Faculty Collaboration Database

Nuclear grade and necrosis predict prognosis in malignant epithelioid pleural mesothelioma: a multi-institutional study. Mod Pathol 2018 Apr;31(4):598-606

Date

01/13/2018

Pubmed ID

29327706

DOI

10.1038/modpathol.2017.170

Scopus ID

2-s2.0-85045563941 (requires institutional sign-in at Scopus site)   73 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 (<0.0001), and mitosis and necrosis score (<0.0001). 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.

Author List

Rosen LE, Karrison T, Ananthanarayanan V, Gallan AJ, Adusumilli PS, Alchami FS, Attanoos R, Brcic L, Butnor KJ, Galateau-Sallé F, Hiroshima K, Kadota K, Klampatsa A, Stang NL, Lindenmann J, Litzky LA, Marchevsky A, Medeiros F, Montero MA, Moore DA, Nabeshima K, Pavlisko EN, Roggli VL, Sauter JL, Sharma A, Sheaff M, Travis WD, Vigneswaran WT, Vrugt B, Walts AE, Tjota MY, Krausz T, Husain AN

Author

Alexander J. Gallan MD Assistant Professor in the Pathology department at Medical College of Wisconsin

MESH terms used to index this publication - Major topics in bold

Adult
Aged
Aged, 80 and over
Cell Nucleus
Female
Humans
Kaplan-Meier Estimate
Lung Neoplasms
Male
Mesothelioma
Middle Aged
Necrosis
Neoplasm Grading
Pleural Neoplasms
Prognosis