Histopathologic features predict survival in diffuse pleural malignant mesothelioma on pleural biopsies

Our plain-English summary of Histopathologic features predict survival in diffuse pleural malignant mesothelioma on pleural biopsies, by C. Habougit, B. Trombert-Paviot, G. Karpathiou, et al (Virchows Archiv, 2017).

The study

• Authors: C. Habougit, B. Trombert-Paviot, G. Karpathiou, F. Casteillo, S. Bayle-Bleuez, P. Fournel, J.M. Vergnon, O. Tiffet, M. Péoc'h, F. Forest
• Journal: Virchows Archiv
• Published: 2017;470(6):639-646
• Cited by: 32 articles, as counted by NIH iCite
• Read it: PubMed · Publisher

Abstract

Malignant pleural mesothelioma is a rare tumor with a poor prognosis. The only universally recognized pathological prognostic factor is histopathological subtype with a shorter survival in non-epithelioid subtypes. Recently, a grading of epithelioid mesothelioma on surgical resection has been proposed. The aim of our work is to assess the prognostic role of several histopathological factors on a retrospective cohort of 116 patients diagnosed as a pleural mesothelioma for more than 95% of patients on pleural biopsy. Our work shows that mitotic count <3/10 HPF (p < 0.0001), the lack of necrosis (p = 0.0379), mild nuclear atypia (p = 0.0054), the lack of atypical mitoses (p = 0.0265), a nucleoli size <3 μm (p = 0.0139), and a nucleoli absent or visible at 200× or higher magnification (p = 0.0170) are significantly associated with a better median overall survival in epithelioid mesothelioma. The presence of atypical mitoses was found to be related to a worse median survival in non-epithelioid mesothelioma. Mitotic count, necrosis, nuclear atypia, and nucleoli size are not associated with overall survival in non-epithelioid mesothelioma. Our work highlights that histopathological prognostic factors can be assessed on pleural biopsies and can predict reliably median overall survival. This is of interest in order to define subgroups of patients who could benefit of different therapies and select patients who could benefit of surgical excision.

In plain English

This retrospective study re-examined tumor tissue from 116 consecutive patients diagnosed with diffuse malignant pleural mesothelioma at Saint Etienne University Hospital, France, between 1993 and 2015. Of these, 112 were diagnosed on a pleural biopsy. Two pathologists, unaware of survival, reviewed the slides. They scored cell division (mitotic count), abnormal divisions (atypical mitoses), nuclear irregularity (atypia), nucleolus size and dead tissue (necrosis). The article did not report asbestos exposure. Sarcomatoid, biphasic and desmoplastic tumors had shorter survival than epithelioid tumors. In epithelioid cases, fewer than 3 mitoses per 10 high-power fields had a median survival of 25 months (confidence interval 17 to 33; 44 patients), against 9 months (3 to 13; 33 patients) with 3 or more. Atypical mitoses, severe nuclear atypia, large nucleoli and necrosis were also linked to shorter survival. In non-epithelioid cases, only atypical mitoses were linked to survival. Median survival was 9 months (4 to 13) for the 18 patients without them and 4 months (1 to 6) for the 18 with them. The authors concluded these features can be assessed on biopsies and predict median survival.

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 single-hospital cohort study, with pathology slides reviewed and tumor features compared with patient survival
• Who was studied: 116 consecutive patients with diffuse malignant pleural mesothelioma diagnosed at Saint Etienne University Hospital, France, 1993 to 2015 (median age 72; 89 men, 27 women; 112 diagnosed on pleural biopsy). Three patients were excluded from the survival analysis.
• Exposure: Asbestos exposure was not studied or reported. The factors examined were microscopic tumor features: histologic subtype, mitotic count, atypical mitoses, nuclear atypia, nucleolus size, necrosis, chromatin pattern and nuclear-to-cytoplasm ratio.
• Main results:
  • Across all patients, the sarcomatoid, biphasic or desmoplastic subtypes had worse median overall survival than the epithelioid subtype (Table 2: median 6 months for non-epithelioid versus 16 months for epithelioid; p = 0.0006).
  • In epithelioid mesothelioma, fewer than 3 mitoses per 10 high-power fields went with a median survival of 25 months (confidence interval 17 to 33; n = 44). Three or more mitoses went with 9 months (confidence interval 3 to 13; n = 33). The p value was less than 0.0001.
  • In epithelioid mesothelioma, median survival was 20 months without atypical mitoses (n = 57) and 11 months with them (n = 20); p = 0.0265.
  • In epithelioid mesothelioma, indistinct nucleoli or nucleoli smaller than 3 micrometres went with a median survival of 17 months (n = 68). Nucleoli larger than 3 micrometres went with 10 months (n = 9). The p value was 0.0139.
  • In epithelioid mesothelioma, necrosis went with a median survival of 10 months (n = 16), against 19 months without necrosis (n = 61); p = 0.0379.
  • In epithelioid mesothelioma, nuclear atypia was associated with survival when mild and moderate atypia were compared with severe atypia (p = 0.0054). Table 2 gives median survivals of 17 months for mild (n = 44), 10 months for moderate (n = 24) and 10 months for severe (n = 9).
  • In epithelioid mesothelioma, chromatin pattern (p = 0.1584) and nuclear-cytoplasmic ratio (p = 0.6156) were not associated with survival.
  • In non-epithelioid mesothelioma (n = 36 in the survival analysis), only atypical mitoses were associated with survival. Median survival was 9 months (confidence interval 4 to 13) for the 18 patients without atypical mitoses and 4 months (confidence interval 1 to 6) for the 18 patients with them (p = 0.0393).
  • In non-epithelioid mesothelioma, mitotic count, nuclear atypia, nucleolus size and necrosis were not related to median overall survival.
  • Among all patients, 23 (20%) were alive at 2 years and 13 (11%) at 5 years. The median time to death was 10 months.
• The authors' conclusion: The authors concluded that these microscopic prognostic features can be assessed on pleural biopsies and can reliably predict median overall survival. They suggested this could help select patients for different treatments, including surgery.
• Limitations the authors state:
  • The authors said they probably found no other significant factors in non-epithelioid mesothelioma because survival was short and there were few cases, which makes statistical differences harder to show.
  • The authors suggested that chromatin pattern was probably not associated with survival because this feature relies on subjective judgment and is hard to reproduce.

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: Malignant Mesothelioma, Pleural Mesothelioma, Prognosis, Non-epithelioid, Epithelioid, Mesothelioma, Surgical Resection, Pleural Biopsy.

Related studies

• A nuclear grading system is a strong predictor of survival in epitheloid diffuse malignant pleural mesothelioma — K. Kadota, K. Suzuki, et al. (2012)
• Histopathological typing in diffuse malignant epithelioid mesothelioma: implication for prognosis and molecular basis — F. Forest, D. Laville, et al. (2021)
• A Histomorphologic Grading System That Predicts Overall Survival in Diffuse Malignant Peritoneal Mesothelioma With Epithelioid Subtype — K. Valente, A.U. Blackham, et al. (2016)
• Nuclear grade and necrosis predict prognosis in malignant epithelioid pleural mesothelioma: a multi-institutional study — L.E. Rosen, T. Karrison, et al. (2018)
• Low ERCC1 expression in malignant pleural mesotheliomas treated with cisplatin and vinorelbine predicts prolonged progression-free survival — Z.G. Zimling, J.B. Sørensen, et al. (2012)
• MiR-score: a novel 6-microRNA signature that predicts survival outcomes in patients with malignant pleural mesothelioma — M.B. Kirschner, Y.Y. Cheng, et al. (2015)

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