• giant cell tumor of bone
• giant tumor
• malignant mimic tumor
• rib tumor

• Giant cell tumor of bone
• Musculoskeletal oncology
• Secondary osteoarthritis
• Total knee arthroplasty

• Enucleation
• Giant cell granuloma
• Mandibular lesion
• Maxillofacial swelling
• Multidisciplinary approach

• differential diagnosis
• giant cell
• immunohistochemical profiling
• various lesions

The diagnosis of osteosarcoma (OSA) depends on clinicopathological and radiological correlation. A biopsy is considered the gold standard for OSA diagnosis. However, since OSA is a great histological mimicker, diagnostic challenges exist. Immunohistochemistry (IHC) can serve as an adjunct for the histological diagnosis of OSA. Special AT-rich sequence-binding protein 2 (SATB2) was recently described as a reliable adjunct immunohistochemical marker for the diagnosis of OSA.

We investigated the IHC expression of SATB2 in 95 OSA and 100 non-osteogenic bone and soft tissue tumors using a monoclonal antibody (clone EPNCIR30A). The diagnostic utility of SATB2 and correlation with clinicopathological parameters were analyzed.

SATB2 IHC was positive in 88 out of 95 cases (92.6%) of OSA and 50 out of 100 cases (50.0%) of primary non-osteogenic bone and soft tissue tumors. Of the 59 bone tumors, 37 cases (62.7%) were positive for SATB2, and of the 41 soft tissue tumors, 13 cases (31.7%) were positive for SATB2. The sensitivity of SATB2 as a diagnostic test was 92.6%, specificity 50%, positive predictive value 63.8%, and negative predictive value 87.7%.

Although SATB2 is a useful diagnostic marker for OSA, other clinical, histological and immunohistochemical features should be considered for the interpretation of SATB2.

Giant cell tumor (GCT) of the anterior rib origin is extremely rare. We report the first case of trauma-induced GCT of the rib.

A 22-year-old female developed a mass over the right anterior chest wall with pain 3 mo after a falling injury with blunt trauma of the right chest wall. Chest computed tomography (CT) showed a tumor originating from the right 6th rib with bony destruction, and a CT-guided needle biopsy revealed a GCT. We completely resected the tumor with chest wall and performed reconstruction. The pathological diagnosis was GCT of the bone. Twelve months after surgery, no signs of recurrence were observed.

GCT of the rib after trauma has not been reported. Meticulous history-taking and image evaluation are essential for the differential diagnosis of unusual chest wall tumors.

• Chest wall tumor
• Giant cell tumor
• Trauma
• Rib
• Bone neoplasm
• Case report

Denosumab is a game-changing drug for giant cell tumor of bone (GCTB); however, its clinical biomarker regarding tumor ossification of GCTB has not been elucidated. In this study, we investigated the relationship between Wnt/β-catenin signaling and the ossification of GCTB and evaluated whether endogenous nuclear β-catenin expression predicted denosumab-induced bone formation in GCTB. Genuine patient-derived primary GCTB tumor stromal cells exhibited osteoblastic characteristics. Identified osteoblastic markers and nuclear β-catenin translocation were significantly upregulated via differentiation induction and were inhibited by treating with Wnt signaling inhibitor, GGTI-286, or selective Rac1-LEF inhibitor, NSC23766. Furthermore, we reviewed the endogenous ossification and nuclear β-catenin translocation of 86 GCTB clinical samples and elucidated that intra-tumoral ossification was significantly associated with the nuclear translocation. Three-dimensional quantitative analyses (n = 13) of tumoral CT images have revealed that the nuclear β-catenin translocation of naïve GCTB samples was significantly involved with the denosumab-induced tumor ossification. Our findings suggest a close relationship between the nuclear β-catenin translocation and the osteoblastic differentiation of GCTB. Investigations of the nuclear β-catenin in naïve GCTB samples may provide a promising biomarker for predicting the ossification of GCTB following denosumab treatment.

• EMMT
• breast carcinoma metastasis
• epithelial-mesenchymal-myeloid transition
• giant cell tumor of bone
• metastasis
• osteoclast
• tumor biology

• Animals
• Epithelial-Mesenchymal Transition/physiology
• Humans
• Neoplasm Metastasis/pathology
• Neoplasms/pathology
• Osteoclasts/pathology

• biopsy
• bone
• diagnostic imaging
• fibro-osseous lesions
• fracture
• neoplasia
• osteosarcoma
• radiology
• reactive bone
• surgical pathology

• Cathepsin K
• NFATc1
• RANKL
• RUNX2
• Uterine leiomyosarcoma with osteoclast-like giant cells

Objective: To find the recurrence and outcomes of giant cell tumors treated with scooping curettage, burr down technique, phenolization, and bone cement.

Method: We conducted a descriptive case series using a non-probability consecutive sampling technique at the Department of Orthopedics, Lahore General Hospital, Lahore, Pakistan, from May 2014 to June 2018. A total of 40 patients aged between 20 to 40 years with Compannacci grade I, II & III giant cell tumors (GCT) were included and patients unfit for the surgery, those with multiple, recurrent, malignant giant cell tumors, tumors involving the axial skeleton, and previously treated cases were excluded. We recorded the side, site of the tumor, post-operative distal neurovascular status, and recurrence of giant cell tumors. The patients were follow-up in the out-patient department (OPD) at the second week, fourth week, 12th week, 24th week, 48th week, 96th week, and 144th week after the surgery. Side, site of the tumor, and post-operative distal neurovascular status were assessed clinically, and recurrence of the tumors was observed clinically and radiologically.

Results: The mean age of all patients was 25.75±5.74 years. Males were 45% (18) and females were 55% (22). Most (12, 30%) tumors were present in the upper limb, and 22 (70%) were present in the lower limb. The majority (24, 60%) tumors were present around the knee joint. Companacci grade I was five (12.5%), grade II was 14 (35%), and grade III was 21 (52%). There were six (15%) pathological fractures. There was no case of distal neurovascular (DNV) injury, and three patients had a recurrence in two years of follow-up.

Conclusion: Giant cell tumor treated with scooping curettage, burr down technique, phenolization and poly-methyl methacrylate showed 7.5% recurrence. The combined use of local adjuvants in the treatment of giant cell tumors is a safe and effective way to reduce the rate of local recurrence.

• bone cementing
• burr down
• gct recurrence
• gct treatment
• giant cell curettage
• phenolization
• scooping curettage

• Wnt signalling pathway
• YJ5
• bone neoplasms
• osteosarcoma

•

Giant cell tumor (GCT) of the spine is uncommon but most aggressive benign tumor of the spine with unpredictable outcome. The purpose of this study was to report on a surgical treatment for the cases of GCT (C2, D4 and C7-D1). In the cervico-dorsal spine, the incidence is extremely low and has been reported very less in the literature.

Giant cell tumor (GCT) of the spine is uncommon but most aggressive benign tumor of the spine with unpredictable outcome. The purpose of this study was to report on a surgical treatment for the cases of GCT (C2, T4 and C7-T1). The spine is not a common site for a Benign GCT, with a 2.5% incidence in the sacrum and 2.9% in the vertebrae above the sacrum. In the cervico-thoracic spine, the incidence is extremely low and has been reported very less in the literature.

This study was conducted on 3 cases of GCT of the spine and evaluated the outcome of different treatment modalities retrospectively. All the cases were treated with intralesional surgical resection but only one developed recurrence.

Cord compression and neurological deficits of varying grades was observed in all the cases. All patients also presented with clinical as well as radiological instability. Overall results were satisfactory, as all patients were symptom-free postoperatively. One out of the three cases had tumour recurrence and needed repeat intervention.

Giant cell tumour of cervico-thoracic spine is a rare entity and should be managed Surgically with en bloc/extralesional resection but due to risk of surrounding neurovascular structures damage they are managed by marginal resection therefore since total resection is not possible there are high chances of recurrences, Hence require close monitoring and follow up for early diagnosis and appropriate management.

• Biopsy
• Excision
• Giant cell tumor of the spine
• Radiotherapy

• Giant cell tumour of bone
• Glycolysis
• Lactate
• Monocarboxylated transporter 4
• Multinucleated cells

• Bone Neoplasms/genetics
• Giant Cell Tumor of Bone/genetics
• Glycolysis
• Humans
• Lactic Acid/metabolism
• Membrane Transport Proteins/metabolism
• Monocarboxylic Acid Transporters/metabolism
• Muscle Proteins/metabolism

• Cyclin A
• Cyclin D1
• Giant cell tumor of bone
• Mononuclear cell cycle fractions
• Neoplastic stromal cells
• Tumor progression
• mcm2
• ploidy

• Adolescent
• Adult
• Aged
• Biomarkers, Tumor/metabolism
• Cell Cycle
• Child
• Child, Preschool
• Cohort Studies
• Disease Progression
• Female
• Giant Cell Tumor of Bone/pathology
• Humans
• Kaplan-Meier Estimate
• Ki-67 Antigen/metabolism
• Male
• Middle Aged
• Models, Biological
• Multivariate Analysis
• Progression-Free Survival
• Risk Factors
• Young Adult

• 3D culture
• bone metastasis
• microenvironment
• sarcoma
• tumor niche

In this study, the influence of the neutrophil-to-lymphocyte ratio (NLR) and the platelet-to-lymphocyte ratio (PLR) on the prognosis of giant cell tumor (GCT) of the extremities were investigated.

The clinical parameters of 163 patients who were diagnosed with GCT of the extremities between July 2008 and January 2018 were retrospectively analyzed. Optimal cutoff values of NLR and PLR were determined using receiver operating characteristic (ROC) analysis. According to optimal cutoff values, patients were divided into high NLR and low NLR groups or high PLR and low PLR groups. Kaplan-Meier and log-rank methods were used to compare the recurrence-free survival (RFS) between the high and low NLR groups, and between the high and low PLR groups. Univariate analysis was performed to determine the influence of age, gender, neutrophil count, lymphocyte count, platelet count, white blood cell count, tumor size, surgical approach and Campanacci stage on the prognosis of giant cell tumor of bone. The main predictors of RFS were determined by Cox multivariate regression analysis.

The optimal cutoff value of NLR in giant cell tumor of the extremities was 2.32, which was used to classify patients into high and low NLR groups. The optimal cutoff value of PLR was 116.81, and was used to classify patients into high and low PLR groups. Campanacci stage, tumor maximum diameter, alkaline phosphatase, and C-reactive protein (CRP) were significantly associated with the high NLR and PLR. Cox multivariate regression analysis revealed that the Campanacci stage (HR = 3.28, 95% CI: 1.24~8.69) and NLR (HR = 4.18, 95% CI: 1.83~9.57) were independent prognostic factors for giant cell tumor of the extremities.

As a novel inflammatory index, NLR has some predictive power for the prognosis of patients with giant cell tumor of the extremities.

• Giant cell tumor
• Neutrophil-to-lymphocyte ratio
• Platelet-to-lymphocyte ratio
• Prognosis

• animal model
• bone environment
• bone lysis
• giant cell tumor of bone
• intratibial injection

• Bisphosphonate
• Bone tumor
• Denosumab
• Giant cell tumor of bone
• Osteoclast

• curettage
• giant cell tumor of bone

High-grade osteosarcoma (OS) is characterized by low incidence, high aggressiveness and moderate 5-years survival rate after aggressive poly-chemotherapy and surgery. Here we used miRNA profiling as a tool to possibly predict and monitor OS's development and therapeutic outcome. First, we evaluated the altered expression of selected miRNAs from a case of Giant Cell Tumor (GCT) apparently evolved into an OS. We found that most of modulated miRs were associated with pathways of bone resorption and osteogenesis. miRNA expression also revealed that GCT and OS were distinct tumors. Second, we validated the observed miRNA profile in two independent casuistries of ten GCT (not evolved into malignant tumors) and sixteen OS patients. Interestingly, we found that miR-181c and other three miRNAs identified in the first step of the study were also consistently de-regulated in all OS patients. Ectopic expression of miR-181c reduced cell viability and enhanced chemotherapeutic-induced cell death of U2OS and SAOS2 cells. These findings indicate that: i) miRNAs aberrantly modulated in GCT could be predictive of its development into OS and ii) miRNAs expression could be useful to monitor the OS therapeutic outcome.

• giant cell tumor
• miRNA profiling
• osteosarcoma
• relapse

• En-bloc resection
• Fibula grafting
• Giant cell tumour

• BONE TUMOURS
• CANCER GENETICS
• IMMUNOCYTOCHEMISTRY

• C2 fixation
• C2 tumors
• giant cell tumor
• pediatric tumors
• retropharyngeal approach

Giant cell tumor of bone (GCTB) is a benign, locally destructive neoplasm, with tumors comprised of mesenchymal fibroblast-like stromal cells; monocytic, mononuclear cells of myeloid lineage; and the characteristic osteoclast-like, multinucleated giant cells. Hampering the study of the complex interaction of its constituent cell types is the propensity of longstanding, repeatedly passaged cell cultures to undergo phenotypic alteration and loss of osteoclast-inducing capacities. In this study, we employed a novel, single-step technique to purify freshly harvested stromal cells using a CD14-negative selection column. Using 9 freshly harvested GCTB specimens and the purified stromal cell component, we performed analyses for markers of osteoblast lineage and analyzed the capacity of the stromal cells to undergo osteoblastic differentiation and induce osteoclastogenesis in co-cultures with monocytic cells. Successful purification of the CD14-negative stromal cells was confirmed via flow cytometric analysis and immunocytochemistry. Osteogenic media upregulated the expression of osteocalcin, suggesting an osteoblastic lineage of the GCTB stromal cells. The effects of the Wnt pathway agonist, SB415286, and recombinant human bone morphogenetic protein (BMP)-2 on osteoblastogenesis varied among samples. Notably, osteogenic media and SB415286 reversed the receptor activator of NF-κB ligand (RANKL)/osteoprotegerin (OPG) expression ratio resulting in diminished osteoclastogenic capacity. Recombinant human BMP2 had the opposite effect, resulting in enhanced and sustained support of osteoclastogenesis. Targeting the giant cell tumor stromal cell may be an effective adjunct to existing anti-resorptive strategies.

• Adolescent
• Adult
• Aminophenols/pharmacology
• Aminophenols/therapeutic use
• Bone Morphogenetic Proteins/metabolism
• Cell Differentiation/drug effects
• Cell Separation
• Culture Media/pharmacology
• Female
• Giant Cell Tumor of Bone/drug therapy
• Giant Cell Tumor of Bone/pathology
• Giant Cell Tumor of Bone/therapy
• Humans
• Ligands
• Male
• Maleimides/pharmacology
• Maleimides/therapeutic use
• Middle Aged
• Osteoblasts/drug effects
• Osteoblasts/metabolism
• Osteoblasts/pathology
• Osteoclasts/drug effects
• Osteoclasts/metabolism
• Osteoclasts/pathology
• Osteogenesis/drug effects
• Osteoprotegerin/metabolism
• Polymerase Chain Reaction
• RANK Ligand/metabolism
• Stromal Cells
• Wnt Signaling Pathway/drug effects
• Young Adult

• Bone Resorption
• Giant Cell Tumor of Bone/pathology
• Humans

• Canadian Institutes of Health Research

• Biomarkers, Tumor/analysis
• Bone Neoplasms/chemistry
• Bone Neoplasms/pathology
• Bone Remodeling
• Cluster Analysis
• Core Binding Factor Alpha 1 Subunit/analysis
• Diagnosis, Differential
• Hedgehog Proteins/analysis
• Humans
• Immunohistochemistry
• Logistic Models
• Nuclear Proteins/analysis
• Predictive Value of Tests
• SOX9 Transcription Factor/analysis
• Sensitivity and Specificity
• Sp7 Transcription Factor
• Tissue Array Analysis
• Transcription Factors/analysis
• Twist-Related Protein 1/analysis

Owing to striking features of numerous multinucleated cells and bone destruction, giant cell tumor (GCT) of bone, often called as osteoclastoma, has drawn major attractions from orthopaedic surgeons, pathologists, and radiologists. The name GCT or osteoclastoma gives a false impression of a tumor comprising of proliferating osteoclasts or osteoclast precursors. The underlying mechanisms for excessive osteoclastogenesis are intriguing and GCT has served as an exciting disease model representing a paradigm of osteoclastogenesis for bone biologists. The modern interpretation of GCT is predominantly osteoclastogenic stromal cell tumors of mesenchymal origin. A diverse array of inflammatory cytokines and chemokines disrupts osteoblastic differentiation and promotes the formation of excessive multi-nucleated osteoclastic cells. Pro-osteoclastogenic cytokines such as receptor activator of nuclear factor kappa-B ligand (RANKL), interleukin (IL)-6, and tumor necrosis factor (TNF) as well as monocyte-recruiting chemokines such as stromal cell-derived factor-1 (SDF-1) and monocyte chemoattractant protein (MCP)-1 participate in unfavorable osteoclastogenesis and bone destruction. This model represents a self-sufficient osteoclastogenic paracrine loop in a localized area. Consistent with this paradigm, a recombinant RANK-Fc protein and bisphosphonates are currently being tried for GCT treatment in addition to surgical excision and conventional topical adjuvant therapies.

• Bone tumor
• Giant cell tumor
• Osteoclast

Giant cell tumor (GCT) of bone is a locally destructive tumor that occurs predominantly in long bones of post-pubertal adolescents and young adults, where it occurs in the epiphysis. The majority are treated by aggressive curettage or resection. Vascular invasion outside the boundary of the tumor can be seen. Metastasis, with identical morphology to the primary tumor, occurs in a few percent of cases, usually to the lung. On occasion GCTs of bone undergo frank malignant transformation to undifferentiated sarcomas. Here we report a case of GCT of bone that at the time of recurrence was found to have undergone malignant transformation. Concurrent metastases were found in the lung, but these were non-transformed GCT.