Histopathology  2001 Dec;39(6):629-37 

Secondary malignant giant-cell tumour of bone: molecular abnormalities of p53
and H-ras gene correlated with malignant transformation.

Oda Y, Sakamoto A, Saito T, Matsuda S, Tanaka K, Iwamoto Y, Tsuneyoshi M.

Department of Anatomic Pathology, Graduate School of Medical Sciences, Kyushu
University, 3-1-1 Maidashi, Higashi-ku, Fukuoka 812-8582, Japan.

AIMS: We report two cases of secondary malignant giant-cell tumour occurring
without irradiation therapy. To elucidate the mechanism of malignant
transformation in this tumour, we searched for the molecular abnormalities of
p53, MDM2 and the H-ras genes. METHODS AND RESULTS: These cases were retrieved
after a review of 103 cases of primary giant-cell tumour of bone, registered in
our institute. One case occurred in the distal femur of a 42-year-old female
after surgical curettage, while the other arose in the acetabulum of a
25-year-old male after en bloc resection. Microscopically, the malignant tumour
in the distal femur was composed of a proliferation of ovoid or fusiform cells
arranged in fascicles with high mitotic activities. The malignant transformed
tumour in the acetabulum was made up of pleomorphic tumour cells with atypical
mitoses. In the tumour of the distal femur, both p53 and H-ras mutations were
detected. Abnormal nuclear accumulation of p53 protein and c-myc expression were
also revealed by immunohistochemistry. In both cases, the recurrent malignant
tumour over-expressed MMP-9 and revealed a higher MIB-1-labelling index compared
with the primary conventional giant-cell tumour. CONCLUSIONS: Our results
suggest that multiple oncogene or tumour suppressor gene mutations may play an
important role during malignant transformation in conventional giant-cell
tumours.

Publication Types:
Review
Review of Reported Cases

PMID: 11903582 [PubMed - indexed for MEDLINE]