Cytopathologic Diagnosis of Epithelioid and Mixed-Type Malignant Mesothelioma: Ten Years of Clinical Experience in Relation to International Guidelines

Our plain-English summary of Cytopathologic Diagnosis of Epithelioid and Mixed-Type Malignant Mesothelioma: Ten Years of Clinical Experience in Relation to International Guidelines, by A. Hjerpe, S. Abd-Own, K. Dobra (Archives of Pathology & Laboratory Medicine, 2018).

The study

• Authors: A. Hjerpe, S. Abd-Own, K. Dobra
• Journal: Archives of Pathology & Laboratory Medicine
• Published: 2018;142(8):893-901
• Cited by: 22 articles, as counted by NIH iCite
• Read it: PubMed · Publisher

Abstract

Context: - Early diagnosis of malignant mesothelioma (MM) is urgently needed because life expectancies and treatment options are limited in advanced stages of the disease. Malignant mesothelioma often presents with recurrent hemorrhagic or inflammatory effusions, which might mask the incipient stages of the disease and thereby delay the diagnosis. Despite difficulties in recognizing the malignant cells present in those early effusions, they are often the first available biologic material for diagnosis. Therefore, awareness is needed, and efforts should be made to distinguish the malignant cells by well-defined morphological criteria, combined with ancillary methods.

Objectives: - To summarize the diagnostic criteria for the cytopathologic diagnosis of MM based on recently published guidelines and to evaluate the clinical utility of those criteria in clinical practice.

Data Sources: - The guidelines for the cytopathologic diagnosis of epithelioid and mixed-type MM and data in recent literature constitute the sources of this review. Eighty-five epithelioid or mixed-type MMs diagnosed between 2004 and 2013 at the Department of Clinical Pathology and Cytology, Karolinska University Hospital, Huddinge (Stockholm, Sweden), were evaluated to determine the clinical utility of the criteria defined by the guidelines.

Conclusions: - A conclusive diagnosis of MM can be obtained based on the criteria defined by the guidelines with high positive predictive value. When diagnosed in this way, subsequent therapy should be initiated without further delay. With the earlier diagnosis obtained by cytology, a better effect of chemotherapy can be expected, as shown by the longer overall survival in these patients compared with those with a histopathologic diagnosis.

In plain English

This article reviewed international guidelines for diagnosing epithelioid and mixed-type malignant mesothelioma from fluid samples (effusions). It also reported the experience of the authors' laboratory at Karolinska University Hospital, Huddinge, Stockholm, Sweden. Of 85 epithelioid or mixed-type mesotheliomas diagnosed there between 2004 and 2013, 76 had an effusion examined. Forty-seven met the guideline criteria for a conclusive diagnosis, a sensitivity of 62%. Including cases reported as suspicious, sensitivity was 79%. Most diagnoses relied on antibody staining. Calretinin was positive in 42 of 43 cases tested. The authors reported that every cytologic diagnosis meeting the criteria proved correct (a positive predictive value of 100%). In 23 of the 76 cases, a biopsy verified the cytologic diagnosis; all patients diagnosed by effusion cytology showed or developed clinical and radiologic evidence of the disease. Mean survival was 20 months after diagnosis by effusion cytology and 12 months for patients diagnosed only by histology. The authors concluded that such diagnoses are reliable enough on their own to start treatment. They suggested cytology-diagnosed patients may be a subgroup with a somewhat better prognosis. The article's background links mesothelioma to asbestos, but the 85 patients' asbestos exposure was not reported.

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: Review of diagnostic guidelines and recent literature, combined with a retrospective review of cases diagnosed at the authors' institution
• Who was studied: 85 cases of epithelioid or mixed-type malignant mesothelioma diagnosed between 2004 and 2013 at Karolinska University Hospital, Huddinge, Stockholm, Sweden; 76 of them had an effusion examined
• Exposure: Asbestos exposure of the 85 patients was not reported. The article's background section, citing other studies, describes mesothelioma as linked to asbestos exposure. The study itself evaluated diagnostic methods applied to effusions: immunocytochemistry, FISH ploidy analysis, electron microscopy and biomarkers.
• Main results:
  • Of the 85 cases, 76 (89%) had an effusion examined in the cytology laboratory
  • 47 of the 76 cases met the guideline criteria for a conclusive cytologic diagnosis, an absolute sensitivity of 62%
  • Including cases reported as suspicious, total sensitivity was 79%
  • Of the 47 conclusive diagnoses, 44 (94%) were based on immunocytochemical criteria and 3 (6%) on electron microscopy of the cell pellet
  • Calretinin was positive in 42 of 43 cases (98%) and EMA in 40 of 42 (95%)
  • FISH ploidy analysis was done in 20 of the 85 cases (24%)
  • FISH showed aneuploidy in 14 of the 20 cases (70%), lower than the 95% found when the test was validated; the difference was not statistically significant
  • Electron microscopy was done in 30 of the 76 cases (39%); 24 of them (80%) showed features diagnostic for mesothelioma
  • Biomarker analysis (hyaluronan and mesothelin) gave a probability of mesothelioma above 0.95 in 34 of 44 cases tested (77%)
  • In 23 of the 76 cases (30%), the cytologic diagnosis was verified by a biopsy taken at the same time or later
  • All patients whose diagnosis was based on effusion cytology showed or developed clinical and radiologic evidence of mesothelioma
  • The positive predictive value of a cytologic diagnosis meeting the guideline criteria was 100%
  • For findings that were suspicious but not conclusive, the positive predictive value was 6 of 8 cases (75%)
  • Mean survival was 20 months after diagnosis by effusion cytology and 12 months for patients diagnosed only by histology
  • The authors interpreted the survival difference as suggesting that patients diagnosable by cytology are a subgroup with a somewhat better prognosis
• The authors' conclusion: The authors concluded that a cytologic diagnosis of mesothelioma made with the guideline criteria is reliable and on its own gives sufficient grounds to start therapy
• Limitations the authors state:
  • Sarcomatoid mesotheliomas cannot be diagnosed by effusion cytology
  • The sensitivity of FISH ploidy analysis may vary
  • Electron microscopy can take 2 to 3 weeks, which may be too slow for clinical needs
  • The choice of antibody panels varied during the 10-year study period

Topics

The National Library of Medicine indexes this study under subjects our site covers: Mesothelioma.

Medical terms in this study, explained in our Lexicon: Epithelioid, Malignant Mesothelioma, Pathology, Cytology, Chemotherapy, Overall Survival.

Related studies

• Guidelines for the cytopathologic diagnosis of epithelioid and mixed-type malignant mesothelioma: Complementary Statement from the International Mesothelioma Interest Group, Also Endorsed by the International Academy of Cytology and the Papanicolaou Society of Cytopathology — A. Hjerpe, V. Ascoli, et al. (2015)
• Guidelines for the cytopathologic diagnosis of epithelioid and mixed-type malignant mesothelioma. Complementary statement from the International Mesothelioma Interest Group, also endorsed by the International Academy of Cytology and the Papanicolaou Society of Cytopathology — A. Hjerpe, V. Ascoli, et al. (2015)
• Guidelines for the cytopathologic diagnosis of epithelioid and mixed-type malignant mesothelioma: Complementary statement from the international mesothelioma interest group, also endorsed by the international academy of cytology and the papanicolaou society of cytopathology. A proposal to be applauded and promoted but which requires updating — M. Sheaff (2020)
• Guidelines for the Cytopathologic Diagnosis of Epithelioid and Mixed-Type Malignant Mesothelioma: a secondary publication — A. Hjerpe, V. Ascoli, et al. (2015)
• Comments on the recently published "Guidelines for the cytopathologic diagnosis of epithelioid and mixed-type malignant mesothelioma" — A. Hjerpe, K. Dobra (2015)
• The differential diagnosis between pleural sarcomatoid mesothelioma and spindle cell/pleomorphic (sarcomatoid) carcinomas of the lung: evidence-based guidelines from the International Mesothelioma Panel and the MESOPATH National Reference Center — A.M. Marchevsky, N. LeStang, et al. (2017)

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