Abstract
Epithelioid mesothelioma is the most prevalent subtype of diffuse malignant peritoneal mesothelioma. A recently described nuclear-grading system predicted survival in patients with epithelioid malignant pleural mesothelioma. The present study was undertaken to validate this grading system in epithelioid malignant peritoneal mesothelioma (EMPM) and to compare to combined grade, including nuclear atypia, mitotic count, and tumor necrosis. Cases of EMPM, from 1995 to 2018, were analyzed from 7 French institutions from RENAPE network. Solid growth, tumor necrosis, nuclear atypia, and mitotic count were evaluated by at least 3 pathologists from the RENAPATH group. The predictions in terms of OS and PFS of nuclear grade and combined grade were analyzed. Nuclear grade was computed combining nuclear atypia score and mitotic count into a grade of I–III. Another system combining nuclear atypia score, mitotic score, and tumor necrosis was evaluated and defined as a combined grade I–III. A total of 138 cases were identified. The median follow-up was 38.9 months (range: 1.1–196.6). Nuclear and combined grades III were independently associated with a shorter OS (p < 0.05), and a shorter PFS (p < 0.05). Patients with combined grade I tumors had the best overall and progression-free survivals, in comparison to nuclear grade I. In this large multicentric study, combined grade and nuclear grade were the best independent predictors of OS and PFS in EMPM. These systems should be easily described by pathologists involved into the management of malignant peritoneal mesothelioma, because of their potential therapeutic implications.
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Acknowledgements
The authors wish to thank Véréna Landel for the English language correction and critical suggestions.
Collaborators
Julio Abba, MD (Department of Digestive Surgery, Grenoble University Hospital, Grenoble, France); Karine Abboud, MD (Department of General Surgery, University Hospital, Saint Étienne, France); Mohammad Alyami, MD (D King Faisal specialist hospital and research center, Riyad, Saudi Arabia); Amroun Koceila, MD (Department of Digestive Surgery, Jean Godinot Cancer Institute, Reims, France); Catherine Arvieux, MD, PhD (Department of Digestive Surgery, Grenoble University Hospital, Grenoble, France); Naoual Bakrin, MD, PhD (Department of Digestive Surgery, Lyon-Sud University Hospital, Lyon, France); Sandrine Barbois, MD (Department of Digestive Surgery, Grenoble University Hospital, Grenoble, France); Houda Ben Rejeb, MD (Department of Pathology, Bergonie Institute, Bordeaux, France); Jean-Marc Bereder, MD, PhD (Department of Digestive Surgery, Archet 2 University Hospital, Nice, France); Frédéric Bibeau, MD, PhD (Department of Pathology, Caen University Hospital, Caen, France); Isabelle Bonnefoy (Department of Digestive Surgery, Lyon-Sud University Hospital, Lyon, France); Pierre-Emmanuel Bonnot, MD (Department of Digestive Surgery, Lyon-Sud University Hospital, Lyon, France); Olivier Bouche, MD, PhD, (Department of Gastroenterology, Reims University Hospital, Reims, France); Dominique Bouzard, MD, (Department of Surgery, Louis Mourier University Hospital, Colombes, France); Cécile Brigand, MD, PhD (Department of Digestive Surgery, Hautepierre University Hospital, Strasbourg, France); Sébastien Carrère, MD (Department of Surgical Oncology, Val d’Aurelle Montpellier Cancer Center, Montpellier, France); Bertrand Célérier, MD (Department of Surgery, Bordeaux Hospital University Center, Bordeaux, France); Cécilia Ceribelli, MD (Department of Surgery, Lorraine Institute of Oncology, Vandoeuvre-les-Nancy, France); Julien Coget, MD (Department of Surgery, Rouen University Hospital, Rouen, France); Thomas Courvoisier, MD (Department of Digestive Surgery, Poitiers University Hospital, Poitiers, France); Cécile de Chaisemartin, MD (Department of Surgical Oncology, Paoli Calmettes Institute, Marseille, France); Jean-Baptiste Delhorme, MD (Department of Digestive Surgery, Hautepierre University Hospital, Strasbourg, France); Anthony Dohan, MD, PhD (Department of Radiology, Cochin University Hospital, Paris, France); Frédéric Dumont, MD (Department of Surgical Oncology, ICO René Gauducheau Cancer Center, Saint-Herblain, France); Sylvaine Durand-Fontanier, MD, PhD (Department of Digestive Surgery, Dupuytren University Hospital, Limoges, France); Clarisse Eveno, MD, PhD (Department of Digestive Surgery, Claude Huriez University Hospital, Lille, France); Gwenaël Ferron, MD, PhD (Department of Surgical Oncology, Claudius Regaud Institute IUTC, Toulouse, France); Johan Gagniere, MD (Department of Digestive Surgery, Estaing University Hospital, Clermont-Ferrand, France); Alexandre Galan, MD (Department of Radiology, Lyon-Sud University Hospital, Lyon, France); Laurent Ghouti, MD (Department of Digestive Surgery, Purpan University Hospital, Toulouse, France); François-Noël Gilly, MD, PhD (Department of Digestive Surgery, Lyon-Sud University Hospital, Lyon, France); Laurence Gladieff, MD (Department of Medical Oncology, Claudius Regaud Institute IUCT, Toulouse, France); Diane Goéré, MD, PhD (Department of Digestive Surgery, Saint Louis University Hospital, Paris, France); Jean-Marc Guilloit, MD (Department of Surgical Oncology, Francois Baclesse Comprehensive Cancer Center, Caen, France); Frédéric Guyon, MD (Department of Surgical Oncology, Bergonie Institute, Bordeaux, France); Bruno Heyd, MD, PhD (Department of Digestive Surgery, Minjoz University Hospital, Besançon, France); Christine Hoeffel, MD, PhD (Department of Radiology, Robert Debré University Hospital, Reims, France); Charles Honoré, MD, PhD, (Department of Surgery, Gustave Roussy Institute, Villejuif, France); Eve Huart, MD (Department of General Surgery, University Hospital, Saint Étienne, France); Martin Hübner, MD, PhD (Department of Surgery, University Hospital, Lausanne, Switzeland); Rachid Kaci, MD (Department of Pathology, Lariboisière University Hospital, Paris, France); Reza Kianmanesh (Department of Digestive Surgery, Robert Debré University Hospital, Reims, France); Jérémie Lefevre, MD, PhD (Department of Digestive Surgery, Saint Antoine University Hospital, Paris, France); Bernard Lelong, MD (Department of Surgical Oncology, Paoli Calmettes Institute, Marseille, France); Justine Lerooy, MD, (Department of Digestive Surgery, Claude Huriez University Hospital, Lille, France); Agnès Leroux-Broussier, MD (Department of Pathology, Lorraine Institute of Oncology, Vandoeuvre-les-Nancy, France); Réa Lo Dico, MD, PhD (Department of Digestive Surgery, Saint Louis University Hospital, Paris, France); Frédéric Marchal, MD, PhD (Department of Surgical Oncology, Lorraine Institute of Oncology, Vandoeuvre-les-Nancy, France); Pascale Mariani, MD (Department of Surgical Oncology, Curie Institute, Paris, France); Pierre Meeus, MD (Department of Surgery, Léon Bérard Comprehensive Cancer Center, Lyon, France); Cédric Nadeau, MD (Gynaecology and Obstetrics Ward, Mother and Child Pole, Poitiers University Hospital, University of Poitiers, Poitiers, France); Cécile Odin (Department of Digestive Surgery, Lyon-Sud University Hospital, Lyon, France); Pablo Ortega-Deballon, MD, PhD (Department of Digestive Surgical Oncology, University Hospital of Dijon, Dijon, France); Brice Paquette, MD (Department of Digestive Surgery, Minjoz University Hospital, Besançon, France); Guillaume Passot, MD, PhD (Department of Digestive Surgery, Lyon-Sud University Hospital, Lyon, France); Patrice Peyrat, MD (Department of Surgery, Léon Bérard Comprehensive Cancer Center, Lyon, France); Denis Pezet, MD, PhD (Department of Digestive Surgery, Estaing University Hospital, Clermont-Ferrand, France); Guillaume Piessen, MD, PhD (Department of Digestive Surgery, Claude Huriez University Hospital, Lille, France); Nicolas Pirro, MD, PhD (Department of Digestive Surgery, Timône University Hospital, Marseille, France); Hélène Plouhinec, MD (Department of Pathology, Gustave Roussy Institute, Villejuif, France); Marc Pocard, MD, PhD (Surgical Oncologic & Digestive Unit, Lariboisière University Hospital, Paris, France); Flora Poizat, MD (Department of Pathology, Paoli Calmettes Institute, Marseille, France); François Quenet, MD (Department of Surgical Oncology, Val d’Aurelle Montpellier Cancer Center, Montpellier, France); Patrick Rat, MD, PhD (Department of Digestive Surgical Oncology, University Hospital of Dijon, Dijon, France); Pierre Rousselot, MD (Department of Pathology, Francois Baclesse Comprehensive Cancer Center, Caen, France); Pascal Rousset, MD, PhD (Department of Radiology, Lyon-Sud University Hospital, Lyon, France); Hélène Senellart (Department of Medical Oncology, ICO René Gauducheau Cancer Center, Saint-Herblain, France); Olivia Sgarbura MD (Department of Surgical Oncology, Val d’Aurelle Montpellier Cancer Center, Montpellier, France); Igor Sielezneff, MD, PhD (Department of Digestive Surgery, La Timône University Hospital, Marseille, France); Isabelle Sourrouille, MD (Department of Surgery, Gustave Roussy Institute, Villejuif, France); Magali Svrcek, MD, PhD (Department of Pathology, Hospital Saint-Antoine AP-HP, Paris, France); Abdelkader Taibi, MD (Department of Digestive Surgery, Dupuytren University Hospital, Limoges, France); Emilie Thibaudeau, MD (Department of Surgical Oncology, ICO René Gauducheau Cancer Center, Saint-Herblain, France); Yann Touchefeu (Department of Gastroenterology, Nantes University Hospital, Nantes); Jean-Jacques Tuech, MD, PhD (Department of Digestive Surgery, Charles Nicolle University Hospital, Rouen, France); Sharmini Varatharajah, MD (Department of Surgical Oncology, Francois Baclesse Comprehensive Cancer Center, Caen, France); Delphine Vaudoyer, MD (Department of Digestive Surgery, Lyon-Sud University Hospital, Lyon, France); Sophie Vermersch, MD (Department of Pediatric Surgery, University Hospital, St Etienne, France); Véronique Verriele-Beurrier, MD (Department of Pathology, ICO Paul Papin Cancer Center, Angers, France); Romuald Wernert, MD (Department of Surgical Oncology, ICO Paul Papin Cancer Center, Angers, France).
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Sylvie Isaac, Juliette Hommell-Fontaine, Peggy Dartigues, and N. Benzerdjeb contributed to the design of the study. Sylvie Isaac, Juliette Hommell-Fontaine, Peggy Dartigues, and N. Benzerdjeb counted the number of mitosis. Irène Villa managed the software Calopix. Nazim Benzerdjeb, Peggy Dartigues, Séverine Valmary-Degano, Eliane Mery, Gerlinde Averous, Anne Chevallier, Marie-Hélène Laverriere, Sylvie Isaac, and Juliette Hommell-Fontaine reviewed slides. N. Benzerdjeb contributed to analysis of the results and writing of the manuscript. Nazim Benzerdjeb, Peggy Dartigues, Vahan Kepenekian, Séverine Valmary-Degano, Eliane Mery, Gerlinde Averous, Anne Chevallier, Marie-Hélène Laverriere, Irène Villa, Françoise Galateau Sallé, Laurent Villeneuve, Olivier Glehen, Sylvie Isaac, Juliette Hommell-Fontaine, and on behalf of the RENAPE Network contributed to writing of the manuscript.
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Benzerdjeb, N., Dartigues, P., Kepenekian, V. et al. Combined grade and nuclear grade are prognosis predictors of epithelioid malignant peritoneal mesothelioma: a multi-institutional retrospective study. Virchows Arch 479, 927–936 (2021). https://doi.org/10.1007/s00428-021-03144-z
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DOI: https://doi.org/10.1007/s00428-021-03144-z