From: Malignancy in giant cell tumor of bone: analysis of an open-label phase 2 study of denosumab
Patient no.a (age range) | Cohort | Site | Malignant histology | Radiation received, dose | Latency period | Duration of denosumab | Malignancy present prior to denosumab | Malignancy outcome |
---|---|---|---|---|---|---|---|---|
Primary malignancies | ||||||||
1 (80–89 y) | Primary resectable | Femur | Initial diagnosis: appearance suspicious of sarcoma based on imaging atypical for GCTB and no lytic bone lesions Diagnosis: Undifferentiated pleomorphic sarcoma | No | 4 y, 3 mo | 2 y, 5 mo | Likelyb | Death after postsurgical complications from femur replacement |
2 (50–59 y) | Recurrent unresectable | Femur | Giant cell tumor with pleiomorphic spindle cells, suspect malignant areas, extensive reactive changes due to fracture Diagnosis: Undifferentiated spindle cell sarcoma | No | 2 y | 10 mo | Likelyb | Chemotherapy with complete response |
3 (20–29 y) | Primary resectable | Pelvis | Numerous cores, largest was 1.5 cm, consisting of brown, friable tissue; GCTB with atypical features and high expression of proliferation markers Diagnosis: Osteogenic sarcoma | No | 13 mo | 6 mo | Likelyb | Lost to follow-up |
4 (70–79 y) | Primary resectable | Sacrum | Spindle cell proliferation and cellular atypia, no giant cells. Suggests malignant transformation characterized by aspects of pleomorphism and cellular atypia with mitotic index elevated Diagnosis: Undifferentiated pleomorphic sarcoma | No | 10 mo | 8 mo | Yes | Death of primary disease 3 mo after malignancy diagnosis |
5 (30–39 y) | Primary resectable | Tibia | Malignant spindle cell sarcoma (no maturation due to denosumab) Diagnosis: Undifferentiated pleomorphic sarcoma | No | 2 y, 8 mo | 2 y, 4 mo | Yes | Patient underwent planned amputation plus chemotherapy |
SMGCTB | ||||||||
6 (40–49 y) | Recurrent unresectable | Metatarsus | Diagnosis: High-grade sarcoma | Yes, 50 Gy | 13 y | 6 y, 3 mo | No | Amputation plus chemotherapy; deceased 12 mo after malignancy diagnosis |
7 (40–49 y) | Recurrent unresectable | Sacrum | At enrollment, lesion contained few giant cells. In foci, sheets of cells exhibiting epithelioid morphology with cytologic atypical and brisk mitotic activity, including atypical mitoses Diagnosis: Undifferentiated pleomorphic sarcoma | No | 25 y | 4 mo | Likelyb | Deceased 6 mo after malignancy diagnosis |
8 (40–49 y) | Recurrent resectable | Tibia | Malignant spindle cell sarcoma (no maturation due to denosumab) Diagnosis: Undifferentiated pleomorphic sarcoma | Yes, 56 Gy | 7 y, 8 mo | 1 mo | Yes | Amputation plus chemotherapy; alive at last follow-up |
9 (20–29 y) | Recurrent resectable | Femur | Areas of solid ABC and GCTB associated with epithelial and spindle cell proliferation. Diagnosis: GCTB with suspect progression to sarcoma | Yes, 56 Gy | 4 y, 8 mo | 6 mo | Likelyb | Lung metastases diagnosed soon after femur malignancy; deceased 5 mo after malignancy diagnosis |
10 (50–59 y) | Recurrent unresectable | Sacrum | Diagnosis: High grade undifferentiated spindle cell sarcoma, consistent with differentiation arising in malignant GCTB | Yes, 25 fractions | 6 y, 7 mo | 1 y, 8 mo | Yes | Surgery (resection and curettage, laminectomy); deceased 2 mo after malignancy diagnosis |
Sarcomatous transformation | ||||||||
11 (30–39 y) | Recurrent unresectable | Distal femur | Diagnosis: Undifferentiated spindle cell sarcoma | No | 11 y | 6 y, 2 mo | No | Amputation and chemotherapy; alive at last follow-up |
12 (60–69 y) | Primary resectable | Tibia | Diagnosis: High-grade osteosarcoma | No | 2 y, 11 mo | 2 y, 2 mo | No | Chemotherapy and amputation; deceased 7 mo after malignancy diagnosis |
13 (30–39 y) | Recurrent resectable | Distal femur | Diagnosis: Undifferentiated spindle cell sarcoma | No | 4 y, 9 mo | 2 y, 5.5 mo | No | Tumor resection and prosthesis plus chemotherapy; alive, no evidence of disease at last follow-up |
14 (50–59 y) | Primary resectable | Distal femur | Microscopic picture corresponds to chondroblastic/osteoblastic osteosarcoma high grade that probably developed from GCTB Diagnosis: High-grade osteosarcoma | No | 1 y, 5 mo | 1 y, 2 mo; progression after only 3 mo of treatment | No | Amputation plus chemotherapy; alive at last follow-up |