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Recently, FN1 fusions to receptor tyrosine kinase genes have been identified in soft tissue tumors with calcified chondroid matrix named calcifying chondroid mesenchymal neoplasms (CCMNs). We collected 33 cases of CCMN from the French network for soft tissue and bone tumors. We performed wholeexome RNA sequencing, expression analysis, and genome-wide DNA methylation profiling in 33, 30, and 20 cases of CCMN compared with a control group of tumors, including noncalcified tenosynovial giant cell tumor (TGCT). Among them, 15 cases showed morphologic overlap with soft tissue chondroma, 8 cases with tophaceous pseudogout, and 10 cases with chondroid TGCT. RNA-sequencing revealed a fusion of FN1 in 76% of cases (25/33) with different 5' partners, including most frequently FGFR2 (14 cases), TEK or FGFR1. Among CCMN associated with FGFR1 fusions, 2 cases had overexpression of FGF23 without tumor-induced osteomalacia. Four CCMN had PDGFRA::USP8 fusions; 3 of which had histologic features of TGCT and were located in the hip, foot, and temporomandibular joint (TMJ). All cases with FN1::TEK fusion were located at TMJ and had histologic features of TGCT with or without chondroid matrix. They formed a distinct cluster on unsupervised clustering analyses based on whole transcriptome and genome-wide methylome data. Our study confirms the high prevalence of FN1 fusions in CCMN. In addition, through transcriptome and methylome analyses, we have identified a novel subgroup of tumors located at the TMJ, exhibiting TGCTlike features and FN1::TEK fusions. [ABSTRACT FROM AUTHOR]

The letter to the editor discusses a study conducted by He and Liu on the expression of hypoxia-inducible factor-1α (HIF-1α) in patients with spinal chordoma. The authors commend the study for its contribution to identifying therapeutic targets in spinal chordoma. However, they raise concerns about the statistical analysis and suggest conducting subgroup analysis and receiver operating curve analysis to validate the significance of HIF-1α in predicting prognosis. They also propose using RNA sequencing for more accurate quantification of gene expression. The authors emphasize the need for further research to better understand the role of HIF-1α in spinal chordoma. [Extracted from the article]

This article discusses a condition called Bowler's Thumb, which is a rare neuropathy of the ulnar digital nerve of the thumb caused by repetitive compression or friction. The article presents three cases of Bowler's Thumb, two of which were effectively managed with conservative measures and one that required surgical intervention. The typical symptoms include discomfort, numbness, and tingling in the thumb or first webspace. Diagnosis is usually made based on clinical symptoms, but soft tissue imaging and electrodiagnostic testing can also be used. Treatment options include conservative measures, corticosteroid injections, and surgical intervention. The article emphasizes the importance of an accurate diagnosis and individualized treatment plan for satisfactory outcomes. [Extracted from the article]

Background A vascularized fibula graft (VFG) is the vascular autograft most frequently used to restore large segmental long bone defects, particularly in the upper limb. Because the use of a vascularized fibula involves an operation in an uninvolved extremity with potential morbidity, it is important to document that this type of reconstruction is successful in restoring function to the humerus. However, the long-term results of VFG after intercalary resection of the humeral diaphysis for bone tumors are still unknown. Questions/purposes (1) What was the complication rate of reconstruction? (2) What was the functional result after surgical treatment, as assessed by the Musculoskeletal Tumor Society (MSTS) score, the American Shoulder and Elbow Society (ASES) score, and Constant score? (3) What was the survivorship of these grafts free from revision and graft removal at 5, 10, and 15 years? Methods Between 1987 and 2021, 127 patients were treated at our institution with en bloc resection for a primary malignant or an aggressive benign bone tumor of the humerus; we excluded patients treated with extra-articular resection or amputation. Of those, 14% (18 of 127) were treated with intercalary resection of the humeral diaphysis for primary bone tumors and reconstruction with VFG, with or without a bulk allograft, and were analyzed in this retrospective study. Generally, our indications for reconstruction with VFG are intercalary resection of the humerus for primary malignant or aggressive benign bone tumors in patients with long life expectancy and high functional demands, in whom adequate bone stock of the proximal and distal epiphysis can be preserved. In 13 patients, VFG was used alone, whereas in five patients, a massive allograft was used. Our policy was to use VFG combined with a massive allograft in patients undergoing juxta-articular joint-sparing resections in which proximal osteotomy was performed close to the anatomic neck of the humerus to obtain more stable fixation and better tendinous reattachment of the rotator cuff and deltoid. All 18 patients who were treated with a VFG were available for follow-up at a minimum of 2 years (median follow-up 176 months, range 26 to 275 months), and although three have not been seen in the past 5 years and are not known to have died, they had 172, 163, and 236 months of follow-up, and were included. The median age at surgery was 25 years (range 2 to 63 years), the median humeral resection length was 15 cm (range 8 to 21 cm), and the median fibular length was 16 cm(range 12 to 23 cm). Complications and functional scores were ascertained by chart review that was performed by an individual not involved in patient care. Functional results were assessed with the MSTS score (range 0 to 30), the ASES score (range 0 to 100), and the Constant score (range 0% to 100%). Survivorship was estimated using a Kaplan- Meier survivorship estimator, which was suitable because there were few deaths in this series. Results Seven patients underwent a revision procedure (one radial nerve transient palsy because of screw impingement, four nonunions in three patients with one humeral head avascular necrosis, treatment for screw-related pain in one patient, and two VFG fractures), and one patient underwent VFG removal. Donor site complications were observed in four patients (one ankle valgus deformity and three claw toes--the first toe in two patients and the other toes in the third). At the final clinical control, at a median follow-up of 176 months (range 26 to 275 months), the median MSTS score was 30 of 30 (range 28 to 30), the median ASES score was 98.3 (range 93 to 100), and the median Constant score was 93.5% (range 79% to 100%). Revision-free survival was 71% (95% CI 53% to 96%) at 5 years and 57% (95% CI 37% to 88%) at 10 and 15 years; VFG removal-free survival was 94% (95% CI 83% to 100%) at 5, 10, and 15 years. Conclusion VFG appears to be an effective reconstructive option after humeral intercalary resection for primary bone tumors. These are complex procedures and should be performed by an experienced team of surgeons who recognize that complications may occur frequently in the first years after the procedure. The frequency of mechanical complications observed in the first 5 years postoperatively may be lessened by using long spanning-plate fixation, and if successful, this reconstruction provides a long-term, durable reconstruction with excellent functional results. Level of Evidence Level IV, therapeutic study. [ABSTRACT FROM AUTHOR]

This article discusses the recurrence rates, complications, and functional outcomes of multiportal arthroscopic synovectomy for patients with knee diffuse-type tenosynovial giant-cell tumors (D-TGCT). The study evaluated a series of 178 patients who underwent this procedure and found a low recurrence risk of 12% at 5 years. The authors also found that postoperative radiotherapy did not reduce the risk of recurrence. The study highlights the importance of local tumor control and suggests that multiportal arthroscopic synovectomy may improve outcomes without increasing complications or impairing knee function. Further research is needed to define the role of traditional treatment approaches, improve techniques, and assess the efficacy and safety of novel systemic treatment options. [Extracted from the article]

Case: We present a 23-year-old man with acute-on-chronic shoulder pain with an aggressive-appearing, destructive lesion of the left proximal humerus and diffuse lung metastases. Biopsy revealed conventional giant cell tumor of bone (GCTB) without sarcomatous differentiation, treated with resection and proximal humerus reconstruction. Without systemic treatment, his pulmonary metastases demonstrated modest spontaneous regression, with no impairment of pulmonary function. Conclusions: Although GCTB is known to metastasize to lungs, these deposits most commonly follow local recurrence. We describe a young adult with diffuse pulmonary nodules at initial presentation, although still following an indolent clinical course without the need for additional systemic therapy. [ABSTRACT FROM AUTHOR]

Background: The double-blind, randomized, placebo-controlled phase 3 study of orally administered PLX3397 in patients with pigmented villonodular synovitis or giant cell tumor of the tendon sheath (ENLIVEN) showed that pexidartinib provides a robust objective tumor response in adults with tenosynovial giant cell tumors (TGCT) not amenable to improvement with surgery. Based on these results, in 2019, pexidartinib received accelerated approval in the United States in this population as a breakthrough therapy under an orphan drug designation. However, the ability of pexidartinib to relieve pain in ENLIVEN was not fully detailed, and the relationship between pain relief and objective tumor response was not described. Questions/purposes: (1) What level of pain relief was achieved by pexidartinib treatment in ENLIVEN? (2) How was pain relief related to objective tumor responses? (3) How durable was pain relief? Methods: The current study included planned primary and exploratory assessments of patient-assessed worst pain at the site of the tumor in the ENLIVEN trial. ENLIVEN was a phase 3 randomized, placebo-controlled clinical trial in which adults with TGCT not amenable to improvement with surgery received pexidartinib or placebo for 24 weeks, after which eligible patients could receive open-label pexidartinib. Of 174 patients assessed for eligibility, 121 were randomized (50% [60] to placebo, 50% [61] to pexidartinib), and 120 were given either placebo or pexidartinib (59 received placebo and 61 received pexidartinib) and were included in an intent-to-treat analysis. Fifty-nine percent (71 of 120) of the overall treated population was female, and 88% (106 of 120) were White. Mean age was 45 ± 13 years. Tumors were mostly in the lower extremities (92% [110 of 120]), most commonly in the knee (61% [73 of 120]) and ankle (18% [21 of 120]). As a secondary outcome, patients scored worst pain at the site of the tumor in the past 24 hours on an 11-point numeric rating scale (NRS). The primary definition of a pain response was a decrease of at least 30% in the weekly mean worst-pain NRS score and increase of less than 30% in narcotic analgesic use between baseline and week 25. Planned exploratory assessments of pain included the frequency of a pain response using alternative thresholds, including a decrease in worst-pain NRS score of 50% or more and a decrease of at least 2 points (minimum clinically important difference [MCID]), the magnitude of pain reduction between baseline and week 25, correlation between worst-pain NRS score and tumor shrinkage by RECIST 1.1 criteria, and the durability of the pain response during the open-label extension. Pain responses during the randomized portion of the trial were compared according to intention-to-treat analysis, with a one-sided threshold of p < 0.025 to reduce the risk of false-positive results. Pain assessment was complete for 59% (35 of 59) of patients in the placebo group and 54% (33 of 61) of patients in the pexidartinib group. Demographic and disease characteristics did not differ between the two treatment groups. Results: A difference in the primary assessment of a pain response was not detected between pexidartinib and placebo (response percentage 31% [19 of 61] [95% CI 21% to 44%] versus 15% [9 of 59] [95% CI 8% to 27%]; one-sided p = 0.03). In the exploratory analyses, pexidartinib provided a modest improvement in pain (response percentage 26% [16 of 61] [95% CI 17% to 38%] versus 10% [6 of 59] [95% CI 5% to 20%]; one-sided p = 0.02 using the 50% threshold and 31% [19 of 61] [95% CI 21% to 44%] versus 14% [8 of 59] [95% CI 7% to 25%]; one-sided p = 0.02 using the MCID threshold). The least-squares mean change in the weekly mean worst-pain NRS score between baseline and week 25 was larger in patients treated with pexidartinib than placebo (-2.5 [95% CI -3.0 to -1.9] versus -0.3 [95% CI -0.9 to 0.3]; p < 0.001), although the mean difference between the two groups (-2.2 [95% CI -3.0 to -1.4]) was just over the MCID. Improvement in the weekly mean worst-pain NRS score correlated with the reduction in tumor size (r = 0.44; p < 0.001) and tumor volume score (r = 0.61; p < 0.001). For patients in the open-label extension, the change in the worst-pain NRS score from baseline was similar to the change at the end of the randomized portion and just above the MCID (mean -2.7 ± 2.2 after 25 weeks and -3.3 ± 1.7 after 50 weeks of receiving pexidartinib). Conclusion: Based on the current study, a modest reduction in pain, just larger than the MCID, may be an added benefit of pexidartinib in these patients, although the findings are insufficient to justify the routine use of pexidartinib for pain relief. Level of Evidence: Level II, therapeutic study. [ABSTRACT FROM AUTHOR]

Background: Irrigation is commonly used as an adjuvant treatment during the intralesional curettage of bone tumors. The goal of the present study was to analyze the in vitro cytotoxicity of commonly used irrigation solutions on chondrosarcoma and giant cell tumor (GCT) cells as there is no consensus on which solution leads to the greatest amount of cell death.Methods: An in vitro evaluation was performed by exposing human GCT and human chondrosarcoma cell lines to 0.9% saline solution, sterile water, 70% ethanol, 3% hydrogen peroxide, 0.05% chlorhexidine gluconate (CHG), and 0.3% povidone iodine solutions independently for 2 and 5 minutes. A low-cytotoxicity control (LCC) and a high-cytotoxicity control (HCC) were established to determine the mean cytotoxicity of each solution and each solution's superiority to LCC and non-inferiority to HCC.Results: The present study demonstrated that 0.05% CHG was non-inferior to the HCC when chondrosarcoma was exposed for 5 minutes and when GCT was exposed for 2 and 5 minutes (mean cytotoxicity, 99% to 102%) (p < 0.003 for all). Sterile water was superior to the LCC when chondrosarcoma was exposed for 5 minutes and when GCT was exposed for 2 minutes (mean, 28% to 37%) (p < 0.05). Sterile water (mean, 18% to 38%) (p < 0.012) and 3% hydrogen peroxide (mean, 7% to 16%) (p < 0.001) were both inferior to the HCC. The 3 other solutions were non-superior to the LCC (mean, -24% to -5%) (p < 0.023).Conclusions: In vitro irrigation in 0.05% CHG provided high cytotoxicity, comparable with the HCC. Therefore, the use of a 0.05% CHG solution clinically could serve as a potential chemical adjuvant during intralesional curettage of chondrosarcoma and GCT.Clinical Relevance: In an effort to reduce the burden of residual tumor cells, irrigation solutions are often utilized as adjuvant local therapy. Use of a 0.05% CHG solution clinically could serve as a potential chemical adjuvant to intralesional curettage of chondrosarcoma and GCT. Further in vivo studies may be indicated to assess clinical outcomes and safety associated with the use of 0.05% CHG in the treatment of chondrosarcoma and GCT. [ABSTRACT FROM AUTHOR]

Case: Distal radius reconstruction after giant cell tumor (GCT) resection is typically performed with free fibular flaps when a vascularized bone is needed. However, vascularized fibular flaps are contraindicated in patients with peroneal artery variants. We present 2 patients with GCTs of the radius and bilateral peronea arteria magna who underwent resection with wrist fusion using an allograft bone and vascularized free medial femoral condyle periosteal flaps. Both patients had excellent outcomes with minimal postoperative morbidity. Conclusion: Allograft bone with vascularized medial femoral condyle periosteal flaps is an effective option for reconstructing distal radius defects after GCT resection when conventional methods fail. [ABSTRACT FROM AUTHOR]

Study Deign: This was a retrospective study about sacral giant cell tumor of bone (GCTB).Objective: This study aimed to investigate whether ultra-short course of neo-adjuvant denosumab treatment for sacral GCTB could (1) induce radiological and histological response? (2) Facilitate nerve-sparing surgery? (3) Achieve satisfactory oncological and functional outcomes?Summary Of Background Data: Previous reports on long course of neo-adjuvant denosumab treatment for GCTB showed significant tumor response and a relatively high recurrent rate after curettage.Methods: Sixty-six patients with sacral GCTB treated with neoadjuvant denosumab and nerve-sparing surgery were categorized into ultra-short course group (≤3 doses and operation within D21 since 1st dose, 41 patients) or conventional group (>3 doses or operation after D21 since 1st dose, 25 patients). The radiological and histological response, operative data, oncological and functional outcomes were compared.Results: The ultra-short course group demonstrated fewer doses of neo-adjuvant denosumab (mean: 2.1 vs. 4.8, P  < 0.001) and shorter time to surgery (12.2 days vs. 72.3 days, P < 0.001). Similar patterns of radiological and histological response were observed in the two groups with less fibrosis and ossification in the ultra-short course group. The operative duration (199.9 min vs. 187.8 min, P = 0.364) and estimated blood loss (1552.4 mL vs. 1474.0 mL, P = 0.740) were comparable. Most (94.8%) of the patients received adjuvant denosumab. After a mean follow-up of 29.4 months, three cases (8.8%) and five cases (20.8%) showed local recurrence in each group (P = 0.255). The estimated recurrence-free survival (56.2 vs. 51.2 months, P = 0.210) and the functional status [Motor-Urination-Defecation scores: 25.9 vs. 25.7, P = 0.762] did not differ between the two groups.Conclusion: Ultra-short course of neo-adjuvant denosumab for sacral GCTB could elicit radiological and histological responses as conventional course did. The less degree of fibrosis and ossification might facilitate nerve-sparing surgery and help to achieve satisfactory local control and functional status.Level of Evidence: 4. [ABSTRACT FROM AUTHOR]

Footnotes 1 I This i CORR Insights® I is a commentary on the article i "Pexidartinib Provides Modest Pain Relief in Patients With Tenosynovial Giant Cell Tumor: Results From ENLIVEN" I by Healey and colleagues available at: i DOI: 10.1097/CORR.0000000000002335. Tenosynovial giant cell tumor (TGCT) includes giant cell tumor of the tendon sheath and pigmented villonodular synovitis. CORR Insights®: Pexidartinib Provides Modest Pain Relief in Patients With Tenosynovial Giant Cell Tumor: Results From ENLIVEN. [Extracted from the article]

Case: A 30-year-old pregnant woman with perivascular epithelioid cell tumor (PEComa) of the tarsal navicular underwent intralesional curettage with allograft at 30 weeks' gestation. She had an uncomplicated delivery at term and is ambulating without tumor recurrence at 1-year follow-up. Conclusion: PEComas are rare tumors most commonly found in soft tissues but have been reported in bone and are occasionally associated with pregnancy. To the best of our knowledge, this is the first reported case of pregnancy-associated PEComa of bone. [ABSTRACT FROM AUTHOR]

Background: Patients with a bone sarcoma who undergo limb-sparing surgery and reconstruction with a tumor prosthesis in the lower extremity have been shown to have reduced self-reported physical function and quality of life (QoL). To provide patients facing these operations with better expectations of future physical function and to better evaluate and improve upon postoperative interventions, data from objectively measured physical function have been suggested.Questions/purposes: We sought to explore different aspects of physical function, using the International Classification of Functioning, Disability, and Health (ICF) as a framework, by asking: (1) What are the differences between patients 2 to 12 years after a bone resection and reconstruction surgery of the hip and knee following resection of a bone sarcoma or giant cell tumor of bone and age-matched controls without walking limitations in ICF body functions (ROM, muscle strength, pain), ICF activity and participation (walking, getting up from a chair, daily tasks), and QoL? (2) Within the patient group, do ICF body functions and ICF activity and participation outcome scores correlate with QoL?Methods: Between 2006 and 2016, we treated 72 patients for bone sarcoma or giant cell tumor of bone resulting in bone resection and reconstruction with a tumor prosthesis of the hip or knee. At the timepoint for inclusion, 47 patients were alive. Of those, 6% (3 of 47) had undergone amputation in the lower limb and were excluded. A further 32% (14 of 44) were excluded because of being younger than 18 years of age, pregnant, having long transportation, palliative care, or declining participation, leaving 68% (30 of 44) for analysis. Thus, 30 patients and 30 controls with a mean age of 51 ± 18 years and 52 ± 17 years, respectively, were included in this cross-sectional study. Included patients had been treated with either a proximal femoral (40% [12 of 30]), distal femoral (47% [14 of 30]), or proximal tibia (13% [4 of 30]) reconstruction. The patients were assessed 2 to 12 years (mean 7 ± 3 years) after the resection-reconstruction. The controls were matched on gender and age (± 4 years) and included if they considered their walking capacity to be normal and had no pain in the lower extremity. Included outcome measures were: passive ROM of hip flexion, extension, and abduction and knee flexion and extension; isometric muscle strength of knee flexion, knee extension and hip abduction using a hand-held dynamometer; pain intensity (numeric rating scale; NRS) and distribution (pain drawing); the 6-minute walk test (6MWT); the 30-second chair-stand test (CST); the Toronto Extremity Salvage Score (TESS), and the European Organisation for Research and Treatment of Cancer Quality of Life Questionnaire (EORTC QLQ-C30). The TESS and the EORTC QLQ-C30 were normalized to 0 to 100 points. Higher scoring represents better status for TESS and EORTC global health and physical functioning scales. Minimum clinically important difference for muscle strength is 20% to 25%, NRS 2 points, 6MWT 14 to 31 meters, CST 2 repetitions, TESS 12 to 15 points, and EORTC QLQ-C30 5 to 20 points.Results: Compared with controls, the patients had less knee extension and hip abduction strength in both the surgical and nonsurgical limbs and regardless of reconstruction site. Mean knee extension strength in patients versus controls were: surgical limb 0.9 ± 0.5 Nm/kg versus 2.1 ± 0.6 Nm/kg (mean difference -1.3 Nm/kg [95% CI -1.5 to -1.0]; p < 0.001) and nonsurgical limb 1.7 ± 0.6 Nm/kg versus 2.2 ± 0.6 Nm/kg (mean difference -0.5 Nm/kg [95% CI -0.8 to -0.2]; p = 0.003). Mean hip abduction strength in patients versus controls were: surgical limb 1.1 ± 0.4 Nm/kg versus 1.9 ± 0.5 Nm/kg (mean difference -0.7 Nm/kg [95% CI -1.0 to -0.5]; p < 0.001) and nonsurgical limb 1.5 ± 0.4 Nm/kg versus 1.9 ± 0.5 Nm/kg (-0.4 Nm/kg [95% CI -0.6 to -0.2]; p = 0.001). Mean hip flexion ROM in patients with proximal femoral reconstructions was 113° ± 18° compared with controls 130° ± 11° (mean difference -17°; p = 0.006). Mean knee flexion ROM in patients with distal femoral reconstructions was 113° ± 29° compared with patients in the control group 146° ± 9° (mean difference -34°; p = 0.002). Eighty-seven percent (26 of 30) of the patients reported pain, predominantly in the knee, anterior thigh, and gluteal area. The patients showed poorer walking and chair-stand capacity and had lower TESS scores than patients in the control group. Mean 6MWT was 499 ± 100 meters versus 607 ± 68 meters (mean difference -108 meters; p < 0.001), mean CST was 12 ± 5 repetitions versus 18 ± 5 repetitions (mean difference -7 repetitions; p < 0.001), and median (interquartile range) TESS score was 78 (21) points versus 100 (10) points (p < 0.001) in patients and controls, respectively. Higher pain scores correlated to lower physical functioning of the EORTC QLQ-C30 (Rho -0.40 to -0.54; all p values < 0.05). Less muscle strength in knee extension, knee flexion, and hip abduction correlated to lower physical functioning of the EORTC QLQ-C30 (Rho 0.40 to 0.51; all p values < 0.05).Conclusion: This patient group demonstrated clinically important muscle weaknesses not only in resected muscles but also in the contralateral limb. Many patients reported pain, and they showed reductions in walking and chair-stand capacity comparable to elderly people. The results are relevant for information before surgery, and assessments of objective physical function are advisable in postoperative monitoring. Prospective studies evaluating the course of physical function and which include assessments of objectively measured physical function are warranted. Studies following this patient group with repetitive measures over about 5 years could provide information about the course of physical function, enable comparisons with population norms, and lead to better-designed, targeted, and timely postoperative interventions.Level Of Evidence: Level III, therapeutic study. [ABSTRACT FROM AUTHOR]

Background: Ten years ago, we reported the results of a procedure in which we translocated the ipsilateral ulna as a vascularized autograft to reconstruct defects of the distal radius after tumor resection, with excellent functional results. At that time, wrist arthrodesis was achieved by aligning the translocated ulna with the scapholunate area of the carpus and usually the third metacarpal. This resulted in wrist narrowing. We then wondered if aligning the translocated ulna with the scaphoid and the second metacarpal would result in ulnar deviation and thereby improve grip strength. We believed lateralization would reduce the wrist narrowing that occurs with fusion to the third metacarpal and would make the cosmesis more acceptable. We also modified the incision to dororadial to make the scar less visible and thus improve the cosmesis.Questions/purposes: (1) Is there an objective improvement in grip strength and functional scores (Musculoskeletal Tumor Society [MSTS] and Mayo wrist) when the translocated ulna is lateralized and the wrist is fused with the translocated ulna and aligned with the second metacarpal versus when the translocated ulna is aligned with the third metacarpal? (2) Did lateralization caused by the wrist fusion aligned with the second metacarpal minimize wrist narrowing as measured by the circumference compared with the fusion aligned with the third metacarpal?Methods: From 2010 and 2018, we treated 40 patients with distal radius tumors at our institution, 30 of whom had a distal radius enbloc resection. Twenty-eight patients had an ipsilateral ulna translocation and wrist arthrodesis in which the radius and translocated ulna were aligned with either the second (n = 15) or the third (n = 13) metacarpals. Two patients in the second metacarpal group and three patients in the third metacarpal group were lost to follow-up before 24 months after surgery and were excluded. A retrospective analysis of 23 patients (20 with giant cell tumors and three with malignant bone tumors) included a review of radiographs and institutional tumor database for surgical and follow-up records to study oncologic (local disease recurrence), reconstruction (union of osteotomy junctions, implant breakage or graft fracture, and wrist circumference), and functional outcomes (MSTS and Mayo wrist scores and objective grip strength assessment compared with the contralateral side). The results were compared for each study group (second metacarpal versus third metacarpal). There was no difference in the incidence of local recurrence or the time to union between the two groups. There were no implant breakages or graft fractures noted in either group.Results: Patients in the second metacarpal group lost less grip strength compared with the unoperated side in the third metacarpal group (median 12% [range -30% to 35%] versus median 28% [15% to 42%], difference of medians 16%; p = 0.006). There were no between-group differences in terms of MSTS (median 30 [24 to 30] versus median 26.5 [22 to 30], difference of medians 3.5; p = 0.21) or Mayo wrist scores (median 83 [65 to 100] versus median 72 [50 to 90], difference of medians 11; p = 0.10). The second metacarpal group also had less wrist narrowing as seen from the median difference in circumference between the operated and unoperated wrists (median narrowing 10 mm [3 to 35 mm] in the second metacarpal group versus median 30 mm [15 to 35 mm] in the third metacarpal group, difference of medians 20 mm; p = 0.04).Conclusion: Wrist arthrodesis after ulna translocation with alignment of the translocated ulna and the second metacarpal provides a functional position with ulnar deviation that offers some improvement in grip strength but no improvement in the MSTS or Mayo scores. Radialization/lateralization of the translocated ulna achieved from the alignment with the second metacarpal decreases the reduction in the wrist circumference and therefore reduces wrist narrowing.Level Of Evidence: Level III, therapeutic study. [ABSTRACT FROM AUTHOR]

Background: There is a lack of evidence regarding long-term outcomes of rotating-hinge knee prostheses with distal femoral replacement in a large oncologic patient series. In this study, we investigated the proportion of patients experiencing complications requiring surgery in the long term, as well as the cumulative incidence of implant removal/revision and amputation at 5, 10, 15, and 20 years through competing risk analyses.Methods: We retrospectively studied 214 patients treated with a Finn/Orthopaedic Salvage System (OSS) knee prosthesis (Zimmer Biomet) after distal femoral resection from 1991 to 2017. The study end points were postoperative complications requiring surgery. Reoperations were classified as major when there was (1) removal of the metal-body femoral component, the tibial component, or the bone-implant fixation; (2) major revision (exchange of the metal-body femoral component, the tibial component, or the bone-implant fixation); or (3) amputation. Minor reoperations were defined as all other reoperations. Competing risk analysis was used to estimate the cumulative incidence of implant removal/revision or amputation.Results: There were 312 reoperations in 113 patients (98 major reoperations in 68 patients and 214 minor reoperations). Seventeen patients (8%) required ≥5 additional operations, and 21 patients (10%) required >1 major reoperation. Although the number of reoperations decreased over time, major and minor reoperations continuously accrued after 10 years. The cumulative incidences of implant removal or revision for any reason at 5, 10, 15, and 20 years were 22.6%, 30.1%, 34.3%, and 42.5%, respectively. Although most implant removals/revisions occurred in the first 10 years, the risk persisted after 10 years, at a mean of 1.24%/year, mainly due to deep infection (1.06%/year).Conclusions: The long-term outcomes of treatment with a Finn/OSS distal femoral rotating-hinge knee prosthesis showed it to be a durable reconstruction technique. The rate of implant removal/revisions after 10 years was gradual (1.24%/year). Deep infection remains a major late-failure mechanism, and lifetime surveillance for prosthetic problems is needed.Level Of Evidence: Therapeutic Level IV. See Instructions for Authors for a complete description of levels of evidence. [ABSTRACT FROM AUTHOR]

Case: A 15-year-old boy with chondroblastoma of the right hemipelvis presented with significant periacetabular bone destruction. Neoadjuvant denosumab treatment facilitated initial joint preserving surgery. Unfortunately, he experienced 2 local recurrences and underwent wide surgical resection 2 years after his initial diagnosis. Conclusion: Inhibition of the receptor activator of NF-kB (RANK)/RANK ligand (RANK-L) pathway with denosumab has been used neoadjuvantly for the treatment of giant cell tumor of bone, but its role in the treatment of chondroblastoma is less understood. This patient's clinical response and effect on cellular RANK/RANK-L activity support the consideration of denosumab in the treatment algorithm for other osteolytic bone tumors such as chondroblastoma. [ABSTRACT FROM AUTHOR]

Case: A 17-year-old boy presented to the clinic complaining of right hip pain after soccer participation. Clinical findings and imaging studies led to the diagnoses of femoroacetabular impingement and diffuse tenosynovial giant cell tumor (TGCT). Comprehensive arthroscopic management and biopsy revealed a diagnosis of osteosarcoma. The patient subsequently underwent chemotherapy, surgical resection, and reconstruction. Conclusion: Osteosarcoma of the proximal femur may mimic TGCT on imaging studies because osteosarcoma may show changes suggestive of inflammation. We recommend heightened clinical awareness and a comprehensive differential workup in the management of presumed TGCT about the hip in the pediatric patient population. [ABSTRACT FROM AUTHOR]

Cases: We used the modified Stoppa approach in a 17-year-old man with a retained bullet in his acetabular fossa. The acetabular hole was used to irrigate the hip joint. We also used this approach in a 29-year-old woman with right hip pain and limping to remove an isolated tenosynovial giant cell tumor ("localized pigmented villonodular synovitis") in the acetabular fossa expanding through the acetabulum. Discussion: We believe that this approach should become more familiar because it offers a simple alternative for treating acetabular pathologies mainly involving the acetabular fossa, sparing patients the hazards of capsulotomy, trochanteric osteotomy, dislocation, and traction and fluid pressure in hip arthroscopy. [ABSTRACT FROM AUTHOR]

Case: A 64-year-old man with a history of giant cell tumor of bone (GCTB) in the fibula 7 years earlier developed a recurrence with histologic features of osteosarcoma. Both the primary GCTB and the secondary osteosarcoma were found to have the H3F3A gene mutation. Despite immediate above-the-knee amputation, the patient died of respiratory failure because of lung metastases 3 months later. Conclusion: This is the first report of proven H3F3A mutation in both the primary GCTB and the secondary osteosarcoma in the same case. Clinicians should consider secondary malignancy in patients presenting with a lesion at the site of a previously treated GCTB after a long interval. [ABSTRACT FROM AUTHOR]

Study Design: This was a subanalysis of an international, multicenter, open-label study.Objective: The aim of this study was to assess the efficacy and safety of denosumab in a subset of patients with giant cell tumors of bone (GCTB) of the spine including the sacrum from an international, open-label, single-arm, phase 2 study (ClinicalTrials.gov: NCT00680992).Summary Of Background Data: Standard GCTB treatment is surgical removal, either by curettage or resection, combined with intraoperative adjuvant therapy; however, some sites may not be amenable to resection (e.g., skull, spine).Methods: Adults or skeletally mature adolescents with pathologically confirmed GCTB of the spine including the sacrum, and radiologically measurable evidence of active disease, were included. Patients received denosumab (120 mg subcutaneously) once every 4 weeks during the treatment phase, with loading doses on days 8 and 15 of the first cycle. Patients had surgically unsalvageable GCTB (Cohort 1), had planned surgery expected to result in severe morbidity (Cohort 2), or were enrolled from a previous GCTB study (Cohort 3).Results: Overall, 132 patients were included in the safety analysis (103 in Cohort 1, 24 in Cohort 2, and five in Cohort 3); 131 patients were included in the efficacy analysis. Kaplan-Meier estimated probabilities of disease progression or recurrence were 3% (95% confidence interval [CI], 0.0-6.2) at year 1 and 7.4% (95% CI, 2.1-12.7) at years 3 and 5 in Cohort 1, and not estimable in Cohorts 2 and 3. Of 23 patients (Cohort 2) with surgery planned at baseline, 10 (43%) had on-study surgery; of these, one patient had reported disease progression or recurrence after the on-study surgery. Clinical benefit was reported in 83% of patients overall (all cohorts).Conclusion: Results from the analysis suggest that denosumab is potentially effective treatment for patients with GCTB of the spine including the sacrum. The adverse event profile was consistent with the full study population.Level of Evidence: 2. [ABSTRACT FROM AUTHOR]

Background Denosumab is an inhibitor of monoclonal receptor activator of nuclear factor-ĸB ligand, approved to treat giant cell tumors of bone (GCTB). It is commonly used for unresectable tumors and for downstaging the tumor to perform less-morbid procedures. Although denosumab has been used extensively for GCTBs, there are no recommendations regarding the duration of therapy. The risk factors associated with local recurrence (LR) in patients receiving preoperative denosumab for GCTB also are unknown. Questions/purposes (1) Is short-course (three doses or fewer) preoperative denosumab treatment as effective as longer course (more than three doses) of treatment in terms of achieving a clinical, radiologic, and histologic response in patients with GCTB? (2) Is there an increased risk of LR after short-course denosumab therapy compared with long-course denosumab therapy; and after controlling for confounding variables, what factors were associated with LR after surgery for GCTB in patients receiving preoperative denosumab? Methods A retrospective study was performed using an institutional database of 161 skeletally mature patients with a histologic diagnosis of GCTB who received denosumab between November 2010 and July 2019 to downstage the tumor before surgery. In general, we used denosumab when we thought it would facilitate either resection or curettage (by formation of a sclerotic rim around the osteolytic lesion), when a less-morbid procedure than initially planned might be performed, and in patients with complex presentations like cortical breech and soft tissue extension, pathological fracture, thinning of more than three cortices of the extremity. From 2010 to late 2015, denosumab was administered for approximately 4 to 6 months; starting in late 2015 through 2020, the number of denosumab doses has been reduced. We divided patients into two groups: Those who received three or fewer doses of denosumab (short-course, n = 98) and those who received more than three doses of denosumab (long-course, n = 63). Comparing those in the long-course group with those in the short-course group whose procedures were performed at least 2 years ago, there were no differences in loss to follow-up before 2 years (3% [3 of 98] versus. 3% [2 of 63]). The mean patient age was 30 years (± 6.1) and the mean number of denosumab doses was 4.4 (range 1 to 14). Overall, 77% (37 of 48) of patients taking short-course denosumab and 75% (27 of 36) of patients on long-course denosumab underwent curettage, and the remaining patients with an inadequate bony shell around the tumor or destruction of articular cartilage in both groups underwent tumor resection. With the numbers available, the patients with short- and long-course denosumab were not different in terms of age, sex, MSTS score on presentation, lesion size, lesion location, Campanacci grade, presence of pathological fracture and pulmonary metastasis on presentation, and the type of surgery performed (curettage versus resection). We analyzed the change in the Musculoskeletal Tumor Society score, change in Campanacci grade, radiologic objective tumor response (defined as a partial or complete response, per the modified inverse Choi criteria), and histologic response (defined as reduction of more than 90% of osteoclast-like giant cells or a reduction of more than 50% of mesenchymal spindle-like stromal cells, along with evidence of lamellar or woven bone formation, when compared with the biopsy sample) between the two groups (short- and long-course denosumab). LR rates were compared between the two groups, and after controlling for confounding variables, factors associated with LR in all operated patients were analyzed with a Cox proportional hazards regression analysis. Results With the numbers available, there was no difference between the short- and long-course denosumab groups in terms of mean percentage improvement in MSTS score (20 [± 18.5] versus 24 [± 12.6]; p = 0.37), radiologic objective tumor response (90% [43 of 48] versus 81% [29 of 36]; p = 0.24) and histologic response (79% [38 of 48] versus 83% [30 of 36]; p = 0.81). With the numbers available, there was no difference between the short- and long-course denosumab groups in terms of Kaplan-Meier survivorship free from LR at 5 years after surgery (73% [95% confidence interval, 68 to 76] versus 64% [95% CI 59 to 68]; log-rank p = 0.50). After controlling for potential confounding variables like age, sex, Campanacci grade and MSTS score on presentation, number of denosumab doses administered before surgery, clinical, radiologic and histologic response to denosumab, and time duration between denosumab therapy and surgery, we found that tumors involving the bones of the hand and the foot (hazard ratio 7.4 [95% CI 2.0 to 27.3]; p = 0.009) and curettage (HR 6.4 [95% CI 2.8 to 23.0]; p = 0.037) were independently associated with a higher risk of LR. Conclusions In this preliminary, single-center study, we found that a short-course of preoperative denosumab (three or fewer doses) was associated with no differences in clinical scores, histological and radiological response, or LR-free survivorship, compared with longer-course of denosumab (more than three doses). Fewer preoperative doses can reduce the complications and costs associated with more-prolonged therapy. Denosumab must be used cautiously before curettage for GCTB, and only if the benefit of joint salvage outweighs the possibility of LR. However, given the small number of patients, potentially clinically important differences might have been missed, and so our findings need to be confirmed by larger, multicenter, prospective trials. [ABSTRACT FROM AUTHOR]

Background En bloc resection of benign tumors is only indicated in aggressive lesions with substantial destruction of the affected bone. Few reports have evaluated the long-term outcome of Grade 3 giant cell tumor of bone (GCTB; defined as severe bone destruction and soft tissue extension) treated with en bloc resection and reconstruction with a massive allograft. We recently reported that patients with benign tumors achieved better allograft reconstruction survivorship compared with those treated for a malignant bone tumor. In light of that finding, we wondered whether osteoarticular allografts would be a viable long-term alternative for Grade 3 GCTB, which could be important in some countries because of greater availability and lower costs compared with endoprostheses. Questions/purposes We analyzed a group of patients with Grade 3 GCTBs treated with en bloc resection and osteoarticular allograft reconstruction in terms of (1) survivorship free from allograft removal at 10 years; (2) survivorship free from reoperation for any reason at 10 years, (3) functional results as measured by the Musculoskeletal Tumor Society (MSTS) score, (4) assessment of arthrosis at the knee. Methods We retrospectively analyzed all patients with a Grade 3 GCTB treated between 1980 and 2007. Only patients treated with en bloc resection and reconstruction with massive osteoarticular allografts were included in the analysis. The indication for osteoarticular reconstruction during that time included severe bone destruction with intraarticular compromise of the tumor, intraarticular fracture because of tumor growth, the presence of inadequate remaining subchondral bone to resist normal loading (for the distal femur or proximal tibia), and the preservation of a soft-tissue component (ligaments or meniscus) for articular stability. During the period, 75 patients were treated with en bloc resection. Patients treated with intralesional curettage (n = 7), reconstruction with an endoprosthesis (n = 2), intercalary arthrodesis (n = 13), or unicondylar reconstruction (n = 14) were excluded. Of the original 75 treated with en bloc resection, 52% (39) were treated with osteoarticular allograft reconstruction, and no patient was lost to follow-up before 2 years or had substantial missing data. However, of the 39 patients, another 21% (8) have not been seen in the last 5 years, but these were included here because they reached the 10-year minimum surveillance period before being lost. Twenty-three of those 39 patients were previously reported by our group and 16 new patients (treated between 1980-1985) were included in this series (eight distal radius, six distal femur, two proximal tibias), extending the follow-up period and including more patients for analysis. The median (range) follow-up duration was 26 years (10 to 34). We assessed survivorship using a Kaplan-Meier analysis, we drew MSTS scores retrospectively from patients´ medical records, and we graded arthrosis using the Ahlbäck scale for the knee (which was by far the most common joint involved, n = 31, and so it was the joint we assessed for the presence of arthrosis). Results The survivorship free from allograft removal was 85% at 10 years (95% CI 74 to 96). The allograft survivorship free from reoperation for any reason at 10 years was 72% (95% CI 59 to 87). The median (range) MSTS score was 28 points (19 to 30). The grade of arthrosis in the knee at last follow-up was analyzed in 20 patients and classified in nine as Ahlbäck Type 4, in six as Type 3, in three as Type 2 and in two as Type 5. Conclusions Osteoarticular allograft reconstruction after a Grade 3 GCTB en bloc resection showed excellent long-term survivorship. We believe these results compare favorably with other studies on endoprosthetic reconstruction and head-to-head studies of these approaches should be performed; these would need to be multicenter trials. In the meantime, in locations where endoprostheses are unavailable or too expensive, we believe our results support the use of osteoarticular allografts. [ABSTRACT FROM AUTHOR]

Case: A 32-year-old pregnant woman presented with new wrist pain after a fall. She had undergone surgical repair to the same wrist 6 years previously for a distal radius fracture. At that time, there was no evidence of a bone lesion. Current radiographs revealed a radiolucent lesion in the metaepiphyseal region. Intraoperative frozen section confirmed a giant cell tumor (GCT). Definitive management consisted of intralesional curettage, burring, and cementation of the distal radius with reapplication of distal radius plate. Conclusion: Currently, there is no known link between GCT and fracture or pregnancy. [ABSTRACT FROM AUTHOR]

Background: Denosumab, a monoclonal antibody that binds to receptor activation of nuclear factor-kappa ß ligand (RANKL), has been used as a drug to treat aggressive giant cell tumors of bone. It is unclear whether preoperative denosumab therapy is associated with the local recurrence risk in patients with giant cell tumors of bone treated with curettage. Early evidence suggests that denosumab treatment is associated with a reduction in local recurrence, but other studies have questioned that premise. Curettage after a short course of denosumab (3 to 4 months) has been recommended, especially for large, aggressive giant cell tumors in which complete curettage is difficult to achieve. No randomized studies have documented the benefit of this approach, and some investigators have reported higher local recurrence after denosumab treatment. Due to this confusion, we performed a systematic analysis of existing reports to attempt to answer this question and determine whether the appropriate preoperative denosumab therapy duration could be established.Questions/purposes: (1) Is the use of preoperative denosumab associated with local recurrence risk in patients with giant cell tumors of bone treated with curettage compared with those treated with curettage alone? (2) Is the preoperative denosumab therapy duration associated with local recurrence after curettage?Methods: We searched the PubMed, EMBASE, and CENTRAL databases on April 26, 2019 and included both randomized and non-randomized studies that compared local recurrence between patients who had giant cell tumors of bone and were treated with curettage after preoperative denosumab and patients treated with curettage alone. Two authors independently screened the studies. There were no randomized studies dealing with denosumab in giant cell tumors of bone, and generally, denosumab was used for more aggressive tumors. We assessed the quality of the included studies using the Risk of Bias Assessment tool for Non-randomized Studies, with a moderate overall risk of bias. We registered our protocol in PROSPERO (registration number CRD42019133288). We selected seven eligible studies involving 619 patients for the final analysis.Results: The proportion of patients with local recurrence ranged from 20% to 100% in the curettage with preoperative denosumab group and ranged from 0% to 50% in the curettage-alone group. The odds ratio of local recurrence ranged from 1.07 to 37.80 in no more than 6 months of preoperative denosumab duration group and ranged from 0.60 to 28.33 in more than 6 months of preoperative denosumab duration group.Conclusions: The available evidence for the benefit of denosumab in more aggressive giant cell tumors is inconclusive, and denosumab treatment may even be associated with an increase in the proportion of patients experiencing local recurrence. Because there are no randomized studies and the existing studies are of poor quality due to indication bias (the most aggressive Campanacci 3 lesions or those where even a resection would be difficult and result in morbidity are generally the patients who are treated with denosumab), the evidence to suggest a disadvantage is weak. Denosumab treatment should be viewed with caution until more definitive, randomized studies documenting a benefit (or not) have been conducted. Furthermore, we could not find evidence to suggest an appropriate length of preoperative denosumab before curettage. [ABSTRACT FROM AUTHOR]

Case: An otherwise healthy 13-year-old girl presented with a firm nodule on the plantar right forefoot that was tender after cheerleading. Initial workup was unremarkable, but magnetic resonance imaging revealed a multilobulated mass surrounding the flexor hallucis longus tendon. Surgical resection revealed a tenosynovial mass without tendon infiltration. Pathologic examination was consistent with tenosynovial giant cell tumor. The patient resumed cheerleading and remained asymptomatic after 1 year. Conclusion: As far as we know, this is the first report of a tenosynovial giant cell tumor of the flexor hallucis longus in a pediatric patient; it illustrates the importance of considering this lesion when diagnosing a pediatric plantar mass. [ABSTRACT FROM AUTHOR]

Background: Massive bone allografts have been used for limb salvage in patients undergoing bone tumor resections as an alternative to endoprostheses. Although several studies on massive allograft reconstructions for bone tumors reported that most complications occur in the first 3 years after surgery, there are no long-term reports on complications to substantiate this contention. We believe such information is important so that surgeons and patients can make more informed decisions when choosing a reconstructive method after tumor resection.Questions/purposes: (1) What is the survival of allografts free from removal, amputation, or joint replacement in patients treated for bone tumors in the lower limb with a minimum of 10 years of followup? (2) What complications occur after 10 or more years of followup? (3) Are there factors associated with allograft survival, such as age, sex, the affected bone, reconstruction type (intercalary or osteoarticular allograft), tumor type (malignant or benign), failure type, and chemotherapy use?Methods: We retrospectively analyzed the records of 398 patients treated in one center with benign or malignant bone tumors in the femur or tibia between 1986 and 2007. During the period in question, our general indications for using allografts (354 patients) included patients with benign or low-grade sarcomas and patients with high-grade sarcomas with clinical and imaging response to neoadjuvant chemotherapy. Other approaches such as endoprostheses (44 patients) were indicated if the patient received radiotherapy, in patients with high-grade sarcomas without clinical and imaging response to neoadjuvant chemotherapy, or with neurovascular tumor involvement. We excluded from the analysis 53 patients treated with allograft-prosthetic composites, 46 with hemicondylar osteoarticular allografts, and 57 with intercalary hemicylindrical allografts. The study was thus performed in 198 patients treated with segmental massive allografts in the long bones of the lower extremity (132 femurs and 66 tibias) after resection of a primary bone tumor, including 120 patients treated with osteoarticular and 78 with segmental intercalary allografts. A total of 32 (16%) of the 198 patients died before 10 years, and graft status was known in all of those patients; these patients were included (mean followup, 192 months; range, 1-370 months). All remaining 166 patients who were not known to have died before 10 years were accounted for at least 10 years after the allograft procedure (mean, 222 months; range, 120-370 months). No patient was lost to followup. The mean age was 22 years (range, 2-55 years); 105 patients were male (53%) and 93 were female. The predominant diagnoses were osteosarcoma (n = 125, 63%), giant cell tumor of bone (n = 27, 14%), and Ewing's sarcoma (n = 19, 10%). In all, 146 patients (74%) underwent chemotherapy. Selected variables were analyzed using multivariate logistic regression analyses to identify risk factors of allograft removal, joint replacement, or amputation. We performed competitive risk analysis with allograft removal, joint replacement, or amputation as the endpoint at 5, 10, and 20 years. Patient function was evaluated using the Musculoskeletal Tumor Society (MSTS)-93 scoring system.Results: The risk of allograft removal, joint replacement, or amputation was 36% at 5 years (95% CI, 30-43), 40% at 10 years (95% CI, 33-47), and 44% at 20 years (95% CI, 37-51). Fractures occurred in 15% (29 patients), infection in 14% (27 patients), nonunion in 12% (23 patients) and tumor recurrence in 7% (13 patients). Thirty-two patients died of disease before 10 years; nine of these patients had a second surgery before death, eight had an amputation, and one underwent graft removal. Of the 166 patients who were still alive 10 years after the allograft procedure, 36 underwent allograft removal, six patients underwent joint replacement, and four had an amputation; however, after 10 years, six more allografts were removed (four due to fractures, one due to infection, and one due to instability), and another patient was amputated due to a second malignancy. After controlling for potentially confounding variables including death, we found that the risk of allograft removal, joint replacement, or amputation in osteoarticular tibial grafts (58% [95% CI, 43-73] at 5, 10, and 20 years) was higher than that of osteoarticular femur allografts (29% [95% CI, 18-39] at 5 years, 30% [95% CI, 19-40] at 10 years, 37% [95% CI, 25-48] at 20 years; p = 0.010) and tibia intercalary allografts (26% [95% CI, 7-45] at 5, 10 and 20 years; p = 0.020). Fractures occurred more frequently in the femur (18% [95% CI, 11-25]) than in the tibia (5% [95% CI, 0-10]; p < 0.010), and infections occurred more frequently in the tibia (24% [95% CI, 14-35]) than in the femur (4% [95% CI, 0-8]; p < 0.001). With the number of patients we had, we found no difference in the proportion of local recurrence in the tibia (12% [95% CI, 4-20]) compared with the femur (5% [95% CI, 1-9]; p < 0.053).Conclusions: Infections were the most common complications associated with allograft removal in the first 2 to 3 years after reconstruction and were more frequently associated with tibial allograft removal. Fractures were more commonly associated with graft removal with longer term followup and were more frequently associated with femoral allograft removal. Although we cannot directly compare our results with other types of reconstructions, we believe that allografts still have a role in the reconstruction of patients with a benign or low-grade bone tumor. Future studies in femoral allograft with longer followup should be performed to analyze factors that may explain why some grafts fail, such as the percent of the length of the bone resected, type and number of plates and screws used and type of fixation (rods versus plates). There was a higher incidence of graft removal in patients with proximal tibia osteoarticular allografts, which has led us to use this type of reconstruction only in pediatric patients over the last 15 years.Level Of Evidence: Level III, therapeutic study. [ABSTRACT FROM AUTHOR]

Case: We present a 37-year-old man with uniarticular, multifocal, localized tenosynovial giant cell tumor (TSGCT) of the knee. He was treated with arthroscopic partial synovectomy of each tumor foci alone without the use of any adjuvants. At a 2-year follow-up, he had painless, full function of the knee with no signs of disease recurrence. Conclusion: There have been several reports of multiple joints or multiple compartments in and around a joint involved with TSGCT in the same patient, but this is the first case reported to our knowledge of multiple discrete foci within the same joint. [ABSTRACT FROM AUTHOR]

Case: A 35-year-old man with a giant cell tumor involving the lateral condyle and trochlea of the right distal femur underwent curettage of the lesion and cement grafting, which resulted in symptomatic patellofemoral osteoarthritis after more than 4 years. A standard follow-up excluded recurrence, whereas infection was ruled out while investigating the symptoms. Finally, a patellofemoral resurfacing prosthesis was implanted while filling the bone defects with tantalum cones. Conclusion: A “tailored” surgical technique with a selected patellofemoral joint arthroplasty could be used in oncologic setting to save further bone stock for possible revisions while permitting full and quick clinical recovery. [ABSTRACT FROM AUTHOR]

Background: The key to intralesional surgical treatment of giant cell tumor of bone (GCTB) is extended curettage. As GCTBis locally aggressive with a high propensity for local recurrence, a primary factor of surgical treatment is the ability to achieve local tumor clearance. GCTB commonly affects the epimetaphyseal region of the bone, which may compromise the integrity of the articular surface. With the exception of expendable bone that may be considered for resection without the challenge of reconstruction (e.g., the proximal aspect of the fibula or the distal aspect of the ulna), a large majority of cases of GCTB can be treated with joint-preserving techniques. In the present article, we share a video demonstration including the surgeon view of intralesional surgery for GCTB, with emphasis on the 360° visualization of the tumor cavity, dilemmas regarding use of adjuvants for extended curettage, and options in cavity reconstruction. Description: The surgical procedure involves 4 essential components. (1) Surgical exposure and isolation of the soft tissues. The technique begins with a complete exposure that allows visualization of the entire tumor cavity. The initial part of the exposure involves getting to the bone and to the soft-tissue mass outside the bone, when present. The muscles are separated from the bone and retracted away from the soft-tissue component of the tumor. Soft tissue is adequately retracted to allow complete visualization of the tumor cavity. The tissues around the cavity are protected by placing hydrogen peroxide-soaked mops around the tumor cavity. The aim is to isolate the bone opening and avoid any contamination of soft tissue by the tumor, as hydrogen peroxide kills GCTB cells on contact1. The soft-tissue mass of the tumor is removed en bloc with a cover of normal tissue in order to prevent spillage into uninvolved tissues. Ward and Li advise the use of cautery for this part of the exposure in order to minimize contamination because high-temperature cautery kills the tumor². The initial opening into the osseous tumor cavity is made smaller in order to control the tumor spillage, and then enlarged in order to gain complete visualization. [ABSTRACT FROM AUTHOR]

Background: There are many treatment modalities for benign cystic lesions of bone, but all methods, except for total resection, are plagued with varying rates of recurrence1. Thorough curettage with the use of a high-speed burr, however, has demonstrated a low recurrence rate of 12% and has been suggested to be the best method for the treatment of benign cystic lesions. Approximately 90% of aneurysmal bone cysts can be controlled adequately with this treatment alone2. Description: Treatment of benign cystic lesions of bone with the use of excisional curettage requires careful preoperative planning and patient positioning before the initial incision is made. The initial incision must be carefully planned to expose the entire lesion without violating multiple compartments unnecessarily. A sizeable cortical window must then be made using a highspeed burr followed by evacuation of all cystic contents via curettage. The cavity is copiously irrigated before an adjuvant is used, and the lesion is stabilized, if necessary, before closing. Alternatives: There are many types of alternatives to curettage, such as wide resection, radiation, and embolization of feeding vessels. Rationale: In orthopaedics, as in all medical specialties, many interventions and techniques have been rendered obsolete and, ultimately, replaced by newer, safer, and more efficient ones. The appeal of curettage has remained because of its procedural simplicity and adaptability in the management of a plethora of diseases such as benign cystic lesions of bone. Additionally, curettage, unlike wide resection, radiation, and embolization of feeding vessels, is minimally invasive and often definitive in nature when used as a treatment modality2. Lastly, curettage grants the performing surgeon the ability to maintain a contained cavity that can be treated with a variety of adjuvant therapies3-17. These reasons listed above make curettage a viable option for the surgical treatment of benign cystic lesions such as giant cell tumors of bone, aneurysmal bone cysts, unicameral bone cysts, chondromyxoid fibromas, and symptomatic nonossifying fibromas. [ABSTRACT FROM AUTHOR]

Study Design: Experimental study.Objective: To examine the role of endothelin-1 (ET-1) and the Notch signaling pathway in giant cell tumor (GCT) of the spine.Summary Of Background Data: Previously published studies have shown that the Notch signaling pathway has a role in tumor invasion and that ET-1 is involved in tumor invasion and angiogenesis. However, the roles of both Notch signaling and ET-1 in GCT of the spine remain unknown.Methods: Expression of ET-1 in tissue samples from patients with spinal GCT, and adjacent normal tissue, were analyzed by immunohistochemistry and western blot. GCT stromal cells (GCTSCs) were isolated and ET-1 expression was demonstrated by immunofluorescence. Cell viability and cell migration of GCTSCs and human vascular endothelial cells following ET-1 treatment were assessed using the cell counting kit-8 assay and a transwell assay. Receptor activator of nuclear factor kappa-B ligand (RANKL) and osteoprotegerin (OPG) mRNA expression was determined following ET-1 treatment of GCTSCs using quantitative real-time polymerase chain reaction. In GCTSCs treated with ET-1 and the ET-1 signaling antagonist, BQ-123, levels of cyclin D1, vascular endothelial growth factor, matrix metalloproteinase-2 and -9 (MMP-2 and MMP-9), Jagged1, Hes1, Hey2, and Notch intracellular domain were examined by western blot.Results: Compared with normal adjacent tissue, ET-1 was highly expressed in GCT tissue. In GCTSCs studied in vitro, treatment with ET-1 significantly increased GCTSC and human vascular endothelial cells growth and migration and increased the expression of RANKL and OPG, meanwhile the ratio of RANKL/OPG was increased, in GCTSCs, it upregulated the production of cyclin D1, vascular endothelial growth factor, MMP-2, MMP-9, Jagged1, Hes1, Hey2, and Notch intracellular domain expression in a dose-dependent manner. Treatment with BQ-123 reversed these effects.Conclusion: In GCT of the spine, ET-1 showed increased expression. In cultured GCTSCs, ET-1 treatment activated the Notch signaling pathway.Level Of Evidence: 2. [ABSTRACT FROM AUTHOR]

Background: Localized-type tenosynovial giant cell tumor (TGCT) is a rare, neoplastic disease with only limited data supporting treatment protocols. We describe treatment protocols and evaluate their oncological outcome, complications, and functional results in a large multicenter cohort of patients. A secondary study aim was to identify factors associated with local recurrence after surgical treatment.Methods: Patients with histologically proven localized TGCT of a large joint were included if they had been treated between 1990 and 2017 in 1 of 31 tertiary sarcoma centers. Of 941 patients with localized TGCT, 62% were female. The median age at initial treatment was 39 years, and the median duration of follow-up was 34 months. Sixty-seven percent of the tumors affected the knee, and the primary treatment at the tertiary center was 1-stage open resection in 73% of the patients. Proposed factors for predicting a first local recurrence after treatment in the tertiary center were tested in a univariate analysis, and those that demonstrated significance were subsequently included in a multivariate analysis.Results: The localized TGCT recurred in 12% of all cases, with local-recurrence-free rates at 3, 5, and 10 years of 88%, 83%, and 79%, respectively. The strongest factor for predicting recurrent disease was a prior recurrence (p < 0.001). Surgical treatment decreased pain and swelling in 71% and 85% of the patients, respectively, and such treatment was associated with complications in 4% of the patients. Univariate and multivariate analyses of the patients who had not undergone therapy previously yielded positive associations between local recurrence and a tumor size of ≥5 cm versus <5 cm (hazard ratio [HR] = 2.50; 95% confidence interval [CI] = 1.32 to 4.74; p = 0.005). Arthroscopy (versus open surgery) was significantly associated with tumor recurrence in the univariate analysis (p = 0.04) but not in the multivariate analysis (p = 0.056).Conclusions: Factors associated with recurrence after resection of localized-type TGCT were larger tumor size and initial treatment with arthroscopy. Relatively low complication rates and good functional outcomes warrant an open approach with complete resection when possible to reduce recurrence rates in high-risk patients.Level Of Evidence: Therapeutic Level III. See Instructions for Authors for a complete description of levels of evidence. [ABSTRACT FROM AUTHOR]

Case: We describe a 33-year-old man who had a giant cell tumor in the ulnar head treated with wide resection and reconstructed using the modified Sauve-Kapandji procedure with an iliac crest bone graft as ulnar support. Conclusions: Due to the destructive nature of the tumor and the important role played by the ulnar head in the distal radioulnar joint (DRUJ), treatment of the giant cell tumor in the distal ulna is a challenge. The modified Sauve-Kapandji procedure is an effective technique to restore DRUJ function, which is performed as an ulnar support arthroplasty. Using an iliac crest bone graft as ulnar support in reconstruction surgery could be a practical method after the ulnar head has been resected. [ABSTRACT FROM AUTHOR]

Giant cell tumor (GCT) of the spine is a rare, benign tumor. Patients typically present with pain and also may experience neurologic deficits from spinal cord and/or nerve root compression. This article describes a patient who presented with acute mid-back pain, was diagnosed with spinal GCT through biopsy, and was treated successfully with surgical resection and instrumentation. [ABSTRACT FROM AUTHOR]

Background: Tenosynovial giant cell tumor (TGCT) is a rare, benign, monoarticular entity. Many case-series in adults are described, whereas TGCT is only incidentally reported in children. Therefore, its incidence rate and natural history in children are unknown.Questions/purposes: (1) How many cases have been reported of this condition, and what were their characteristics? (2) What is the standardized pediatric incidence rate for TGCT? (3) Is there a clinical difference in TGCT between children and adults? (4) What is the risk of recurrence after open resection in children compared with adults?Methods: Data were derived from three sources: (1) a systematic review on TGCT in children, seeking sources published between 1990 and 2016, included 17 heterogeneous, small case-series; (2) the nationwide TGCT incidence study: the Dutch pediatric incidence rate was extracted from this nationwide study by including patients younger than 18 years of age. This registry-based study, in which eligible patients with TGCT were clinically verified, calculated Dutch incidence rates for localized and diffuse-type TGCT in a 5-year timeframe. Standardized pediatric incidence rates were obtained by using the direct method; (3) from our nationwide bone and soft tissue tumor data registry, a clinical data set was derived. Fifty-seven children with histologically proven TGCT of large joints, diagnosed and treated between 1995 and 2015, in all four tertiary sarcoma centers in The Netherlands, were included. These clinically collected data were compared with a retrospective database of 423 adults with TGCT. Chi-square test and independent t-test were used to compare children and adults for TGCT type, sex, localization, symptoms before diagnosis, first treatment, recurrent disease, followup status, duration of symptoms, and time to followup. The Kaplan-Meier method was used to evaluate recurrence-free survival at 2.5 years.Results: TGCT is seldom reported because only 76 pediatric patients (39 female), 29 localized, 38 diffuse, and nine unknown type, were identified from our systematic review. The standardized pediatric TGCT incidence rate of large joints was 2.42 and 1.09 per million person-years in localized and diffuse types, respectively. From our clinical data set, symptoms both in children and adults were swelling, pain, and limited ROM with a median time before diagnosis of 12 months (range, 1-72 months). With the numbers available, we did not observe differences in presentation between children and adults in terms of sex, symptoms before diagnosis, first treatment, recurrent disease, followup status, or median time to followup. The 2.5-year recurrence-free TGCT survival rate after open resection was not different with the numbers available between children and adults: 85% (95% confidence interval [CI], 67%-100%) versus 89% (95% CI, 83%-96%) in localized, respectively (p = 0.527) and 53% (95% CI, 35%-79%) versus 56% (95% CI, 49%-64%) in diffuse type, respectively (p = 0.691).Conclusions: Although the incidence of pediatric TGCT is low, it should be considered in the differential diagnosis in children with chronic monoarticular joint effusions. Recurrent disease after surgical treatment of this orphan disease seems comparable between children and adults. With targeted therapies being developed, future research should define the most effective treatment strategies for this heterogeneous disease.Level Of Evidence: Level III, therapeutic study. [ABSTRACT FROM AUTHOR]

Background: Denosumab is a monoclonal RANKL antibody, which was originally introduced for the treatment of osteoporosis and bone metastases from solid tumors, but more recently has been used for treatment of giant cell tumor of bone (GCTB). In GCTB, denosumab has been used as a single agent in patients with inoperable tumors; it also has been used before surgery in some patients with the aim to downstage the tumor to facilitate a joint-preserving procedure (curettage) rather than a resection. However, few studies are available evaluating the benefits and risks of denosumab for the latter indication.Questions/purposes: (1) Does preoperative treatment with denosumab reduce the risk of local recurrence in patients treated for GCTB? (2) Are there adverse effects of short-term denosumab use before surgery and, if so, what are they?Methods: All patients with a diagnosis of GCTB surgically treated at our institution from June 2009 to June 2016 with curettage and cryotherapy were retrospectively evaluated to compare patients treated with curettage alone versus patients treated with curettage after preoperative therapy with denosumab. During that period, we treated 97 patients for GCTB; 30 patients were excluded because they received a resection; 34 patients were excluded because they received curettage without cryotherapy. Of the remaining 33 patients, four were excluded because they received denosumab only after surgery, one because she received zoledronic acid, one because she received a curettage after her refusal of a resection that was the advised procedure, two because they were lost to followup early, and four because they were treated for recurrence rather than a new diagnosis of GCTB. The remaining 21 patients were included. Twelve lesions had been treated with surgery after denosumab and nine with surgery alone. During the study period, we preferentially used denosumab for the more aggressive-looking lesions. After curettage, cryotherapy of the residual bone walls was performed with argon cryoprobes to -150° C after pouring gel into the cavity, and we then used cement (17 patients) or morcellized allograft (four patients). Tumors were Campanacci Grade 3 in eight of 12 patients in the denosumab group and in two of nine patients in the surgery-only group (p = 0.08), but the extent of epiphyseal juxtaarticular bone involvement was not different between the groups with the numbers available. Median followup was 39 months (range, 14-55 months) in the denosumab group and 27 months (range, 18-92 months) in the surgery-only group. We used chart review to record the proportion of patients in each treatment group who had a local recurrence and to tally adverse events.Results: With the numbers available, there was no difference in the proportion of patients experiencing a recurrence (five of 12 in the denosumab group and one of nine in the surgery-only group; p = 0.18). We found no adverse effects associated with denosumab either during or after treatment; specifically, we found no alterations in electrolyte levels, blood count, or liver and renal function parameters. In this small series, no patient has developed osteonecrosis of the jaw.Conclusions: In this small series, use of denosumab before surgery for GCTB appeared to allow the reforming of a bone peripheral rim around the tumor, perhaps facilitating curettage rather than osteoarticular resection in some patients. However, we did not observe a decrease in the risk of local recurrence with the use of denosumab, suggesting that it may not decrease the aggressiveness of the disease; according to our preliminary results, we cannot exclude that the rate of local recurrence could be even higher after curettage in denosumab-treated patients than in nontreated patients, and until or unless larger studies demonstrate such a reduction, primary intralesional surgery without denosumab seems more prudent when curettage is feasible at presentation. We did not observe any adverse effects with denosumab, but we caution readers that this study was underpowered to detect even relatively common complications and relatively large differences in the risk of local recurrence. Future studies should evaluate denosumab prospectively; given the relative rarity of this tumor, we suspect multicenter studies are needed to achieve this.Level Of Evidence: Level III, therapeutic study. [ABSTRACT FROM AUTHOR]

Background: Although giant cell tumors (GCTs) are benign, their aggressiveness and tendency to recur locally challenge the orthopaedic surgeon's ability to perform joint-preserving intralesional surgery with an acceptably low risk of local recurrence. Denosumab has emerged as a possible medical treatment of GCT because it seems to halt the progression of GCT, alleviate pain, and increase perilesional bone formation, but its exact role has been questioned, and specifically its efficacy and associated complications are not well characterized.Questions/purposes: (1) Does denosumab reduce the risk of recurrence after resection or intralesional surgery? (2) What are the complications associated with the use of denosumab?Methods: Fifty-four patients with 30 primary and 25 recurrent tumors between November 2013 and July 2016 were treated with denosumab after a confirmed histopathologic diagnosis of GCT. Another 17 patients in the same period were treated without denosumab. During the study period, we encouraged the use of denosumab in all patients except those who refused, could not afford it, or where it was contraindicated (eg, in pregnancy). In all patients undergoing intralesional surgery, we arbitrarily planned six doses before surgery. Variations in total doses before surgery were dependent on patient-related factors; in some, we gave less doses because patients expressed the inability to afford any more doses, whereas in some patients, extra doses were added when the patient wished to delay surgery as well as the because of surgeon judgment wherein in some patients, we stopped before six doses when we thought adequate bone had formed for intralesional curettage. The mean number of doses was 6.8 per patient (median, 6; range, 3-17) preoperatively. The minimum followup was 12 months (median, 27 months; range, 12-42 months). Every patient showed improvement clinically in terms of pain and halting of tumor progression within three to four doses. This was seen radiologically as a sharply defined soft tissue mass as well as hazy ossification within the tumor. For a case-matched comparison study, we identified controls as 34 patients undergoing curettage from the retrospective analysis of 68 patients curetted without denosumab between February 2010 and July 2016 matched to 25 denosumab-treated patients in terms of site, size, Campanacci grade, and recurrent versus primary status, and with a minimum 2 years followup for the control group. Fisher's exact test was used for statistical study. Patients undergoing resection were planned for surgery after three doses of denosumab to allow the tumor to solidify and potentially decrease tumor spillage at the time of surgery. The resections could not be case-matched for comparison owing to the smaller numbers.Results: We observed 14 recurrences out of the 37 curetted tumors (38%). In the case-matched analysis, 11 of 25 patients in the denosumab-treated curettage group had recurrences (44%) compared with seven of 34 (21%) in the nondenosumab-treated control group. The risk of denosumab-treated patients experiencing local recurrence as compared with the nondenosumab-treated patients was nonsignificant with a two-tailed p value of 0.085 (significance at p < 0.05) as derived from Fisher's exact test (odds ratio, 3.03; 95% confidence interval, 0.96-9.54). There was no recurrence in the resection group. Because we do not have a control group for resection, we are unable to comment on the importance of this finding. One major complication that we observed was a recurrence with malignant transformation in a patient with a proximal humeral GCT. We did not observe any other complications related to the denosumab therapy.Conclusions: Although we could not demonstrate a higher risk of local recurrence with preoperative denosumab for intralesional surgery in the dose and frequency we administered, we advise caution in its routine use for intralesional procedures because it may be important to curette up to margins on pretreatment imaging owing to the potential residual tumor within the denosumab-mediated thick bony shell, which may result in local recurrence. We believe that denosumab treatment before resection of a large tumor aids resection without tumor spillage, particularly where important structures like the neurovascular bundle are dissected away from the tumor margin, although we cannot confirm that it helps lower the incidence of recurrence. We are concerned regarding the malignancy-causing potential from our observation in one patient as well as reports of this by others and recommend judicious use of this drug in patients with GCT.Level Of Evidence: Level III, therapeutic study. [ABSTRACT FROM AUTHOR]

Study Design: A case report.Objective: The aim of this study was to highlight that rapid progression or recurrence of giant cell tumor of the bone (GCTB) can still occur with cessation of Denosumab in the management of unresectable GCTB even in cases with prior demonstration of excellent response to treatment and stable disease over a protracted length of surveillance despite dose reduction. The close proximity of unresectable GCTB to vital structures makes it prudent that we monitor these patients closely given its locally aggressive nature.Summary Of Background Data: Cervical spine GCTB is extremely rare. Unresectable GCTB has historically been a challenge to treat due to the lack of prospective, randomized clinical trials to guide treatment. Radiotherapy has fallen out of favor due to the risk of malignant transformation, especially as most GCTB patients are young.In recent years, improved understanding of the receptor activator of nuclear factor-κB ligand (RANKL) in the pathophysiology of GCTB has led to the use of Denosumab in patients with recurrent/unresectable/metastatic GCTB and in patients whom surgical resection carries a high morbidity. To date, the optimal dosage and duration of therapy in the treatment of GCTB is unknown.Methods: We report a case of cervical spine GCTB in a 53-year-old male with positive surgical margins managed with Denosumab.Results: This is the first reported case of a cervical spine GCTB managed with Denosumab showing excellent response to treatment, recurrence of disease post cessation of Denosumab despite earlier satisfactory disease control and stabilization achieved even with dose reduction, and again an excellent response with recommencement of the drug.Conclusion: Denosumab is an excellent option in patients with unresectable GCTB or when surgery will result in excessive morbidity. However, further studies are required to determine optimal dosing, treatment duration, side effect profile, and whether Denosumab is truly able to achieve partial or complete disease remission in the long run.Level Of Evidence: 4. [ABSTRACT FROM AUTHOR]

Background: Recent clinical studies have suggested that denosumab is associated with tumor response and reduced surgical morbidity in patients with giant-cell tumor of bone (GCTB). We therefore evaluated the recurrence-free survival rate of patients who had GCTB in an extremity and were treated with surgery and denosumab, to determine the influence of denosumab and clinical factors on the risk of local recurrence.Methods: We retrospectively reviewed the medical records of 408 patients treated for GCTB in an extremity in a single institution from 1990 through 2013. Two hundred and forty-seven patients underwent curettage (intralesional surgery) with a high-speed burr, and 161 underwent resection. Phenol adjuvant was used in 221 of the 247 patients who had curettage. We also reviewed the medical records of 30 patients treated surgically (25 with curettage and 5 with resection) and with denosumab from 2010 through 2013 and compared their clinical results with 378 historical control subjects. The overall minimum duration of follow-up was 24 months.Results: The local recurrence rates were 60% (15) of 25 patients treated with curettage and denosumab and 16% (36) of 222 patients treated with curettage alone. The joint preservation rates were 80% (20) of 25 patients treated with curettage and denosumab and 94% (209) of 222 patients treated with curettage alone. Univariate and multivariable analyses showed that denosumab was the only independent factor associated with a poor prognosis when recurrence-free survival and joint preservation were considered. The overall median duration of follow-up was 85.6 months (interquartile range, 54.3 to 125.1 months). Viable tumor was present in all 30 specimens from patients treated with denosumab.Conclusions: There was a higher rate of recurrence in the cohort exposed to denosumab. Because there were substantial differences in the cohorts and randomization was not applied, however, causation could not be evaluated.Level Of Evidence: Therapeutic Level III. See Instructions for Authors for a complete description of levels of evidence. [ABSTRACT FROM AUTHOR]

Background: Although there is widespread acceptance of core needle biopsy (CNB) for diagnosing solid tumors, there is reluctance by some clinicians to use CNB for aneurysmal bone cysts (ABCs) as a result of concerns of safety (bleeding, nerve injury, fracture, readmission, or infection) and reliability, particularly to rule out malignant diagnoses like telangiectatic osteosarcoma. This is especially true when CNB tissue is sent from an outside hospital, where the technique used to obtain the tissue may be spurious.Questions/purposes: (1) Is CNB effective (provided adequate information to indicate appropriate surgical treatment without further open biopsy) as an initial diagnostic test for ABC? (2) Is CNB accurate (pathology consistent with the subsequent definitive surgical pathologic diagnosis) in differentiating between benign lesions such as primary or secondary ABCs and malignant radiolucent lesions such as telangiectatic osteosarcoma? (3) What are the complications of CNB? (4) Is there any difference in the effectiveness or accuracy of CNB performed at outside institutions when compared with a referral center?Methods: A retrospective study of our musculoskeletal tumor board pathology database (1990-2016) was performed using search criteria "aneurysmal bone cyst" or "telangiectatic osteosarcoma." Only patients undergoing a CNB who proceeded to definitive surgical resection with final pathology were included. Excluding outside CNBs, CNB was performed after presentation at a musculoskeletal tumor board as a result of atypical features on imaging or history concerning for malignancy. Outside CNB tissue was reviewed by our pathologists. If there was sufficient tissue for diagnosis, the patient proceeded to definitive surgery. If not, the patient underwent open biopsy. CNB diagnosis, open biopsy results, and open surgical resection pathology were reviewed. Complications, including bleeding, infection, nerve injury, readmission, or fracture, between the CNB and definitive open surgical procedure (mean 1.6 months) were documented. CNBs were considered "effective" if they yielded pathology considered sufficient to proceed with appropriate definitive surgery without additional open biopsy. CNBs were considered "accurate" if they were effective and yielded a pathologic diagnosis that matched the subsequent definitive surgical pathology. The sensitivity, specificity, positive predictive value (PPV), and negative predictive value (NPV) of obtaining a malignant diagnosis using CNB were also calculated.Results: A total of 81% (59 of 73) of CNBs were effective. Ninety-three percent (55 of 59) of CNBs were classified as accurate. Diagnostic CNBs had a sensitivity and specificity of 89% (eight of nine) and 100% (51 of 51), respectively. The PPV was 1.00 and the NPV was 0.82. There were no complications. With the numbers available, there was no difference in efficacy (90% [37 of 41 versus 14 of 15]; odds ratio, 0.97 [95% confidence interval {CI}, 0.41-2.27], p = 0.94) or accuracy (92% [34 of 37 versus 13 of 14]; odds ratio, 0.87 [95% CI, 0.08-9.16], p = 0.91) between CNBs performed in house and those referred from outside.Conclusions: These data suggest that CNBs are useful as an initial diagnostic test for ABC and telangiectatic osteosarcoma. Tissue from outside CNBs can be read reliably without repeat biopsy. If confirmed by other institutions, CNB may be considered a reasonable approach to the diagnosis of aggressive, radiolucent lesions of bone.Level Of Evidence: Level III, diagnostic study. [ABSTRACT FROM AUTHOR]

Background: Giant cell lesions are locally aggressive intraosseous neoplasms with capacity to metastasize. The role of immune surveillance in the pathophysiology of giant cell lesions is poorly understood, and understanding what role the immune system plays in giant cell lesions may lead to the development of more effective treatment. The aim of this study was to explore the role of immune surveillance in giant cell lesions by examining the expression of the HLA class I and class II antigens and tumor infiltrating lymphocytes. In addition, we examined the role of the immune modulating surface antigen B7-H3, which belongs to the B7 superfamily, a group of molecules that modulates T-cell responses.Questions/purposes: (1) Is an immune response elicited by giant cell lesions? (2) Do clinically relevant human leukocyte antigen (HLA) defects exist in giant cell lesions? (3) Is B7-H3 a clinically relevant immune modulator?Methods: The study sample was derived from the population of patients presenting to the Massachusetts General Hospital for evaluation and management of giant cell lesions from 1993 to 2008. We included patients with histologically confirmed giant cell lesions with a minimum followup of 6 months. Patients with systemic diseases (n = 4 [3%]), syndromes associated with giant cell lesions (n = 4 [3%]), and those without sufficient followup (n = 26 [19%]), inadequate records (n = 7 [5%]), or inadequate tissue available (n = 2 [1%]) were excluded. Tissue microarray, containing 288 tissue cores for 93 patients, was carefully constructed. This contained tissue from 45 patients with maxillofacial lesions, 38 with aggressive and seven with nonaggressive lesions, and 48 patients with axial and appendicular lesions, 30 with aggressive lesions and 18 with nonaggressive lesions. The population mean age was 28 ± 12 years and the duration of followup was 4 ± 3 years. The tissue microarray was immunohistochemically stained with monoclonal antibodies specific for HLA classes I and II and B7-H3 antigens and analyzed for tumor infiltrating lymphocytes. Antigen expression was examined in multinucleated giant cells and mononuclear stromal cells. The results were correlated with local invasion and tumor aggressiveness, which is based on accepted staging criteria.Results: Tumor infiltrating lymphocytes were detected in all the tumors. The mean number of CD8+ T cell infiltration was lower in aggressive tumors (median, 4.8; interquartile range [IQR], 0.4-13.4), when compared with nonaggressive tumors (median, 15.8; IQR, 4.3-46.3; p = 0.007). HLA class I antigens were highly expressed by multinucleated giant cells in all tumors, but were lightly expressed on mononuclear stromal cells in 53% (45 of 84) to 73% (56 of 77) of tumors. HLA class I antigen low expression in mononuclear stromal cells was associated with tumor aggressiveness (odds ratio [OR], 4.3; p = 0.005). Low HLA class I expression combined with low CD8+ T cell infiltration was most highly associated with tumor aggressiveness (OR, 7.81; p = 0.011). B7-H3 antigen was expressed in 36.9% mononuclear stroma cells and also was associated with local tumor invasion (OR, 1.36; p < 0.001). Similarly, giant cell lesions with high B7-H3 expression and low CD8+ tumor infiltrating lymphocytes were associated with increased tumor aggressiveness (OR, 8.89; p = 0.0491).Conclusions: Locally aggressive giant cell lesions are associated with low HLA class 1 antigen expression, low CD8+T cell infiltration, and high expression of the immune modulator B7-H3.Clinical Relevance: Failure of immune surveillance implies that there may be an opportunity to target aspects of the immune surveillance machinery to treat giant cell lesions. [ABSTRACT FROM AUTHOR]

Study Design: Multicenter, ambispective observational study.Objective: The aim of this study was to quantify local recurrence (LR) and mortality rates after surgical treatment of spinal giant cell tumor and to determine whether en bloc resection with wide/marginal margins is associated with improved prognosis compared to an intralesional procedure.Summary Of Background Data: Giant cell tumor (GCT) of the spine is a rare primary bone tumor known for its local aggressiveness. Optimal surgical treatment remains to be determined.Methods: The AOSpine Knowledge Forum Tumor developed a comprehensive multicenter database including demographics, presentation, diagnosis, treatment, mortality, and recurrence rate data for GCT of the spine. Patients were analyzed based on surgical margins, including Enneking appropriateness.Results: Between 1991 and 2011, 82 patients underwent surgery for spinal GCT. According to the Enneking classification, 59 (74%) tumors were classified as S3-aggressive and 21 (26%) as S2-active. The surgical margins were wide/marginal in 27 (36%) patients and intralesional in 48 (64%) patients. Thirty-nine of 77 (51%) underwent Enneking appropriate (EA) treatment and 38 (49%) underwent Enneking inappropriate (EI) treatment. Eighteen (22%) patients experienced LR. LR occurred in 11 (29%) EI-treated patients and six (15%) EA-treated patients (P = 0.151). There was a significant difference between wide/marginal margins and intralesional margins for LR (P = 0.029). Seven (9%) patients died. LR is strongly associated with death (Relative Risk 8.9, P < 0.001). Six (16%) EI-treated patients and one (3%) EA-treated patients died (P = 0.056). With regards to surgical margins, all patients who died underwent intralesional resection (P = 0.096).Conclusion: En bloc resection with wide/marginal margins should be performed when technically feasible because it is associated with decreased LR. Intralesional resection is associated with increased LR, and mortality correlates with LR.Level Of Evidence: 3. [ABSTRACT FROM AUTHOR]

Background: The Musculoskeletal Tumor Society (MSTS) scoring system developed in 1993 is a widely used disease-specific evaluation tool for assessment of physical function in patients with musculoskeletal tumors; however, only a few studies have confirmed its reliability and validity.Questions/purposes: The aim of this study was to validate the MSTS scoring system for the upper extremity (MSTS-UE) in Japanese patients with musculoskeletal tumors for use by others in research. Does the MSTS-UE have: (1) sufficient reliability and internal consistency; (2) adequate construct validity; and (3) reasonable criterion validity in comparison to the Toronto Extremity Salvage Score (TESS) or SF-36?Methods: Reliability was performed using test-retest analysis, and internal consistency was evaluated with Cronbach's alpha coefficient. Construct validity was evaluated using a scree plot to confirm the construct number and the Akaike information criterion network. Criterion validity was evaluated by comparing the MSTS-UE with the TESS and SF-36.Results: The test-retest reliability with intraclass correlation coefficient (0.95; 95% CI, 0.91-0.97) was excellent, and internal consistency with Cronbach's α (0.7; 95% CI, 0.53-0.81) was acceptable. There were no ceiling and floor effects. The Akaike Information Criterion network showed that lifting ability, pain, and dexterity played central roles among the components. The MSTS-UE showed substantial correlation with the TESS scoring scale (r = 0.75; p < 0.001) and fair correlation with the SF-36 physical component summary (r = 0.37; p = 0.007). Although the MSTS-UE showed slight correlation with the SF-36 mental component summary, the emotional acceptance component of the MSTS-UE showed fair correlation (r = 0.29; p = 0.039).Conclusions: We can conclude that the MSTS is not an adequate measure of general health-related quality of life; however, this system was designed mainly to be a simple measure of function in a single extremity. To evaluate the mental state of patients with musculoskeletal tumors in the upper extremity, further study is needed. [ABSTRACT FROM AUTHOR]

Background: Liquid nitrogen has been used as adjuvant cryotherapy for treating giant cell tumor (GCT) of bone. However, the liquid phase and ultrafreezing (-196° C) properties increase the risk of damage to the adjacent tissues and may lead to perioperative complications. A novel semisolid cryogen, freezing nitrogen ethanol composite, might mitigate these shortcomings because of less-extreme freezing. We therefore wished to evaluate freezing nitrogen ethanol composite as a coolant to determine its properties in tumor cryoablation.Questions/purposes: (1) Is freezing nitrogen ethanol composite-mediated freezing effective for tumor cryoablation in an ex vivo model, and if yes, is apoptosis involved in the tumor-killing mechanism? (2) Does freezing nitrogen ethanol composite treatment block neovascularization and neoplastic progression of the grafted GCTs and is it comparable to that of liquid nitrogen in an in vivo chicken model? (3) Can use of freezing nitrogen ethanol composite as an adjuvant to curettage result in successful short-term treatment, defined as absence of GCT recurrence at a minimum of 1 year in a small proof-of-concept clinical series?Methods: The cryogenic effect on bone tissue mediated by freezing nitrogen ethanol composite and liquid nitrogen was verified by thermal measurement in a time-course manner. Cryoablation on human GCT tissue was examined ex vivo for effect on morphologic features (cell shrinkage) and DNA fragmentation (apoptosis). The presumed mechanism was investigated by molecular analysis of apoptosis regulatory proteins including caspases 3, 8, and 9 and Bax/Bcl-2. Chicken chorioallantoic membrane was used as an in vivo model to evaluate the effects of freezing nitrogen ethanol composite and liquid nitrogen treatment on GCT-derived neovascularization and tumor neoplasm. A small group of patients with GCT of bone was treated by curettage and adjuvant freezing nitrogen ethanol composite cryotherapy in a proof-of-concept study. Tumor recurrence and perioperative complications were evaluated at a minimum of 19 months followup (mean, 24 months; range, 19-30 months).Results: Freshly prepared freezing nitrogen ethanol composite froze to -136° C and achieved -122° C isotherm across a piece of 10 ± 0.50-mm-thick bone with a freezing rate of -34° C per minute, a temperature expected to meet clinical tumor-killing requirements. Human GCT tissues revealed histologic changes including shrinkage in morphologic features of multinucleated giant cells in the liquid nitrogen (202 ± 45 μm; p = 0.006) and freezing nitrogen ethanol composite groups (169 ± 27.4 μm; p < 0.001), and a decreased nucleated area of neoplastic stromal cells for the 30-second treatment. Enhanced counts of terminal deoxynucleotidyl transferase dUTP nick end labeling (TUNEL)-positive cells verified the involvement of DNA fragmentation in cryoablated GCT tissues. Western blotting analysis on the expression of apoptosis regulatory proteins showed enhancement of proteocleavage-activated caspases 3, 8, and 9 and higher ratios of Bax/Bcl2 in the liquid nitrogen- and freezing nitrogen ethanol composite-treated samples. Numbers of blood vessels and human origin tumor cells also were decreased by freezing nitrogen ethanol composite and liquid nitrogen treatment in the GCT-grafted chicken chorioallantoic membrane model. Seven patients with GCT treated by curettage and adjuvant cryotherapy by use of freezing nitrogen ethanol composite preparation had no intra- or postoperative complications related to the freezing, and no recurrences during the study surveillance period.Conclusions: These preliminary in vitro and clinical findings suggest that freezing nitrogen ethanol composite may be an effective cryogen showing ex vivo and in vivo tumor cryoablation comparable to liquid nitrogen. The semisolid phase and proper thermal conduction might avoid some of the disadvantages of liquid nitrogen in cryotherapy, but a larger clinical study is needed to confirm these findings.Level Of Evidence: Level IV, therapeutic study. [ABSTRACT FROM AUTHOR]

The article discusses the study of the use cryotherapy of human giant cell tumor of bone. It states that the study analysis the extent of apoptosis in tumors subjected to cryotherapy in vitro. It mentions that the interest in cryotherapy has increased due to the understanding of the immune system and research into how tissues can autoimmunize.

Study Design: Case report and literature review.Objective: To describe treatment of a unique case of acute airway obstruction by a large C7 giant cell tumor (GCT) with preoperative denosumab followed by surgical resection, and review the literature on this rare entity.Summary Of Background Data: Standard treatment for GCTs includes surgical resection or curettage and packing. Large lesions in the spine may require preoperative therapy with denosumab, a human monoclonal antibody to RANKL, to facilitate surgery. It is highly unusual for GCT arising in cervical spine to present with acute asphyxia (requiring tracheostomy).Methods: We report a patient with large C7 GCT that caused tracheal compression with almost complete airway obstruction requiring emergency intubation.Results: The tumor responded to subcutaneously administered denosumab with marked decrease in size and relief of symptoms. Increased tumor mineralization in response to therapy facilitated subsequent successful surgical tumor resection. The patient remains symptom-free 2 years after surgery without tumor recurrence.Conclusion: Denosumab can shrink the size of large GCTs, providing symptom relief before surgery and facilitate tumor resection.Level Of Evidence: 5. [ABSTRACT FROM AUTHOR]

Background: Many techniques have been described for reconstruction after distal radius resection for giant cell tumor with none being clearly superior. The favored technique at our institution is total wrist fusion with autogenous nonvascularized structural iliac crest bone graft because it is structurally robust, avoids the complications associated with obtaining autologous fibula graft, and is useful in areas where bone banks are not available. However, the success of arthrodesis and the functional outcomes with this approach, to our knowledge, have only been limitedly reported.Questions/purposes: (1) What is the success of union of these grafts and how long does it take? (2) How effective is the technique in achieving tumor control? (3) What complications occur with this type of arthrodesis? (4) What are the functional results of wrist arthrodesis by this technique for treating giant cell tumor of the distal radius?Methods: Between 2005 and 2013, 48 patients were treated for biopsy-confirmed Campanacci Grade III giant cell tumor of the distal radius. Of those, 39 (81% [39 of 48]) were treated with wrist arthrodesis using autogenous nonvascularized iliac crest bone graft. Of those, 27 (69% [27 of 39]) were available for followup at a minimum of 24 months (mean, 45 months; range, 24-103 months). During that period, the general indications for this approach were Campanacci Grade III and estimated resection length of 8 cm or less. Followup included clinical and radiographic assessment and functional assessment using the Disabilities of the Arm, Shoulder and Hand (DASH) score, the Musculoskeletal Tumor Society (MSTS) score, grip strength, and range of motion at every followup by the treating surgeon and his team. All functional results were from the latest followup of each patient.Results: Union of the distal junction occurred at a mean of 4 months (± 2 months) and union of the proximal junction occurred at a mean of 9 months (± 5 months). Accounting for competing events, at 12 months, the rate of proximal junction union was 56% (95% confidence interval [CI], 35%-72%), whereas it was 67% (95% CI, 45%-82%) at 18 months. In total, 11 of the 27 patients (41%) underwent repeat surgery on the distal radius, including eight patients (30%) who had complications and three (11%) who had local recurrence. The mean DASH score was 9 (± 7) (value range, 0-100, with lower scores representing better function), and the mean MSTS 1987 score was 29 (± 1) (value range, 0-30, with higher scores representing better function) as well as 96% (± 4%) of mean MSTS 1993 score (value range, 0%-100%, with higher scores representing better function). The mean grip strength was 51% (± 23%) of the uninvolved side, whereas the mean arc of forearm rotation was 113° (± 49°).Conclusions: Reconstruction of defects after resection of giant cell tumor of the distal radius with autogenous structural iliac crest bone graft is a facile technique that can be used to achieve favorable functional results with complications and recurrences comparable to those of other reported techniques. We cannot show that this technique is superior to other options, but it seems to be a reasonable option to consider when other reconstruction options such as allografts are not available.Level Of Evidence: Level IV, therapeutic study. [ABSTRACT FROM AUTHOR]