The key histomorphologic feature is, as the name of the entity suggests, (multinucleated) giant cells with up to a hundred nuclei that have prominent nucleoli.

[citation needed] On X-ray, giant-cell tumors (GCTs) are lytic/lucent lesions that have an epiphyseal location and grow to the articular surface of the involved bone.

However, axial views of the subarticular bone (bony area adjacent to the articular cartilage) is not accurate due to voxel signal averaging.

MRI is also useful in determining the extension outside the bone and evaluating the involvement articular surface, skip lesions within bony matrix, and medullary cavity.

[citation needed] General treatment regimens have not changed much in the past 30 years, in part due to the lack of randomized clinical trials.

[13] However caution is employed since a majority of recurrent tumors with transformations to the malignant sarcoma phenotype have been in patients receiving radiotherapy for their primary benign lesion.

[14] Pharmacotherapy for GCTOB, includes bisphosphonates such as Zoledronate, which are thought to induce apoptosis in the MNGC fraction, preventing tumor-induced osteolysis.

[2][4] More recently, humanized monoclonal antibodies such as Denosumab targeting the RANK ligand have been employed in treatment of GCTOB in a phase II study.

[16] It is slightly more common in females, has a predilection for the epiphyseal/metaphyseal region of long bones,[2][17] and generally occurs in the third to fourth decade.

[14] Although classified as a benign tumor, GCTOB has been observed to metastasize to the lungs in up to 5% of cases, and in rare instances (1-3%) can transform to the malignant sarcoma phenotype with equal disease outcome.