Summary Giant Cell Tumors are benign, aggressive tumors typically found in the epiphysis of long bones, most commonly at the distal femur and proximal tibia. Patients typically present between ages 30 and 50 with insidious onset of pain of the involved extremity with activity, at night, or at rest. Diagnosis is made with a biopsy showing mononuclear stromal cells that resemble interstitial fibroblasts with numerous giant cells dispersed throughout. Treatment is generally curettage, adjuvant treatment, and reconstruction as necessary depending on the location of the lesion. Epidemiology Incidence 1.7 per million people Demographics more common in females (unlike most bone tumors which show male predominance) ages 30-50 years Anatomic location distal femur > proximal tibia > distal radius > sacral ala 50% occur around knee (distal femur or proximal tibia) 10% in sacrum and vertebrae (sacral ala is most common site in axial skeleton) login to view 1 more bullet phalanges of the hand is also a very common location may arise in the apophysis (like chondroblastoma) Etiology Genetics mutations metastatic lesions often noted to have altertions in c-myc oncogene or p53 Associated conditions malignancy primary malignant giant cell tumor login to view 2 more bullets secondary malignant giant cell tumor login to view 1 more bullet Presentation Symptoms pain insidious onset of pain of the involved extremity with activity, at night, or at rest pain referable to involved joint night pain (result of tumor expansion) difficulty ambulating swelling Physical exam inspection & palpation palpable mass tenderness over mass soft tissue swelling login to view 1 more bullet motion decreased range of motion around affected joint gait antalgic Imaging Radiographs recommended views extremity involved chest x-ray login to view 1 more bullet findings eccentric lytic epiphyseal/metaphyseal lesion that often extends into the distal epiphysis and borders subchondral bone "neo-cortex" is characteristic of benign aggressive lesions, and not unique to GCT CT recommend views chest CT login to view 1 more bullet findings lung metastases are usually benign (histologically similar to primary bone tumor) MRI indications to evalute for extent of lesion findings tumor blushing cystic degeneration shows clear demarcation on T1 image between fatty marrow and tumor login to view 1 more bullet Bone scan findings Can be variable Studies Histology characteristic cells type I cell login to view 3 more bullets type II cell login to view 2 more bullets type III cell login to view 6 more bullets secondary ABC degeneration is not uncommon molecular biology type II and III cells have IGF-I and IGF-II activity 80% of patients with GCT have telomeric associations (tas) abnormality in half the cells overexpression of RANKL by mononuclear stromal cells considered the instrumental pathogenic pathway login to view 1 more bullet Differential Brown tumor of hyperparathyroidism can look like GCT on radiographs except it occurs as multiple lesions and associated with serum calcium level abnormalities Chondroblastoma epiphyseal location may also demonstrate ABC formation has extensive surrounding soft tissue and marrow edema may have sclerotic margin and central calcification of chondroid matrix "ring and arcs" pattern Osteosarcoma telangiectatic OS giant cell-rich OS fibroblastic OS Chordoma (mimics GCT sacrum) occurs in midline Differential of Giant Cell tum Epiphyseal lesion Treatment is USUALLY curettage and bone grafting Giant Cell Tumor o o Chondroblastoma o o Aneurysmal Bone cyst o Osteoblastoma o Chondromyoid fibroma (CMF) o Treatment Nonoperative radiation therapy indications login to view 2 more bullets outcomes login to view 1 more bullet medical management (denosumab, bisphosphanates) indications login to view 2 more bullets outcomes login to view 2 more bullets Operative extensive curettage, adjuvant treatment and reconstruction indications login to view 3 more bullets outcomes login to view 1 more bullet complete resection and reconstruction indications login to view 2 more bullets outcomes login to view 1 more bullet amputation indications login to view 1 more bullet outcomes login to view 1 more bullet Techniques Radiation therapy technique external beam radiation Medical management technique bisphosphonates login to view 1 more bullet denosumab login to view 4 more bullets complications login to view 6 more bullets Extensive curettage, adjuvant treatment and reconstruction extensive curettage technique login to view 5 more bullets adjuvant treatment login to view 7 more bullets reconstruction login to view 3 more bullets Complete resection and reconstruction approach based on location in the spine (lumbar, thoracic, cervical) anterior, posterior, or combined login to view 1 more bullet technique login to view 5 more bullets Amputation technique resection of phalangeal or metacarpal lesions with ray transfer or allograft reconstruction Complications Malignant transformation to high grade sarcoma incidence very rare (<1% prevalence) latency login to view 2 more bullets treatment surgical resection of metastatic lesions interferon treatment radiation Secondary ABC incidence between 10-14% differentiate from primary ABC because of enhancing soft-tissue component in GCT (not present in primary ABC) Recurrence incidence local recurrence occurs in 20% cases diagnose with CT guided biopsy risk factors not using adjuvant treatment during surgery Pathologic fracture risk factors peri-articular lesions using crytherapy as an adjuvant Prognosis Risk of malignancy < 5 % metastatic GCT has a 5 year 76% disease-free survival rate and a 17% mortality rate.