Orthopaedic Surgery - Giant Cell Tumor

Basics

Giant cell tumor of bone is a benign but frequently locally aggressive primary bone neoplasm characterized histologically by numerous evenly distributed osteoclast-like multinucleated giant cells within a background of proliferating mononuclear stromal cells.

Although histologically benign in most cases, the tumor can behave aggressively, destroy surrounding bone, extend into soft tissues, recur after treatment, and rarely metastasize.

Typical Location

Giant cell tumors usually occur near the articular end of a long bone in skeletally mature patients.

Approximately half arise around the knee, particularly in the distal femur and proximal tibia.

Other common sites include the:

Distal radius, proximal femur, proximal humerus, distal tibia, and sacrum.

Flat Bones

When flat bones are affected, the sacrum and pelvis are the most common locations.

Giant cell tumors associated with Paget disease may involve flat bones, including the craniofacial skeleton.

Multifocal Disease

Multifocal giant cell tumor is rare.

Most patients have a single lesion.

Classification

The Musculoskeletal Tumor Society, or Enneking staging system, can be used to describe the biologic behavior of giant cell tumors.

The stages are based on symptoms, radiographic appearance, biologic activity, and local extent.

Stage I: Latent

Stage I tumors account for fewer than approximately 5% of cases.

They are usually minimally symptomatic or completely asymptomatic and may be discovered incidentally.

Radiographs or CT typically show a lesion with a well-defined sclerotic rim.

The tumor may demonstrate relatively little activity on bone scintigraphy.

Histologically, it remains benign.

Pathologic fracture can occasionally occur.

Stage II: Active

Stage II tumors account for approximately 70–85% of cases.

Patients are usually symptomatic.

The lesion expands the cortex but does not yet clearly break through it.

Bone scintigraphy is generally active.

Pathologic fracture may occur.

Histologically, the tumor remains benign.

Stage III: Aggressive

Stage III tumors represent approximately 10–15% of cases.

They typically present with increasing pain, swelling, and a rapidly enlarging mass.

Imaging demonstrates cortical destruction with extension into surrounding soft tissues.

Bone-scan activity may extend beyond the margins visible on plain radiographs.

The tumor may appear markedly hypervascular on angiographic studies.

Although the lesion remains histologically benign, it demonstrates aggressive local behavior with cortical violation and soft-tissue invasion.

Epidemiology

Age

Peak incidence occurs during the third decade of life, with frequency gradually decreasing thereafter.

The tumor is uncommon after approximately 55 years of age.

Skeletal Maturity

Giant cell tumor almost always develops after closure of the growth plates.

Approximately 10–15% of patients are younger than 20 years, but most of these individuals are already skeletally mature.

Fewer than approximately 2% of giant cell tumors occur adjacent to an open physis.

Therefore, the diagnosis should be reconsidered carefully when a similar lesion occurs in a skeletally immature child.

Frequency

Giant cell tumor accounts for approximately 5% of biopsied primary bone tumors and approximately 20% of benign bone tumors.

It is among the more common primary osseous neoplasms.

Sex

Females are affected slightly more often than males, with reported female-to-male ratios of approximately 1.3–1.5:1.

Risk Factors

Paget disease of bone is a rare predisposing condition.

Etiology

The precise cause of most giant cell tumors is not fully explained by conventional clinical risk factors.

Rare tumors may arise in association with pre-existing Paget disease of bone.

Associated Conditions

Paget Disease

Giant cell tumor can rarely complicate Paget disease.

Such tumors may involve different anatomic sites from conventional giant cell tumor, including the craniofacial skeleton.

Secondary Aneurysmal Bone Cyst

Secondary aneurysmal bone cyst formation is a relatively common associated histologic finding.

These cystic changes can alter the imaging appearance and complicate interpretation.

Diagnosis

Signs and Symptoms

Clinical presentation is often nonspecific.

Because the tumors frequently occur close to joints, patients may initially present with symptoms that resemble primary joint disease.

Pain

Approximately 90% of patients complain of pain.

Pain may be accompanied by localized swelling or a palpable mass.

Pathologic Fracture

Approximately 5–10% of patients present with a pathologic fracture through the weakened bone.

Joint Symptoms

Patients may complain of reduced motion, joint stiffness, or discomfort with weight bearing if the lesion is close to an articular surface.

Physical Examination

There is no pathognomonic physical examination finding.

Localized tenderness is commonly present over the involved epiphyseal region adjacent to a joint.

Swelling

A palpable mass or swelling may develop as the lesion expands.

Joint Effusion and Motion

Joint effusion or restriction of motion may occur when the lesion has substantially weakened or approached the subchondral cortex.

Laboratory Tests

Routine serum chemistry studies are generally normal.

Calcium and Phosphate

Serum calcium and phosphate should be assessed when the differential diagnosis includes hyperparathyroidism.

Evaluation may also include parathyroid hormone testing when clinically appropriate.

This is particularly important because a brown tumor of hyperparathyroidism can histologically and radiographically resemble a giant cell tumor.

Imaging

Plain Radiographs

Radiographs typically show an eccentric, expansile, radiolucent lesion near the end of a long bone.

The lesion is usually sharply defined but often lacks a prominent surrounding rim of reactive sclerosis.

Epiphyseal Involvement

A classic feature is involvement of the epiphysis in a skeletally mature patient.

The tumor commonly extends from the metaphysis toward the subchondral bone and articular surface.

Cortical Expansion

The cortex may become progressively thinned and expanded.

Aggressive lesions may break through the cortex and extend into adjacent soft tissues.

Reactive Sclerosis

Unlike many other benign bone lesions, giant cell tumor typically has little or no reactive sclerosis around its margin.

Spinal Involvement

When the spine is affected, the lesion usually involves the anterior vertebral body.

Multicentric Disease

Multicentric giant cell tumor is rare, occurring in approximately 1% of cases.

Chest Imaging

Chest imaging is appropriate during staging because a small proportion of patients develop pulmonary metastases despite histologically benign primary disease.

Historically, approximately 2% of patients have been reported to develop lung metastases.

Bone Scintigraphy

Bone scans are frequently positive because of increased metabolic activity around the lesion.

However, some lesions may demonstrate relatively little uptake, particularly less active tumors.

Pathological Findings

Microscopically, the tumor consists of a proliferating population of relatively uniform mononuclear stromal cells with numerous multinucleated giant cells distributed evenly throughout the lesion.

Mononuclear Cells

The stromal cells are generally round, oval, epithelioid, or spindle shaped.

They have relatively large nuclei and inconspicuous nucleoli.

These stromal cells represent the neoplastic component of the tumor.

Giant Cells

Multinucleated osteoclast-like giant cells are dispersed relatively uniformly among the mononuclear cells.

Their nuclei often resemble those of the surrounding stromal cells.

Mitotic Activity

Mitotic figures may be frequent, even in histologically benign tumors.

The presence of mitoses alone does not necessarily imply malignant transformation.

Aneurysmal Bone Cyst Component

A secondary aneurysmal bone cyst may be present within the tumor.

Vascular Invasion

Tumor cells may occasionally extend into blood vessels.

Involutional Changes

Some lesions contain lipid-laden histiocytes or other degenerative changes.

Differential Diagnosis

Brown Tumor of Hyperparathyroidism

A brown tumor may closely resemble giant cell tumor histologically and radiographically.

Serum calcium, phosphate, and parathyroid hormone levels help distinguish the two conditions.

Giant Cell Reparative Granuloma

Giant cell reparative granuloma may also contain numerous giant cells but generally has a different clinical setting and histologic organization.

Nonossifying Fibroma

NOF can produce an eccentric lucent lesion but usually occurs in younger patients, is metaphyseal rather than epiphyseal, and typically has a sclerotic border.

Benign Fibrous Histiocytoma

Benign fibrous histiocytoma may share fibrohistiocytic features but usually has a different histologic pattern and distribution.

Aneurysmal Bone Cyst

A primary aneurysmal bone cyst may resemble a giant cell tumor, particularly when secondary aneurysmal cystic change is prominent.

Telangiectatic Osteosarcoma

Telangiectatic osteosarcoma is an important malignant differential diagnosis because it can appear expansile and cystic.

Biopsy and careful histopathologic interpretation are essential.

Treatment

General Principles

Treatment aims to eradicate local disease while preserving the adjacent joint and maintaining limb function whenever possible.

Patients with large lesions at risk for pathologic fracture may be advised to use crutches or protected weight bearing until definitive treatment.

Radiotherapy

Radiotherapy is generally avoided whenever complete surgical treatment is feasible.

Historically, irradiation was associated with an increased risk of secondary malignant transformation.

It is now reserved for uncommon situations in which surgery is not feasible or would carry unacceptable morbidity.

Physical Therapy

Physical therapy is used after treatment to restore joint range of motion, strength, gait, and function.

Surgery

The standard surgical approach for many accessible giant cell tumors consists of extended intralesional curettage.

Curettage

The tumor is removed from the cavity while preserving as much normal bone and articular surface as possible.

High-Speed Burr

A high-speed burr is commonly used to remove microscopic residual tumor from the walls of the cavity and extend the margin of curettage.

Local Adjuvant Treatment

Local adjuvants may be used to reduce residual tumor cells.

Historically, agents such as phenol have been applied to the cavity.

Other modern local adjuvant techniques may also be used depending on surgeon preference and anatomic location.

Polymethylmethacrylate Cement

The resulting cavity may be filled with polymethylmethacrylate (PMMA) bone cement.

Cement provides immediate structural support and facilitates radiographic recognition of recurrent lytic disease at the cement-bone interface.

Bone Grafting

Cancellous or structural bone graft may be used, particularly near the subchondral surface when preservation of the joint is important.

Subchondral Reconstruction

Bone graft can help restore the subchondral region and reduce direct loading of articular cartilage overlying a large defect.

Internal Fixation

Internal fixation may be required when the remaining bone is structurally weak or when there is a pathologic fracture.

Wide Resection

Wide resection may be appropriate when the tumor involves an expendable bone such as the fibula, when there is extensive soft-tissue extension, or when recurrent disease has destroyed the adjacent joint.

Reconstruction

Large periarticular resections may require complex reconstruction.

Around the knee, options may include prosthetic replacement, osteoarticular allograft reconstruction, or arthrodesis, depending on patient factors and extent of disease.

Amputation

Amputation is rarely necessary.

It may be considered for extremely advanced neglected tumors with extensive soft-tissue involvement or for selected uncontrollable recurrent lesions.

Follow-Up

Prognosis

Giant cell tumors have a substantial tendency to recur locally.

Simple Curettage

Historically, recurrence rates after simple curettage alone have been reported as high as 40–60%.

Modern Extended Curettage

With extended curettage using high-speed burring and local adjuvant techniques, recurrence rates are substantially lower, commonly around 10–15%.

Timing of Recurrence

Most recurrences occur within the first 2 years following treatment.

Nearly all are detected within approximately 5 years, although longer surveillance may still be appropriate.

Complications

Local Recurrence

Local recurrence is the most important complication after limb-preserving treatment.

Pathologic Fracture

Structural weakening of bone can produce fracture before treatment or occasionally during follow-up.

Pulmonary Metastasis

A small proportion of histologically benign giant cell tumors metastasize to the lungs.

These metastases may behave relatively indolently but require specialist assessment.

Secondary Malignant Giant Cell Tumor

A secondary malignant giant cell tumor occurs when a sarcoma develops at the site of a previously treated giant cell tumor.

Postirradiation Sarcoma

Historically, approximately 10–15% of irradiated giant cell tumors were reported to develop postirradiation sarcoma in older series.

This risk is one reason radiotherapy is now used very selectively.

Sarcomatous Transformation Without Radiation

Malignant transformation can also occur without previous radiation, particularly in recurrent tumors, but it is uncommon.

Patient Monitoring

Close postoperative surveillance is required because of the risk of recurrence.

Patients may initially be reviewed approximately every 3 months during the first 2 years, with clinical examination and local imaging.

Chest Surveillance

Periodic chest imaging is appropriate because of the small risk of pulmonary metastasis.

Historically, annual chest radiography has been used.

Long-Term Monitoring

Follow-up should assess pain, swelling, joint motion, structural integrity, radiographic evidence of recurrence, pulmonary disease, and complications of reconstruction.