Giant cell tumors (GCTs)

ALSO KNOWN AS: Osteoclastomas

RELATED CONDITIONS: Differential diagnosis includes other giant cell lesions, such as the brown tumor seen in hyperparathyroidism, giant cell reparative granuloma, chondroblastoma, pigmented villonodular synovitis, and giant cell tumor of the tendon sheath.

DEFINITION: Giant cell tumors (GCTs) are relatively uncommon, typically benign (though presenting as malignant in some rare cases), and locally aggressive bone neoplasms. The tumors are large, reddish-brown, and subject to frequent cystic degeneration. They are composed of uniform oval mononuclear cells with scattered osteoclast-type giant cells containing one hundred or more nuclei. The mononuclear cells are the proliferating component of the tumor. Secondary features include Necrosis, hemorrhage, hemosiderin (iron) deposition, and reactive bone formation.

Risk factors: No known predisposing factors place a person at risk for having a giant cell tumor. Genetic changes (mutations) trigger the condition, but researchers do not know what conditions or factors might promote such mutations. Those diagnosed with this condition, however, will have an increased risk for joint collapse degeneration and pathologic fractures. The incidence of metastasis is rare.

Etiology and the disease process: The tumor is in the metaphysis or epiphysis of long bones, with about half of the lesions occurring around the knee. The proximal humerus and distal radius are common locations, as are the pelvis and sacrum. Typically, the lesion presents as a painful, slowly enlarging mass. With the proliferation of the mononuclear cells, tissue expansion creates a bone defect described as lytic (bringing about disintegration or dissolution), with sharply circumscribed margins. The lesion is often described as having an “eccentric soap bubble” pattern. There may be thinning of the cortex (outer ring of bone), and the lesion may extend into the subchondral bone of the adjacent joint. Most tumors are solitary. However, multiple tumors do occur, especially in the distal extremities. Malignant degeneration is rare.

Data strongly suggest a close molecular genetic relationship between the benign giant cell tumors of bone and the malignant osteosarcomas (bone cancer). These conditions have similar genetic alterations in the oncogenes (genetic material incorporated into chromosomes associated with various malignancies). Molecular genetic studies have found a higher incidence of p53 protein and alterations in the MYC gene in both tumors.

Incidence: Giant cell tumors usually occur in people between ages twenty-five and forty, with a slight female predominance. They are exceedingly rare in patients younger than thirteen, and only about 10 percent of cases occur in individuals over sixty-five. Most giant cell tumors arise around the knee, but any bone may be involved, including the sacrum, pelvis, spine, and small bones of the hands and feet. Between 1.2 and 1.7 people per million are impacted each year.

Symptoms: The location of these tumors in the ends of bones near joints frequently causes patients to complain of arthritic symptoms. Individuals may complain of pain, show signs of local swelling, or have a through the lesion. Movement may be limited in impacted joints.

Screening and diagnosis: Diagnosis is based on X-ray evidence and confirmed by tissue biopsy. Magnetic resonance imaging (MRI) scans often define bone margins and soft-tissue involvement.

The staging system is based on imaging studies. Stage I (latent-quiescent) delineates a lesion in cancerous bone with minimal cortical involvement. The most common stage is stage II (active), which denotes extensive cortical thinning and creating the “soap bubble” pattern. Stage III (aggressive) has a greater risk of recurrence. A more aggressive surgical approach is recommended for tumors in stage III.

Treatment and therapy: In most cases, surgical excision is the treatment of choice. The use of radiation therapy is restricted to difficult lesions in the pelvis and spine, where an adequate surgical resection is not feasible because of anatomical considerations, as radiation carries the risk of malignant tumor recurrence.

Surgical excision involves extensive exteriorization (removal of a large cortical window over the lesion), curettage with hand and power instruments, and chemical cauterization with phenol (a caustic chemical that destroys cells) or hydrogen peroxide, cryosurgery, or other methods of cavity sterilization. The resulting defect is usually reconstructed with prosthetics, subchondral bone grafts, and methyl methacrylate cement. Surgery with curettage and bone graft alone is associated with a 40 to 60 percent recurrence rate. This rate tends to be lower if bone cement is used. Curettage followed by sterilization agents and bone cement reduces the recurrence rate to approximately 10 to 29 percent. Although benign, up to 4 percent of operative cases will metastasize to the lungs after surgery, suggesting dislodgement of tumor emboli. Lesions with significant extension into adjacent soft tissue require en bloc resection (complete removal of affected bone and surrounding tissue). In this more radical procedure, modified arthrodesis (fusion of a joint), allograft (replacement of bone segment with donor bone), or prosthetic reconstruction (artificial joint implant) is indicated. This operation may require extensive bone resection in the knee, necessitating a total knee replacement.

Prognosis, prevention, and outcomes: Malignancy may occur as a primary malignant giant cell tumor or a secondary malignant giant cell tumor. Fewer than 5 to 10 percent of giant cell tumors are malignant. Secondary tumors occur following radiation treatment of a giant cell tumor or following multiple local recurrences. The most common scenario is associated with a patient who has a large, aggressive giant cell tumor that is inoperable and thus treated with radiation. This procedure has a high success rate, but in approximately 15 percent of cases, develops in the irradiated field over an extended latency period of three to fifty years.

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