Cytogenetic-Morphologic Correlations in Aneurysmal Bone Cyst, Giant Cell Tumor of Bone and Combined Lesions. A Report from the CHAMP Study Group

Abstract

Aneurysmal bone cyst and giant cell tumor of bone are relatively rare bone tumors that sometimes coexist. We examined the karyotypes of 3 aneurysmal bone cysts, 12 giant cell tumors, and 3 combined lesions. All aneurysmal bone cysts showed involvement of chromosome segments 17p11-13 and/or 16q22. In addition, in 1 of the 3 giant cell tumors with secondary aneurysmal bone cyst, both chromosome bands were rearranged as well, albeit not in a balanced translocation. Seven out of 12 giant cell tumors were characterized by telomeric associations. One giant cell tumor showed a dup(16)(q13q22), suggesting the presence of a (minor) secondary aneurysmal bone cyst component, despite the absence of histological proof. Our results, combined with literature data further substantiate that segments 16q22 and 17p11-13 are nonrandomly involved in at least some aneurysmal bone cysts, irrespective of subtype (primary, secondary, intra/extraosseous, solid or classic). These findings strongly suggest that some aneurysmal bone cysts are true neoplasms. In addition, telomeric associations are the most frequent chromosomal aberrations in giant cell tumor of bone, the significance of which remains elusive. In combined giant cell tumor/aneurysmal bone cyst each component seems to retain its own karyotypic abnormality.

Cytogenetic and molecular cytogenetic findings in 43 aneurysmal bone cysts: aberrations of 17p mapped to 17p13.2 by fluorescence in situ hybridization

“…Previous cytogenetic studies of aneurysmal bone cyst have revealed 17 cases with clonal chromosomal abnormalities (Table 2), 3,[6][7][8][9][10][11][12][13] Six of these 17 (35%) cases showed a t(16;17)(q22;p13), while seven additional cases demonstrated rearrangement of 17p11-13 with a chromosome partner other than 16q22. Conversely, 16q22 abnormalities exclusive of 17p11-13 abnormalities have been detected in two aneurysmal bone cysts.…”

“…Overall, the following chromosomal bands have been detected as 17p11-13 rearrangement partners in aneurysmal bone cyst: 1p34.1-34.3, 2p23, 6p21, 9p22, 14q11.2, 16q22, and 17q12. 3,[6][7][8][9][10][11][12][13] Observation of repeated involvement of 17p11-13 suggests that a putative oncogene important in the pathogenesis of aneurysmal bone cyst lies within this chromosomal region and the manner of its activation is diverse based on the variable 17p chromosomal rearrangement partners. 19 In addition to the apparent nonrandom partnership of 16q22 and 17p11-13, the current study reveals two more breakpoints that appear to be recurrently rearranged with 17p13.…”

“…7,9 Interestingly, an inversion of chromosome 17 [inv(17)(p13q11.2-12)] involving similar breakpoints was observed in case 37 of the present study (Figure 3). Although rearrangements of the 17q12 band have not been reported as [3],del(7)(q32) [3],À9 [3],+12 [2],+13 [2], inv(16)(p13.1q24) [4],À17 [3],À19 [4],À20 [3] Current study prominent in mesenchymal tumors, the 17q12 locus has received considerable attention because of the localization of the Her-2neu (a.k.a. c-erbB-2, erythroblastic leukemia viral oncogene homolog 2) and RARA (retinoic acid receptor, alpha) genes to this chromosomal band.…”

“…Aneurysmal bone cyst most commonly arises in young patients and typically involves the metaphyseal region of long bones and vertebrae. 2,3 Histopathologically, the lesion is composed of varying sized blood-filled spaces separated by connective tissue septa containing bony trabeculae and giant osteoclastic cells. 4 Aneurysmal bone cysts are frequently locally aggressive and exhibit a strong tendency to recur.…”

“…3,[6][7][8][9][10][11][12][13] Clonal abnormalities of the short arm of chromosome 17 appear to be recurrent and some authors have postulated that alterations of a 'yet to be determined' gene on 17p13 may play an important role in the development of aneurysmal bone cyst. 3,[7][8][9][10]12,13 In this study, the cytogenetic findings of 43 aneurysmal bone cyst samples from 38 patients are reported; several exhibiting novel rearrangements. Moreover, molecular cytogenetic data collected from efforts to further localize the key breakpoint on 17p are described.…”