Real-World Patient Experience of Pexidartinib for Tenosynovial Giant-Cell Tumor.

BACKGROUND: Pexidartinib (Turalio) is the only systemic therapy approved by the FDA for the treatment of adult patients with symptomatic tenosynovial giant-cell tumor (TGCT) associated with severe morbidity or functional limitations, and not amenable to improvement with surgery. This study assessed patient-reported treatment experiences and symptom improvement among patients receiving pexidartinib. METHODS: A cross-sectional, web-based survey collected data on demographics, disease history, pexidartinib dosing, and symptoms before and after pexidartinib use. RESULTS: Of 288 patients enrolled in the Turalio REMS program in May 2021, 83 completed the survey: mean age was 44.2 years, 62.7% were female, and most common tumor sites were in knee (61%) and ankle (12%). Mean initial dose was 622 mg/day: 29 patients reported reduction from initial dose and 8 had dose reduction after titrating up to a higher dose. At the time of survey completion, median time on pexidartinib was 6.0 months; 22 (26.5%) patients discontinued pexidartinib due to physician suggestion, abnormal laboratory results, side effect, or symptom improvement. Compared with before pexidartinib initiation, most patients reported improvement in overall TGCT symptom (78.3%) and physical function (77.2%) during pexidartinib treatment. Significant improvement was reported during pexidartinib treatment in worst stiffness numeric rating scale (NRS) (3.0 vs. 6.2, P < .05) and worst pain NRS (2.7 vs. 5.7, P < .05). CONCLUSION: Findings from this cross-sectional survey confirmed the benefit of pexidartinib in improving symptoms and functional outcomes among patients with symptomatic TGCTs from the patients' perspective. Future research is warranted to examine the long-term benefit and risk of pexidartinib.

Medium-term Outcomes of Excision Using Surgical Microscope of Tenosynovial Giant Cell Tumors of the Hand.

BACKGROUND/AIM: The recurrence rate following the excision of tenosynovial giant cell tumors (TSGCT) of the hand is very high. Intraoperative application of a surgical microscope has been reported. However, to date, there are no reports of medium-term outcomes related to this technique. This study aimed to evaluate the medium-term outcomes of tumor excision using surgical microscope for TSGCT of the hand. PATIENTS AND METHODS: A total of 27 patients, who underwent an initial surgery for histologically-confirmed TSGCT of the hand, between 2008 and 2020, were included and evaluated. The mean follow-up time postoperatively was 6.8 years. Tumor recurrence and preoperative tumor characteristics were assessed. RESULTS: All tumors were adherent to tendons, tendon sheaths, neurovascular structures or periarticular ligaments and capsules. Bony lesions were observed in 11 tumors. The surgical microscope was used in 13 tumors. Recurrences were observed in three tumors (overall recurrence rate: 11%). Tumor characteristics were similar in both groups, but the recurrence rate in the group treated using the surgical microscope was 0%, whereas the recurrence rate in the group treated without the surgical microscope was 21%. Re-operations using the surgical microscope for recurrent tumors were performed, without recurrence postoperatively. CONCLUSION: Among patients with TSGCT of the hand treated with tumor excision using the surgical microscope, the postoperative recurrence rate was 0%. Based on the results of this study, the surgical microscope might be used for excision of TSGCTs of the hand.

A Rare Clinical Presentation With a Difficult Imaging Diagnosis of an Intra-articular Clear Cell Sarcoma of the Knee.

ABSTRACT: Clear cell sarcoma, a highly aggressive cell sarcoma with melanotic differentiation, typically occurs in the tendon and aponeuroses of the lower extremities and rarely develops in the intra-articular region. Herein, we present an extremely rare case of clear cell sarcoma originating from the intra-articular knee and suspected as benign tumors due to the benign-looking findings on MRI and PET/CT. The image results in our case were completely consistent with a tenosynovial giant cell tumor, resulting in the misdiagnosis. For differential diagnosis, especially malignant melanoma, histopathology, including IHC and FISH, was indispensable.

Clinical retrospective analysis with a predictive model for diffused-tenosynovial giant cell tumors of the temporomandibular joint.

BACKGROUND: This study aimed to find out the characteristics in relation to tumor recurrence in diffused-tenosynovial giant cell tumor of temporomandibular joint and to develop and validate the prognostic model for personalized prediction. METHODS: From April 2009 to January 2021, patients with diffused-tenosynovial giant cell tumor of temporomandibular joint at a single center were included in this study. The clinical features and local recurrence-free survival were assessed through the expression of the Ki-67 index and colony-stimulating factor 1 receptor expression. Both univariate and multivariate analyses were performed on the prognostic factors for local recurrence-free survival. An independent predictor nomogram and pertinent tumor characteristics were included. RESULTS: The retrospective study enrolling seventy eligible patients at the Ninth People's Hospital, Shanghai Jiao Tong University School of Medicine. During the follow-up time, eleven patients suffered tumor recurrence. Age was an independent risk factor for local recurrence-free survival (P = 0.032). The Ki-67 index varied significantly in different sites (P = 0.034) and tumor volume (P = 0.017). Multivariate logistic regression was used to develop the prediction model using both statistical significance and prognostic indicators. The C-index of the nomogram based on age, site, Ki-67, and colony-stimulating factor 1 receptor was 0.833. These variates provided good predicted accuracy for a nomogram on local recurrence-free survival. Diffused-tenosynovial giant cell tumor from the temporomandibular joint is extremely uncommon, and certain clinical traits are linked to the tumor proliferation index. CONCLUSIONS: We identified the risk indicators and developed a nomogram in this study to forecast the likelihood of local recurrence-free survival in patients with diffused-tenosynovial giant cell tumor from temporomandibular joint.

Tenosynovial giant cell tumor: a case report.

BACKGROUND: This case reports the synchronous diagnosis of two rare unrelated diseases; leiomyosarcoma and tenosynovial giant cell tumor of the knee. It focuses on the challenges of diagnosing tenosynovial giant cell tumor, including cognitive biases in clinical medicine that delay diagnosis. It also demonstrates the pathogenic etiology of tenosynovial giant cell tumor, evidenced by the transient deterioration of the patients' knee symptoms following the administration of prophylactic granulocyte colony-stimulating factor given as part of the chemotherapeutic regime for leiomyosarcoma. CASE PRESENTATION: A 37-year-old Caucasian man presented with a left groin lump and left knee pain with swelling and locking. Investigations including positron emission tomography-computed tomography and biopsy revealed leiomyosarcoma in a lymph node likely related to the spermatic cord, with high-grade uptake in the left knee that was presumed to be the primary site. His knee symptoms temporarily worsened each time granulocyte colony-stimulating factor was administered with each cycle of chemotherapy for leiomyosarcoma to help combat myelosuppressive toxicity. Subsequent magnetic resonance imaging and biopsy of the knee confirmed a tenosynovial giant cell tumor. His knee symptoms relating to the tenosynovial giant cell tumor improved following the completion of his leiomyosarcoma treatment. CONCLUSIONS: Tenosynovial giant cell tumor remains a diagnostic challenge. We discuss the key clinical features and investigations that aid prompt diagnosis. The National Comprehensive Cancer Network clinical practice guidelines for soft tissue sarcoma have recently been updated to include the pharmacological management of tenosynovial giant cell tumor. Our case discussion provides an up-to-date review of the evidence for optimal management of patients with tenosynovial giant cell tumor, with a particular focus on novel pharmacological options that exploit underlying pathogenesis.

A Mass on the Sole Revealing a Giant-Cell Tumor of the Tendon Sheath.

A 61-year-old woman presented with a 3-year history of painless soft-tissue mass on the right sole. The patient reported gradual growth, with a rapid increase in size over the past few months, leading to difficulty in walking. She had no history of past trauma. Examination revealed a 4-cm ovoid mass located over the ball of the foot. It was firm in consistency, with well-defined margins, a smooth surface, and an overlying normal skin (Figure 1). An ultrasound image revealed an eccentric, hypoechoic, nonvascular subcutaneous lobular mass. A magnetic resonance imaging (MRI) of the foot revealed a well-defined mass arising from the flexor tendon sheath of the right foot. The lesion was heterogeneously hyperin-tense on T1- and T2-weighted images with an avid contrast enhancement. All of the surrounding soft tissues indicated normal signal intensity patterns. There was no associated bony destruction. Histopathologic examination after complete excision of the mass established a well-circumscribed lesion composed of osteoclast-like giant cells and mononuclear cells in a hyalinized stroma, consistent with a giant cell tumor of the tendon sheath (GCT-TS) (Figure 2). There was no recurrence during a 6-month follow-up period (Figure 3).

Tenosynovial giant cell tumour of the finger: a case report.

Giant cell tumour most commonly occuring in epiphysis of the long bone, present and with pain, tenderness and swelling. It is a solitary lesion with restricted movement and tenderness over the lesion. The tendon sheath is where tenosynovial giant cell tumours typically develop. Because of its remarkably peculiar position, we present a case of giant cell tumour (GCT) tenosynovial of bone in the middle phalaynx in a 33-year-old female with complaints of swelling, pain in ring finger of left hand since 2 months which is rarely seen. After clinical, radiological, pathological investigations tenosynovial giant cell tumour was diagnosed. Following fine needle aspiration cytology, histopathology was utilized to confirm the tumour's diagnosis which was later treated as resection of excision of the tumour with allo/autograft reconstruction. Our case report showed no evidence of recurrence in 2 years of follow-up. Hence our case report proves that early and complete resection of the tumour shows evidence of regain of complete range of motion and decrease recurrence rate.

Multimodal management of tenosynovial giant cell tumors (TGCT) in the landscape of new druggable targets.

Tenosynovial giant cell tumor (TGCT) is a rare, benign, locally aggressive synovial based neoplastic process that can result in functional debilitation and end-stage arthrtitis. Although surgical resection is the primary treatment modality, novel systemic therapies are emerging as part of the multimodal armamentarium for patients with unresectable or complex disease burden. This review discusses the pathogenesis of TGCT, potential druggable targets and therapeutic approaches. It also evaluates the safety and efficacy of different systemic therapies.

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.

Cytomorphologic panorama of giant cell tumour of tendon sheath.

BACKGROUND: Giant Cell Tumour of Tendon Sheath (GCTTS) is a slow growing benign soft tissue tumour arising from synovium of tendon sheath or joint. These tumours occur more frequently in upper limbs, especially hands. In the present study, we aimed to evaluate the cytomorphological spectrum of GCTTS. METHODS: This retrospective study includes a total of 56 cases of GCTTS diagnosed over a period of 8 years. The clinical and radiological details of these cases were retrieved from the cytopathology records and detailed cytomorphological features were studied and analysed. Histopathological correlation was done in 16/56 cases, where follow-up was available. RESULTS: The mean age of patients at the time of presentation was 32 years and were predominantly females (68%). The most common site of GCTTS was fingers (76%), followed by foot, wrist and toes. The most consistent finding on cytology was stromal cells (100%) of polygonal, spindle and plasmacytoid morphology with interspersed multinucleated osteoclastic giant cells (100%), followed by binucleated stromal cells (75%), xanthoma cells (61%) and hemosiderin laden macrophages (52%). Presence of proteinaceous fluid background was also observed in 50% of the cases. CONCLUSION: GCTTS can be diagnosed with certainty on FNAC based on characteristic cytomorphological features in an appropriate clinical and radiological setting. FNAC plays a pivotal role in diagnosing GCTTS and differentiating it from other giant cell rich lesions, thus obviating the need of tissue biopsy for diagnosis, which in turn helps the clinician in timely and adequate management of the patient.

Giant Cell Tumour of Tendon Sheath of Distal Phalanx of Thumb: A Case Report.

Giant cell tumour of tendon sheath is an uncommon benign soft tissue tumour. Histopathological examination plays a crucial role in the definitive diagnosis of giant cell tumour although pre-operative imaging supports its suspicion. We report a case of a giant cell tumour of the tendon sheath in a 26-year-old man as a painless, firm, localized, slow-growing benign soft tissue tumour of the thumb; managed by complete excision. The patient continues to do well at 7 months post-surgery with no complaints and no signs of recurrence. Giant cell tumour of the phalanges is a locally aggressive entity; therefore delayed or missed diagnosis of giant cell tumour especially of the thumb distal phalanx can be extremely debilitating. Hence, high degree of suspicion and early en bloc resection is the key to its management. Keywords: case reports; giant cell tumors; tendons; thumb.

Updates on the Treatment of Tenosynovial Giant Cell Tumor.

Tenosynovial giant cell tumor (TGCT) is a rare inflammatory disorder affecting the joint synovium, bursae, and tendon sheaths that causes non-specific and often insidious joint discomfort. The application of systemic chemotherapy has been limited due to poor and unsustained disease responses. Surgery with or without adjuvant radiation is the primary treatment modality for TGCT. With its locally destructive nature and increased recurrence, multiple surgical interventions become necessary throughout the course of the disease, leading to disfigurement, decreased quality of life, and increased mortality. However, owing to recent evidence demonstrating the overexpression of colony-stimulating factor 1 (CSF-1) in TGCT, selective tyrosine kinase inhibitors targeting CSF-1 receptors are being developed. Pexidartinib is the first CSF-1 receptor inhibitor approved for the treatment of TGCT. Here, we discuss various available treatment strategies and ongoing investigations and trials targeting diffuse TGCT, which include nilotinib, lacnotuzumab, cabiralizumab, vimseltinib, and emactuzumab.

Understanding the Effect of Osteoarthritis on Surgical Treatment Patterns, Healthcare Resource Utilization, and Costs Among Patients With Tenosynovial Giant Cell Tumors.

BACKGROUND: Tenosynovial giant cell tumor (TGCT) may be misdiagnosed as osteoarthritis (OA), or the chronic course of TGCT may lead to development of secondary OA. However, little is known about the effect of comorbid OA on long-term surgical patterns and costs among TGCT patients. METHODS: This cohort study used claims data from the Merative MarketScan Research Databases. The study included adults diagnosed with TGCT from January 1, 2014, to June 30, 2019, who have at least 3 years of continuous enrollment before and after the first TGCT diagnosis (date of the first TGCT diagnosis = index date) and no other cancer diagnosis during the study period. Patients were stratified by the presence of an OA diagnosis relative to the index date. Outcomes included surgical procedure patterns, healthcare resource utilization, and costs in the 3-year pre- and postindex periods. Multivariable models were used to assess the effect of OA on the study outcomes, controlling for baseline characteristics. RESULTS: The study included 2856 TGCT patients: 1153 (40%) had no OA before or after index (OA[-/-]), 207 (7%) had OA before index but not after (OA[+/-]), 644 (23%) had OA after index but not before (OA[-/+]), and 852 (30%) had OA before and after index (OA[+/+]). The mean age was 51.6 years, and 61.7% were female. During the postperiod, joint surgery was more common among OA(-/+) and OA(+/+) patients compared with OA(-/-) and OA(+/-) patients (55.7% vs 33.2%). The mean all-cause total costs in the 3-year postperiod were $19,476 per patient per year. Compared with OA(-/-) patients, OA(-/+) and OA(+/+) patients had a higher risk of undergoing recurrent surgery and higher total healthcare costs postindex. DISCUSSION: Higher rates of surgery and increased healthcare cost observed in TGCT patients with postindex OA underscore the need for effective treatment options to reduce joint damage, especially among patients with comorbid OA.

18F-FDG PET/CT image of tenosynovial giant cell tumor in the thoracic vertebra.

Diffuse-type tenosynovial giant cell tumor (D-TSGCT) is a destructive benign tumor-like proliferative disease. Diffuse-type tenosynovial giant cell tumorrarely arises from the axial skeleton. We report a case of image findings of D-TSGCT in the thoracic vertebra. On fluorine-18-fluorodeoxyglucose (18F-FDG) positron emission tomography/computed tomography (PET/CT) image, it presented a lytic bone destruction of 6th thoracic vertebra, vertebral processes as well as adjacent sixth rib with intense 18F-FDG uptake. Our case hints another unusual D-TSGCT image characteristic, which should be considered as a differential diagnosis when we interpret similar sign on 18F-FDG PET/CT.

Management of tenosynovial giant cell tumour of the temporomandibular joint: a systematic review.

Diffuse type tenosynovial giant cell tumour of the temporomandibular joint (D-TGCT-TMJ) is a rare proliferative disorder. The aim of this study was to perform a systematic review of the literature to summarize D-TGCT-TMJ management regimes and recurrence rates with at least 12 months of follow-up. Our secondary aim was to propose a minimum period of post-operative follow-up. A medline search for any D-TGCT-TMJ case detailing treatment, follow-up of at least 12 months, and presence of recurrence was undertaken. The following variables were extracted from the studies: patient's age and sex, presence of middle cranial fossa invasion, treatment undertaken, total length of follow-up, and presence of recurrence. All studies were assessed for bias as per the Joanna Briggs Institute systematic reviews appraisal tool. There were 63 cases reviewed and were predominantly managed with total resection (60.3%). Other modalities included: arthroplasty, subtotal resection with or without postoperative radiotherapy, medical therapy and surveillance. The recurrence rate was 9.52% and the longest follow-up period where recurrence was observed was at 60 months. Total resection and arthroplasty are common D-TGCT-TMJ management regimes. Patients with D-TGCT-TMJ should be followed up annually for at least 5 years postoperatively to assess for recurrence.

Image findings of tendon sheaths affected by diffuse tenosynovial giant cell tumors of the skull base.

OBJECTIVE: This study investigated radiographic images and the differential diagnosis of intracranial diffuse tenosynovial giant cell tumor (D-TGCT) in order to better understand the disease and improve the rate of preoperative diagnosis. PATIENTS AND METHODS: Images and clinical data of patients with D-TGCT were retrospectively analyzed. Routine Computer Tomography (CT), routine Magnetic Resonance Imaging (MRI), and contrast-enhanced MRI were performed for nine cases. Susceptibility-weighted imaging (SWI) was also performed for one case. RESULTS: We reviewed nine patients (6 males and 3 females) aged between 24 and 64 years, with a mean age of 47.33 ± 14.92 years. The most frequent complaints were hearing loss (5/9, 55.6%), pain (4/9, 44%), masticatory symptoms (2/9, 22.2%), and mass (4/9, 44.4%), with a mean duration of 22 ± 21.43 months. All cases were centered on the base of the skull, and showed hyper-density soft-tissue mass with osteolytic bone destruction on CT. The tumor signal mainly showed iso-intensity or hypo-intensity on T1WI compared with that in the brain parenchyma in all patients. On T2WI, nine lesions mainly showed hypo-intensity. Among these nine lesions, three displayed cystic region showing hyper-intensity on T2WI and hypo-intensity on T1WI (Figure 2A, 2B) in the lesion. Nine lesions showed hypo-intensity on DWI sequences. SWI images presented low signal in two cases, showing the "flowering effect". Nine patients showed heterogeneous enhancement, and two patients had meningeal thickening. CONCLUSIONS: Intracranial D-TGCT is extremely rare, but must be differentiated from other tumors. Osteolytic bone destruction in the area of the skull base with hyper-density soft-tissue mass and hypo-intensity on T2WI images are indicative of D-TGCT.

Giant cell tumor of tendon sheath: A report of 216 cases.

BACKGROUND: In this article on giant cell tumor of tendon sheath (GCTTS), we intend to summarize and analyze the clinical and pathological features of GCTTS hoping to improve clinical management and patient treatment. METHODS: The study retrospectively reviewed 216 patients of GCTTS, registered at the Affiliated Hospital of Southwest Medical University from January 2010 to December 2020. These cases were diagnosed by surgical excision. The clinicopathological features and the prognosis were reviewed in the light of the current literature. RESULTS: Of these 216 GCTTS patients, 72 were males (33.3%) and 144 females (66.7%), with a ratio male-to-female of 1:2. The patients' age ranged from 5 to 82, the average being 41.5 years at diagnosis. A total of 96 cases (44.4%) occurred in the hand region, followed by 35 cases (16.2%) in the knee, 32 cases (14.8%) in the foot, 25 cases (11.6%) in the ankle, 12 cases (5.6%) in the wrist, 12 cases (5.6%) in the leg, 2 cases (0.9%) in the head, 1 case (0.5%) in the forearm, and 1 case (0.5%) inside and outside the spinal channel. Histopathology mainly revealed large synovial-like monocytes, small monocytes, and osteoclast-like giant cells. CONCLUSION: Our results confirm that GCTTS predominantly occurs in the hands of young women. Complete surgical resection with long-term follow-up is the preferred management.