Giant cell tumor of bone

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Editor-In-Chief: C. Michael Gibson, M.S., M.D. [1]

Synonyms and keywords: Osteoclastoma; Giant cell myeloma; Giant cell tumor

Pathophysiology

Giant cell tumor of bone occurs commonly in the distal femur, the proximal tibia, the distal radius and the sacrum. Giant cell tumors (GCT) usually prefers the epiphyses of long bones.

Location

Giant cell tumor of bone typically occur as single lesions. Although any bone can be affected, the most common sites are:

• Around the knee: distal femur and proximal tibia: 50-65%
• Distal radius: 10-12%
• Sacrum: 4-9%
• Vertebral body
• Multiple locations: 1%

Gross Pathology

• Macroscopically, giant cell tumors are variable in appearance, depending on amount of hemorrhage, presence of co-existent aneurysmal bone cyst, and degree of fibrosis.

Microscopic Pathology

• Giant cell tumor of bone is characterized by the presence of numerous Cathepsin-K producing, CD33 +, CD14 - multinucleated osteoclast-like giant cells and plump spindle-shaped stromal cells that represent the main proliferating cell population.
• The spindle-shaped mononuclear cells are believed to represent the neoplastic population and are characterized at the cytogenetic level by telomeric associations and a peculiar telomere-protecting capping mechanism.
• Areas of regressive change such as necrosis or fibrosis as well as extensive hemorrhage are frequently present.
• It recurs from time to time and rates between 25–50% have been reported. In very rare cases, a malignant change may occur.

Epidemiology and Demographics

Prevalence

• Giant cell tumor of bone accounts for 4-5% of primary bone tumors and 18.2% of benign bone tumors .

Age

• Giant cell tumor of bone almost invariably (97-99%) occur when the growth plate has closed and are therefore typically observed in early adulthood, with 80% of cases reported between the ages of 20 and 50, with a peak incidence between 20 and 30.

Gender

• Giant cell tumor of bone is more common in females with the rate of growth enhanced in pregnancy. Female to male ratio 1.5:1.

Differentiating Giant cell tumor of bone from other Diseases

A number of tumors have giant cells, but are not true benign giant cell tumors. These include:

• Aneurysmal bone cyst
• Chondroblastoma
• Simple bone cyst
• Osteoid osteoma
• Osteoblastoma
• Osteosarcoma
• Giant cell reparative granuloma
• Brown tumor of hyperparathyroidism
• Non-ossifying fibroma
• Giant cell reparative granuloma

Natural History, Complications and Prognosis

Complications

• Malignant transformation

• Malignant transformation is far more common in men (M:F of ~3:1)
• Sarcomatous transformation is observed, especially in radiotherapy treated inoperable tumors.

• Recurrence

• Local recurrence rate of giant cell tumor of bone is 10 to 40%.
• Recurrence rates are higher when the tumor bone arises at a surgical inaccessible location locations such as spine and sacrum.

• Metastasis

• Giant cell tumor of bone may occasionally metastasize to vital organs such as the lung. Hence, this entity has been called benign metastasising giant cell tumor.

Diagnosis

History and Symptoms

• Patients usually present with pain and limited range of motion caused by tumor's proximity to the joint space.
• There may be swelling as well, if the tumor has been growing for a long time.
• Some patients may be asymptomatic until they develop a pathologic fracture at the site of the tumor.

Physical Examination

Physical examination findings will depend on the location of the osteosarcoma. Most osteoosarcomas are located in the long bone of extremities.

Extremities

A palpable firm non tender or tender mass may be appreciated on physical examination. The assessment of osteosarcoma during physical examination include:

• Size
• Location
• Involvement of adjacent structures (such as peripheral nerves or veins)
• Edema

X Ray

General radiographic features include:

• Narrow zone of transition: a broader zone of transition is seen in more aggressive giant cell tumors.
• No surrounding sclerosis: 80-85%
• Overlying cortex is thinned, expanded or deficient
• Periosteal reaction is only observed in 10-30% of cases
• Soft tissue mass is not infrequent
• Pathological fracture may be present
• No matrix calcification/mineralisation

On x-ray, giant cell tumors (GCTs) have a metaepiphyseal location and grow to the articular surface of the involved bone . They are distinguishable from other bony tumors in that GCTs usually have a non-sclerotic and sharply defined border. Because giant cell tumors are known to metastasize, when the diagnosis of giant cell tumor is suspected, a chest x-ray or CT may be needed.

(Images courtesy of RadsWiki)

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  Giant cell tumor: Distal part of the femur

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  Giant cell tumor: Distal part of the femur

MRI

Typical signal characteristics on MRI of giant cell tumor of bone include:

T1:

• Low to intermediate solid component
• Low signal periphery
• Solid components enhance, helping distinguish giant cell tumor with aneurysmal bone cyst from pure aneurysmal bone cyst
• Some enhancement may also be observed in adjacent bone marrow

T2:

• Heterogenous high signal with areas of low signal intensity (variable) due to haemosiderin or fibrosis
• If an aneurysmal bone cyst component present, then fluid-fluid levels can be observed
• High signal in adjacent bone marrow thought to represent inflammatory edema

T1 C+ (Gd):

• Solid components will enhance, helping differentiate from aneurysmal bone cyst

Scintigraphy: Bone Scan

• Most giant cell tumors demonstrate increased uptake on delayed images, especially around the periphery, with a central photopenic region (doughnut sign).
• Increased blood pool activity is also observed, and can be observed in adjacent bones due to generalised regional hyperaemia.

Treatment

Surgery

• Classically, treatment is with curettage and packing with bone chips or polymethylmethacrylate (PMMA).
• Local recurrence is from the periphery of the lesion and has historically occurred in up to 40-60% of cases.
• Newer intraoperative adjuncts such as thermal or chemical treatment of the resection margins have lowered the recurrence rate to 2.5-10%.
• Wide local excision is associated with a lower recurrence rate, but has greater morbidity.

References

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