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Reliability of Histopathologic and Radiologic Grading of Cartilaginous Neoplasms in Long Bones

Investigation coordinated from the University of Iowa, Iowa City, Iowa

Disclosure: The authors did not receive any outside funding or grants in support of their research for or preparation of this work. Neither they nor a member of their immediate families received payments or other benefits or a commitment or agreement to provide such benefits from a commercial entity. No commercial entity paid or directed, or agreed to pay or direct, any benefits to any research fund, foundation, division, center, clinical practice, or other charitable or nonprofit organization with which the authors, or a member of their immediate families, are affiliated or associated.

This manuscript was prepared by the Skeletal Lesions Interobserver Correlation among Expert Diagnosticians (SLICED) Study Group, c/o Kevin B. Jones, MD, Department of Orthopaedics and Rehabilitation, University of Iowa Hospitals and Clinics, 200 Hawkins Drive, 01051 John Pappajohn Pavilion, Iowa City, IA 52242. E-mail address: kbjones{at}post.harvard.edu. Principal Investigators: Kevin B. Jones, MD, and Joseph A. Buckwalter, MD, MS (University of Iowa Hospitals and Clinics). Pathology Lead Investigators: Edward F. McCarthy, MD (Johns Hopkins Medical Institutions) and Barry R. DeYoung, MD (University of Iowa Hospitals and Clinics). Radiology Lead Investigator: Georges Y. El-Khoury, MD (University of Iowa Hospitals and Clinics). Statistical Planning and Analysis: Lori Dolan, PhD. Pathologists: Barry R. DeYoung, MD (University of Iowa Hospitals and Clinics), Francis H. Gannon, MD (Baylor College of Medicine), Carrie Y. Inwards, MD (Mayo Clinic Rochester), Michael J. Klein, MD (University of Alabama at Birmingham), Michael Kyriakos, MD (Washington University, St. Louis), Edward F. McCarthy, MD (Johns Hopkins Medical Institutions), Andrew E. Rosenberg, MD (Massachusetts General Hospital), Gene P. Siegal, MD, PhD (University of Alabama at Birmingham), K. Krishnan Unni, MD (Mayo Clinic Rochester). Radiologists: Georges Y. El-Khoury, MD (University of Iowa Hospitals and Clinics), Laura Fayad, MD (Johns Hopkins Medical Institutions), Mark J. Kransdorf, MD (Mayo Clinic Jacksonville), Mark D. Murphey, MD (Armed Forces Institute of Pathology), David M. Panicek, MD (Memorial Sloan-Kettering Cancer Center), David A. Rubin, MD (Washington University, St. Louis), Murali Sundaram, MD (Cleveland Clinic), and Daniel Vanel, MD (Institut Gustave Roussy, Villejuif CEDEX, France).

Methods: Nine recognized musculoskeletal pathologists and eight recognized musculoskeletal radiologists reviewed forty-six consecutive cases of cartilaginous lesions in long bones that underwent open biopsy or intralesional curettage. All diagnosticians had a bulleted history and preoperative conventional radiographs for review. Pathologists reviewed the original hematoxylin and eosin-stained glass slides from each case. Radiologists reviewed any additional imaging that was available, variably including serial radiographs, magnetic resonance imaging, and computed tomography scans. Each diagnostician classified a lesion as benign, low-grade malignant, or high-grade malignant. Kappa coefficients were calculated as a measure of reliability.

Results: Kappa coefficients for interrater reliability were 0.443 for the pathologists and 0.345 for the radiologists (p < 0.0001 for both). Kappa coefficients for a subgroup of cases determined to be high risk by subsequent clinical course were poorer at 0.236 and 0.206, respectively (p < 0.0001 for both). Slightly improved agreement among radiologists was noted for the twenty lesions that had magnetic resonance imaging available (Kappa = 0.437, p < 0.0001), but not for the lesions analyzed with serial plain radiographs or computed tomography scans.

Conclusions: This study demonstrates low reliability for the grading of cartilaginous lesions in long bones, even among specialized and experienced pathologists and radiologists. This included low reliability both in differentiating benign from malignant lesions and in differentiating high-grade from low-grade malignant lesions, both of which are critical to the safe treatment of these neoplasms. This may explain in part the wide variation in outcomes reported for chondrosarcomas treated in different medical centers. New diagnostic and grading strategies linked to protocol-driven treatments are needed, but they must be measured against the long-term gold standard of patient outcomes.

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