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FOS Expression in Osteoid Osteoma and Osteoblastoma

A Valuable Ancillary Diagnostic Tool

Amary, Fernanda MD, PhD*,†; Markert, Eva MD*; Berisha, Fitim MSc*; Ye, Hongtao PhD*; Gerrand, Craig MD*; Cool, Paul MD; Tirabosco, Roberto MD*; Lindsay, Daniel MD*; Pillay, Nischalan MD, PhD*,†; O’Donnell, Paul MD*; Baumhoer, Daniel MD, PhD§; Flanagan, Adrienne M. MD, PhD*,†

The American Journal of Surgical Pathology: December 2019 - Volume 43 - Issue 12 - p 1661–1667
doi: 10.1097/PAS.0000000000001355
Original Articles

Osteoblastoma and osteoid osteoma together are the most frequent benign bone-forming tumor, arbitrarily separated by size. In some instances, it can be difficult to differentiate osteoblastoma from osteosarcoma. Following our recent description of FOS gene rearrangement in these tumors, the aim of this study is to evaluate the value of immunohistochemistry in osteoid osteoma, osteoblastoma, and osteosarcoma for diagnostic purposes. A total of 337 cases were tested with antibodies against c-FOS: 84 osteoblastomas, 33 osteoid osteomas, 215 osteosarcomas, and 5 samples of reactive new bone formation. In all, 83% of osteoblastomas and 73% of osteoid osteoma showed significant expression of c-FOS in the osteoblastic tumor cell component. Of the osteosarcomas, 14% showed c-FOS expression, usually focal, and in areas with severe morphologic atypia which were unequivocally malignant: 4% showed more conspicuous expression, but these were negative for FOS gene rearrangement. We conclude that c-FOS immunoreactivity is present in the vast majority of osteoblastoma/osteoid osteoma, whereas its expression is usually focal or patchy, in no more than 14% of osteosarcoma biopsies. Therefore, any bone-forming tumor cases with worrying histologic features would benefit from fluorescence in situ hybridization analysis for FOS gene rearrangement. Our findings highlight the importance of undertaking a thorough assessment of expression patterns of antibodies in the light of morphologic, clinical, and radiologic features.

*Royal National Orthopaedic Hospital, Stanmore

Cancer Institute, University College London, London

The Robert Jones and Agnes Hunt Orthopaedic Hospital, Oswestry and Keele University, Owestry, UK

§Basel Bone Tumour Reference Centre (BBTRC), University Hospital Basel and University of Basel, Basel, Switzerland

Conflicts of Interest and Source of Funding: Supported by funding from the Tom Prince Cancer Trust, the Skeletal Cancer Action Trust UK and the Royal National Orthopaedic Hospital NHS Trust R&D program. A.M.F. is an NIHR senior investigator, and A.M.F. and N.P. are supported by the National Institute for Health Research, UCLH Biomedical Research Centre and the UCL Experimental Cancer Centre. N.P. is a Cancer Research UK clinician scientist; grant number 18387. For the remaining authors none were declared.

Correspondence: Fernanda Amary, MD, PhD, Royal National Orthopaedic Hospital, Brockley Hill, Stanmore, Middlesex HA7 4LP, UK (e-mail:

Online date: September 4, 2019

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