Correlation between clinicopathological features and karyotype in 100 cartilaginous and chordoid tumours. A report from the Chromosomes and Morphology (CHAMP) Collaborative Study Group

Abstract

The evaluation of chondroid lesions requires full integration of clinical, radiographic, and pathological data; tumour typing is often a challenge for the diagnostic pathologist. Although a variety of chromosomal abnormalities have been documented in chondroid lesions, the potential usefulness of cytogenetic analysis remains unclear. This study has critically reviewed and analysed 117 karyotyped samples from 100 patients with cartilaginous and chordoid tumours. Cases were selected based on successful chromosomal analysis and adequacy of clinical, radiographic, and pathological information. To ensure objective evaluation, the cytogenetic results were correlated in a double-blind setting with consensus diagnoses independently determined on each case, after complete review of the histological, radiographic, and clinical findings. Karyotypic aberrations were identified in 41/92 cartilaginous tumours (5/11 osteochondromas, 2/3 chondromyxoid fibromas, 0/4 chondroblastomas, 11/29 chondromas, 0/3 chondroid tumours of undetermined malignant potential, 22/40 chondrosarcomas and 1/2 miscellaneous cartilaginous lesions) and 5/8 chordomas. Complex karyotypic changes were a feature of malignant tumours (chondrosarcoma and chordoma) and of chondrosarcoma among cartilaginous tumours, where they correlated with high tumour grade. Among primary well-differentiated cartilaginous lesions of bone, the finding of an abnormal karyotype was consistently associated with a grade 1 chondrosarcoma diagnosis. Among karyotypically abnormal cartilaginous tumours, loss of distal 8q was associated with osteochondroma, +5 with synovial chondroma/chondromatosis and parosteal or soft tissue chondroma, alterations of chromosome arm 6q with chondromyxoid fibroma, +7 with bone chondrosarcoma, and 17p1 alterations with grade 3 chondrosarcoma. Alterations involving 12q13 characterized synovial chondroma/chondromatosis in the chondroma group and myxoid chondrosarcoma of bone in the chondrosarcoma group. In conclusion, cytogenetic abnormalities in chondroid lesions are common and are not randomly distributed. They are associated with malignancy/tumour grade as well as with specific diagnoses in many cases, and can therefore be of potential value for tumour typing.

Heterogeneous and Complex Rearrangements of Chromosome Arm 6q in Chondromyxoid Fibroma

“…In the latter case, a breakpoint occurred in the proximal 6q13 region, most likely outside COL12A1. By reviewing the given probe map sequence, as reported by Yasuda et al, 9 we discovered discrepancies between the initially reported size and the recently revised size. As the length of BAC RP11-209D8 is not 10,206 bp but 166,681 bp, there is an overlap of 48,892 bp between the distal and proximal probe.…”

“…† Already reported. 9 N, normal; NP, not performed; SA, split apart; SA/CO, split apart and co-localization; EG, extra green signal without increased centromeric signal (partial trisomy); HD, hemizygous deletion loss of both green and red signal for one allele.…”

Frequent deletion of the CDKN2A locus in chordoma: analysis of chromosomal imbalances using array comparative genomic hybridisation

“…Several histological subtypes have been described; classical chordoma, which is the most common entity, chondroid chordoma, featuring regions resembling cartilage, and so-called 'dedifferentiated' chordoma, a rare subtype showing high-grade features. Histologically, chordomas are composed of physaliphorous cells expressing a particular low molecular weight cytokeratin pattern embedded in a mucomyxoid background (Mertens et al, 1994;Hazelbag et al, 1996;Dalpra et al, 1999;Scheil et al, 2001;Tallini et al, 2002). Clinically, chordomas manifest as slowly growing, locally destructive lesions with a tendency to infiltrate into adjacent tissues.…”

“…Recurrent chromosomal aberrations in chordomas, identified using G-banding, metaphase comparative genomic hybridisation (mCGH), and fluorescence in situ hybridisation (FISH), include loss of the entire or parts of chromosomes 3, 4, 10, 13, and 18; loss or rearrangement of 1p and 9p; and gain of chromosome 7 (Sawyer et al, 2001;Scheil et al, 2001;Tallini et al, 2002;Kuzniacka et al, 2004;Brandal et al, 2005). However, neither by mCGH nor cytogenetics has any consistent structural chromosome aberration been detected.…”

New chondrosarcoma cell lines and mouse models to study the link between chondrogenesis and chemoresistance

“…Indeed, a variety of chromosomal abnormalities and gene mutations can occur in CS, especially with high tumoral grade. 4 These abnormalities often comprise 12q13 amplification, the region harboring the p53 inhibitor MDM2 and cyclin-dependent kinase 4 (CDK4), but also 9p21 deletion. This chromosomal region includes the CDKN2A locus, coding for p16 INK4A and p14 ARF , which ensures a link between the RB and p53 pathways.…”