שנה שפה:

IDH1 and IDH2 Mutational Analysis can Help Distinguish between Chondroblastic Osteosarcoma and Dedifferentiated Chondrosarcoma in Histologically Ambiguous Cases



Eyal Ramu1, Qingxia Wei3, Kenneth Gundle4, Anthony Griffin2, Brendan Dickson5, Rita Kandel5, Peter Ferguson2, Benjamin Alman3,6, Jay Wunder2
1 Orthopedic Surgery, Sheba Medical Center, Tel-Hashomer, Israel
2 University Musculoskeletal Oncology Unit, Mount Sinai Hospital, and Division of Orthopaedic Surgery, Department of Surgery, University of Toronto, Toronto, Canada
3 Program in Development and Stem Cell Biology, Hospital for Sick Children, Toronto, Canada
4 Department of Orthopaedics & Rehabilitation, Oregon Health & Science University, Portland, USA
5 Department of Pathology and Laboratory Medicine, Mount Sinai Hospital, Toronto, Canada
6 Department of Orthopedic Surgery, Duke University, Durham, USA

Background: Distinguishing chondrosarcoma from osteosarcoma can be challenging in the setting of a biopsy specimen. The importance of this distinction is critical for appropriate treatment decision making. The treatment of osteosarcoma is neoadjuvant chemotherapy and surgical resection. However chondrosarcoma is typically chemo-resistant and treated by surgical resection alone. The chondroblastic subtype of osteosarcoma contains both chondroid and osteoid-forming areas, as such sampling the chondroid portion can lead to an erroneous diagnosis of chondrosarcoma. Similarly, the dedifferentiated chondrosarcoma contains non-cartilaginous component, commonly resembling osteosarcoma. Sampling the non-cartilaginous component can result in an erroneous histological diagnosis of osteosarcoma. Mutations in the Isocitrate dehydrogenase genes (IDH1 and IDH2) have been described in a variety of tumors and recently in chondrosarcoma. Currently, no IDH1/2 mutations have been identified in osteosarcoma. The purpose of this study was to determine if IDH mutational status could be support the differentiation between osteosarcoma and chondrosarcoma when biopsy results are equivocal.

Methods: Five patients with primary bone tumors based on radiological imaging, but with ambiguous histological diagnoses between osteosarcoma and chondrosarcoma were analyzed. The genomic DNA of each tumor was prospectively assessed for IDH1/2 mutations using Sanger sequencing after PCR amplification of exon 4 of both genes.

Results: IDH mutations were identified in 3 tumors. These patients were older and had radiological imaging consistent with chondrosarcoma. The 2 patients with wild type IDH1/2 tumors were younger and had radiological imaging consistent with osteosarcoma. One patient, with an IDH1 mutation, was initially treated with neoadjuvant chemotherapy due to the initial histological diagnosis of chondroblastic osteosarcoma. The chemotherapy treatment was stopped due to continued tumor growth. Following surgical resection, the diagnosis was changed to dedifferentiated chondrosarcoma.

Conclusion: Our study supports the use of IDH1/2 mutation analysis to support the differentiation between osteosarcoma and chondrosarcoma in the histologically ambiguous cases.

העלאת קובץ המאמר או המצגת

Eyal Ramu