What is the management approach for a giant cell tumor of soft tissue in adults?

Giant Cell Tumor of Soft Tissue: Management Approach

Complete surgical excision with negative margins is the definitive treatment for giant cell tumor of soft tissue (GCTST), and all patients must be managed through a specialized sarcoma multidisciplinary team (MDT) given the tumor's intermediate malignancy potential and unpredictable biological behavior. 1, 2, 3

Initial Diagnostic Pathway

Immediate Referral

• Refer urgently to a specialist sarcoma MDT within 2 weeks for any patient presenting with a soft tissue mass suspicious for GCTST 1, 4
• This centralized referral is mandatory because GCTST is classified as a locally aggressive mesenchymal neoplasm of intermediate malignancy requiring specialized multidisciplinary expertise 1, 2

Imaging Studies

• MRI is the primary imaging modality for extremity and superficial trunk lesions, providing optimal detail for surgical planning 1
• Plain radiographs should be obtained to detect any reactive bone formation (present in approximately 50% of cases) and to rule out primary bone involvement 2, 5
• CT chest is mandatory to exclude pulmonary metastases, as GCTST has demonstrated higher metastatic rates compared to giant cell tumor of bone 1, 3, 5
• CT or MRI typically shows a solid, nonhomogeneous, frequently hemorrhagic mass 3

Tissue Diagnosis

• Multiple core needle biopsies (≥14-16G needles) are the standard diagnostic approach 1
• The biopsy must be planned by the sarcoma MDT so the biopsy tract can be safely excised during definitive surgery 1, 4
• Excisional biopsy may be appropriate only for superficial lesions <3-5 cm 1

Histopathological Confirmation

Key Diagnostic Features

• GCTST shows uniformly scattered osteoclast-like multinucleated giant cells intimately admixed with mononuclear cells, histologically resembling giant cell tumor of bone 2, 6, 5
• Critical distinction: GCTST lacks H3-3A gene mutations that characterize giant cell tumor of bone, confirming different pathogenesis 2
• CD68 immunostaining is positive in multinucleated giant cells and focally in mononuclear cells 6, 5

Malignant Features Assessment

• High-grade histological features indicate significantly higher metastatic risk: nuclear atypia, pleomorphism, and elevated mitotic activity (>25 mitoses per 10 HPF) in mononuclear cells 2, 5
• Primary or secondary malignant transformation has been described and portends worse prognosis 2
• Specialist pathology review is essential given the 8-11% major discordance rate for soft tissue tumors diagnosed outside sarcoma centers 4

Definitive Treatment

Surgical Management

• Wide surgical excision with microscopically negative margins (R0 resection) is the standard of care 2, 3, 6
• Incomplete excision is directly associated with local recurrence, which occurs more frequently than with giant cell tumor of bone 3, 5
• Surgery should be performed at a sarcoma reference center treating high volumes of patients annually 1

Radiation Therapy

• Radiation therapy may be considered when critical anatomical structures prevent achievement of negative surgical margins 2
• This represents a compromise approach when R0 resection would result in unacceptable functional morbidity 2

Systemic Therapy

• Systemic treatment options for advanced or metastatic GCTST are extremely limited 2
• Unlike giant cell tumor of bone, denosumab efficacy in GCTST is not established given the different molecular pathogenesis 2

Follow-Up and Surveillance

Monitoring Strategy

• Close long-term clinical follow-up is mandatory due to unpredictable biological behavior 3, 6
• GCTST demonstrates lower local recurrence rates than bone giant cell tumors but higher rates of distant metastasis and mortality 3, 5
• Surveillance imaging should include chest CT given the propensity for pulmonary metastases 1, 3

Critical Pitfalls to Avoid

• Do not confuse GCTST with other giant cell-rich soft tissue lesions (nodular fasciitis, giant cell malignant fibrous histiocytoma, extraskeletal osteosarcoma, dermatofibrosarcoma protuberans with giant cells) as clinical behavior, prognosis, and treatment differ significantly 7, 6
• Never perform definitive surgery outside a specialized sarcoma center as inadequate initial excision compromises outcomes and increases recurrence risk 1, 3
• Do not assume benign behavior based on histology alone—even histologically benign-appearing GCTST requires complete excision and long-term surveillance given documented cases of late recurrence and metastasis 3, 6, 5
• Avoid relying solely on ultrasound for diagnosis as it is highly user-dependent; proceed to MRI when any diagnostic uncertainty exists 1