Histopathological features of epithelioid malignant pleural mesotheliomas in patients with extended survival

Our plain-English summary of Histopathological features of epithelioid malignant pleural mesotheliomas in patients with extended survival, by J. Paajanen, S. Laaksonen, E. Kettunen, et al (Human Pathology, 2020).

The study

• Authors: J. Paajanen, S. Laaksonen, E. Kettunen, I. Ilonen, T. Vehmas, J. Salo, J. Räsänen, E. Sutinen, H. Ollila, M.I. Mäyränpää, M. Myllärniemi, H. Wolff
• Journal: Human Pathology
• Published: 2020;98:110-119
• Cited by: 14 articles, as counted by NIH iCite
• Read it: PubMed · Publisher

Abstract

Diffuse malignant mesothelioma (DMM) of the pleura is a rare and aggressive disease, wherein the long-term survival (LTS) rate is low. The epithelioid subtype is the most prevalent form of DMM with the best prognosis. To study prognostic histopathologic factors associated with extended survival in epithelioid DMM, we examined 43 tumors from patients with survival more than five years (LTSs) and compared the findings with 84 tumors from a reference group (RG) with average survival. We analyzed the tumors considering previously published histopathological prognostic features and attempted to identify additional morphological features predictive of extended survival. Most of the LTS tumors presented with nuclear grade I (n = 34, 90%) and a tubulopapillary growth pattern (n = 30, 70%). One LTS tumor had necrosis. In contrast, nuclear grade II (n = 49, 61%) and solid growth pattern (n = 59, 70%) were more frequent in the RG, and necrosis was present in 16 (19%) tumors. We also evaluated the association of asbestos lung tissue fiber burden quantified from autopsy samples with histopathological features and found that elevated asbestos fiber was associated with higher nuclear grade (P < 0.001) and the presence of necrosis (P = 0.021). In univariate survival analysis, we identified the following three novel morphological features associated with survival: exophytic polypoid growth pattern, tumor density, and single mesothelium layered tubular structures. After adjustments, low nuclear grade (P < 0.001) and presence of exophytic polypoid growth (P = 0.024) were associated with prolonged survival. These results may aid in estimating DMM prognosis.

Copyright © 2020 The Author(s). Published by Elsevier Inc. All rights reserved.

In plain English

This Finnish study compared microscopic tumor features in people with epithelioid diffuse malignant mesothelioma of the pleura. Patients came from the Finnish Cancer Registry and were diagnosed in 2000 to 2012. The authors examined 127 tumors: 43 from patients surviving more than five years and 84 from a reference group with average survival. Median survival was 79.3 months and 11.3 months, respectively. Of 38 long-term survivors' tumors that could be graded, 34 (90%) were nuclear grade I, and 30 of all 43 (70%) were tubulopapillary. Of 81 gradable reference tumors, 49 (61%) were grade II, and 59 of 84 (70%) were solid. Necrosis (dead tumor tissue) appeared in 1 long-term survivor's tumor and 16 (19%) reference tumors. After adjustment, low nuclear grade and an exophytic polypoid growth pattern were associated with longer survival. Some patients had asbestos fiber counts measured in lung tissue taken at autopsy. In them, higher fiber levels were associated with higher nuclear grade and with necrosis. However, fiber counts were available for only 14 long-term survivors and 60 reference patients. The authors concluded that these features may help in predicting prognosis.

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: Comparison of tumor tissue features (histopathology) between long-term survivors and a reference group with average survival, drawn from a registry-based patient cohort, with survival analysis
• Who was studied: 127 epithelioid pleural diffuse malignant mesothelioma tumors from Finnish patients: 43 long-term survivors (more than five years) and 84 reference patients with average survival. All were selected from 1010 patients with pleural diffuse malignant mesothelioma diagnosed in 2000 to 2012 and identified in the Finnish Cancer Registry. Follow-up ended September 9, 2018.
• Exposure: Asbestos fiber burden in lung tissue from forensic autopsies, measured by transmission electron microscopy as million fibers per gram of dry lung. Fiber types were not reported. Fiber counts were available for 14 long-term survivors and 60 reference patients. The overall median was 3.95 million fibers per gram.
• Main results:
  • Median survival was 79.3 months in the long-term survivor group and 11.3 months in the reference group.
  • Nuclear grade could not be assessed in 8 tumors because the samples were too small. Of the 38 long-term survivor tumors that could be graded, 34 (90%) were grade I and 4 (10%) were grade II. Of the 81 reference group tumors that could be graded, 28 (34%) were grade I, 49 (61%) were grade II and 4 (5%) were grade III.
  • Of all 43 long-term survivor tumors, 30 (70%) were tubulopapillary. Of all 84 reference group tumors, 59 (70%) were solid.
  • Necrosis was present in 1 (2%) long-term survivor tumor and in 16 (19%) reference group tumors (P = 0.007).
  • An exophytic polypoid growth pattern was present in 11 (26%) long-term survivor tumors and in 1 (1%) reference group tumor.
  • In the analysis adjusted for age, gender, treatment and other features, only low nuclear grade and exophytic polypoid growth were independently associated with longer survival. Compared with grade I, the hazard ratio was 4.43 (95% CI 2.51 to 7.82) for grade II and 16.39 (95% CI 4.57 to 58.76) for grade III. The hazard ratio for polypoid growth was 0.43 (95% CI 0.21 to 0.89, P = 0.024).
  • When three tumors with features of well-differentiated papillary mesothelioma with invasive foci were removed, the statistical significance of polypoid features was reduced (P = 0.057).
  • Among patients with fiber counts, lung asbestos fiber concentration was associated with nuclear grade (P less than 0.001). Median concentrations were 0.60 million fibers per gram in grade I (n = 27), 13.0 in grade II (n = 39) and 280.0 in grade III (n = 3). Fiber concentration was associated with mitotic count (r = 0.41, P = 0.001) but not with nuclear atypia (P = 0.071).
  • Higher lung fiber content was found in tumors with necrosis (median 64.50 million fibers per gram) than in tumors without necrosis (median 1.90 million fibers per gram; P = 0.021).
• The authors' conclusion: The authors concluded that several tissue features are associated with long-term survival. They found that polypoid growth pattern and nuclear grade were the only independent predictors of survival, and they believe these features may be helpful in predicting prognosis in diffuse malignant mesothelioma.
• Limitations the authors state:
  • Asbestos fiber analysis was available for only 14 (33%) long-term survivors and 60 (71%) reference patients.
  • Necrosis was uncommon, which the authors say could explain why it was significant only in the unadjusted analysis and not in the adjusted analysis.
  • The number of tumors with polypoid features was small, so the authors say no definite conclusion can be drawn about polypoid features versus degree of invasiveness.
  • Assessing nuclear atypia is subjective, and counting mitoses can be time-consuming and prone to errors.

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: Epithelioid, Pleural Mesothelioma, Malignant Mesothelioma, Pleura, Prognosis, Nuclear Grade, Tubulopapillary, Necrosis.

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• Dedifferentiated Liposarcoma With Epithelioid/Epithelial Features — N. Makise, A. Yoshida, et al. (2017)
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• Epithelioid malignant mesothelioma presenting with features of esophageal tumor — M.W. Khalil, A.P. Campbell, et al. (2011)
• A nuclear grading system is a strong predictor of survival in epitheloid diffuse malignant pleural mesothelioma — K. Kadota, K. Suzuki, et al. (2012)

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