A large, locally aggressive giant cell tumour arising from the laryngeal cartilage: A Rare Case Report.

Giant cell tumour is a growth predominantly found in long bones of the body. Giant cell tumour has a rare occurrence in the head and neck. A case of a 31 year old male with no known comorbidities at the ENT Department, Shifa International Hospital, Islamabad presented with anterior neck swelling and hoarseness of voice. Patient was diagnosed as having Giant Cell Tumour of Larynx (GTCL) proven on FNA cytology and post-operative biopsy. GCTL is an uncommon entity with only 45 reported cases in the world.

A Successful Arthroscopic Management of a Benign but Locally Aggressive Tenosynovial Giant Cell Tumour in the Shoulder.

Introduction Pigmented villonodular synovitis (PVNS) is a relatively rare disorder affecting the synovial membrane and tendon sheath of a joint. It rarely affects the shoulder joint. This prospective study aims to document the challenges encountered in achieving total synovectomy and assesses the clinical outcomes of arthroscopic synovectomy for PVNS in shoulder patients. Methods This is a prospective study conducted from April 2017 to September 2023. This monoarticular disease was observed among six patients (four females and two males). All patients underwent arthroscopic extensile synovectomy with biopsy and culture. The outcomes were measured using Constant score, American Shoulder and Elbow Surgeons (ASES), and University of California Los Angeles (UCLA) scores. All patients were followed up for a minimum of 36 months after arthroscopic synovectomy. Results All intraoperative findings were consistent with PVNS and confirmed with histopathological examination. All patients achieved a satisfactory, painless range of movements following surgery. The individual Constant score improved from a mean value of 64.83 to 94.50, the ASES score improved from a mean value of 81.15 to 99.73, and the UCLA score improved from a mean value of 23.16 to 34.83 post-arthroscopic intervention, proving its effectiveness. No recurrences were reported after 36 months of follow-up. Conclusion PVNS can be easily missed, and one must have a high index of suspicion to diagnose early. Delayed presentation of the disease had led to severe destruction of the joint. Early diagnosis and arthroscopic intervention prior to joint destruction are crucial for achieving a good functional outcome. Incomplete excision may lead to recurrence of the disease. Therefore, we propose extensile arthroscopic synovectomy of the shoulder, wherein by expecting and addressing the intraoperative challenges, complete excision can be achieved, thus preventing recurrence.

Limb Reconstruction Using the Ilizarov Technique Following Giant Cell Tumour Excision in the Proximal Tibia of a 19-Year-Old Female: A Case Report.

Giant cell tumours (GCTs) of the proximal tibia are a relatively uncommon lesion among all benign tumours. They can occur at various sites including distal femur, proximal tibia and distal end radius. Various management modalities of GCTs occurring in the knee joint have been described for reconstruction as well as arthrodesis. We present a case of a 19-year-old adolescent patient with GCT of the proximal tibia with cortical breach with the collapse of the medial articular surface of the tibia. The patient reported experiencing knee pain and swelling for a long duration. Radiological investigations were suggestive of GCT of the proximal tibia with the medial cortical breach and collapse of the medial tibial articular surface. The patient was managed with a resection followed by arthrodesis using intramedullary nails with bone grafting, followed by Ilizarov reconstruction due to osteomyelitis of the surgical site. When dealing with relatively aggressive tumours that have breached the cortex, wide resection of the tumour is required. Following this, the reconstruction procedure must ensure good biomechanical tenacity, biological healing, infection resistance, and intact function of the knee joint extension. One option for achieving this is total knee replacement with a customized prosthesis, though this can be costly. Another option is joint arthrodesis with intramedullary nailing or the Ilizarov fixator, which is strongly supported by the existing literature. This case was managed successfully with the above-described method, and complete healing was observed. In conclusion, periarticular long bone tumours, especially around the knee joint, can be managed effectively with the Ilizarov method. Though it has a few disadvantages, such as a long duration of external fixator, non-compliance, and pin tract infections, it still stands as a viable alternative for limb reconstruction due to its cost-effectiveness and time-tested efficacy.

Time to full weight-bearing with the use of a calcium sulfate-calcium phosphate bone substitute as a bone void filler following extended curettage in the treatment of primary benign bone tumours.

PURPOSE: The primary objective of this study was to determine time to full weight-bearing after the use of a calcium-sulfate-calcium phosphate bone substitute (CaSO4/CaPO4) as a bone void filler in the treatment of primary benign bone tumours following intralesional curettage. The secondary objectives were to determine surgical complications and recurrence rates. METHODS: Retrospective review of patients identified from a surgeon-specific orthopaedic oncology database, who underwent curettage of benign bone tumours and subsequent bone void filling with CaSO4/CaPO4. RESULTS: A total of 39 patients (20 males, 19 females) met inclusion criteria with an average age of 31 years (range: 13 to 62 years), a median follow-up of 3.7 years, and a maximum follow-up of 11 years. The most common tumour diagnosis was giant cell tumour of bone (GCT) (n = 19), and the most common location was the proximal tibia (n = 9). The mean volume of tumour excised was 74.1 cm3 including extraosseous bone expansion due to tumour growth, with a mean of volume of 21.4 mL of CaSO4/CaPO4 used to fill the intraosseous cavitary defects to restore normal bone anatomy. None of the lesions required additional internal fixation. The primary outcome measure, average time to full weight-bearing/full range of motion, was 11 weeks and 6 weeks for upper and lower extremity lesions, respectively. Secondary outcomes included tumour recurrence requiring reoperation in five patients and infection requiring reoperation in two patients. CONCLUSION: This study demonstrates that CaSO4/CaPO4 is a viable option as a bone void filler in the reconstruction of cavitary defects following removal of primary benign bone tumours. CaSO4/CaPO4 provides sufficient bone regeneration early in the post-operative period to allow progression to full weight-bearing within weeks without the need for internal fixation. There were no graft-specific complications noted.

Central Giant Cell Granuloma: Negotiating the Diagnostic and Management Dilemmas.

Introduction: Giant cell lesions of orofacial region although rare in presentation, have diagnostic and treatment challenges due to overlapping clinical, radiological, and histopathological signs. Background: We happened to come across a case, which presented to us with an aggressive jaw lesion of nonodontogenic origin, mimicking a malignancy and putting us in a conundrum with regard to work up and treatment. The sequential work up not only helped us reach a definitive diagnosis but also led us the draw algorithms for diagnosis of Giant cell lesions and management of Central giant cell granuloma. Conclusion: Meticulous planning along with molecular studies helps in better delineating one giant cell lesion from other.

Recurrent Localized Tenosynovial Giant Cell Tumor of the Left Ring Finger: A Case Report and Literature Review.

Here, we report the case of recurrent swelling and pain in the proximal interphalangeal joint of the left ring finger, which was later diagnosed as a localized tenosynovial giant cell tumor in a young adult female. The first presentation was at the same anatomical site four years prior. Examination at presentation showed a firm skin-colored nodule in the volar aspect of the left ring finger. The swelling was seen to be partly attached to underlying structures and was non-tender. After a careful physical examination and plain radiograph imaging of the hand, the two differential diagnoses considered were tenosynovial giant cell tumor and ganglion cyst. A surgical excision was performed, and histopathologic evaluation showed features consistent with a tenosynovial giant cell tumor, localized type. The resection margins were clear of tumor. The patient had no intraoperative or postoperative complications. Postoperative physiotherapy was recommended. No recurrence was seen after postoperative surgical follow-up for one year. This report highlights the importance of histopathologic evaluation and confirmation of clear surgical margins in the management of tenosynovial giant cell tumors. In recurrent cases, surgical re-excision with clear margins provides good clinical outcomes. Before surgical excision, patients should be informed about the biologic nature of the lesion and the high risk of recurrence. The management modalities to prevent recurrence and the need for long-term follow-up should also be discussed with the patient.

Denosumab induction and Zoledronic acid maintenance therapy for recurrent unresectable giant cell tumour of the distal tibia: A case report with sustained tumour control after drug withdrawal.

A 31-year-old woman was diagnosed with a recurrent and rapidly growing giant cell tumour of distal tibia with skin ulceration after intralesional curettage. The patient started on Denosumab 120 mg subcutaneously, once per month with additional loading doses on Days 8 and 15 attempting to avoid below-knee amputation. Twelve doses of Denosumab were administered in 9 months, resulting in resolution of pain, reduction of tumour size and calcification. Hence, the local surgical treatment was delayed and bisphosphonate maintenance therapy was initiated as skin healing was incomplete. The patient was given Zoledronic acid infusions at a dose of 4 mg. After the third infusion, the skin healed. As tumour remained stable, it was decided to continue maintenance. Overall, six doses of Zoledronic acid at 6 months intervals were administrated over 3 years. At the end of the maintenance, the patient experienced no pain and satisfied with her limb function. Since the lesion remained stable over 3 years after Denosumab discontinuation, it was suggested to stop further medical treatment and proceed to active surveillance. The patient's disease is still stable clinical remission with no serious adverse events 41 months after Denosumab cessation and 10 months after the last bisphosphonate infusion. The present case confirmed the high effectiveness of denosumab as induction therapy in advanced recurrent giant cell tumour. We speculate that following the Denosumab-induced tumour ossification, high Zoledronic acid uptake in lesion may prevent tumour reactivation due to its improved pharmacodynamics with an assumed irreversible anti-tumoral effect on residual mutated cells. This hypothesis requires confirmation in future studies.

Pathology of intra-articular tumours and tumour-like lesions: pearls, pitfalls and rarities from a general surgical pathology practice.

Intra-articular tumours are uncommonly encountered in routine practice and may present diagnostic challenges to pathologists. Challenges unique to this site include distinction from more common reactive synovial conditions, which are far more common; histologic variability; superimposed reactive changes; and often, lack of provided clinicoradiological context. This article reviews the pathology of the synovial tumours and tumour-like lesions, including diagnostic pearls, pitfalls and rare entities.

Acetabular Reconstruction in a Rare Case of Ligamentum Teres Tenosynovial Giant Cell Tumour (TGCT) Causing Extensive Destruction.

Tenosynovial giant cell tumour (TGCT), previously called pigmented villonodular tenosynovitis (PVNS), is a rare benign, locally aggressive condition that primarily affects the synovial lining of large joints, such as the knee, the hip, and the ankle. TGCT of the hip joint is a relatively scarce entity, and its diagnosis is often challenging. This article reports a case of TGCT affecting the left acetabulum, the left femoral head, and the ligamentum teres of the hip joint in a 39-year-old woman who presented to our clinic three months after the onset of symptoms. The patient underwent a biopsy, computer tomography (CT), and magnetic resonance imaging (MRI). All tests were inconclusive. Total hip arthroplasty (THA) was subsequently performed, leading to healing of the lesion previously present. Following surgery, a second biopsy classified this lesion as TGCT. By sharing our experience with this rare manifestation, we aim to contribute to the growing body of knowledge on the diagnosis and management of TGCT, specifically when it occurs in the hip joint.

Non-vascularized toe phalangeal transfer for reconstruction of a giant cell tumour of the proximal phalanx.

This article describes a 50-year-old woman with a giant cell tumour involving the base of the proximal phalanx, which was resected and reconstructed with a non-vascularised toe phalanx graft. The toe phalanx graft united well, and there was no tumour recurrence at the 24-month follow-up.

Repercussions of Denosumab in Patients With Giant Cell Tumor of Bone: An Observational Study.

BACKGROUND AND OBJECTIVES: The advent of denosumab has rendered giant cell tumors (GCT) of the bone amenable. It makes sense to evaluate its effect on the patient's symptoms and the histopathological outcomes. The aim of the study is to ascertain the effect of 24-week neoadjuvant denosumab therapy on the following parameters: visual analogue scale (VAS), musculoskeletal tumor society (MSTS) scores, tumor size, and the number of giant and stromal cells. MATERIAL AND METHODS: This observational study was conducted from February 2022 to April 2023 at SCB Medical College and Hospital, India. Fifty-four GCT participants had their VAS and MSTS scores assessed at baseline and then every four weeks for the next 24 weeks. At 24 weeks, changes in their tumor size and the number of giant and stromal cells per high-power field (hpf) were also evaluated. RESULTS: Fifty-four (82%) out of the 66 enrolled participants completed the study. Among those 54, 29 (54%) participants were female. The study population had a mean age of 39.0 ± 4.7 years. The median VAS scores were (female: 7.0, male: 7.0; p = 0.51) at baseline and (female: 2.0, male: 2.0; p = 0.39) at 24 weeks. The median MSTS scores at baseline and 24 weeks were (female: 8.0, male: 8.0; p = 0.41) and (female: 15.0, male: 16.0; p = 0.66), respectively. The median reductions in tumor size, the number of giant, and stromal cells (per hpf) were (female: 6.0 mm, male: 5.0 mm; p = 0.11), (female: 25, male: 27; p = 0.07), and (female: 1200, male: 2100; p < 0.001), respectively. CONCLUSION: After receiving neoadjuvant denosumab for 24 weeks, the study participants' clinical symptoms and histological indicators improved. With the exception of the stromal cells, there was no statistically significant difference between the male and female participants.

Current indications for denosumab in benign bone tumours.

Denosumab is a fully humanised monoclonal antibody to RANK ligand, inhibiting the RANK-RANKL pathway. It promotes the apoptosis of osteoclast-like giant cells, a secondary ossification and connective tissue formation. Given its high efficacy, denosumab is the standard treatment of unresectable or metastatic giant cell tumour of bone (GCTB) requiring morbid surgery. Neoadjuvant administration of denosumab may be justified to enable the resection of the tumour in certain cases; it should be considered, however, with caution for joint-saving surgery due to high local recurrence rates. In cases of unresectable or metastatic GCTB, however, denosumab treatment should be administered for years or even as a lifelong therapy. This poses many yet unanswered questions concerning the frequency of denosumab treatment as well as the ratio of the adverse events in the following years. Denosumab suppresses, not directly targets, the neoplastic stromal cells of GCTB. Ongoing in vitro studies suggest that other drugs alone or in combination (e.g. sunitinib) with denosumab may target both the neoplastic and the giant cells. Promising results have been reported regarding the off-label use of denosumab in other giant cell-rich tumours/tumour-like lesions, i.e. aneurysmal bone cysts and central giant cell granulomas. Data are derived, however, mostly from case reports and case series. Large prospective clinical trials are needed to evaluate the role and also the side effects of denosumab in the treatment of these rare diseases.

Identification of potential diagnostic biomarkers for tenosynovial giant cell tumour by integrating microarray and single-cell RNA sequencing data.

PURPOSE: Tenosynovial giant cell tumour (TGCT) is a benign hyperplastic and inflammatory disease of the joint synovium or tendon sheaths, which may be misdiagnosed due to its atypical symptoms and imaging features. We aimed to identify biomarkers with high sensitivity and specificity to aid in diagnosing TGCT. METHODS: Two scRNA-seq datasets (GSE210750 and GSE152805) and two microarray datasets (GSE3698 and GSE175626) were downloaded from the Gene Expression Omnibus (GEO) database. By integrating the scRNA-seq datasets, we discovered that the osteoclasts are abundant in TGCT in contrast to the control. The single-sample gene set enrichment analysis (ssGSEA) further validated this discovery. Differentially expressed genes (DEGs) of the GSE3698 dataset were screened and the Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway enrichment analyses of DEGs were conducted. Osteoclast-specific up-regulated genes (OCSURGs) were identified by intersecting the osteoclast marker genes in the scRNA-seq and the up-regulated DEGs in the microarray and by the least absolute shrinkage and selection operator (LASSO) regression algorithm. The expression levels of OCSURGs were validated by an external dataset GSE175626. Then, single gene GSEA, protein-protein interaction (PPI) network, and gene-drug network of OCSURGs were performed. RESULT: 22 seurat clusters were acquired and annotated into 10 cell types based on the scRNA-seq data. TGCT had a larger population of osteoclasts compared to the control. A total of 159 osteoclast marker genes and 104 DEGs (including 61 up-regulated genes and 43 down-regulated genes) were screened from the scRNA-seq analysis and the microarray analysis. Three OCSURGs (MMP9, SPP1, and TYROBP) were finally identified. The AUC of the ROC curve in the training and testing datasets suggested a favourable diagnostic capability. The PPI network results illustrated the protein-protein interaction of each OCSURG. Drugs that potentially target the OCSURGs were predicted by the DGIdb database. CONCLUSION: MMP9, SPP1, and TYROBP were identified as osteoclast-specific up-regulated genes of the tenosynovial giant cell tumour via bioinformatic analysis, which had a reasonable diagnostic efficiency and served as potential drug targets.

Denosumab Induces Neoplastic Stromal Cell Apoptosis via p62 Downregulation Dependent on Autophagy Pathway in Giant Cell Tumour of Bone.

BACKGROUND: As the only humanized monoclonal antibody against receptor activator of nuclear factor-κB ligand (RANKL) for giant cell tumour of bone (GCTB) therapy, denosumab has limited antitumour effect on neoplastic stromal cells. Nevertheless, its mechanism of action has not yet been clarified. A previous study has revealed that p62 may play an important role in the antitumour activity of denosumab. OBJECTIVE: The study aimed to investigate if the mechanism by which denosumab inhibits GCTB neoplastic stromal cells growth is via p62 modulation and other related mechanisms. METHODS: p62 expression before and after denosumab therapy was analysed by RT‒qPCR, western blot, ELISA, and immunohistochemical assays. Two primary neoplastic stromal cells were isolated from fresh GCTB tumour tissue (L cell) and metastatic tissue (M cell). Cell proliferation, migration, apoptosis, and autophagy were investigated in p62 knockdown neoplastic stromal cells transfected by short hairpin RNA lentivirus in vitro. Tumor growth was evaluated in the chick chorioallantoic membrane model in vivo. RESULTS: p62 expression was found to be downregulated following denosumab therapy. The patients with a decrease in p62 expression had lower recurrence-free survival rates. The proliferation of M cells was not inhibited by denosumab therapy, but it was restored by p62 knockdown. Moreover, p62 knockdown inhibited tumour growth in vivo. Denosumab induced M cell apoptosis and arrested the cell cycle at the G1/G0 transition and these effects were also enhanced by p62 knockdown. Autophagic flux assays revealed p62 modulation to be dependent on autophagy following denosumab incubation. CONCLUSION: Denosumab induced neoplastic stromal cells apoptosis via p62 downregulation dependent on autophagy pathway. The combination of p62 and RANKL knockdown might be a better strategy than RANKL knockdown alone for GCTB targeted therapy.

Demystifying Giant Cell Tumours of Tendon Sheath (GCTTS): A Case Series of 18 Cases with Review of Literature.

Background: The giant cell tumour of the tendon sheath (GCTTS) is the second most frequent soft tissue tumour affecting the hand. No consensus exists on the etiology, prognostic factors, or recurrence rate of GCTTS. This article presents a series of 18 cases supplemented by a literature review that examines the epidemiology, presentation, gross and microscopic characteristics, and recurrence rate of GCTTS. Methods: A total of 18 patients with a histo-pathological diagnosis of a GCTTS of the hand or finger were reviewed. The location for the tumour was limited to the wrist and hand. All cases were operated under Wide Awake Local anaesthesia (WALANT), and using a magnifying loupe. Results: A total of 18 patients presented at our institution with a diagnosis of GCTTS from 2016 to 2018. Of the 18 patients, 11 were female and 7 were male. The mean age of included patients was 43.6 years (31-59 years). The most common site for the lesion was the middle finger (4/18), followed by the index finger, wrist, and thumb (3/18 each). The little and ring finger were least commonly affected with one case each. The mean size of the tumour was 2.4 cm (0.5-5 cm). None of the patients reported recurrence of the lesion on an average follow-up of 18.8 months. Conclusion: GCTTS is a benign, slowly growing lesion of the hand that typically does not cause any symptoms and is treated with surgical resection. Meticulous excision of the GCTTS using magnification loupes to ensure appropriate wide excision of the tumour is the treatment of choice to prevent a recurrence. In addition, a radiographic and histopathological examination must be performed on the tumour to rule out other diagnoses. Finally, the function of the hand should be reconstructed to minimize the loss of any functional unit.

Magnetic Resonance Imaging (MRI) Findings in a Case of Pigmented Villonodular Synovitis of the Knee.

Pigmented villonodular synovitis (PVNS) is a rare benign condition of tenosynovial proliferation that mostly affects the knee joint. In this case report, we present a 39-year-old female with a ten-year history of gradual progression in the size of painful soft tissue swelling in her left knee. Our case report emphasizes the MRI's ability to provide detailed information on tendon sheath and synovium involvement, as well as extensive extra-articular involvement and hemosiderin deposition.

A Rare Case of Giant Cell Tumour of the Medial Epicondyle of the Humerus Managed With Curettage and Bone Grafting.

Giant cell tumours (GCTs) of the medial epicondyle of the humerus are rare. These are generally benign tumours but have the potential to be locally aggressive. They can invade the adjacent joint or the surrounding soft tissues or, in rare cases, cause distant metastasis. Locally aggressive GCTs are generally treated with wide resection, curettage, and bone grafting, followed by joint reconstructions. Here we present a case of a 49-year-old female with a history of swelling over the medial epicondyle of the humerus for six months. The patient was diagnosed with a locally aggressive GCT and was managed with wide excision of the tumour followed by sandwich bone grafting. A two-year follow-up of the patient shows no signs of recurrence. The patient is pain-free and has decent elbow function.

Giant Cell Tumor of Tendon Sheath: A Common Benign Entity With a Sore Note.

Giant cell tumor of the tendon sheath (GCTTS) is a slow-growing benign lesion that is reported to be the second most common soft tissue tumor of the hand. Etiopathogenesis remains unexplained, and pre-operative diagnosis is lacking in the majority of cases. A high recurrence rate remains a challenge for the surgeons, with incomplete excision being the most consensually accepted reason. A standard operative protocol of using a magnifying loupe/operating microscope for surgery helps in meticulous dissection and thus reduces the incidence of recurrence in GCTTS. We present the case of a 30-year-old female with a slowly growing nodular lesion on her right index finger, reported as GCTTS post-operatively; however, there was no recurrence at 18 months follow-up because of the use of a magnifying loupe during surgery.

Outcomes of Tenosynovial Giant Cell Tumor of the Foot and Ankle.

BACKGROUND: Tenosynovial giant cell tumor (TGCT) is a benign proliferative disease affecting synovial membranes. There are 2 forms, localized (L-TGCT) and diffuse (D-TGCT), which although histologically similar behave differently. It is locally invasive and is treated in most cases by operative excision. The aim of this study was to assess current practice, how the patients' presentation affected their outcome, as well as review the recurrence rates and complications. METHODS: A retrospective analysis of 123 cases was performed in patients treated between 2003 and 2019 with TGCT of the foot and/or ankle. Data were collected on age at presentation, radiologic pattern of disease, location of disease, treatment provided, and recurrence rates. The minimum follow-up was 2 years with a mean of 7.7 years. RESULTS: There were 61.7% female patients with a mean age of 39 (range, 11-76) years. L-TGCT accounted for 85 (69.1%) cases and D-TGCT for 38 (30.9%). The most prevalent preoperative symptoms were a palpable mass (78/123) and pain (65/123). Radiologically confirmed recurrence in the operative group was noted in 14.5% (16/110) cases. This comprised 4% (3/75) of operatively treated L-TGCT and 37% (13/35) of operatively treated D-TGCT. Patients with pain on presentation and those with erosive changes on presenting magnetic resonance imaging (MRI) were more likely to have persistent postoperative pain (P < .001 for both). Where patients had both preoperative pain and erosive changes, 57.1% had postoperative pain. Thirteen cases were managed nonoperatively where symptoms were minimal, with 1 case requiring surgery at a later date. CONCLUSION: Outcomes of TGCT management are dependent on the disease type, extent of preoperative erosive changes, and presence of preoperative pain. These data are useful for counseling patients regarding the outcomes of surgical intervention and help guide the timing of intervention. LEVEL OF EVIDENCE: Level III, retrospective cohort study.