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Clinical outcome of low-grade central osteosarcoma and role of CDK4 and MDM2 immunohistochemistry as a diagnostic adjunct

  • Original Article
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Journal of Orthopaedic Science

Abstract

Introduction

Low-grade osteosarcoma encompasses parosteal osteosarcoma (POS) and low-grade central osteosarcoma (LCOS), with LCOS more rare than POS. LCOS is also more likely to be misdiagnosed and inappropriately treated with an intralesional procedure, due to its misleading radiological features and the overlap of its pathological characteristics with those of benign bone tumors. Therefore, as a diagnostic adjunct for LCOS, immunohistochemical assay with murine double-minute type 2 (MDM2) and cyclin-dependent kinase 4 (CDK4) have been tried with controversial results. We investigated (1) the clinical course and surgical outcome of LCOS, and (2) the diagnostic role of immune-histochemical markers (CDK4, MDM2) and their correlation with clinico-radiologic findings.

Materials and methods

We retrospectively reviewed 16 LCOS patients with regard to age, gender, tumor location, plain radiographic pattern, tumor volume, extraosseous extension, initial diagnosis, initial treatment, definitive diagnosis, definitive treatment, surgical margins, histochemical markers, and oncological outcome.

Results

Final survival status was continuous disease-free in 14, alive with disease in 1, and remaining 1 patient died of other cancer. Except for 1 patient who had not undergone excision of their primary lesion, no patients developed a local recurrence. Eight tumors (50 %) showed diffuse immunostaining for CDK4. Three of 8 tumors labeled for CDK4 were also positive for MDM2. Six (75 %) of 8 CDK4-positive tumors displayed lytic lesions on a plain radiograph; in contrast, 2 (33 %) of 6 tumors showing a sclerotic pattern on a plain radiograph were positive for CDK4.

Conclusions

The diagnosis of LCOS is challenging; however, if it is properly diagnosed, there is a high chance of a cure with wide excision alone. Positive immunostaining for CDK4 or MDM2 may be used as a diagnostic adjunct, although negative immunostaining cannot rule out this tumor. The clinical, radiological, and typical pathological findings are vital in raising the suspicion of this rare tumor.

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Acknowledgments

This work was supported by a grant of the KRP (KCCH Research Competence Promotion), Korea Institute of Radiological and Medical Sciences (50247-2014).

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The authors declare that they have no conflict of interest.

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Correspondence to Dae-Geun Jeon.

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Jeon, DG., Koh, J.S., Cho, W.H. et al. Clinical outcome of low-grade central osteosarcoma and role of CDK4 and MDM2 immunohistochemistry as a diagnostic adjunct. J Orthop Sci 20, 529–537 (2015). https://doi.org/10.1007/s00776-015-0701-0

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  • DOI: https://doi.org/10.1007/s00776-015-0701-0

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