Original ArticlesAssessment of Interobserver Variability and Histologic Parameters to Improve Reliability in Classification and Grading of Central Cartilaginous TumorsEefting, Daniël MD*; Schrage, Yvonne M. MSc*; Geirnaerdt, Maartje J. A. MD, PhD†; Le Cessie, Saskia PhD‡; Taminiau, Anthonie H. M. MD, PhD§; Bovée, Judith V. M. G. MD, PhD*; Hogendoorn, Pancras C. W. MD, PhD*On behalf of the EuroBoNeT consortiumAuthor Information Departments of *Pathology †Radiology ‡Medical Statistics §Orthopedic Surgery, Leiden University Medical Center, Leiden, The Netherlands ∥EuroBoNeT, an European Commission granted network of excellence to study the biology and pathology of bone tumors Funding: Netherlands Organization for Scientific Research (908-02-018 to Y.M.S and 917-76-315 to J.V.M.G.B.). The study was performed within the EuroBoNeT consortium (018814). Pancras C. W. Hogendoorn is recipient of a research grant of the OPTIMIX foundation for fundamental research. Participants of this study are listed in supplementary data 1. Daniël Eefting and Yvonne M. Schrage contributed equally. Correspondence: Pancras C. W. Hogendoorn, MD, PhD, Department of Pathology, Leiden University Medical Center, L-1Q, PO Box 9600, 2300 RC Leiden, The Netherlands (e-mail: P.C.W.Hogendoorn@lumc.nl). The American Journal of Surgical Pathology: January 2009 - Volume 33 - Issue 1 - p 50-57 doi: 10.1097/PAS.0b013e31817eec2b Buy SDC Metrics Abstract The distinction between benign and malignant cartilaginous tumors of bone is one of the most difficult subjects in surgical pathology. The grading of chondrosarcoma also seems to vary considerably among pathologists. However, clinical management differs. The purpose of this study was (1) to investigate interobserver variability in histological diagnosis and grading of central cartilaginous tumors and (2) to assess the diagnostic value of defined histologic parameters in differentiating enchondroma and central grade I chondrosarcoma. The interobserver variability was assessed using a set of 16 cases evaluated by 18 specialized pathologists. Subsequently, 20 enchondromas and 37 central grade I chondrosarcomas diagnosed in a multidisciplinary team with full clinical, radiologic, and pathologic data available with 10 years of follow-up were collected. Cytologic and tissue-architectural features were assessed to find an optimal set of parameters to differentiate enchondroma from central grade I chondrosarcoma. We demonstrate considerable variation in the histologic assessment of cartilaginous tumors (weighted κ=0.78). The distinction between enchondroma and grade I chondrosarcoma was shown to be the most disconcordant (κ coefficient=0.54), and also the differentiation between grade I and grade II chondrosarcoma was subjected to variation (κ coefficient=0.80). The application of a combination of 5 parameters (high cellularity, presence of host bone entrapment, open chromatin, mucoid matrix quality, and age above 45 y) allowed optimal differentiation between enchondromas and central grade I chondrosarcomas. With a classification tree based on 2 parameters (mucoid matrix degeneration more than 20% and/or host bone entrapment present), 54 of the 57 (94.7%) cases were assessed correctly (sensitivity 95% and specificity 95%). Our study confirms the low reliability of the diagnosis and grading of central chondrosarcoma. However, these classifications guide therapeutic decision making in daily practice. Therefore, we propose a classification model that, combined with a tailored radiologic assessment, may improve reliability of the diagnosis of cartilaginous tumors. © 2009 Lippincott Williams & Wilkins, Inc.