Denosumab combined with microwave ablation excisional scraping for giant cell tumor of the thoracic spine: a case report and literature review.

Denosumab has recently become an important part of the treatment regime for spinal giant cell tumors of the bone (GCTB). Its use has significantly reduced the risk of surgery and postoperative complications in patients with spinal GCTB. However, the use of denosumab has not yet been optimized to reap the maximum benefits. Here, we have reported the case of a patient who was treated with denosumab in combination with excision and scraping for GCTB of the T10 vertebrae, which achieved good tumor control and no recurrence at the 2-year postoperative follow-up. We have also reviewed the case in the light of relevant literature as well as presented our ideas and recommendations for the optimal use of denosumab.

Locking plate augmentation of polymethylmethacrylate-filled distal femoral defects: A biomechanical study.

Benign, locally aggressive tumors of the distal femur are typically treated with intralesional curettage and polymethylmethacrylate (PMMA) cementation. However, it is not known whether plate fixation should be added to biomechanically augment these PMMA-filled defects. The purpose of this study was to evaluate the performance of two competing techniques for reconstruction of a distal femoral defect. For this biomechanical study, we used 12 composite femurs with properties comparable to bone. In nine femurs, identical contained medial distal femoral defects were created using a robotic arm. Group A contained three intact femurs, Group B three femurs with an unfilled defect, Group C three femurs reconstructed with PMMA alone, and Group D three femurs reconstructed with PMMA plus a medial locking plate. Locations of greatest stress concentration were determined by PhotoStress analysis, then three strain gauges were applied to each specimen at these high-stress locations. Specimens were loaded within a physiologic range followed by loading to failure. Outcome measures included construct stiffness, strain along the distal femur, and load at failure. Results showed that stiffness and strain were not significantly different between reconstructive techniques; however, both techniques reduced tensile strain along the popliteal surface by approximately 40% compared to non-reconstructed specimens. All specimens failed at the femoral neck before failing at the distal femur. These findings suggest that plate augmentation of PMMA-filled distal femoral defects like the one in this study offers insignificant biomechanical benefit within physiologic loads and therefore may be unnecessary.

Clinicopathologic and prognostic characteristics of tumor budding-like in giant cell tumor of bone.

BACKGROUND: Currently, tumor budding (TB) is defined as an important factor for a poor prognosis in various types of cancers. The authors identified a significant presence of TB-like structures at the tumor invasive front in giant cell tumor of bone (GCTB), which may have the same biologic function as TB. The objective of this report was to describe the distribution of TB in GCTB and investigate its correlation with clinicopathologic characteristics, the immune microenvironment, survival prognosis, and response to denosumab treatment. METHODS: This multicenter cohort study included 426 patients with GCTB who received treatment between 2012 and 2021 at four centers. Two independent pathologists performed visual assessments of TBL structures in hematoxylin-and-eosin-stained tumor sections. Immunohistochemistry was used to evaluate tumor-infiltrating lymphocyte subtypes (CD3-positive, CD4-positive, CD8-positive, CD20-positive, programmed cell death protein-1-positive, programmed cell death-ligand 1positive, and FoxP3-positive) as well as Ki-67 expression levels in 426 tissue samples. These parameters were then analyzed for associations with patient outcomes (local recurrence-free survival [LRFS] and overall survival [OS]), clinicopathologic characteristics, and response to denosumab treatment. RESULTS: High-grade TB was associated with poorer LRFS and OS in both patient groups. In addition, TB was correlated with various clinicopathologic features, tumor-infiltrating lymphocyte expression, and response to denosumab treatment. TB outperformed the traditional Enneking and Campanacci staging systems in predicting patient LRFS and OS. CONCLUSIONS: The current data support the assessment of TBL structures as a reliable prognostic tool in GCTB, potentially aiding in the development of personalized treatment strategies for patients.

Functional Outcomes of Limb Salvage Surgery in Patients with Giant Cell Tumor of Bone of the Lower Extremities: A Cross-sectional Comparative Study.

Background and Objectives: Giant cell tumor of bone (GCTB) is a benign aggressive tumor primarily treated with surgery. Neoadjuvant treatment with denosumab or zoledronic acid is a common adjunct given to down-stage tumors and facilitate limb sparing surgery. This study sought to determine the characteristics, outcomes, and occurrence of complications following resection (RS) or extended curettage (EC) for GCTB of the lower extremities. Correlation of neoadjuvant therapy with the occurrence of complications was also investigated. Methods: This is an analytical cross-sectional study of 30 patients diagnosed with GCTB of the lower extremity treated between 2015 to 2022 in a single tertiary hospital. Functional outcomes were determined using the 1993 version of the Musculoskeletal Tumor Society (MSTS) score. Mean follow-up for all patients was 2.6 years (SD 1.8). Twenty-two patients (73%) underwent resection, while eight (27%) patients underwent extended curettage. Of the 30 patients, 26 (87%) patients received neoadjuvant therapy, with 21 (81%) given denosumab and five (19%) given zoledronic acid. Results: Functional outcomes were excellent for 23 patients (77%), with no significant difference between RS and EC groups. Nine complications occurred in the RS group, including dehiscence (n=3), superficial infection (n=2), implant failure (n=1), nonunion (n=1), palsy (n=1), and implant irritation (n=1). Five complications occurred in the EC group, four of which were noted to be recurrences, with one case of deep infection. Recurrence was noted to be significantly higher (p=0.0004) in the EC group. Separate correlation analysis showed no significant difference in incidence of complications but found that duration of surgery was significantly longer (p=0.0001), and intraoperative blood loss was significantly higher (p=0.0072) in the RS group. No significant difference (p=0.78) was noted in complication rate between patients given denosumab versus zoledronic acid. Conclusions: Functional outcomes of EC and RS appear to be comparable, including the incidence of complications. However, recurrence was noted to be significantly higher in EC. There appears to be no clear advantage between denosumab or zoledronic acid for GCTB. As a neoadjuvant medication and/or to control tumor progression, zoledronic acid may be the more economic option especially for patients in developing countries.

Free Osteoarticular Metatarsal Autograft in the Reconstruction of Giant Cell Tumor of Metacarpal: Report of Two Cases and Description of a Technique.

Giant cell tumors are benign but locally aggressive bone neoplasms containing many multinucleated giant cells similar to osteoclasts. The author reports the case of two patients with giant cell tumor in the metacarpals, one of whom was multicentric. Giant cell tumor in the hand is a rare condition, and, at this location, it commonly presents at an advanced stage, with extensive bone destruction. Thus, its safe resection, associated with a large resulting bone failure, represents a great challenge to the orthopedist. The various treatment options described in the literature cause severe cosmetic and/or functional impairment to the hand. Thinking about it, the author describes the treatment technique through the transfer of metatarsus-free osteoarticular graft to the metacarpal with good functional and cosmetic results.

Giant cell tumor of bone of temporal bone and skull base: report of 6 cases.

OBJECTIVE: Five cases of giant cell tumor of bone (GCTB) in the head and neck region were reported, with a main focus on the radiological findings to identify common characteristics for the diagnosis of GCTB in these sites. MATERIALS AND METHODS: Five consecutive patients diagnosed with GCTB were retrospectively selected. Radiological features on conventional and advanced MR sequences and CT were analyzed. HE staining and immunohistochemical examination were performed using antibodies against p63 and CD68. RESULTS: The common clinical features were local mass (3/5), tinnitus (3/5) and headache (2/5). Radiologically, all the cases were well-circumscribed osteolytic lesion, majority of cases demonstrated an expansile growth pattern and "soap bubble" appearance on CT (4/5). On MRI, the tumors showed predominantly hypointensity both on T1WI and T2WI, and no evidence of restricted diffusion on DWI. Intratumoral hemorrhage (2/5), cystic alternation (2/5) and very low signal on T2WI in the periphery region of the tumor (4/5) was found. Fluid-fluid level was noted in one case, which was eventually verified to be GCTB with secondary aneurysmal bone cyst (ABC). With contrast agent, all the cases showed striking (3/5) or mild to intermediate (2/5) enhancement. CONCLUSIONS: Although the above described radiological findings are not specific for GCTB in head and neck region, a well-defined osteolytic lesion in the bones of head and neck region with "soap bubble" appearance on CT and hypointensity on T2WI with very low signal in the peripheral region of the tumor on MRI highly suggest GCTB for patient ages 20 to 40.

Rare features of giant cell tumors of the bone: A case report.

Giant cell tumors of the bone are local invasive diseases that are mainly composed of neoplastic monocytes and nonneoplastic multinucleated giant cells, mostly in the long bones of patients with mature bones. A specific H3F3A mutation is the key to its diagnosis. The present paper reports a case of giant cell tumor of the bone (GCTB) characterized by diffuse cholesterol crystals with few multinucleated giant cells. Imaging examination combined with immunohistochemical H3.3 G34W positivity was used to diagnose the patient with GCTB. Understanding the unique histological morphology of this patient will help doctors correctly diagnose giant cell tumors of bone and avoid misdiagnosis.

Combined preoperative denosumab and adjuvant microwave ablation for high-risk giant cell tumor of bone: a retrospective study in a single center.

BACKGROUND: Giant cell tumor of bone (GCTB) is a locally aggressive neoplasm with a high propensity for recurrence following intralesional curettage. The introduction of denosumab, a RANKL inhibitor, has shown potential in facilitating joint-sparing surgery. However, concerns exist regarding its impact on local recurrence rates. This study aimed to evaluate the efficacy and safety of combined preoperative denosumab with adjuvant microwave ablation (MWA) for the treatment of high-risk GCTB. METHODS: We conducted a retrospective review of 19 patients with high-risk GCTB who underwent preoperative denosumab treatment followed by curettage and adjuvant MWA. The primary outcome measure was the local recurrence rate, with secondary outcomes including functional status assessed by the Musculoskeletal Tumor Society (MSTS) score and safety profile of the treatment. RESULTS: In this retrospective analysis, we evaluated the outcomes of 19 patients with high-risk GCTB treated with preoperative denosumab and adjuvant MWA. The median follow-up duration was 33.1 months, 3 patients (15.8%) experienced local recurrence at a median of 21.6 months postoperatively and the local recurrence-free survival was 81.2% at two years. Notably, no patient developed lung metastasis, and all recurrences were successfully managed with repeat curettage and MWA, with a mean MSTS score of 27.3. No patient required joint replacement due to tumor recurrence, resulting in a 100% joint preservation rate. CONCLUSION: The combination of preoperative denosumab and adjuvant MWA is a feasible and effective strategy for the management of high-risk GCTB, providing effective local control with preserved joint function. This approach may offer a surgical alternative for young patients where joint preservation is paramount.

Treatment of a Carpal Giant Cell Tumor of Bone With Curettage and Cemented Capitohamate Fusion.

Carpal giant cell tumor of bone spanning multiple bones is a rare condition. We present a case of a man in his fifth decade with wrist pain who was found to have giant cell tumor of bone involving his capitate and hamate bones. This condition was successfully treated with intralesional curettage, argon beam coagulation, chemical cauterization and a cemented limited carpal fusion with satisfactory outcomes and no recurrence at 1-year postoperative follow-up.

Efficacy and safety of denosumab de­escalation in giant cell tumor of bone.

Giant cell tumor of bone (GCTB) is a locally aggressive intermediate bone tumor. Denosumab has shown effectiveness in GCTB treatment; however, the benefits of denosumab de-escalation for unresectable GCTB have not been well discussed. The present study investigated the efficacy and safety of denosumab de-escalation for GCTB. The medical records of 9 patients with unresectable GCTB or resectable GCTB not eligible for resection, who received de-escalated denosumab treatment at Okayama University Hospital (Okayama, Japan) between April 2014 and December 2021, were retrospectively reviewed. The denosumab treatment interval was gradually extended to every 8, 12 and 24 weeks. The radiographic changes and clinical symptoms during standard and de-escalated denosumab therapy were assessed. The denosumab interval was de-escalated after a median of 12 months of a standard 4-weekly treatment. Imaging showed that the re-ossification of osteolytic lesions obtained with the 4-weekly treatment were sustained with 8- and 12-weekly treatments. The extraskeletal masses reduced significantly with standard treatment, while tumor reduction was sustained during de-escalated treatment. During the 24-weekly treatment, 2 patients remained stable, while 2 patients developed local recurrence. The clinical symptoms improved significantly with standard treatment and remained improved during de-escalated treatment. There were severe adverse events including osteonecrosis of the jaw (2 patients), atypical femoral fracture (1 patient) and malignant transformation of GCTB (1 patient). In conclusion, 12-weekly de-escalated denosumab treatment showed clinical benefits as a maintenance treatment in patients with unresectable GCTB, in addition to sustained stable tumor control and improved clinical symptoms with standard treatment. A 24-weekly treatment can also be administered, with careful attention paid to detecting local recurrence.

Giant Cell Tumor of the Rib: A Report of Two Patients.

Giant cell tumor of the bone is a locally aggressive and rarely metastasizing tumor that typically affects the ends of long bones. Less than 1% of giant cell tumor of bone occur in the ribs. Our patients were a 32-year-old woman and a 45-year-old man and were detected following chest traumas. No bone alterations were detected in radiological studies performed immediately after local trauma. Six- and one- months, respectively, following chest trauma, both giant lytic heterogeneous masses arising on an anterior rib arc were radiologically observed. In the computerized tomography-guided needle biopsy, giant cell tumor of bone were diagnosed. Both tumors were completely removed by bloc resection including the adjacent ribs and posterior reconstruction were performed. One patient was preoperatively treated with denosumab. Neither local recurrences nor metastasis have been detected in follow-up. Despite its low frequency and its low degree of suspicion, giant cell tumor of bone should be included in the differential diagnosis of a rapid growing chest mass.

The tumor-stroma ratio in giant cell tumor of bone: associations with the immune microenvironment and responsiveness to denosumab treatment.

BACKGROUND: Currently, there is limited understanding regarding the clinical significance of the tumor-stroma ratio (TSR) in giant cell tumor of bone (GCTB). Hence, we aimed to investigate the distribution of TSR in GCTB and explore its correlation with various clinicopathologic factors, immune microenvironment, survival prognosis, and denosumab treatment responsiveness. METHODS: We conducted a multicenter cohort study comprising 426 GCTB patients treated at four centers. TSR was evaluated on hematoxylin and eosin-stained and immunofluorescent sections of tumor specimens. Immunohistochemistry was performed to assess CD3+, CD4+, CD8+, CD20+, PD-1+, PD-L1+, and FoxP3+ TIL subtypes as well as Ki-67 expression levels in 426 tissue specimens. These parameters were then analyzed for their correlations with patient outcomes [local recurrence-free survival (LRFS) and overall survival (OS)], clinicopathological features, and denosumab treatment responsiveness. RESULTS: Low TSR was significantly associated with poor LRFS and OS in both cohorts. Furthermore, TSR was also correlated with multiple clinicopathological features, TIL subtype expression, and denosumab treatment responsiveness. TSR demonstrated similar predictive capabilities as the conventional Campanacci staging system for predicting patients' LRFS and OS. CONCLUSION: The results of this study provide evidence supporting the use of TSR as a reliable prognostic tool in GCTB and as a predictor of denosumab treatment responsiveness. These findings may aid in developing individualized treatment strategies for GCTB patients in the future.

The diagnostic and prognostic value of tartrate-resistant acid phosphatase isoform 5b for giant cell tumor of bone.

BACKGROUND: Serum level of tartrate-resistant acid phosphatase 5b (TRACP5b) is an excellent serum marker of bone resorption. In patients with giant cell tumor of bone (GCTB), TRACP5b levels are reportedly elevated. This study investigated whether TRACP5b could be a diagnostic serum marker and be useful for detecting postoperative disease progression for GCTB. METHODS: Cohort 1: We abstracted data from 120 patients with TRACP5b measurements from our database: 49 patients with GCTB and 71 patients non-GCTB. We compared serum TRACP5b values between the GCTB and non-GCTB groups. Cohort 2 included 47 patients with GCTB who had more than 6 months of follow-up and multiple TRACP5b values. For patients with local recurrence, TRACP5b change rate was calculated by comparing the TRACP5b value just before progression (a) with the value at the time of progression (b): Change rate = [(b)-(a)]/(a). In the non-progression group, the change rate was calculated from the two consecutive TRACP5b values, (c) and (d): Change rate =[(c)-(d)]/(c). We compared TRACP5b change rates between the progression and non-progression groups. RESULTS: Cohort 1: The GCTB group had a significantly higher mean TRACP5b value (1756 ± 2021 mU/dL) than the non-GCTB group (415 ± 219 mU/dL) (p < 0.0001). Cohort 2: The mean TRACP5b change rate of the progression group was significantly higher than the non-progression group (8.53 ± 8.52 and 0.24 ± 0.27, respectively; p < 0.0001). CONCLUSION: TRACP5b is a useful diagnostic marker in GCTB. The rate of change in serum TRACP5b values is a highly sensitive marker for predicting local recurrence in GCTB.

Multimodal imaging in the diagnosis of bone giant cell tumors: A retrospective study.

BACKGROUND: Giant cell tumor of bone is a locally aggressive and rarely metastasizing tumor, and also a potential malignant tumor that may develop into a primary malignant giant cell tumor. AIM: To evaluate the role of multimodal imaging in the diagnosis of giant cell tumors of bone. METHODS: The data of 32 patients with giant cell tumor of bone confirmed by core-needle biopsy or surgical pathology at our hospital between March 2018 and March 2023 were retrospectively selected. All the patients with giant cell tumors of the bone were examined by X-ray, computed tomography (CT) and magnetic resonance imaging (MRI), and 7 of them were examined by positron emission tomography (PET)-CT. RESULTS: X-ray imaging can provide overall information on giant cell tumor lesions. CT and MRI can reveal the characteristics of the internal structure of the tumor as well as the adjacent relationships of the tumor, and these methods have unique advantages for diagnosing tumors and determining the scope of surgery. PET-CT can detect small lesions and is highly valuable for identifying benign and malignant tumors to aid in the early diagnosis of metastasis. CONCLUSION: Multimodal imaging plays an important role in the diagnosis of giant cell tumor of bone and can provide a reference for the treatment of giant cell tumors.

Giant Cell Tumor of the Temporal Bone with Direct Invasion into the Middle Ear and Skull Base: A Case Report.

Giant cell tumor (GCT) of bone is a rare, benign, osteolytic neoplasm that most commonly occurs in early adulthood and often involves the long bones of the body. Although GCT largely affects the epiphyses of long bones, several reports of GCT involvement of the cranial and facial bones exist in the literature. In addition to reviewing other reported cases of GCT of the lateral skull base in the literature, the authors report here on the clinical presentation, radiographic findings, and management of a patient found to have a GCT of the squamous part of temporal bone invading the middle ear and infratemporal fossae, which was treated by en bloc resection of the lateral skull base.

Management of Recurrent Giant Cell Tumor of Distal Tibia With Intramedullary Hindfoot Fusion Nail and Trabecular Metal Implant Construct.

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.

Giant cell tumor of bone and secondary osteoarthritis.

Giant cell tumor of bone is a commonly encountered aggressive epiphyseal bone tumor, most often treated surgically. The natural history and presentation are classically described but the histopathology is poorly understood. Intralesional curettage is the mainstay of treatment, but there is significant variation in the use of adjuvant and cavity filling modalities. No gold standard has been agreed upon for treatment, and a variety of techniques are currently in use. Given its location, secondary osteoarthritis is a known long-term complication. This review examines the natural history of giant cell tumors, treatment options and complications, and subsequent development of osteoarthritis. Arthroplasty is usually indicated for secondary osteoarthritis although data is limited on its efficacy. Further directions will likely center on improved pharmacological treatments as well as improved arthroplasty techniques.

Intralesional curettage and surgical adjuvants in the treatment of giant cell tumor of bone: meta-analysis and systematic review.

BACKGROUND: The ideal treatment for giant cell tumor of bone (GCTB) is still controversial. Various surgical adjuvants have been introduced following intralesional curettage to improve local control rates. However, findings from relevant studies are inconsistent, and no consensus has been reached. The purpose of this study is to determine what intraoperative adjuvant is effective in decreasing the recurrence of GCTB. METHODS: We performed a systematic review and meta-analysis of articles published in the PubMed and Embase electronic databases which assessed the recurrence rate of GCTB following intralesional curettage with or without various surgical adjuvants. Two authors independently evaluated all publications. Meta-analysis was performed with Stata/MP (Version 17.0, StataCorp LLC, TX, USA) and Review Manager (RevMan, Version 5.4.1, The Cochrane Collaboration, 2020). Pooled risk ratio (RR) was used for analysis, with P values less than 0.05 considered statistically significant. RESULTS: Twenty-four studies involving 2,579 patients were included in this analysis. The overall recurrence rates for patients treated with or without high-speed burring (HSB) are 11.9% (26/218) and 47.7% (92/193), respectively. The pooled RR for tumor recurrence is 0.33 (95% CI: 0.22 to 0.49, P<0.001). In the meanwhile, the overall recurrence rates for patients treated with or without chemical adjuvants are 23.5% (77/328) and 26.1% (73/280), respectively, with a pooled RR of 0.84 (95% CI: 0.63 to 1.10, P=0.89). Additionally, the overall recurrence rates for patients treated with or without polymethyl methacrylate (PMMA) are 20.4% (205/1,006) and 33.4% (314/939), respectively, with a pooled RR of 0.59 (95% CI: 0.50 to 0.69, P<0.001). CONCLUSIONS: Intraoperative application of HSB or PMMA has an additional antitumor effect, while the use of phenol or H2O2 fails to make any significant difference (PROSPERO: CRD42022344262).

Micro-CT, Mechanical, and Histological Examination of the Effect of Local Adjuvants on Porcine Cortical Bone Following Intralesional Curettage of Bone Tumors.

BACKGROUND AND OBJECTIVES: Curettage is the removal of a tumor from the bone while preserving the surrounding healthy cortical bone, and is associated with higher rates of local recurrence. To lower these rates, curettage should be combined with local adjuvants, although their use is associated with damage to nearby healthy bone. OBJECTIVE: The purpose of this analysis is to determine the effect of local adjuvants on cortical porcine bone by using micro-computed tomography (micro-CT) along with histological and mechanical examination. METHODS: Local adjuvants were applied to porcine specimens under defined conditions. To assess changes in bone mineral density (BMD), a micro-CT scan was used. The pixel gray values of the volume of interest (VOI) were evaluated per specimen and converted to BMD values. The Vickers hardness test was employed to assess bone hardness (HV). The depth of necrosis was measured histologically using hematoxylin and eosin-stained tissue sections. RESULTS: A noticeable change in BMD was observed on the argon beam coagulation (ABC) sample. Comparable hardness values were measured on samples following electrocautery and ABC, and lowering of bone hardness was obtained in the case of liquid nitrogen. Extensive induced depth of necrosis was registered in the specimen treated with liquid nitrogen. CONCLUSION: This study determined the effect of local adjuvants on cortical bone by using micro-CT along with histological and mechanical examination. Phenolization and liquid nitrogen application caused a decrease in bone hardness. The bone density was affected in the range of single-digit percentage values. Liquid nitrogen induced extensive depth of necrosis with a wide variance of values.

En bloc resection and iliac crest bone grafting for giant cell tumor of the finger.

A case of a rapidly progressing giant cell tumor of the middle phalanx is presented. The patient underwent en bloc resection with iliac crest grafting and distal interphalangeal fusion. Surgical technique and patient's functional outcomes are described.