Diffuse tenossinovial giant cell tumor: A systematic review on management and treatment strategies

Diffuse-type tenosynovial giant cell tumor (D-TGCT) is a rare and benign tumor that originates in the synovial lining of joints, tendon sheaths, or bursae. Despite being benign, it is associated with locally aggressive behavior and high risk of recurrence, leading to pain, swelling and significant functional impairment. Several treatment options exist, but there is still no clear consensus on the most effective approach, particularly for recurrent or inoperable cases. This systematic review explores current evidence on the management of D-TGCT, focusing on treatment strategies, recurrence rates, and outcomes, while also discussing new therapeutic alternatives. By bringing together all recent advances, this review aims to help clinicians make informed and patient-tailored decisions when managing this tumor. A systematic search was conducted in PubMed, Scopus, and Web of Science, including studies published between 2000 and January 2025. Original articles reporting treatment outcomes in patients with D-TGCT were selected. To ensure accuracy and reduce bias, two reviewers independently selected studies and extracted relevant data. The methodological quality of the included studies was assessed using the JBI Critical Appraisal Checklist for Cohort Studies. Due to the heterogeneity across study methodologies and outcomes, a narrative synthesis was considered the most appropriate method to summarize the results. Fifty-two studies, including 4279 patients, were reviewed. Surgery, especially open synovectomy, remains the standard of treatment but is associated with considerably high recurrence rates. Adjuvant radiotherapy can help reduce recurrence in selected patients. In inoperable or recurrent tumors, systemic therapies, such as CSF1R inhibitors, have shown some short-term benefits. However, their toxicity and long-term effects are still unclear. For asymptomatic patients, active surveillance can be a viable option. The management of D-TGCT requires a tailored and multidisciplinary approach, coordinated in a referral center. While treatment options have expanded over the years, there is still no standardized treatment algorithm. Therefore, further research is needed to establish clearer guidelines and treatment protocols. Multimodal strategies combining surgery, radiotherapy, and systemic therapies can offer the best outcomes particularly when individualized to the patient's condition and tumor behavior. Diffuse-type tenosynovial giant cell tumor (D-TGCT) is a benign yet aggressive synovial tumor with high recurrence rates. This systematic review analyzed 52 studies involving 4279 patients. Surgery remains the primary treatment, though recurrence is common. Radiotherapy can be beneficial as an adjuvant therapy. In recurrent or inoperable cases, CSF1R inhibitors show promise despite limited long-term data. Active surveillance is viable for asymptomatic patients. A multimodal, individualized, and multidisciplinary approach remains essential for optimizing outcomes in D-TGCT management.