| Disease | Locally destructive, benign and mono-ostotic tumoral lesion, typically presenting in the meta-epiphysis of long tubular bones with predilection for the knee region of skeletally mature patients (more than 95% of the patients is older than 25 years). Poly-ostotic lesions are exceptionally rare, counting for less than 1% of all cases. In these cases especially brown tumour of hyperparathyreoidism should be considered, which may look histologically identical. Although defined as a benign lesion, adjacent soft tissue invasion, angiovascular invasion and pulmonary metastases (1%) may occur. |
| Phenotype / cell stem origin | Not yet determined. |
| Embryonic origin | Mesoderm. |
| Etiology | The exact origin is still unknown, but data obtained from ultrastructural analyses and cell cultures, suggest that the "stromal" cell, or mononuclear spindle cell, is neoplastic. The mononuclear rounded cells and the osteoclastic giant cells are seen as reactive. Therefore, some suggest that "stromal cell tumour" is a better name, because this fits more precisely the concept of the mononuclear spindled cell (stromal cell) as neoplastic. |
| Epidemiology | This tumour represents 8% of all primary and approximately 20% of benign primary bone tumours. Mostly affecting adults in the third, fourth and fifth decade of life (72%). It is very rarely seen under the age of 10 years (1,3%). There is a slight female predominance (male/female ratio: 46,6%/53,4%). |
| Clinics | Pain of several weeks to months duration and a constantly expanding mass on X-ray, primary in the epiphysis, leading to cortex destruction, pathological fracture and soft tissue invasion. Finally ulceration of the skin occurs if not threatened. A pathological fracture could occasionally be the first sign of this tumour. |
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| Mixture of three cellular components composites the tumour: tumoral spindle shaped mononuclear cells, reactive rounded mononuclear cells and diffusely scattered osteoclast type giant cells. Note that mitoses are strictly limited to the first cell type. |
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| Pathology | A mixture of four components can be distinguished: spindled-shaped and rounded mononuclear cells, osteoclastic-type giant cells and small blood vessels.
The spindle-shaped mononuclear cells are regarded as neoplastic on results from electron microscopy and cell cultures. The origin of this cell type is still unknown, but it is thought to arise from the primitive mesenchymal stromal cell. Conventional mitotic figures are restricted to mononuclear cells. If atypical forms or strong nuclear atypia is noted, a secondary sarcomatous malignancy is almost always present. Secondary changes may be present like osteoid deposits, foci of fibrosis, collections of foamy cells or cystic degeneration. Secondary aneurysmal bone cyst formation is present in 6,5% of the cases. Mostly this is restricted to younger patients (median of 14 years) and low histological grade giant cell tumours. As mentioned earlier, this tumour can histological be graded into 3 grades according to Jaffe (1940) or into 4 grades (Netherlands Committee on Bone Tumours). According to the latter grading system, grade 1 en 2 are considered as being benign, grade 3 as borderline malignant and grade 4 as malignant tumours. Grade 4 tumours show histological overlap with malignant fibrous hystiocytoma of bone. Although many authors are sceptic about grading giant cell tumours, this shows a good correlation with clinical outcome. In that time no adjuvant chirurgical treatment, like cryosurgery or phenol additive was used. Nowadays the usefulness of grading in relation to recurrences is highly influenced by more effective surgical adjuvant techniques. According to literature still 20% of the giant cell tumours will recur, despite of these new surgical techniques. Together with the risk of developing pulmonal metastases, grading of giant cell tumours is in our view still valuable. In this grading system mitoses, pleiomorphism of the spindled mononuclear cells, giant cells and the individual size of the giant cells will be taken into account. Most important is the mitotic activity. When mitoses are occasional observed the risk of developing recurrences and pulmonal metastases is neglectable. If more than 1 mitosis is present per 1 high power field, patients are significantly at risk for developing recidives and pulmonal metastases (23%). Grade 2 tumours do have the highest prevalency (grade 1: 4%, grade 2: 88%, grade 3: 5%, grade 4: 3%). |
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| Table : Grading of giant cell tumours according to the Netherlands Committee on Bone Tumors. |
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| Treatment | Surgical intervention is the only treatment of choice. Mostly a curettage followed by local adjuvant cryosurgery or phenol instillation is sufficient to eradicate this lesion and to save the joint. The use of polymethylmetacrylate for filling the cavity after curettage additively decreases the percentage of recurrences. An added advantage of using cement is that recurrences are detected sooner. Sometimes 'en bloc' resection is needed to be curative. Pulmonal metastases are treated by local excision. |
| Evolution | Non-treatment always leads to destruction of cortical bone, to soft tissue invasion and finally to ulceration of the skin. Local recurrences can occur following proper treatment, mostly indicating less radical initial resection. |
| Prognosis | Good, despite of recurrences and pulmonary metastases. In general much is depending on the surgical technique and expertise in combination with the histological grade of this tumour. Although pulmonary metastases may occur in rare cases, angiovascular invasion does not have any significant influence on its prognosis. The mortality rate due to giant cell tumour is about 4%. |
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