Giant cell tumour (GCT) is still one of the most obscure and intensively examined tumours of bone. Its histogenesis is uncertain. The histology does not predict the clinical outcome; and there are still many unanswered questions with regard to both its treatment and prognosis.The World Health Organisation has classified GCT as "an aggressive, potentially malignant lesion", 1 which means that its evolution based on its histological features is unpredictable. Statistically, 80% of GCTs have a benign course, with a local rate of recurrence of 20% to 50%. About 10% undergo malignant transformation at recurrence and 1% to 4% give pulmonary metastases even in cases of benign histology.
PathogenesisGCT is a true neoplastic process originating from the undifferentiated mesenchymal cells of the bone marrow. Multinucleated giant cells and mononuclear stromal cells can be distinguished by light microscopy. These giant cells are derived from stromal cells, either by the fusion of mononuclear cells or, less probably, by amitotic division or nuclear segmentation of the stromal cells without the corresponding cytoplasmic division.2 These multinucleated giant cells resemble osteoclasts in their phenotype and function: their size is approximately 60 µm; their numerous nucleoli are centrally located in the cytoplasm. They stain positive for tartrate-resistant acid phosphatase and naphthyl alpha esterase enzymes, 3 and possess receptor sites for calcitonin, a phenotypic marker for osteoclasts.Further histochemical, immunohistochemical, cytogenetic, and molecular-genetic studies in cell cultures derived from GCTs have confirmed that there are two different cell lines within the mononuclear stromal cells. One population consists of mononuclear round cells, which are non-neoplastic and express monocyte-macrophage markers (tartrate-sensitive acid phosphatase, naphthyl alpha esterase) and react with monoclonal antibodies to CD 13 and CD 68 which suggests that these cells have a monocyticmacrophage origin.
4-6The second cell line which appears as mononuclear spindle-shaped (fibro-osteoblast-like) stromal cells is considered to be responsible for the neoplastic character of the GCT. It produces type-I and type-II collagens and alkaline phosphatase, has receptor sites for parathormone and proliferates extensively. This cell line is genetically unstable, as has been found in recent molecular genetic studies. It shows chromosomal abnormalities, a higher incidence of expression of p53 protein and alterations in different oncogenes (C-myc, C-fos, N-myc) which are also found in frankly malignant osteosarcomas. 7,8 These spindle-shaped stromal cells secrete a variety of cytokines and differentiation factors (macrophage colony stimulating factor (M-CSF), interferon-gamma (IFN-gamma), tumor necrosis factor alpha (TNF-alpha)), which have chemotactic, differentiationinducing and activating effects on monocytes-macrophages and are essential for the differentiation of osteoclasts.These features support the hypothesis that the genetically unstable spi...