Chondrogenic tumors

2022-03-02   Judith VMG Bovée , Paola Dal Cin 

1.Leiden University Medical Center, Leiden, The Netherlands
2.Brigham and Women's Hospital , Harvard Medical School, Boston , MA (USA)



Chondrogenic tumors are the most frequent primary bone tumors. Benign chondrogenic bone tumors are frequent incidental findings at imaging. However, some lesions previously thought to be reactive are locally aggressive and demonstrate reproducible molecular abnormalities. 1 Radiological parameters may be helpful for identification, characterization, and differential diagnosis. 2 Chondrosarcomas are a heterogeneous group of tumors and together constitute the third most common primary malignancy of bone accounting for 20 -27% of primary malignant osseous neoplasms. 3,4 Isocitrate dehydrogenase 1 (IDH1) and 2 (IDH2) mutations in cartilaginous tumors are relatively specific for enchondroma and conventional central chondrosarcoma. 5

Chondrogenic tumors Genetic marker(s)
Subungual exostosis t(X;6)(q24-q26;q15-q25), mainly as the sole aberration, 6,7 with breakpoints near by COL12A1 and IRSA, without any fusion transcript product. 8
Bizarre parosteal osteochondromatous proliferation (BPOP) Recurrent abnormalities as t(1;7)(q32;q21) 9 and inv(7)(q22q32) paired with inv(6)(p25q15). 10
Periosteal chondroma IDH1 (p.Arg132Cys) the most common mutation, 11 12q13-15 rearrangements may be recurrent but that HMGA2 is not expressed. 12 No recurrent chromosome aberrations. 13
Enchondroma IDH1 (p.Arg132) or IDH2 ( p.Arg172) in 52 % of sporadic cases, 14,15and in 90% of enchondromas in patients with enchondromatosis, 16 either Ollier disease OMIM:16600 or Maffucci syndrome OMIM:614569
Osteochondroma Chromosome aberrations involving 8q22-q24 EXT1 or 11p11.2 EXT2.17,18 Biallelic inactivation of EXT1 (80% in sporadic tumors) or EXT2.14
Chondroblastoma H3-3B p.Lys36Met mutation more frequent than in H3-3A. 15,19,20 No recurrent chromosome aberrations. 21
Chondromyxoid fibroma Heterogeneous and complex rearrangements of 6q24 region identified GRM1 recombined with several 5' partners FRMD6, MYO1E and MEF2A. 22,23
Osteochondromyxoma Inactivating mutations in PRKAR1A.24,25
Synovial chondromatosis Diploid or near-diploid abnormal clones with recurrent involvement of chromosome 6. 26 Rearrangements of FN1 and/or ACVR2A, in both benign and malignant lesions. 27,28 Single case with FN1::NFATC2 fusion. 28
Central atypical cartilaginous (ACT) / chondrosarcoma grade 1 (CS1) Heterozygous point mutations in IDH1 (predominanly p.Arg132C) and IDH2 15 in 50% of the cases
Secondary peripheral atypical cartilagenous tumors (ACT)/ chondrosarcoma grade 1 (CS1) Homozygous deletions of EXT1or EXT2 are much less frequently (40%), 29 with other genetic factor involved e.g. CDKN2A 3,30
Central Chondrosarcoma , grade 2 and 3 Beside complex karyotypes 31 and IDH1 or IDH1 mutations in ~50% cases, 14 as mechanism of progression from echondroma: additional alterations in the signaling pathways of p53, RB1 , mTOR, Hedgehog, SRC and AKT. (18624751} Mutations of COL2A1 and TP53 been the most fequent, and less frequently YEATS2, EGFR,NRAS and IHH signaling. (23770606, 25024164,29581779}
Secondary peripheral chondrosarcoma, grade 2 and 3 Chromosomal instability and complex karyotypes. 32,33 Additional non-specific alterations in p53 and RB1 pathways. 33 IDH1 ,IDH2 and NRAS mutations are absent. 14
Periosteal chondrosarcoma IDH1 and IDH2 mutations in a subset 34,35
Clear cell chondrosarcoma Clonal aberration in diploid or near diploid karyotype with abnormalities of chr.9 /-9, (but not CDKN2A alteration 36 and gain chr. 20 been the most frequent. 37 Single case with H3-3B p.Lis36Met mutation. 19
Mesenchymal chondrosarcoma HEY1::NCOA2fusion, arising froma cryptic del(8)(q13.3q21.1) in almost all cases. 38 Single case report with t(1;5)(q42;q32) associated with IRF2BP2::CDX1 fusion. 39
Dedifferentiated chondrosarcoma Complex karyoype by microarray, including loss 17p (TP53).36 IDH1 orIDH2 mutations , COL2A1, andTERT promoter mutations being common in dedifferentiated chondrosarcoma as likely early events in progression, whereas inactivating mutation of TP53 and high-level copy number alterations may be later events in the dedifferentiated phenotype. 40


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Judith VMG Bovée ; Paola Dal Cin

Chondrogenic tumors

Atlas Genet Cytogenet Oncol Haematol. 2022-03-02

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