CENTRAL GIANT CELL GRANULOMA: PATHOGENESIS, CLINICAL FEATURES, HISTOPATHOLOGY & TREATMENT
Author: Sanketh DS, MDS
Central giant cell granuloma (CGCG), first described by Jaffe in 1953 is a benign intra-osseous lesion characterised by the presence of giant cells histologically. Jaffe described it as a reactive and reparative granulation tissue reaction occurring in the bones as a result of trauma and did not consider it to be a true neoplasm. He called them “giant cell reparative granuloma”. There is much debate as to whether this lesion is a reactive process or a benign neoplasm. However, there is not much evidence to support its “reparative” nature and many aggressive lesions have been reported in literature describing its close resemblance to “giant cell tumor(GCT)” of the long bones. In fact many researchers and pathologists consider it to be a benign neoplasm and that CGCG and GCT represent a spectrum of the same disease process influenced by the age of the patient and site of occurrence.
The etiology is unknown but there is evidence pointing to a genetic-related etiology. However, it is generally not agreed that all CGCGs may have a genetic component to its cause. CGCG contains several types of cells. Characteristic of the lesion are the presence of giant cells amidst numerous spindle shaped stromal cells. The spindle shaped cells are hypothesized to be the proliferating tumor cells. The spindle shaped stromal cells are osteoblast like cells, since they express many proteins like osteonectin, osteopontin, alkaline phosphatase, Runx2, RANKL and many others usually expressed by an osteoblast. These spindle cells produce chemokines that attract monocytes from adjacent blood vessels. Following their recruitment, monocytes differentiate to express proteins like TRAP and RANK under the influence of cytokine M-CSF produced by spindle cells. RANKL produced by spindle cells interact with RANK receptors on the differentiated monocytes, inducing them to fuse with other monocytes, to form multinucleated giant cells.
CGCG occurs predominantly in patients less than 30 years of age although it can have a wide age range. It has twice the predilection for females than males and occurs in the mandible 70% of the times. It occurs most often in the anterior jaws and very often crosses the midline. CGCG has been categorised based on its biologic behaviour as
a) Non-aggressive lesions
b) Aggressive lesions
Are more common than aggressive lesions, are small and are usually asymptomatic. There may be a painless, slow growing swelling without cortical perforation or root resorption.
These lesions are characterised by pain, paraesthesia, rapid growth and swelling with cortical perforation, teeth displacement and root resorption. Unlike non-aggressive lesions, aggressive ones are larger, have a greater chance of recurrence and occur in the young.
Radiographically, CGCG may show unilocular (usually non-aggressive) or multilocular (usually aggressive) appearance. Aggressive lesions are large and may show teeth displacement, root resorption, bone resoption and cortical plate expansion. Multilocular lesions resemble ameloblastoma radiographically and small unilocular ones may be confused with cysts.
Microscopically, CGCG exhibits few to numerous giant cells amidst many spindle shaped stromal cells. Giant cells vary in size and shape, sometimes being small with a few nuclei and at times being large with as many as 20-50 nuclei. The stroma is vascular and hypercellular with older lesions being more fibrous. There may be focal areas of haemorrhage and osteoid formation. It is hypothesized that aggressive lesions may have an increased number of giant cells, larger giant cells and a high mitotic index.
Surgical curettage is the most common form of treatment for CGCG, although sometimes recurrent lesions are treated with en bloc resection. There may be an overall recurrence of 11-49% for most lesions although aggressive lesions may have a recurrence rate as high as 72% at times. If the surgical removal of a large lesion may result in a deformity, alternate forms of non-surgical treatment like intra-lesional corticosteroid injections, calcitonin, IFNα and imatinib may be could be administered. Although these non-surgical approaches still require more study and research.
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