Osteoid osteoma and osteoblastoma with clonal chromosome changes.

We cytogenetically investigated six osteoid osteomas, one osteoblastoma and one aggressive osteoblastoma, and observed clonal structural changes in one osteoid osteoma and in the aggressive osteoblastoma. Clonal chromosome changes had not been reported previously in osteoid osteoma, whereas the only reported chromosome change in osteoblastoma was different from the one presented here.

phvsis or shaft of long bone. It is found most frequently in the second decade of life and there is a pronounced male predominance. The tumour has a remarkable histological similarity to osteoblastoma. Arbitrarily. a lesion less than 1.5 cm is considered A to be an osteoid osteoma and a larger lesion is called an osteoblastoma. Osteoblastomas tend to involve the spine, especially the posterior elements. Transformation of osteoblastoma into osteosarcoma has been described (Unni. 1996). The difficulty in separating osteoblastoma from osteosarcoma has led to the concepts of 'aggressive' and 'malignant' osteoblastoma (Fechner and Mills. 1992: Della Rocca and Huvos. 1996).
Reports on cytogenetic investigations of benign bone-forming Fgure 1 Two-dime ren in the sagittal of the tumours are scarce compared with osteosarcomas. their malignant preoperatrve CT scan of the right ankle showing the hyperostotic-appearing counterpart (Sandberg and Bridge. 1994). In total. tu-o osteoid zone of previous surgery and. above and below this region, a tyc zone with some calcifications or ossifications in the centre. suggesting a locally osteomas and six osteoblastomas have been reported so far. and recurrent osteoid osteoma (case no. 2) chromosome abnormalities have been observed in only one case of osteoblastoma (Teyssier and Ferre. 1989: Mascarello et al. 1993: Tarkkanen et al. 1993.
We report the finding of clonal chromosome aberrations in a locally aggressive osteoblastoma. and present the first abnormal karyotype ever found in osteoid osteoma.

MATERIALS AND METHODS
Eight bone-forming tumoral lesions were investigated as part of an ongoing study on the cytogenetic characterization of bone tumours. Clinical data of the patients with these lesions are summarized in Table 1. The clinical history of the two cases (nos 2 and 8) showina clonal chromosomal abnormalities is presented in detail below,. _ Case no. 2 A-as a 21 -year-old man who had undergone surgery for a soft. rounded bone lesion on the right talar neck 3 years  Figure 1). The patient underx-ent surgery once aaain for this relapsing or recurrent osteoid osteoma. A sample of this tumour was cytogenetically investigated. Case no. 8. a man of 35 years. with no medical history except for a night femoral fracture. had suffered from pain in the right hip and gluteal region for three months and had noticed a lump in the right buttock 2 weeks previously. On clinical examination the onlv significant finding was a deep hard lump of 3 x 3 cm in this area. Relevant laboratory investigations all showed normal results. A radiograph of the pelvic bone showed a sharply delineated lytic lesion in right iliac bone. which was tracer accumulating on bone scintigraphy. On CT scan the osteolytic tumour near the sacro-iliac joint also had a posterior soft tissue extension of 4 x 5 cm. No other lesions were detected by bone scintigraphy. radiograph of the skeleton or CT scan of the thorax and abdomen. Bone marrow examination and trephine biopsy did not reveal abnormal cells. An incisional biopsy was performed for pathological and cytogenetic investigation. A few days later. partial resection of the iliac bone wxith the overlying gluteal muscle was performed. keeping a small rim of bone between the pelvic bone and the sacrum. Pathological examination revealed the presence of tumour tissue in the medial margin of the resected specimen and 3 months later local tumour progression was obvious. with osteolysis of the right hemisacrum ( Figure 2). The patient was treated bv chemotherapy but the tumour did not respond to methotrexate. doxorubicin. ifosfamide or cisplatinum. A pathological fracture occurred and the fifth lumbar vertebra was invaded. Radiation therapy (60 Gy) was delivered without effect. The patient became paraplegic and died without evidence of distant metastasis 2 vears after diagnosis.
G-banded metaphases were obtained from short-term cultures (3-5 days) after overnight collagenase disaggregation of each of the eight tumour biopsy specimens received. Culture time never exceeded 5 days.

RESULTS
Among the eight tumoral lesions. seven were characterized by trabeculae of woven bone set in a vascular loosely fibrous stroma. The nidus was usually surrounded by hyperostotic lamellar bone ( Figure 3). A diagnosis of osteoid osteoma was made in six lesions. and of osteoblastoma in seventh case. The remaining lesion was much more cellular. and the osteoblasts showed a more epithelioid aspect. In addition. numerous mitoses were present in the stromal cells. Most bone trabeculae still showed osteoblastic rimming ( Figure 4A and B). This lesion was diagnosed as aggressive osteoblastoma.
-21 ,+3mar osteoblastoma. which showed several identifiable chromosome changes plus unidentified marker chromosomes and a karyotype comparable with those generallv seen in osteosarcomas (Bn'dge et al. 1997). In these malignant bone tumours no consistent chromosome abnormalities have so far been identified. Karvotypes are mostly complex with many rearraneed chromosomes and v-ariation in chromosome number and composition. which may complicate the identification of possiblyspecific abnormalities. Our case of aggressive osteoblastoma had a chromosome 13 missing. but we do not know whether this observation has anv meaninc with regard to a possible relationship with osteosarcomas. in which anomalies of 13 and corresponding loss of the Rb gene may be important for pathogenesis (Wadayama et al. 1994). As for the other gene frequently involved in osteosarcomas (Miller et al. 1990). we did not at the time investigate p53: both chromosomes 17 looked normal. in contrast with the case of Mascarello in which one 17 was abnormal.
The histological picture in tumour no. 8 is particular as the extension of the tumour into the soft tissue and the histological outlook in this case clearly differ from classical osteoblastoma and suggest a more aggressive behaviour. Borderline tumours with features intermediate between osteoblastoma and osteosarcoma have been described. and there is considerable dispute regarding the nature of these lesions and their appropriate terminoloav (Fechner and Mills. 1992). The terms pseudomalignant osteoblastoma. aggressive osteoblastoma. malignant osteoblastoma and osteoblastoma-like osteosarcoma have been used to describe this spectrum of lesions to which the case we describe clearly belonas (Fechner and Mills. 1992: Della Rocca and Huvos. 1996: Cheung et al. 1997. Although the permeation into the soft tissues could justify the term osteosarcoma (Unni. 1996). Della Rocca and Huvos (1996) stress that an aggressive clinical behaviour is not related to a particular histolooical feature. but rather to the skeletal location. In addition. invasion of adjacent bones has been described in aogressive osteoblastoma (Steiner. 1977). Finally. the bony trabeculae were delineated by a single layer of osteoblasts.
without evidence of mitotic figures in these cells. The increased mitotic activity was present in the stromal spindle cells. This feature might suggest a malignant transformation of the stromal component. This could provide an explanation for the aggressive clinical behaviour.
No karyotypic changes had ever been reported in osteoid osteoma. Our case is the first abnormal karvotype found in this basically benign proliferation.