Atlas of Genetics and Cytogenetics in Oncology and Haematology OPEN ACCESS JOURNAL AT INIST-CNRS Solid Tumour Section Mini Review Bone: Giant cell tumour Ramses G Forsyth, Pancras CW Hogendoorn N. Goormaghtigh Institute of Pathology, University Hospital Ghent, B-9000 Gent, Belgium (RGF); Department of Pathology, Leiden University Medical Center, Leiden, the Netherlands (PCWH) Published in Atlas Database: June 2003 Online updated version: http://AtlasGeneticsOncology.org/Tumors/BoneGiantCellTumID5150.html DOI: 10.4267/2042/37996 This work is licensed under a Creative Commons Attribution-Noncommercial-No Derivative Works 2.0 France Licence. © 2003 Atlas of Genetics and Cytogenetics in Oncology and Haematology Identity A characteristic well-defined eccentric, lytic subchondral lesion involving the epiphysis and metaphysis. The borders are well defined and usually not sclerotic. Pathologic fracture is present in 5-10% of giant cell tumours. Dynamic MRI shows a fast uptake and a slow wash out of contrast. Atlas Genet Cytogenet Oncol Haematol. 2003; 7(3) 194 Bone: Giant cell tumour Forsyth RG, Hogendoorn PCW Alias Pathology Osteoclastoma; Giant cell tumour of bone A mixture of four components can be distinguished: - spindled-shaped and rounded mononuclear cells, Clinics and pathology - osteoclastic-type giant cells and small blood vessels. Disease The spindle-shaped mononuclear cells are regarded as neoplastic on results from electron microscopy and cell Locally destructive, benign and mono-ostotic tumoral cultures. The origin of this cell type is still unknown, lesion, typically presenting in the meta-epiphysis of but it is thought to arise from the primitive long tubular bones with predilection for the knee region mesenchymal stromal cell. Conventional mitotic of skeletally mature patients (more than 95% of the figures are restricted to mononuclear cells. If atypical patients is older than 25 years). Poly-ostotic lesions are forms or strong nuclear atypia is noted, a secondary exceptionally rare, counting for less than 1% of all sarcomatous malignancy is almost always present. cases. In these cases especially brown tumour of Secondary changes may be present like osteoid hyperpara-thyreoidism should be considered, which deposits, foci of fibrosis, collections of foamy cells or may look histologically identical. Although defined as cystic degeneration. Secondary aneurysmal bone cyst a benign lesion, adjacent soft tissue invasion, angio- formation is present in 6,5% of the cases. Mostly this is vascular invasion and pulmonary metastases (1%) may restricted to younger patients (median of 14 years) and occur. low histological grade giant cell tumours. Phenotype / cell stem origin As mentioned earlier, this tumour can histological be graded into 3 grades according to Jaffe (1940) or into 4 Not yet determined. grades (Netherlands Committee on Bone Tumours). Embryonic origin According to the latter grading system, grade 1 en 2 are Mesoderm. considered as being benign, grade 3 as borderline malignant and grade 4 as malignant tumours. Grade 4 Etiology tumours show histological overlap with malignant The exact origin is still unknown, but data obtained fibrous hystiocytoma of bone. Although many authors from ultrastructural analyses and cell cultures, suggest are sceptic about grading giant cell tumours, this shows that the "stromal" cell, or mononuclear spindle cell, is a good correlation with clinical outcome. neoplastic. The mononuclear rounded cells and the In that time no adjuvant chirurgical treatment, like osteoclastic giant cells are seen as reactive. Therefore, cryosurgery or phenol additive was used. Now-adays some suggest that "stromal cell tumour" is a better the usefulness of grading in relation to recurrences is name, because this fits more precisely the concept of highly influenced by more effective surgical adjuvant the mononuclear spindled cell (stromal cell) as techniques. According to literature still 20% of the neoplastic. giant cell tumours will recur, despite of these new Epidemiology surgical techniques. Together with the risk of developing pulmonal metastases, grading of giant cell This tumour represents 8% of all primary and tumours is in our view still valuable. In this grading approximately 20% of benign primary bone tumours. system mitosis, pleiomorphism of the spindled Mostly affecting adults in the third, fourth and fifth mononuclear cells, giant cells and the individual size of decade of life (72%). It is very rarely seen under the the giant cells will be taken into account. Most age of 10 years (1,3%). There is a slight female important is the mitotic activity. When mitoses are predominance (male/female ratio: 46,6%/53,4%). occasional observed the risk of developing recurrences Clinics and pulmonal metastases is neglectable. If more than 1 Pain of several weeks to months duration and a mitosis is present per 1 high power field, patients are constantly expanding mass on X-ray, primary in the significantly at risk for developing recidives and epiphysis, leading to cortex destruction, patholo-gical pulmonal metastases (23%). Grade 2 tumours do have fracture and soft tissue invasion. Finally ulceration of the highest prevalency (grade 1: 4%, grade 2: 88%, the skin occurs if not threatened. A pathological grade 3: 5%, grade 4: 3%). fracture could occasionally be the first sign of this tumour. Atlas Genet Cytogenet Oncol Haematol. 2003; 7(3) 195 Bone: Giant cell tumour Forsyth RG, Hogendoorn PCW 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. Table : Grading of giant cell tumours according to the Netherlands Committee on Bone Tumors. Treatment surgical technique and expertise in combination with the histological grade of this tumour. Although Surgical intervention is the only treatment of choice. pulmonary metastases may occur in rare cases, Mostly a curettage followed by local adjuvant angiovascular invasion does not have any significant cryosurgery or phenol instillation is sufficient to influence on its prognosis. The mortality rate due to eradicate this lesion and to save the joint. The use of giant cell tumour is about 4%. polymethylmetacrylate for filling the cavity after curettage additively decreases the percentage of Cytogenetics recurrences. An added advantage of using cement is that recurrences are detected sooner. Sometimes 'en Note bloc' resection is needed to be curative. Pulmonal No recurrent chromosomal structural or numeric metastases are treated by local excision. aberrations of importance have been detected yet. When confronted with a rearrangement, especially Evolution concerning 16q22 or 17p3, an associated aneurys-mal Non-treatment always leads to destruction of cortical bone cyst should be excluded. bone, to soft tissue invasion and finally to ulceration of Cytogenetics Morphological the skin. Local recurrences can occur following proper treatment, mostly indicating less radical initial The most frequent chromosomal anomaly is telomeric resection. association. Comparing telomere length of giant cell tumours to this of leukocytes of the same patient, a Prognosis reduction has been demonstrated. Most commonly Good, despite of recurrences and pulmonary affected telomeres are 11p, 13p, 14p, 15p, 19q, 20q and metastases. In general much is depending on the 21p. Atlas Genet Cytogenet Oncol Haematol. 2003; 7(3) 196 Bone: Giant cell tumour Forsyth RG, Hogendoorn PCW Masui F, Ushigome S, Fujii K. Giant cell tumor of bone: a References clinicopathologic study of prognostic factors. Pathol Int. 1998 Sep;48(9):723-9 Bridge JA, Neff JR, Bhatia PS, Sanger WG, Murphey MD. Cytogenetic findings and biologic behavior of giant cell tumors Siebenrock KA, Unni KK, Rock MG. Giant-cell tumour of bone of bone. Cancer. 1990 Jun 15;65(12):2697-703 metastasising to the lungs. A long-term follow-up. J Bone Joint Surg Br. 1998 Jan;80(1):43-7 Bridge JA, Neff JR, Mouron BJ. Giant cell tumor of bone. Chromosomal analysis of 48 specimens and review of the Zheng MH, Siu P, Papadimitriou JM, Wood DJ, Murch AR. literature. Cancer Genet Cytogenet. 1992 Jan;58(1):2-13 Telomeric fusion is a major cytogenetic aberration of giant cell tumors of bone. Pathology. 1999 Nov;31(4):373-8 Mulder JD, Kroon HM, Schütte HE, Taconis WK.. Radiologic Atlas of Bone Tumors. Amsterdam: Elsevier, 1993. Sciot R, Dorfman H, Brys P, Dal Cin P, De Wever I, Fletcher CD, Jonson K, Mandahl N, Mertens F, Mitelman F, Rosai J, Schwartz HS, Dahir GA, Butler MG. Telomere reduction in Rydholm A, Samson I, Tallini G, Van den Berghe H, Vanni R, giant cell tumor of bone and with aging. Cancer Genet Willén H. Cytogenetic-morphologic correlations in aneurysmal Cytogenet. 1993 Dec;71(2):132-8 bone cyst, giant cell tumor of bone and combined lesions. A Tarkkanen M, Kaipainen A, Karaharju E, Böhling T, report from the CHAMP study group. Mod Pathol. 2000 Szymanska J, Heliö H, Kivioja A, Elomaa I, Knuutila S. 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