Central Giant Cell Lesion (Granuloma)

Detailed Review

Central Giant Cell Lesion (Granuloma)

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The central giant cell (reparative) lesion, also commonly called the central giant cell granuloma is presumably an inflammatory proliferation of osteoclastic and stromal cells of the periodontal ligament.  It must be distinguished from the more aggressive neoplasm, the giant cell tumor, but this can often not be done on the basis of microscopic features alone.  It also may be stimulated or produced by excessive levels of parathormone, in which case it has traditionally been called a brown tumor of hyperparathyroidism.  It is similar to its gingival counterpart, the peripheral giant cell lesion (granuloma) but occurs five times less frequently and is typically a young person's lesion, while the peripheral examples occur more frequently in middle-aged and older persons.  

Jaffe is usually credited with first separating this entity from the true giant cell tumor of long bones, suggesting the name "giant cell reparative granuloma."  However, Berger and others before him had independently described the entity and an apparent central giant cell lesion was reported as early as 1856 by the French surgeon Giraldes, who was fascinated by the presence of cells he called "myeloplaxes" with up to 30 nuclei.  There is no convincing evidence that it is, indeed, a reparative process but the exact pathoetiology is not known.  Trauma does not seem to be an important etiologic factor.

Clinical Features: The central giant cell lesion occurs much more frequently in women than in men (M:F ratio = 2:1), and almost 80% occur during the first three decades of life, 60% of patients are younger than 20 years of age.  This predilection for young persons is so strong that it is often forgotten that the lesion can occur at any age.  Two-thirds of all cases present in the mandible, almost always anterior to the first molars.  Maxillary lesions also are typically in the anterior region, and this location predilection often (20% of cases) leads to a lesion which crosses the midline, whether it is in the upper or lower jaw.

The lesion typically has a multilocular or soap bubble radiolucent appearance (Figures 1 & 2), similar to ameloblastoma, odontogenic myxoma, ameloblastic fibroma, etc.  The septa betweethe loculations are usually fibrous in nature but occasionally will be residual, atrophied and remodeled trabeculae.  A thin sclerotic rim is often seen at the periphery, which is typically scalloped.  Expansion and thinning of the facial, and to a lesser extent the lingual, cortex is common for the larger lesions and may be marked because the central giant cell lesion may achieve a size of 9 cm. or more over time (hyperparathyroidism should be suspected with large lesions).  Enlargement is characteristically slow but may be alarmingly rapid in the early stages, especially if associated with infection, trauma (extraction) or hyperparathyroidism.  

Large lesions with very thin overlying cortex will have a blue/red, often bosselated appearance clinically, and the cortex can easily be broken by hand pressure, often giving the sound of egg shells cracking.  Even those with this bluish hue will not have enough pooled blood to allow a positive aspiration, because the blood is usually outside the vessels and literally oozing through the lesion.  Rarely, a central giant cell lesion will connect to an overlying peripheral giant cell lesion (granuloma) via a small cortical perforation.  The more aggressive lesions may also be painful and may resorb the adjacent roots of teeth.

Pathology and Differential Diagnosis: The central giant cell lesion is composed of primitive mesenchymal stroma with moderate cellularity and with lesional cells appearing as spindle-shaped or ovoid with moderate amounts of cytoplasm and a moderately large, open nucleus (Figures 3 & 4).  Collagenic fibers are seen in variable amounts in the stroma and multinucleated giant cells with randomly located nuclei (up to 60 per cell, usually less than 10 per cell) are scattered throughout.  The nuclei in the giant cells are identical to those of the stroma.  Also scattered throughout are focal areas of erythrocyte extravasation and it is not unusual to see more blood outside vessels than within vessels -- the lesion is like a blood-soaked sponge with oozing blood.  The focal hemorrhage gives the cut surface on gross examination a mottled tan and brown appearance (Figure 5). Hemosiderin deposits may be seen as a sign of old hemorrhage, but most of the time the extravasated erythrocytes seem to not become trapped in the lesion, although how they leave from or escape to to the systemic circulation is unknown.  

The stroma may be densely collagenic in older lesions, while lesions in very young persons (less than 7 years of age) may appear very biologically active, with numerous mitotic figures.  The stroma may also be myxomatous in some lesions or regions of lesions, and at least 10% of cases will show reactive new bone formation, located especially toward the periphery of the lesion. Occasional areas of necrosis and healing may mimic aneurysmal bone cyst, and some authors have considered these two lesions as simple variations of the same phenomenon.

The differential diagnosis for central giant cell lesion includes the brown tumor of hyperparathyroidism, aneurysmal bone cyst and cherubism.  The lesion is, for all practical purposes, indistinguishable from the brown tumor, but it can be separated from the aneurysmal bone cyst because it lacks the large blood-filled spaces without endothelial lining of the latter lesion.  Also, it does not have the connective tissue septae with embedded multinucleated giant cells which are so characteristic of the latter entity.  The stroma of cherubism is much more loose and less cellular than that of the giant cell lesion, and the number of giant cells is considerably less, often only a few surrounding occasional blood vessels.  Extravasation of erythrocytes is not a feature of cherubism.  Additionally, the clinical and radiographic presentation of cherubism is usually quite different, with multiple quadrants of involvement.  The pathologist must, as usual, evaluate the stroma for signs of dysplasia which might indicate osteosarcoma or fibrosarcoma of bone. 

Treatment and Prognosis: The central giant cell lesion is treated by curettage, although those with a more aggressive biological behavior are often treated by local resection, including a margin of radiographically normal bone.  About 15%-20% of cases will recur with curettage (up to 50% in one study), but the long-term prognosis is good and recurrence can be treated also with curettage.  Radiographic follow-up should last for at least 3 years.  Hyperparathyroidism should be ruled out with the larger or painful or rapidly growing tumors.

References (Chronologic Order)

Note: Click on underlined author's names for additional detail.

General references:

Neville BW, Damm DD, Allen CM, Bouquot JE. Oral and maxillofacial pathology. Philadelphia, W. B. Saunders; 1995.

Elder D, Elenitsas R, Jaworsky C, Johnson B Jr. Lever's Histopathology of the skin, 8th edition. Philadelphia; Lippincott-Raven, 1997.

Sapp JP, Eversole LR, Wysocki GP. Contemporary oral and maxillofacial pathology. Mosby; St. Louis, 1997.

Odell EW, Morgan PR. Biopsy pathology of the oral tissues. London; Chapman & hall Medical, 1998.

Specific references:

Pictures

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		Figure 3:  The characteristic multinucleated giant cells are scattered in a fibro-cellular stroma with extravasated erythrocytes.  [return to text]
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