Active surveillance of diffuse-type tenosynovial giant cell tumors: A retrospective, multicenter cohort study.

BACKGROUND: Diffuse-type tenosynovial giant cell tumor (D-TGCT) is a mono-articular, soft-tissue tumor. Although it can behave locally aggressively, D-TGCT is a non-malignant disease. This is the first study describing the natural course of D-TGCT and evaluating active surveillance as possible treatment strategy. METHODS: This retrospective, multicenter study included therapy naïve patients with D-TGCT from eight sarcoma centers worldwide between 2000 and 2019. Patients initially managed by active surveillance following their first consultation were eligible. Data regarding the radiological and clinical course and subsequent treatments were collected. RESULTS: Sixty-one patients with primary D-TGCT were initially managed by active surveillance. Fifty-nine patients had an MRI performed around first consultation: D-TGCT was located intra-articular in most patients (n = 56; 95 %) and extra-articular in 14 cases (24 %). At baseline, osteoarthritis was observed in 13 patients (22 %) on MRI. Most of the patients' reported symptoms: pain (n = 43; 70 %), swelling (n = 33; 54 %). Eight patients (13 %) were asymptomatic. Follow-up data were available for 58 patients; the median follow-up was 28 months. Twenty-one patients (36 %) had radiological progression after 21 months (median). Eight of 45 patients (18 %) without osteoarthritis at baseline developed osteoarthritis during follow-up. Thirty-seven patients (64 %) did not clinically deteriorate during follow-up. Finally, eighteen patients (31 %) required a subsequent treatment. CONCLUSION: Active surveillance can be considered adequate for selected therapy naïve D-TGCT patients. Although follow-up data was limited, almost two-thirds of the patients remained progression-free, and 69 % did not need treatment during the follow-up period. However, one-fifth of patients developed secondary osteoarthritis. Prospective studies on active surveillance are warranted.

Management of tenosynovial giant cell tumour of the foot and ankle.

AIMS: Tenosynovial giant cell tumour (TGCT) is one of the most common soft-tissue tumours of the foot and ankle and can behave in a locally aggressive manner. Tumour control can be difficult, despite the various methods of treatment available. Since treatment guidelines are lacking, the aim of this study was to review the multidisciplinary management by presenting the largest series of TGCT of the foot and ankle to date from two specialized sarcoma centres. METHODS: The Oxford Tumour Registry and the Leiden University Medical Centre Sarcoma Registry were retrospectively reviewed for patients with histologically proven foot and ankle TGCT diagnosed between January 2002 and August 2019. RESULTS: A total of 84 patients were included. There were 39 men and 45 women with a mean age at primary treatment of 38.3 years (9 to 72). The median follow-up was 46.5 months (interquartile range (IQR) 21.3 to 82.3). Localized-type TGCT (n = 15) predominantly affected forefoot, whereas diffuse-type TGCT (Dt-TGCT) (n = 9) tended to panarticular involvement. TGCT was not included in the radiological differential diagnosis in 20% (n = 15/75). Most patients had open rather than arthroscopic surgery (76 vs 17). The highest recurrence rates were seen with Dt-TGCT (61%; n = 23/38), panarticular involvement (83%; n = 5/8), and after arthroscopy (47%; n = 8/17). Three (4%) fusions were carried out for osteochondral destruction by Dt-TGCT. There were 14 (16%) patients with Dt-TGCT who underwent systemic treatment, mostly in refractory cases (79%; n = 11). TGCT initially decreased or stabilized in 12 patients (86%), but progressed in five (36%) during follow-up; all five underwent subsequent surgery. Side effects were reported in 12 patients (86%). CONCLUSION: We recommend open surgical excision as the primary treatment for TGCT of the foot and ankle, particularly in patients with Dt-TGCT with extra-articular involvement. Severe osteochondral destruction may justify salvage procedures, although these are not often undertaken. Systemic treatment is indicated for unresectable or refractory cases. However, side effects are commonly experienced, and relapses may occur once treatment has ceased. Cite this article: Bone Joint J 2021;103-B(4):788-794.

Management of Tenosynovial Giant Cell Tumor: A Neoplastic and Inflammatory Disease.

BACKGROUND: Patients with diffuse tenosynovial giant cell tumor (TGCT) face a high risk of recurrence, progression, and disability. This systematic review assesses the recent evidence of surgical, adjuvant, and systemic treatments for TGCT. METHODS: We searched PubMed and Ovid with the terms "Giant cell tumor of tendon sheath" OR "pigmented villonodular synovitis" OR "tenosynovial giant cell" AND "treatment" OR "surgery." INCLUSION CRITERIA: published 2013 to present; prospective or retrospective design; English language; > 20 patients with histopathological confirmed diagnosis of TGCT; and ≥ 1 efficacy and/or safety outcome from surgery, systemic drug therapy, or adjuvant yttrium radiosynoviorthesis. RESULTS: Of the 434 studies identified, 25 met the inclusion criteria. Of 11 studies in patients with disease in the knee, nine examined surgical treatment approaches, and two evaluated adjuvant yttrium radiosynoviorthesis. Of 11 studies in patients with mixed sites of disease, six assessed surgical treatment approaches, and five evaluated systemic drug therapies. Three studies assessed surgery in patients with TGCT in the hand, hip, and ankle or foot. DISCUSSION: The high rates of recurrence and risks associated with surgery emphasize the need for novel treatments in patients with symptomatic, advanced TGCT. Systemic therapy may be valuable as part of a multidisciplinary approach.

Treatments of tenosynovial giant cell tumours of the temperomandibular joint: a report of three cases and a review of literature.

Tenosynovial giant cell tumours (TGCTs) are benign lesions affecting synovial joints. The classified subtypes are localized and diffuse. They seldom occur in the temporomandibular joint (TMJ). The aim of this study is to report on three new cases and to review the literature. One patient had surgical debulking with adjuvant external beam radiation therapy (EBRT). After 1year of follow-up, no evidence of disease was presented. The second patient was misdiagnosed and treated with denosumab. Debulking with adjuvant EBRT followed. Ten months postoperatively, no disease progression was seen. The third patient received systemic nilotinib and remained stable for over 5years. The literature review included 106 cases of which 95 had diffuse subtype. Most patients, had surgical excision. Thirteen (14%) patients received adjuvant EBRT. Eleven (14%) recurrences were identified. After 1-, 5- and 10 years of follow-up, an overall progression-free survival (PFS) of 99% (95% confidence interval (CI) 0.96-1), 80% (95% CI 0.68-0.94), 67% (95% CI 0.51-0.90) was calculated, respectively. Treatments for diffuse-TGCT-TMJ should be individualized depending on age, severity of symptoms, extent of disease and progression, expected mutilation of surgical interference, and current systemic treatment options. In stable disease a 'wait and see' policy, is a viable option. Additional treatments should be reserved for symptomatic, irresectable tumours or residual disease after surgical treatment with persistent complaints.

Burden of Illness Associated with Tenosynovial Giant Cell Tumors.

PURPOSE: Little is known about the burden of illness in patients with tenosynovial giant cell tumors (TGCT), which are rare, typically benign, lesions of the synovial tissue including giant cell tumor of the tendon sheath (GCT-TS) and pigmented villonodular synovitis (PVNS). The objective of this study was to describe health care resource use and costs for patients with GCT-TS and PVNS, which are rare and typically benign TGCT. METHODS: A retrospective cohort study design was used to analyze administrative claims for adult commercial and Medicare Advantage health plan enrollees with evidence of GCT-TS and PVNS from January 1, 2006 through March 31, 2015. Participants were continuously enrolled for 12 months before (pre-index period) and 12 months after (post-index period) the date of the first tenosynovial giant cell tumor (TGCT) claim (index date). Preindex and postindex measures were compared using the McNemar test and Wilcoxon signed-rank test. Results were stratified by TGCT type. FINDINGS: The study identified 4664 patients with TGCT, 284 with GCT-TS, and 4380 with PVNS. Mean age (GCT-TS group: 50 years; PVNS group: 51 years) and sex distributions (GCT-TS group: 60.2% female; PVNS group: 59.5% female) were similar for each group. Most patients with GCT-TS (78.2%) had at least one postindex surgery, compared with 38.7% of patients with PVNS. Mean total health care costs increased from $8943 in the preindex period to $14,880 in the postindex period (P < 0.001) for GCT-TS and from $13,221 in the preindex period to $17,728 in the postindex period (P < 0.001) for PVNS. Preindex to postindex ambulatory costs increased nearly 120% for patients with GCT-TS ($4340 to $9570, P < 0.001) and 50% for patients with PVNS ($6782 to $10,278, P < 0.001), and physical therapy use increased significantly during the same period (GCT-TS: 18% to 40%, P < 0.001; PVNS: 38% to 60%, P < 0.001). IMPLICATIONS: Costs increased substantially 1 year after the first TGCT claim, with more than half the costs covering ambulatory care. These results suggest a high health care burden once TGCT is identified.

Locally Aggressive Connective Tissue Tumors.

In this review, we highlight the complexities of the natural history, biology, and clinical management of three intermediate connective tissue tumors: desmoid tumor (DT) or aggressive fibromatosis, tenosynovial giant cell tumor (TGCT) or diffuse-type pigmented villonodular synovitis (dtPVNS), and giant cell tumor of bone (GCTB). Intermediate histologies include tumors of both soft tissue and bone origin and are locally aggressive and rarely metastatic. Some common aspects to these tumors are that they can be locally infiltrative and/or impinge on critical organs, which leads to disfigurement, pain, loss of function and mobility, neurovascular compromise, and occasionally life-threatening consequences, such as mesenteric, bowel, ureteral, and/or bladder obstruction. DT, PVNS, and GCTB have few and recurrent molecular aberrations but, paradoxically, can have variable natural histories. A multidisciplinary approach is recommended for optimal management. In DT and PVNS, a course of observation may be appropriate, and any intervention should be guided by symptoms and/or disease progression. A surgical approach should take into consideration the infiltrative nature, difficulty in obtaining wide margins, high recurrence rates, acute and chronic surgical morbidities, and impact on quality of life. There are similar concerns with radiation, which especially relate to optimal field and transformation to high-grade radiation-associated sarcomas. Systemic therapies must be considered carefully in light of acute and chronic toxicities. Although standard and novel therapies are promising, many unanswered questions, such as duration of therapy and optimal end points to evaluate efficacy of drugs in clinical practice and trials, exist. Predictive biomarkers and novel clinical trial end points, such as volumetric measurement, magnetic resonance imaging T2 weighted mapping, nuclear imaging, and patient-reported outcomes, are in development and will require validation in prospective trials.

Tenosynovial giant cell tumors of the temporomandibular joint and lateral skull base: Review of 11 cases.

OBJECTIVES: To elucidate the clinical behavior, treatment, and outcomes of tenosynovial giant cell tumors (TGCT) involving the temporomandibular joint (TMJ) and adjacent temporal bone. STUDY DESIGN: Retrospective case series with histopathologic review. METHODS: A retrospective chart review was performed identifying and collecting data from all cases of TGCT involving the TMJ and adjacent temporal bone that were treated at the authors' center between January 1960 and December 2015. RESULTS: Eleven histopathologically confirmed cases met inclusion criteria. The median age at diagnosis was 49 years, eight patients were men, and the median follow-up was 116 months. Computed tomographic (CT) imaging revealed a lytic expansile mass centered on the TMJ. Magnetic resonance imaging (MRI) most commonly exhibited hypointense signal on precontrast T1- and T2-weighted sequences and variable postcontrast enhancement. The median delay in diagnosis was 24 months, and the most common presenting symptoms were hearing loss and pain. All patients underwent surgical resection, eight receiving gross total removal, one receiving near total removal, and two patients from early in the series receiving subtotal resection with neoadjuvant or adjuvant radiation. Histopathological review of surgical specimens revealed chondroid metaplasia in seven tumors. Eight of nine cases receiving gross total or near total resection have no evidence of recurrence to date. CONCLUSIONS: TGCT of the TMJ and temporal bone are rare and locally aggressive tumors that commonly present with nonspecific symptoms. A careful review of CT and MRI followed by early biopsy is critical in establishing an accurate diagnosis and facilitating appropriate treatment. TGCT of the TMJ more commonly contain chondroid metaplasia when compared to TGCT at other anatomic locations. Gross total resection is achievable in most cases and offers long-term cure. Radiation may be considered for recurrent disease or adjuvant therapy following subtotal resection. LEVEL OF EVIDENCE: 4. Laryngoscope, 127:2340-2346, 2017.

Diffuse-type tenosynovial giant cell tumour: Current treatment concepts and future perspectives.

At present, the optimal treatment strategy in patients with diffuse-type tenosynovial giant cell tumour (D-TGCT) is unclear. The purpose of this review was to describe current treatment options, and to highlight recent developments in the knowledge of the molecular pathogenesis of D-TGCT as well as related therapeutic implications. Epidemiology, clinical features, and the pathogenesis of D-TGCT and the most widely used treatment modalities are described. D-TGCT is a benign clonal neoplastic proliferation arising from the synovium. Patients are often symptomatic and require multiple surgical procedures during their lifetime. Currently, surgery is the main treatment for patients with D-TGCT, with relapse rates ranging from 14% to 55%. Radiosynovectomy and external beam radiotherapy have been used in combination with surgical excision or as single modalities. The finding that D-TGCT cells overexpress colony-stimulating factor 1 (CSF1), resulting in recruitment of CSF1 receptor (CSF1R)-bearing macrophages that are polyclonal and make up the bulk of the tumour, has led to clinical trials with CSF1R inhibitors. These inhibitors include small molecules such as imatinib, nilotinib, PLX3397, and the monoclonal antibody RG7155. In conclusion, D-TGCT impairs patients' quality of life significantly. The evidence that the pathogenetic loop of D-TGCT can be inhibited could potentially change the therapeutic armamentarium for this condition. Clinical trials of agents that target D-TGCT are currently ongoing. In the meantime, international registries should be activated in order to provide useful information on this relatively rare tumour.