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

Our plain-English summary of 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, by A.M. Marchevsky, N. LeStang, K. Hiroshima, et al (Human Pathology, 2017).

The study

• Authors: A.M. Marchevsky, N. LeStang, K. Hiroshima, G. Pelosi, R. Attanoos, A. Churg, L. Chirieac, S. Dacic, A. Husain, A. Khoor, S. Klebe, S. Lantuejoul, V. Roggli, J.M. Vignaud, B. Weynard, J. Sauter, D. Henderson, K. Nabeshima, F. Galateau-Salle
• Journal: Human Pathology
• Published: 2017;67:160-168
• Type of article: Meta-analysis, Systematic review
• Cited by: 47 articles, as counted by NIH iCite
• Read it: PubMed · Publisher

Abstract

Immunohistochemistry is used to distinguish sarcomatoid malignant mesotheliomas (SMM) from spindle cell and pleomorphic carcinomas (SPC) but there are no guidelines on how to interpret cases that show overlapping or equivocal immunohistochemical findings. A systematic literature review of the immunophenotype of these lesions was performed and the experience with 587 SMM and 46 SPC at MESOPATH was collected. Data were analyzed with Comprehensive Meta-Analysis 2.0 software (Biostat, Englewood, NJ). There were insufficient data to evaluate the differential diagnosis between SPC and localized SMM or peritoneal SMM. Meta-analysis showed considerable overlap in the immunophenotype of these neoplasms and significant data heterogeneity amongst many of the results. Survival data from MESOPATH patients showed no significant differences in overall survival between SMM and SPC patients. Best available evidence was used to formulate several evidence-based guidelines for the differential diagnosis between pleural SMM and SPC. These guidelines emphasize the need to correlate the histopathological findings with clinical and imaging information. Diffuse SMM can be diagnosed with certainty in the presence of malignant spindle cell pleural lesions showing immunoreactivity for cytokeratin and mesothelial markers and negative staining for epithelial markers. Criteria for the interpretation of various other combinations of immunoreactivity for cytokeratin and mesothelial and/or epithelial markers are proposed. Localized sarcomatoid mesotheliomas can only be diagnosed in the presence of spindle cell malignancies that exhibit immunoreactivity for cytokeratin and mesothelial markers and negative immunoreactivity for epithelial lesions, in patients that show no multifocal or diffuse pleural spread and no evidence for extrapleural lesions.

Copyright © 2017. Published by Elsevier Inc.

In plain English

This article combined a systematic review and meta-analysis of 14 published studies with cases from France's MESOPATH reference center (587 sarcomatoid mesotheliomas and 46 spindle cell/pleomorphic lung carcinomas diagnosed 1998 to 2016). The aim was to write guidelines for telling the two cancers apart. Staining patterns overlapped considerably, and results varied significantly between studies. In the meta-analysis, the mesothelial marker D2-40 was positive in 74.0% (47.7% to 89.9%) of sarcomatoid mesotheliomas but in 20.1% (14.2% to 27.7%) of the carcinomas. At MESOPATH, 2-year overall survival was 4% (95% CI 2% to 6%) for mesothelioma patients and 3% (95% CI 0% to 9%) for carcinoma patients; the difference was not significant. The authors concluded that a diffuse malignant spindle cell pleural tumor that stains for keratin and mesothelial markers, but not epithelial markers, in a patient without another primary tumor, can be definitively diagnosed as sarcomatoid mesothelioma. They stressed checking imaging and clinical history. They noted the guidelines rest on limited, somewhat controversial evidence and panel opinion, with too few data on localized or peritoneal mesothelioma. 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: Systematic literature review and meta-analysis combined with a review of reference-center case records (age, sex, staining results, 2-year survival), followed by an expert panel consensus that produced diagnostic guidelines
• Who was studied: 587 patients with sarcomatoid malignant mesothelioma and 46 patients with spindle cell/pleomorphic carcinoma diagnosed at the MESOPATH National Reference Center, France, January 1998 to June 2016, plus 14 published case series of more than 10 patients each
• Exposure: Not studied. The article concerns diagnostic staining (immunohistochemistry), not asbestos or other exposures. One illustrated case of lung spindle cell carcinoma was in a patient with a history of asbestos exposure.
• Main results:
  • MESOPATH survival: 2-year overall survival was 4% (95% CI 2% to 6%) in 587 sarcomatoid mesothelioma patients and 3% (95% CI 0% to 9%) in 46 spindle cell/pleomorphic carcinoma patients. Median survival was 5 months and 3 months respectively. The difference was not significant.
  • MESOPATH patients with sarcomatoid mesothelioma were older (median 74 years) than those with carcinoma (median 68.5 years; p = 0.0003). The proportion of men did not differ significantly (83% vs 78%; p = 0.40).
  • MESOPATH staining (positive defined as 10% or more of cells): p63 was positive in 8 of 11 carcinomas (73%) vs 2 of 155 mesotheliomas (1%). Other epithelial markers were positive in 6% to 33% of carcinomas. Calretinin was positive in 230 of 512 mesotheliomas (45%) vs 3 of 43 carcinomas (7%), p less than 0.0001.
  • Meta-analysis: D2-40 was positive in 74.0% (47.7% to 89.9%) of sarcomatoid mesotheliomas and in 20.1% (14.2% to 27.7%) of spindle cell/pleomorphic carcinomas. The authors said this finding cannot be used as an absolute criterion.
  • Meta-analysis: keratin stains did not separate the tumors. Keratin AE1/AE3 was positive in 89.4% (85.1 to 92.6) of mesotheliomas vs 88.1% (79.8 to 93.3) of carcinomas. CAM 5.2 was positive in 90.7% (81.6 to 95.6) vs 91.4% (85.0 to 95.2).
  • Results for most markers showed significant heterogeneity between studies.
  • Panel guideline: a diffuse malignant spindle cell tumor that stains for keratin and mesothelial markers and is negative for epithelial markers, in a patient without other primary tumors, can be definitively diagnosed as sarcomatoid mesothelioma.
  • Panel members did not fully agree on how to classify a diffuse pleural tumor that stains only for keratin.
  • Localized sarcomatoid mesothelioma should be diagnosed only when the tumor stains for cytokeratin and mesothelial markers, is negative for epithelial markers, and there is no extrapleural tumor or diffuse pleural spread.
• The authors' conclusion: The authors concluded that their guidelines rest on limited and somewhat controversial evidence and on panel opinion, but hoped the guidelines would make diagnoses more standardized. The guidelines emphasize correlating microscope findings with clinical and imaging information.
• Limitations the authors state:
  • Too few published data on peritoneal or localized mesothelioma, so the analysis was restricted to lung carcinomas and pleural sarcomatoid mesothelioma
  • Survival was not compared through a comprehensive literature review; only MESOPATH survival data were used
  • There is no evidence beyond panel members' opinions for a specific cut-off defining a positive stain
  • None of the published studies listed the clinical, radiologic or pathologic features used to classify the tumors
  • Published studies did not say whether the stains being evaluated had been used to make the original diagnoses, raising possible circularity bias
  • The guidelines rely on a somewhat oversimplified division of pleural tumors into diffuse or localized

Topics

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

Medical terms in this study, explained in our Lexicon: Differential Diagnosis, Sarcomatoid, Mesothelioma, Spindle Cell, Pleomorphic, Carcinoma, Immunohistochemistry, Malignant Mesothelioma.

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