoh, H. Yoshioka, J. Watanabe
• Journal: Acta Cytologica
• Published: 2013;57(5):509-15
• Read it: PubMed · Publisher

Abstract

Objective: Morphological discrimination between malignant mesothelioma (MM) and reactive mesothelium (RM) is often difficult. Stereological analysis of nuclear luminance using centrifuged smear samples from coelomic fluid and discriminant analysis based on Mahalanobis distance may help to more accurately discriminate between MM and RM. In the present study, discriminant analysis was conducted on cytological specimens using the auto-smear method in a blinded manner with regard to histological results.

Study Design: Coelomic fluid samples of 28 cases, cytologically diagnosed using the auto-smear method, were analyzed to determine pixel counts, the number of focus layers, 3-dimensional variation in the coefficient of variation of nuclear luminance between the focus layers as well as roundness in about 30-50 atypical cell nuclei per case. These measurements were employed to determine malignancy based on Mahalanobis distance.

Results: Discrimination rates were as high as 91.7% for MM and 82.7% for RM. The discrimination rates of MM with histology were >80% in 8 of 10 suspicious cases with the initial cytology.

Conclusion: Our method allowed accurate discrimination between MM and RM and provides a useful alternative for the diagnosis of suspicious cases where morphological diagnosis of malignancy is difficult.

In plain English

This laboratory study from Japan tested whether computer measurement of cell nuclei could tell malignant mesothelioma (MM) apart from reactive mesothelium (RM), a non-cancerous change in lining cells, in body-cavity fluid. It used 28 cases from Kitasato University Hospital: 24 pleural effusions, 3 ascites and 1 pericardial fluid. The authors photographed 1,066 atypical nuclei in layers, choosing cells without knowing the diagnoses. They measured nuclear size, three-dimensional structure, chromatin variation and roundness, then compared the results with tissue diagnoses. All four measures differed significantly between MM and RM (p less than 0.01). After uncertain 'gray zone' cells were set aside, 91.7% of cells from MM cases and 82.7% of cells from RM cases were classed correctly. There were 10 cases first judged 'suspicious' on cytology but later diagnosed as MM on tissue. In 8 of them, at least 80% of the cells outside the gray zone were classed as MM. A cut-off from the authors' earlier study classed only 25.7% of RM cells correctly. The authors concluded the method was useful for difficult cases. Patients' asbestos exposure was not studied.

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: Diagnostic laboratory study: computer image analysis of nuclei in stored cytology specimens, with cells selected blind to diagnosis and results compared with histological diagnosis
• Who was studied: Body-cavity fluid samples from 28 patients at Kitasato University Hospital, Japan: 24 pleural effusion, 3 ascites and 1 pericardial fluid. There were 8 MM cases (292 nuclei) and 10 RM cases (458 nuclei) where cytology matched histology. There were also 10 cases judged suspicious on cytology and later diagnosed as MM by histology (316 nuclei). In total, 1,066 nuclei were measured.
• Exposure: Not studied; the article does not report asbestos or other exposures of these patients. It assesses a diagnostic measurement method.
• Main results:
  • All four nuclear measures differed significantly between MM and RM (p less than 0.01). The number of focus layers was 4.67 ± 0.82 for MM and 3.79 ± 0.53 for RM. The pixel count (nuclear area) was 1,854 ± 650 for MM and 1,425 ± 339 for RM.
  • Gray zone cells were excluded from these rates, and the rates are per cell, not per patient. In MM specimens, 91.7% of nuclei were classed correctly as MM (232 of 253; 39 gray zone cells). In RM specimens, 82.7% of nuclei were classed correctly as RM (310 of 375; 83 gray zone cells).
  • There were 10 cases judged suspicious on cytology and later diagnosed as MM on histology. In 8 of them, at least 80% of cells outside the gray zone were classed as MM. In the other 2 cases, 73.7% and 71.4% were classed as MM. Gray zone cells were excluded from these percentages. For example, case 8 had 54 MM cells out of 67 non-gray-zone cells (80.6%), and 10 more cells fell in the gray zone.
  • The authors applied a cut-off of 0.072 from their earlier direct-smear study to the present auto-smear data, leaving out roundness. With that cut-off, 97.6% of MM cells were classed correctly, but only 25.7% of RM cells were.
• The authors' conclusion: The authors concluded that their method allowed discrimination between MM and RM. They said it was useful for cases where diagnosing malignancy from cell appearance was difficult.
• Limitations the authors state:
  • The authors said that excluding mesothelial cells that looked clearly benign mainly explained the lower correct-classification rate for RM.
  • Cut-off values did not carry over between slide-preparation methods. The authors said cut-offs should be set separately for each sampling condition.
  • The authors said difficult MM cases still need to be studied prospectively before the method can be used in practice.

Topics

Medical terms in this study, explained in our Lexicon: Malignant Mesothelioma, Mesothelium, Histology, Cytology.

Related studies

• Discriminant analysis of malignant mesothelioma and reactive mesothelium using three-dimensional nuclear estimation — K. Washiya, K. Narumi, et al. (2012)
• Immunocytochemistry of CD146 is useful to discriminate between malignant pleural mesothelioma and reactive mesothelium — A. Sato, I. Torii, et al. (2010)
• Differential diagnosis of reactive mesothelial cells and malignant mesothelioma cells using the cell proliferation markers minichromosome maintenance protein 7, geminin, topoisomerase II alpha and Ki-67 — F. Kimura, I. Okayasu, et al. (2013)
• Highly expressed EZH2 in combination with BAP1 and MTAP loss, as detected by immunohistochemistry, is useful for differentiating malignant pleural mesothelioma from reactive mesothelial hyperplasia — M. Yoshimura, Y. Kinoshita, et al. (2019)
• Detection of malignant mesothelioma using nuclear structure of mesothelial cells in effusion cytology specimens — A.B. Tosun, O. Yergiyev, et al. (2015)
• CD44H expression in reactive mesothelium, pleural mesothelioma and pulmonary adenocarcinoma — R.L. Attanoos, R. Webb, et al. (1997)

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