State of the Art and New Concepts in Giant Cell Tumor of Bone: Imaging Features and Tumor Characteristics

SIMPLE SUMMARY: The 2020 World Health Organization classification of soft tissue and bone tumors classified the giant cell tumor of bone (GCTB) as an intermediate malignant tumor, with locally aggressive behavior and high recurrence rate. Imaging plays a pivotal role in the assessment of GCTB, and this review tries to summarize the main concepts about GCTB histopathogenesis and new biomarkers, describing those GCTB imaging findings which could possibly be explained by tumor molecular alterations. We have illustrated pre-operative imaging features related to prognosis and radiological findings for response evaluation after surgical treatment and denosumab administration. We have also reported the results described in literature regarding the role of radiomics in aiding GCTB diagnosis, predicting possible post-treatment recurrence and providing a quantitative assessment of the response to denosumab treatment. ABSTRACT: Giant cell tumor of bone (GCTB) is classified as an intermediate malignant tumor due to its locally aggressive behavior, burdened by high local recurrence rate. GCTB accounts for about 4–5% of all primary bone tumors and typically arises in the metaphysis and epiphyses of the long tubular bones. Mutation of gene H3F3A is at the basis of GCTB etiopathogenesis, and its immunohistochemical expression is a valuable method for practical diagnosis, even if new biomarkers have been identified for early diagnosis and for potential tumor recurrence prediction. In the era of computer-aided diagnosis, imaging plays a key role in the assessment of GCTB for surgical planning, patients’ prognosis prediction and post treatment evaluation. Cystic changes, penetrating irregular margins and adjacent soft tissue invasion on preoperative Magnetic Resonance Imaging (MRI) have been associated with a higher rate of local recurrence. Distance from the tumor edge to the articular surface and thickness of unaffected cortical bone around the tumor should be evaluated on Computed Tomography (CT) as related to local recurrence. Main features associated with local recurrence after curettage are bone resorption around the graft or cement, soft tissue mass formation and expansile destruction of bone. A denosumab positive response is represented by a peripherical well-defined osteosclerosis around the lesion and intralesional ossification. Radiomics has proved to offer a valuable contribution in aiding GCTB pre-operative diagnosis through clinical-radiomics models based on CT scans and multiparametric MR imaging, possibly guiding the choice of a patient-tailored treatment. Moreover, radiomics models based on texture analysis demonstrated to be a promising alternative solution for the assessment of GCTB response to denosumab both on conventional radiography and CT since the quantitative variation of some radiomics features after therapy has been correlated with tumor response, suggesting they might facilitate disease monitoring during post-denosumab surveillance.