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Nuclear grade and necrosis predict prognosis in malignant epithelioid pleural mesothelioma: A multi-institutional study

  • Lauren E. Rosen
  • , Theodore Karrison
  • , Vijayalakshmi Ananthanarayanan
  • , Alexander J. Gallan
  • , Prasad S. Adusumilli
  • , Fouad S. Alchami
  • , Richard Attanoos
  • , Luka Brcic
  • , Kelly J. Butnor
  • , Françoise Galateau-Sallé
  • , Kenzo Hiroshima
  • , Kyuichi Kadota
  • , Astero Klampatsa
  • , Nolween Le Stang
  • , Joerg Lindenmann
  • , Leslie A. Litzky
  • , Alberto Marchevsky
  • , Filomena Medeiros
  • , M. Angeles Montero
  • , David A. Moore
  • Kazuki Nabeshima, Elizabeth N. Pavlisko, Victor L. Roggli, Jennifer L. Sauter, Anupama Sharma, Michael Sheaff, William D. Travis, Wickii T. Vigneswaran, Bart Vrugt, Ann E. Walts, Melissa Y. Tjota, Thomas Krausz, Aliya N. Husain
  • The University of Chicago
  • Loyola University Medical Center
  • Memorial Sloan-Kettering Cancer Center
  • Cardiff & Vale University Health Board
  • Medical University of Graz
  • University of Vermont Medical Center
  • Centre Léon Bérard
  • Tokyo Women's Medical University
  • Kagawa University
  • University of Pennsylvania
  • Cedars-Sinai Medical Center
  • Mid and South Essex NHS Foundation Trust
  • Royal Brompton and Harefield NHS Foundation Trust
  • University of Leicester
  • Fukuoka University
  • Duke University
  • Barts Health NHS Trust
  • University of Zurich

Research output: Contribution to journalArticlepeer-review

94 Scopus citations

Abstract

A recently described nuclear grading system predicted survival in patients with epithelioid malignant pleural mesothelioma. The current study was undertaken to validate the grading system and to identify additional prognostic factors. We analyzed cases of epithelioid malignant pleural mesothelioma from 17 institutions across the globe from 1998 to 2014. Nuclear grade was computed combining nuclear atypia and mitotic count into a grade of I-III using the published system. Nuclear grade was assessed by one pathologist for three institutions, the remaining were scored independently. The presence or absence of necrosis and predominant growth pattern were also evaluated. Two additional scoring systems were evaluated, one combining nuclear grade and necrosis and the other mitotic count and necrosis. Median overall survival was the primary endpoint. A total of 776 cases were identified including 301 (39%) nuclear grade I tumors, 354 (45%) grade II tumors and 121 (16%) grade III tumors. The overall survival was 16 months, and correlated independently with age (P=0.006), sex (0.015), necrosis (0.030), mitotic count (0.001), nuclear atypia (0.009), nuclear grade (o0.0001), and mitosis and necrosis score (o0.0001). The addition of necrosis to nuclear grade further stratified overall survival, allowing classification of epithelioid malignant pleural mesothelioma into four distinct prognostic groups: nuclear grade I tumors without necrosis (29 months), nuclear grade I tumors with necrosis and grade II tumors without necrosis (16 months), nuclear grade II tumors with necrosis (10 months) and nuclear grade III tumors (8 months). The mitosis-necrosis score stratified patients by survival, but not as well as the combination of necrosis and nuclear grade. This study confirms that nuclear grade predicts survival in epithelioid malignant pleural mesothelioma, identifies necrosis as factor that further stratifies overall survival, and validates the grading system across multiple institutions and among both biopsy and resection specimens. An alternative scoring system, the mitosis-necrosis score is also proposed.

Original languageEnglish
Pages (from-to)598-606
Number of pages9
JournalModern Pathology
Volume31
Issue number4
DOIs
StatePublished - Apr 1 2018

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