Giant cell tumor of bone is a locally aggressive primary bone neoplasm.

Primitive mesenchymal stromal cell.

Mesoderm.

The exact origin is still unknown, but data obtained from ultrastructural analyses and cell cultures, as well as novel molecular data, 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.

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%).

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.

A mixture of four components can be distinguished:

S pindled-shaped and rounded mononuclear cells,

Osteoclastic-type giant cells and small blood vessels.
The spindle-shaped mononuclear cells are regarded as neoplastic. This cell type 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).

In the 2013 WHO classification, grading of histopathological features of GCTB is not considered predictive for clinical behaviour including risk for recurrent or metastatic disease. Originally, giant cell tumors of bone were histological graded into 3 grades according to Jaffe (1940) or into 4 grades (Netherlands Committee on Bone Tumours).

Surgical intervention is the treatment of choice and therapeutic inhibition of osteoclast formation and activity with denosumab (RANK-RANKL inhibitor) provides another modality of treatment. 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.

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.

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%.

The most frequent chromosomal anomaly is telomeric association. Comparing telomere length of giant cell tumours to this of leukocytes of the same patient, a reduction has been demonstrated. Most commonly affected telomeres are 11p, 13p, 14p, 15p, 19q, 20q and 21p.

When confronted with a rearrangement, especially concerning 16q22 or 17p3, an associated aneurysmal bone cyst should be excluded.

A specific driver mutation in the histone 3.3 gene H3F3A (p.Gly34) was recently identified in approximately 92% of giant cell tumours of bone. H3F3A mutation detection can be used as a diagnostic tool for the distinction of giant cell tumor of bone from other giant cell-containing tumors. A subset of the mutations can be easily detected using a G34W mutation specific antibody.