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

Department of Pathology, University of Leuven, Belgium.
Modern Pathology (Impact Factor: 6.19). 10/2000; 13(11):1206-1210. DOI: 10.1038/modpathol.3880224


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, albeitnot 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.Keywords: Aneurysmal bone cyst, Chromosomes, Correlations, Cytogenetics, Giant cell tumor, Morphology

Download full-text


Available from: Paola Dal Cin, Apr 18, 2014
21 Reads
  • Source
    • "Telomeric associations (TAS) have been reported as one of the most common genetic aberrations in GCT (4–6). It has been proposed that telomeric instability is responsible for a large degree of intra-tumor heterogeneity and the telomere serves as a precursor lesion to subsequent clonal structural aberrations of chromosome 11 in GCT. "
    [Show abstract] [Hide abstract]
    ABSTRACT: Giant cell tumor of bone (GCT) is a destructive neoplasm of uncertain etiology that affects the epiphyseal ends of long bones in young adults. GCT stromal cells (GCTSCs) are the primary neoplastic cells of this tumor and are the only proliferating cell component in long-term culture, which recruits osteoclast-like giant cells that eventually mediate bone destruction. The oncogenesis of GCT and factors driving the neoplastic stromal cells to proliferate extensively and pause at an early differentiation stage of pre-osteoblast lineage remain unknown. Overexpression of p63 was observed in GCTSCs and there is growing evidence that p63 is involved in oncogenesis through different mechanisms. This study aimed to understand the specific role of p63 in cell proliferation and oncogenesis of GCTSCs. We confirmed p63 expression in the mononuclear cells in GCT by immunohistochemical staining. By real-time PCR analysis, we showed a higher level (>15‑fold) of TAp63 expression in GCTSCs compared to that in mesenchymal stem cells. Furthermore, we observed that knockdown of the p63 gene by siRNA transfection greatly reduced cell proliferation and induced cell cycle arrest at S phase in GCTSCs. We found that the mRNA expression of CDC2 and CDC25C was substantially suppressed by p63 knockdown at 24-72 h. Moreover, p63 was found to be recruited on the regulatory regions of CDC2 and CDC25C, which contain p53-responsive elements. In summary, our data suggest that p63 regulates GCTSC proliferation by binding to the CDC2 and CDC25C p53-REs, which may inhibit the p53 tumor suppressor activity and contribute to GCT tumorigenesis.
    International Journal of Oncology 12/2012; 42(2). DOI:10.3892/ijo.2012.1727 · 3.03 Impact Factor
  • Source
    • "Although ABCs are known to be non-neoplastic and probably reactive lesions, more recent studies have shown that at least some of the ABCs of all types are of a neoplastic nature, owing to clonal chromosomal aberrations [6,18,19]. Recent cytogenetic data have shown clonal rearrangements of chromosomal bands 16q22 and 17p13, indicating a neoplastic basis in at least some ABCs [5,6,19]. "
    [Show abstract] [Hide abstract]
    ABSTRACT: An aneurysmal bone cyst is a benign but often rapidly expanding osteolytic multi-cystic osseous lesion that occurs as a primary, secondary, intra-osseous, extra-osseous, solid or conventional lesion. It frequently coexists with other benign and malignant bone tumors. Although it is considered to be reactive in nature, there is evidence that some aneurysmal bone cysts are true neoplasms. The solid variant of aneurysmal bone cyst is a rare subtype of aneurysmal bone cyst with a preponderance of solid to cystic elements. Such a case affecting the heel, an unusual site, is reported. A 26-year-old Caucasian man presented with pain and swelling in his left lower extremity. A plain radiograph demonstrated an intra-osseous, solitary, eccentric mass in the front portion of the left heel. Computed tomography and magnetic resonance imaging scans showed that the lesion appeared to be sub-cortical, solid with a small cystic portion without the characteristic fluid-fluid level detection but with distinct internal septation. Bone images containing fluid-fluid levels are usually produced by aneurysmal bone cysts. The fluid-fluid level due to bleeding within the tumor followed by layering of the blood components based density differences, but it was not seen in our case. An intra-lesional excision was performed. Microscopic examination revealed fibrous septa with spindle cell fibroblastic proliferation, capillaries and extensive areas of mature osteoid and reactive woven bone formation rimmed by osteoblasts. The spindle cells had low mitotic activity, and atypical forms were absent. The histological features of the lesion were consistent with the solid variant of an aneurysmal bone cyst. Solid aneurysmal bone cysts have been of great interest to pathologists because they may be mistaken for malignant tumors, mainly in cases of giant cell tumors or osteosarcomas, because of cellularity and variable mitotic activity. It is rather obvious that the correlation of clinical, radiological and histological findings is necessary for the differential diagnosis. The eventual diagnosis is based on microscopic evidence and is made when a predominance of solid to cystic elements is found. The present case is of great interest because of the nature of the neoplasm and the extremely unusual location in which it developed. Pathologists must be alert for such a diagnosis.
    Journal of Medical Case Reports 04/2011; 5:145. DOI:10.1186/1752-1947-5-145
  • Source
    • "der(13)t(5;13)(q11;q14) 59, 64 À12 30LR, 68 Tarkkanen et al., 1993; Molenaar et al., 1995; McComb et al., 1996; Bay et al., 1999 tas(13;14)(p13;p13) 48, 61, 64, 65 À13 25 c , 30LR c Molenaar et al., 1995; Bay et al., 1999; Garcia et al., 2006 tas(13;15)(p13;p13) 46, 48, 49, 57, 64 À18 25 c , 82 Molenaar et al., 1995; Bay et al., 1999; Garcia et al., 2006 tas(13;19)(p13;q13) 30LR, 81 À22 68 Noguera et al., 1989; Schwartz et al., 1991; Bay et al., 1999 tas(13;21)(p13;p13) 11, 48, 52, 64 ÀY 68, 87 Sciot et al., 2000 tas(13; "
    [Show abstract] [Hide abstract]
    ABSTRACT: Giant cell tumor of bone (GCTB) is a benign but locally aggressive tumor with metastatic potential. We performed cytogenetic analysis on 101 GCTB from 92 patients. Karyotypes were obtained from 95 tumors, 47 of which had clonal aberrations. The majority of the cytogenetically abnormal GCTB had multiple, up to 28 per tumor, clones. Clonal telomeric associations (tas) and other structural and numerical changes were found in about 70, 60, and 30%, respectively, of clonally abnormal tumors. Forty-seven aberrations were recurrent, of which 35 are novel. The vast majority of the recurrent aberrations were tas, confirming the important role of telomeric fusions in the development of GCTB. The frequency of tas in GCTB cultures increased with passaging, suggesting a selective advantage of tas-positive cells in vitro. The termini most frequently involved in tas were 22p, 13p, 15p, 21p, 14p, 19q, 1q, 12p, 11p, and 20q. The frequency of tas (irrespective of their clonality) was significantly higher in tumors carrying clonal changes, indicating that tas are precursors of other types of aberrations. In line with this assumption, the chromosomes preferentially involved in tas in a given tumor were also the ones most often affected by other rearrangements. We did not find the previously reported amplicon in 20q11.1, assessed by fluorescence in situ hybridization in 10 tumors. Nor did we find any association between cytogenetic features and adverse clinical outcome. Thus, local recurrences probably depend more on the adequacy of surgical treatment than on the intrinsic biology of the tumors.
    Genes Chromosomes and Cancer 07/2009; 48(7):583-602. DOI:10.1002/gcc.20667 · 4.04 Impact Factor
Show more