ArticleJournal of bone oncology2025
Malignant and metastatic giant cell tumors of bone; clinical course of primary or secondary malignant and pulmonary metastatic variants.
Article in Journal of bone oncology, 2025. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Not yet cited in PubMed.
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Abstract
Aims: Giant cell tumor of bone (GCTB) is a rare, locally aggressive, intermediate-grade neoplasm. While typically benign, GCTB can exhibit atypical behavior, including indolent pulmonary metastases and malignant transformation. This study characterizes malignant and metastatic GCTB, distinguishing primary malignant GCTB (PM-GCTB), secondary malignant GCTB (SM-GCTB), and secondary osteosarcoma, and evaluates their outcomes. Methods: A retrospectively review of 520 patients with suspected GCTB treated between 1985-2021 was performed, with malignant cases followed through 2025. Diagnosis was confirmed histologically and, where available, by H3F3A/H3F3B mutation testing. PM-GCTB was defined as a de novo high-grade sarcoma. SM-GCTB and secondary osteosarcoma were defined as malignant transformations of previously benign, histologically proven GCTB. Benign pulmonary metastases were analyzed separately. Outcomes were descriptively assessed. Results: Twelve patients (2.4 %) had malignant GCTB: five PM-GCTB (1.0 %), five SM-GCTB (1.0 %), and two secondary osteosarcoma (0.4 %). Three patients (0.6 %) developed histologically benign pulmonary metastases with indolent behavior. Three SM-GCTB patients transformed within one year despite benign baseline pathology, indicating true rapid malignant progression rather than diagnostic error. Median latency to malignant transformation was 7.5 years for SM-GCTB and up to 35 years for secondary osteosarcoma. SM-GCTB showed the highest disease-specific mortality (80 %), compared to PM-GCTB (20 %) and secondary osteosarcoma (0 %). None malignant transformations occurred following denosumab or radiotherapy. Conclusion: Three aggressive GCTB variants were identified: benign pulmonary metastatic GCTB, PM-GCTB, and secondary malignant transformation. SM-GCTB and osteosarcoma arise from benign GCTB but differ in morphology and prognosis. Because malignant transformation is exceptionally rare and symptomatic, a patient-centered, symptom-driven follow-up strategy is preferred over routine lifelong radiologic surveillance.
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