Giant Cell Tumor of Bone Workup

Updated: Oct 06, 2021
  • Author: Valerae O Lewis, MD; Chief Editor: Harris Gellman, MD  more...
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Workup

Radiography

Radiographically, giant cell tumors (GCTs) are lucent and eccentrically located within the bone. These lesions can appear aggressive and are often characterized by extensive local bony destruction, cortical breakthrough, and soft-tissue expansion (see the images below).

Giant cell tumor. Anteroposterior radiograph of di Giant cell tumor. Anteroposterior radiograph of distal femur reveals expansile lytic metaphyseal-epiphyseal lesion.
Giant cell tumor. Lateral radiograph of same dista Giant cell tumor. Lateral radiograph of same distal femur as in previous image reveals expansile lytic metaphyseal-epiphyseal lesion.
Giant cell tumor. Anteroposterior radiograph of di Giant cell tumor. Anteroposterior radiograph of distal radius reveals aggressive lesion characterized by extensive local bony destruction, cortical breakthrough, and significant soft-tissue expansion.
Giant cell tumor. Lateral radiograph of same dista Giant cell tumor. Lateral radiograph of same distal radius as in previous image reveals aggressive lesion characterized by extensive local bony destruction, cortical breakthrough, and significant soft-tissue expansion.

When located in the epiphysis, GCTs generally extend to the articular surface (see the images below).

Giant cell tumor. Anteroposterior radiograph of di Giant cell tumor. Anteroposterior radiograph of distal tibia demonstrates extension of lesion to articular surface.
Giant cell tumor. Lateral radiograph of same dista Giant cell tumor. Lateral radiograph of same distal tibia as in preceding image demonstrates extension of lesion to articular surface.

Although radiographs of GCTs demonstrate a narrow zone of transition, GCTs generally lack the dense peripheral sclerosis seen in nonossifying fibromas. Mineralization of the primary lesion is rare. However, when GCTs occur in the soft tissue (metastasis or local recurrence), peripheral calcifications are common (see the image below).

Anteroposterior radiograph of wrist arthrodesis pe Anteroposterior radiograph of wrist arthrodesis performed for giant cell tumor. Soft-tissue recurrence is present. Note peripheral mineralization about soft-tissue recurrence (arrow).

Campanacci et al proposed a grading system for GCTs that was based on the radiographic appearance of the tumors. [37]  The Campanacci grading system is similar to that proposed by Enneking for benign bone tumors. [53]

  • A grade 1 lesion (latent) has a well-defined margin and an intact cortex
  • A grade 2 lesion (active) has a relatively well-defined margin but no radiopaque rim, and the cortex is thinned and moderately expanded
  • A grade 3 lesion (aggressive) has indistinct borders and cortical destruction) [2, 37]
  • No correlation exists between the grading systems and the incidence of local recurrence or metastases
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Magnetic Resonance Imaging

Magnetic resonance imaging (MRI) often is performed to delineate the extent of the neoplasm. In the typical GCT, the signal intensity is homogeneous, and the lesion is well circumscribed. The lesions have low signal intensity on T1-weighted images and intermediate signal intensity on T2-weighted images (see the images below).

Sagittal T1-weighted MRI shows giant cell tumor wi Sagittal T1-weighted MRI shows giant cell tumor with low signal intensity.
Sagittal T2-weighted MRI shows giant cell tumor wi Sagittal T2-weighted MRI shows giant cell tumor with intermediate-to-high signal intensity.
Giant cell tumor. Sagittal MRI of same distal radi Giant cell tumor. Sagittal MRI of same distal radius as in previous two images reveals aggressive lesion characterized by extensive local bony destruction, cortical breakthrough, and significant soft-tissue expansion.
Giant cell tumor. Sagittal MRI of same distal tibi Giant cell tumor. Sagittal MRI of same distal tibia as in previous two images demonstrates extension of lesion to articular surface.
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Computed Tomography

Computed tomography (CT) scans of the lesion reveal an absence of bone and intralesional mineralization (see the image below).

Giant cell tumor. CT scan of distal femur reveals Giant cell tumor. CT scan of distal femur reveals absence of matrix within lesion.
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Histologic Findings

On gross inspection, these lesions are characteristically chocolate brown, soft, spongy, and friable (see the image below).

Gross specimen of  same giant cell tumor in the di Gross specimen of same giant cell tumor in the distal femur as in preceding image displays typical chocolate-brown and spongy appearance.

Yellowish-to-orange discoloration due to hemosiderin may be present. Cystic cavities within the tumor are common. Often, these cavities are blood-filled (see the image below).

Bisected gross specimen of giant cell tumor in pre Bisected gross specimen of giant cell tumor in preceding image reveals blood-filled cystic areas and inner yellow and orange discoloration.

Examination of the resected specimen reveals a variable degree of cortical expansion and disruption. Despite the cortical disruption, the periosteum remains intact (see the image below). [18]

Gross specimen of giant cell tumor that fills enti Gross specimen of giant cell tumor that fills entire distal radius. Despite cortical disruption, periosteum remains intact (arrow). Once again, note blood-filled cystic areas and areas of orange discoloration.

Histologically, the lesions tend to be cellular. Although the multinucleated giant cell is the characteristic cell type, these lesions have a background network of stromal mononuclear cells (see the images below).

Photomicrograph of giant cell tumor reveals typica Photomicrograph of giant cell tumor reveals typical appearance. Multinucleated giant cells are dispersed throughout on background of mononuclear cells.
Photomicrograph of giant cell tumor reveals typica Photomicrograph of giant cell tumor reveals typical appearance. Multinucleated giant cells are dispersed throughout on background of mononuclear cells.

The mononuclear cells are plump and round, oval, or spindle-shaped. They may have prominent mitotic activity, but cellular atypia is rare (see the images below). The degree of mitotic activity has no prognostic significance.

Photomicrograph of giant cell tumor reveals promin Photomicrograph of giant cell tumor reveals prominent mitotic activity and rare cellular atypia.
Photomicrograph of giant cell tumor reveals promin Photomicrograph of giant cell tumor reveals prominent mitotic activity and rare cellular atypia.

Multinucleated giant cells, as the name suggests, have numerous centrally located nuclei as opposed to the peripherally located nuclei of Langerhans-type giant cells seen in atypical infections (see the images below). The nuclei tend to be compact and oval and contain prominent nucleoli. These are similar in appearance to those of the surrounding stromal cells, and the giant cell often appears to be a syncytium of these stromal cells. [55, 56]

Giant cell tumor. Photomicrograph of multinucleate Giant cell tumor. Photomicrograph of multinucleated giant cell. Note centrally located nuclei.
Giant cell tumor. Photomicrograph of multinucleate Giant cell tumor. Photomicrograph of multinucleated giant cell. Note centrally located nuclei.
Giant cell tumor. Photomicrograph of multinucleate Giant cell tumor. Photomicrograph of multinucleated giant cell. Note centrally located nuclei.

Giant cells generally are distributed throughout the lesion. The concentration of multinucleated giant cells varies considerably from tumor to tumor. Some tumors have many multinucleated giant cells, whereas others have a few giant cells nestled in swirls of spindle-shaped stromal cells (see the images below).

Photomicrograph of giant cell tumor with few multi Photomicrograph of giant cell tumor with few multinucleated giant cells but abundant swirls of spindle-shaped stromal cells.
Photomicrograph of giant cell tumor with few multi Photomicrograph of giant cell tumor with few multinucleated giant cells but abundant swirls of spindle-shaped stromal cells.

The concentration of multinucleated giant cells is not related to the incidence of local recurrence or metastases. In some lesions, giant cells invade the small perforating vessels (see the image below). This intravascular invasion can be found in approximately 5% of cases. This invasion, although appearing aggressive, is not correlated with the prognosis. [27]

Photomicrograph of giant cell tumor with intravasc Photomicrograph of giant cell tumor with intravascular invasion of multinucleated giant cells.

At histologic analysis, the differential diagnosis includes brown tumors of hyperparathyroidism; aneurysmal bone cysts; and, rarely, chondroblastoma, osteoblastoma, or osteosarcoma.

In an attempt to relate the histologic features with the clinical course, several histologic grading systems have been developed. The earliest was devised by Jaffe et al in 1940 and comprised three grades, as follows:

  • In grade I, at the benign end of the spectrum, giant cells are numerous, mononuclear cells are rare, and mitotic activity is absent
  • In grade II, mononuclear stromal cells are numerous, and moderate atypia and mitotic activity is seen
  • In grade III, giant cells are few and small, atypia and pleomorphism are common, and mitotic activity is frequent

However, this grading system has no prognostic significance. [2, 57, 8, 58] In an attempt to improve the prognostic relevance of the histologic grading system, several authors have modified the staging system of Jaffe et al. [27] Generally, these staging systems include sarcomatous lesions as grade III lesions. Unfortunately, these modified systems, like that of Jaffe et al, have been of little value in predicting patient outcomes.

A study by Hui et al suggested that the degree of p63 expression may be useful for distinguishing GCTs of bone from other giant cell–containing lesions of bone. [59] A mean p63 labeling value in excess of 50% was found to make the diagnosis of GCT of bone likely.

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