Reconstruction options for giant cell tumors (GCTs) of bone are limited and challenging due to the amount of structural compromise and the high recurrence rates. This is especially true for GCTs of the foot and ankle, as the area is vital for weight bearing and function. The typical treatment for GCTs is currently excision, curettage, and cementation, although that is not always effective. A 36-year-old otherwise healthy female presented with an original diagnosis of a large aneurysmal bone cyst (ABC) of the distal tibia that had recurred despite two previous attempts at treatment with resection and cementation. She was treated with surgical resection of the lesion, reconstruction, and ankle and subtalar joint arthrodesis with a tibiotalocalcaneal intramedullary nail in combination with a trabecular metal cone. The final pathology of the intraoperative samples was consistent with GCT. Postoperatively, she recovered well, and her imaging was consistent with a successful fusion. This case report provides evidence that tibiotalocalcaneal fusion with a unique combination of hindfoot nail and trabecular metal cone construct in a single procedure is a successful option for the treatment of large, recurrent GCT lesions in the distal tibia.

A giant cell tumor of the bone is among the most common bone tumors encountered by orthopedic surgeons. These benign and aggressive tumors are most commonly present around the knee joint; however, rare cases may involve the distal fibula. An 18-year-old man presented with a painless swelling of the lateral aspect of the left ankle. Clinical examination, radiologic evaluation, and biopsy confirmed the diagnosis of a giant cell tumor of the distal fibula. The patient was treated with resection of the distal fibula followed by reconstruction using an ipsilateral proximal fibula graft. The post-operative recovery was uneventful, and the patient was doing well on the last visit, one month after the intervention.

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A 60-year-old female sustained a distal radius fracture and underwent open reduction internal fixation with a volar locking plate. The patient had an uneventful recovery until four months postoperatively when the patient clinically regressed, and an expansile, radiolucent metaepiphyseal lesion was found. Further workup revealed this was a giant cell tumor of bone (GCTB). Definitive management consisted of extensive curettage, cryoablation, and cementation of the lesion, and the hardware was left intact. The current case presents an uncommon presentation of GCTB. The case illuminates the importance of thorough scrutiny of postoperative radiographs when clinical improvement plateaus or regresses and the need to pursue additional workup when the clinical course is atypical. The authors query the possibility of a sub-radiological presentation of GCTB.

Giant cell tumor (GCT) of the bone is a benign, locally aggressive neoplasm of epiphyseal origin. Most common sites for GCTs include the distal femur, proximal tibia, and the distal end of radius with the distal humerus being involved rarely. GCT is predominantly managed by extended curettage followed by adjuvant therapy to reduce recurrence. Juxta-articular GCTs are difficult to manage due to the destruction of the articular cartilage and subchondral bone which necessitates the need for joint reconstruction or fusion to salvage the joint. Aggressive and recurrent GCTs can be managed by wide resection of the tumor to reduce local recurrence followed by joint reconstruction or fusion. Joint reconstruction using a total elbow arthroplasty has been described for limb salvage as it provides a good functional outcome. We present a case of an aggressive GCT of the distal humerus that was treated using wide resection with humero-ulnar arthrodesis as an alternative in situations where joint reconstruction is not possible due to the unavailability of the prosthesis or socio-economic factors. The patient was asymptomatic after two years of follow-up, had no signs of recurrence, and had good hand functions.

Giant cell tumors of bone (GCTBs) are benign osteolytic neoplasms that can be treated with either gross-total resection or subtotal resection with adjuvant radiotherapy. For the rare GCTB of the temporal bone, close proximity to critical structures can produce functional deficits and make gross-total resection difficult to achieve without significant morbidity. We present the case of a 28-year-old woman with progressive facial paresis, otalgia, neck pain, imbalance, and subjective hearing loss. She was found to have a facial nerve mass centered at the geniculate ganglion extending into the labyrinthine segment and vestibule. We achieved gross-total resection with preserved facial nerve function as the tumor did not originate from the facial nerve and could be dissected free from the nerve. Final pathology was consistent with GCTB.

Dysregulation of angiogenesis is associated with tumor development and is accompanied by altered expression of pro-angiogenic factors. EGFL7 is a newly identified antigenic factor that plays a role in various cancers such as breast cancer, lung cancer, and acute myeloid leukemia. We have recently found that EGFL7 is expressed in the bone microenvironment, but its role in giant-cell tumor of bone (GCTB) and osteosarcoma (OS) is unknown. The aims of this study are to examine the gene expression profile of EGFL7 in GCTB and OS and compare with that of VEGF-A-D and TNFSF11 using single-cell RNA sequencing data. In-depth differential expression analyses were employed to characterize their expression in the constituent cell types of GCTB and OS. Notably, EGFL7 in GCTB was expressed at highest levels in the endothelial cell (EC) cluster followed by osteoblasts, myeloid cells, and chondrocytes, respectively. In OS, EGFL7 exhibited highest expression in EC cell cluster followed by osteoblastic OS cells, myeloid cells 1, and carcinoma associated fibroblasts (CAFs), respectively. In comparison, VEGF-A is expressed at highest levels in myeloid cells followed by OCs in GCTB, and in myeloid cells, and OCs in OS. VEGF-B is expressed at highest levels in chondrocytes in GCTB and in OCs in OS. VEGF-C is strongly enriched in ECs and VEGF-D is expressed at weak levels in all cell types in both GCTB and OS. TNFSF11 (or RANKL) shows high expression in CAFs and osteoblastic OS cells in OS, and osteoblasts in GCTB. This study investigates pro-angiogenic genes in GCTB and OS and suggests that these genes and their expression patterns are cell-type specific and could provide potential prognostic biomarkers and cell type target treatment for GCTB and OS.

Giant-cell tumor of bone is a rare, locally aggressive and rarely metastasizing primary bone tumor. The mainstay of treatment remains controversial and is decided by the balance between adequate surgical margin and sufficient adjacent joint function. Although curettage with a high-speed burr and local adjuvants can maintain normal joint function, many reports have revealed a high local recurrence rate. Conversely, en bloc resection and reconstruction with prostheses for highly aggressive lesions have reportedly lower local recurrence rates and poorer functional outcomes. Denosumab-a full human monoclonal antibody that inhibits receptor activator of nuclear factor-kappa β ligand-was approved by the Food and Drug Authority in 2013 for use in surgically unresectable or when resection is likely to result in severe morbidity for skeletally mature adolescents and adults with giant-cell tumor of bone. However, subsequent studies have suggested that the local recurrence rate would be increased by preoperative use of denosumab. In systematic reviews of the local recurrence rate after preoperative use of denosumab, conclusions vary due to the small sample sizes of the studies reviewed. Therefore, controversy regarding the treatment of giant-cell tumor of bone is ongoing. Here, this review elucidates the management of giant-cell tumor of bone, especially with the local adjuvant and neoadjuvant use of denosumab, and presents the current, evidence-based treatment for giant-cell tumor of bone.

Giant-cell tumor (GCT) of the bone affecting the hand is a rare lesion that is usually diagnosed at an advanced stage and has a high rate of recurrence. In the current literature, GCT is described as a predominantly osteoclastogenic stromal cell tumor of mesenchymal origin. It is composed of three cell types: the neoplastic GCT stromal cells; mononuclear monocyte cells; and multinucleated giant cells. Clinical imaging is basic for the diagnosis of a GCT. This tumor within the hand tends to be less eccentric and most often central. GCT of metacarpals is noted to be a rare location, with the incidence being as low as 2%. GCT on hand as compared to other sites is locally more aggressive, grows faster, and has a higher recurrence rate. A 22-year-old male patient presented with swelling over the left hand for 7 months, spontaneous in onset, gradually progressive in size, and painfully restricting the joint movement, with no history of fall or trauma. On examination, diffuse swelling of size 5 × 5 × 3 cm was tender on palpation, restricting the movement at the 4th metacarpophalangeal joint. A plain radiograph followed by an MRI scan revealed a Campanacci\'s Grade III GCT of the 4th metacarpal. An open biopsy showed an expanded and lytic mass with areas of hemorrhage and necrosis. There were few mitotic figures and the tumor was diagnosed to be a GCT. On surgical resection, friable tumor tissue was noted over the region of the entire 4th metacarpal except for the base. The patient was managed by surgical intralesional excision of the mass, followed by Kirschner-wire fixation and reconstruction with synthetic bone graft. The excised tissue was sent for histopathological examination. The patient was followed up at regular intervals, with initial splinting, followed by wire removal at 6-week post-op, and with adequate physiotherapy, as tolerated by the patient. On a 3-month follow-up, the range of motion had returned to a functional level, with good uptake of graft, and no other complications. GCT of the hand is a rare presentation of the disease and requires meticulous workup, including a thorough clinical exam, hematological, radiological, and pathological workup. The various treatment modalities described in the literature for GCTs are curettage alone, curettage and bone graft, en-bloc resection, amputation, and resection with reconstruction, but curettage alone or curettage with bone graft is not effective even for GCTs of long bones and hand, too. Such a procedure creates a skeletal void and hence furthers the need for a challenging reconstructive procedure requiring reconstruction using autograft, allograft, or silastic (synthetic) implant.

Giant-cell tumor of bone (GCTB) is an intermediate type of primary bone tumor characterized by locally aggressive growth with metastatic potential. The aim of this study was to identify new druggable targets among the cell signaling molecules involved in GCTB tumorigenesis. Profiles of activated signaling proteins in fresh-frozen tumor samples and tumor-derived cell lines were determined using phosphoprotein arrays. Analysis of the obtained data revealed epidermal growth factor receptor (EGFR) and platelet-derived growth factor receptor beta (PDGFRβ) as potential targets, but only the PDGFR inhibitor sunitinib caused a considerable decrease in stromal cell viability in vitro. Furthermore, in the case of a 17-year-old patient suffering from GCTB, we showed that the addition of sunitinib to the standard treatment of GCTB with the monoclonal antibody denosumab resulted in the complete depletion of multinucleated giant cells and mononuclear stromal cells in the tumor tissue. To summarize, the obtained data showed that a specific receptor tyrosine kinase (RTK) signaling pattern is activated in GCTB cells and plays an important role in the regulation of cell proliferation. Thus, activated RTKs and their downstream signaling pathways represent useful targets for precision treatment with low-molecular-weight inhibitors or with other types of modern biological therapy.