Soft tissue recurrence in giant cell tumor of Bone: A comprehensive review of pathogenesis, imaging features, and clinical management.

Background: Giant cell tumor of bone (GCTB) is a benign but locally aggressive neoplasm with a high risk of recurrence. Among its patterns of relapse, soft-tissue recurrence (STR) is an uncommon but clinically significant entity, often presenting as ossified or non-ossified perilesional nodules. Despite its rarity, STR poses diagnostic and therapeutic challenges that require clarification. Methods: A comprehensive literature review was performed across PubMed, Embase, and Google Scholar from 1980 through January 2025, focusing on the epidemiology, pathogenesis, imaging features, histopathology, management, and outcomes of STR in GCTB. Case reports, series, and retrospective studies explicitly distinguishing STR from intraosseous recurrence were included, and findings were synthesized narratively. Results: STR occurs in approximately 2-3 % of GCTB cases, typically within 6-12 months after surgery. Major risk factors include curettage procedures, pathological fractures, cortical breaches, and unrecognized microscopic soft-tissue extension. Imaging reveals three distinct patterns: peripheral "eggshell" ossification, central nodular calcification, and purely soft-tissue lesions. Histology mirrors primary GCTB, often with osteogenic metaplasia, while molecular testing confirms retention of H3F3A mutations. Surgical excision with clear margins remains the mainstay of treatment, yielding excellent functional outcomes. However, up to 60 % of patients experience multiple recurrences, highlighting the need for vigilant surveillance. Systemic agents such as denosumab or bisphosphonates remain investigational, and radiotherapy is generally contraindicated due to malignant transformation risk. Conclusion: STR represents a rare but distinct subset of GCTB recurrences. Awareness of risk factors, early imaging-based detection, and complete surgical excision are critical for optimal outcomes. Further multicenter studies are required to define surveillance protocols, validate molecular predictors, and clarify the role of systemic therapy in this challenging condition.