Virchows Archiv

, Volume 470, Issue 6, pp 639–646 | Cite as

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

  • Cyril Habougit
  • Béatrice Trombert-Paviot
  • Georgia Karpathiou
  • François Casteillo
  • Sophie Bayle-Bleuez
  • Pierre Fournel
  • Jean-Michel Vergnon
  • Olivier Tiffet
  • Michel Péoc’h
  • Fabien Forest
Original Article

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.

Keywords

Mesothelioma, malignant Neoplasm grading Mitosis Survival analysis 

Notes

Compliance with ethical standards

Authorization to use human biological samples for research was obtained (no. AC-2013-1835). Institutional ethical approval was obtained in compliance with the Declaration of Helsinki.

Conflict of interest

The authors declare that they have no conflict of interest.

Funding

No funding was received.

References

  1. 1.
    Karpathiou G, Stefanou D, Froudarakis ME (2015) Pleural neoplastic pathology. Respir Med 109:931–943CrossRefPubMedGoogle Scholar
  2. 2.
    Taioli E, Wolf AS, Flores RM (2015) Meta-analysis of survival after pleurectomy decortication versus extrapleural pneumonectomy in mesothelioma. Ann Thorac Surg 99:472–480CrossRefPubMedGoogle Scholar
  3. 3.
    Jassem J, Ramlau R, Santoro A, Schuette W, Chemaissani A, Hong S, Blatter J, Adachi S, Hanauske A, Manegold C (2008) Phase III trial of pemetrexed plus best supportive care compared with best supportive care in previously treated patients with advanced malignant pleural mesothelioma. J Clin Oncol 26:1698–1704CrossRefPubMedGoogle Scholar
  4. 4.
    Stahel RA, Riesterer O, Xyrafas A et al (2015) Neoadjuvant chemotherapy and extrapleural pneumonectomy of malignant pleural mesothelioma with or without hemithoracic radiotherapy (SAKK 17/04): a randomised, international, multicentre phase 2 trial. Lancet Oncol 16:1651–1658CrossRefPubMedGoogle Scholar
  5. 5.
    Kadota K, Suzuki K, Colovos C, Sima CS, Rusch VW, Travis WD, Adusumilli PS (2012) A nuclear grading system is a strong predictor of survival in epitheloid diffuse malignant pleural mesothelioma. Mod Pathol 25:260–271CrossRefPubMedGoogle Scholar
  6. 6.
    Travis WD (ed) (2015) WHO classification of tumours of the lung, pleura, thymus and heart, 4th edn. International Agency for Research on Cancer, LyonGoogle Scholar
  7. 7.
    Husain AN, Colby T, Ordonez N et al (2013) Guidelines for pathologic diagnosis of malignant mesothelioma: 2012 update of the consensus statement from the International Mesothelioma Interest Group. Arch Pathol Lab Med 137:647–667CrossRefPubMedGoogle Scholar
  8. 8.
    Galateau-Sallé F, Gilg Soit Ilg A, Le Stang N et al (2014) The French mesothelioma network from 1998 to 2013. Ann Pathol 34:51–63CrossRefPubMedGoogle Scholar
  9. 9.
    Thompson LD (2002) Pheochromocytoma of the adrenal gland scaled score (PASS) to separate benign from malignant neoplasms: a clinicopathologic and immunophenotypic study of 100 cases. Am J Surg Pathol 26:551–566CrossRefPubMedGoogle Scholar
  10. 10.
    Fuhrman SA, Lasky LC, Limas C (1982) Prognostic significance of morphologic parameters in renal cell carcinoma. Am J Surg Pathol 6:655–663CrossRefPubMedGoogle Scholar
  11. 11.
    Moch H (2016) WHO classification of tumours of the urinary system and male genital organs. IARC Press, LyonGoogle Scholar
  12. 12.
    Ramael M, Jacobs W, Weyler J, Białasiewicz P, Van den Bossche J, Buysse C, Vermeire P, Van Marck E (1994) Proliferation in malignant mesothelioma as determined by mitosis counts and immunoreactivity for proliferating cell nuclear antigen (PCNA). J Pathol 172:247–253CrossRefPubMedGoogle Scholar
  13. 13.
    Koyuncu A, Koksal D, Ozmen O, Demirag F, Bayiz H, Aydogdu K, Berkoglu M (2015) Prognostic factors in malignant pleural mesothelioma: a retrospective study of 60 Turkish patients. J Cancer Res Ther 11:216–222PubMedGoogle Scholar
  14. 14.
    Perry A, Stafford SL, Scheithauer BW, Suman VJ, Lohse CM (1997) Meningioma grading: an analysis of histologic parameters. Am J Surg Pathol 21:1455–1465CrossRefPubMedGoogle Scholar
  15. 15.
    Elston CW, Ellis IO (1991) Pathological prognostic factors in breast cancer. I. The value of histological grade in breast cancer: experience from a large study with long-term follow-up. Histopathology 19:403–410CrossRefPubMedGoogle Scholar
  16. 16.
    Duregon E, Molinaro L, Volante M, Ventura L, Righi L, Bolla S, Terzolo M, Sapino A, Papotti MG (2014) Comparative diagnostic and prognostic performances of the hematoxylin-eosin and phospho-histone H3 mitotic count and Ki-67 index in adrenocortical carcinoma. Mod Pathol 27:1246–1254CrossRefPubMedGoogle Scholar
  17. 17.
    Dalton LW, Page DL, Dupont WD (1994) Histologic grading of breast carcinoma. A reproducibility study. Cancer 73:2765–2770CrossRefPubMedGoogle Scholar
  18. 18.
    Kalatova B, Jesenska R, Hlinka D, Dudas M (2015) Tripolar mitosis in human cells and embryos: occurrence, pathophysiology and medical implications. Acta Histochem 117:111–125CrossRefPubMedGoogle Scholar
  19. 19.
    Cerruto CA, Brun EA, Chang D, Sugarbaker PH (2006) Prognostic significance of histomorphologic parameters in diffuse malignant peritoneal mesothelioma. Arch Pathol Lab Med 130:1654–1661PubMedGoogle Scholar
  20. 20.
    Valente K, Blackham AU, Levine E, Russell G, Votanopoulos KI, Stewart JH, Shen P, Geisinger KR, Sirintrapun SJ (2016) A histomorphologic grading system that predicts overall survival in diffuse malignant peritoneal mesothelioma with epithelioid subtype. Am J Surg Pathol 40:1243–1248CrossRefPubMedPubMedCentralGoogle Scholar
  21. 21.
    Zink D, Fischer AH, Nickerson JA (2004) Nuclear structure in cancer cells. Nat Rev Cancer 4:677–687CrossRefPubMedGoogle Scholar
  22. 22.
    Bignold LP (2003) Pathogenetic mechanisms of nuclear pleomorphism of tumour cells based on the mutator phenotype theory of carcinogenesis. Histol Histopathol 18:657–664PubMedGoogle Scholar
  23. 23.
    Gisselsson D (2002) Tumour morphology—interplay between chromosome aberrations and founder cell differentiation. Histol Histopathol 17:1207–1212PubMedGoogle Scholar

Copyright information

© Springer-Verlag Berlin Heidelberg 2017

Authors and Affiliations

  • Cyril Habougit
    • 1
  • Béatrice Trombert-Paviot
    • 2
  • Georgia Karpathiou
    • 1
  • François Casteillo
    • 1
  • Sophie Bayle-Bleuez
    • 3
  • Pierre Fournel
    • 4
  • Jean-Michel Vergnon
    • 3
  • Olivier Tiffet
    • 5
  • Michel Péoc’h
    • 1
  • Fabien Forest
    • 1
  1. 1.Department of Pathology, North HospitalUniversity Hospital of Saint EtienneSaint EtienneFrance
  2. 2.Department of Public Health and Medical Informatics, North HospitalUniversity Hospital of Saint EtienneSaint EtienneFrance
  3. 3.Department of Pneumology, North HospitalUniversity Hospital of Saint EtienneSaint EtienneFrance
  4. 4.Department of OncologyLucien Neuwirth Cancer InstituteSaint-Priest-en-JarezFrance
  5. 5.Department of Thoracic Surgery, North HospitalUniversity Hospital of Saint EtienneSaint EtienneFrance

Personalised recommendations