Chondrogenic tumors

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

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

Classification

Definition

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

Bibliography

Reference Number	Pubmed ID	Last Year	Title	Authors
1	33946096	2022	Some Reactive Lesions of Bone Are Probably Neoplasms.	Memon RA et al
2	31575404	2019	Imaging Features of Bone Tumors: Conventional Radiographs and MR Imaging Correlation.	Gemescu IN et al
3	30519452	2018	Chondrosarcoma: biology, genetics, and epigenetics.	Chow WA et al
4	34742483	2021	Malignant Cartilage-Forming Tumors.	Hameed M et al
5	33480599	2021	The 2020 WHO Classification of Tumors of Bone: An Updated Review.	Choi JH et al
6	9885985	1999	Clonal chromosome abnormalities in a so-called Dupuytren's subungual exostosis.	Dal Cin P et al
7	15252309	2004	Distinct chromosomal rearrangements in subungual (Dupuytren) exostosis and bizarre parosteal osteochondromatous proliferation (Nora lesion).	Zambrano E et al
8	20340132	2011	The t(X;6) in subungual exostosis results in transcriptional deregulation of the gene for insulin receptor substrate 4.	Mertens F et al
9	15926071	2005	Bizarre parosteal osteochondromatous proliferation with a t(1;17) translocation.	Endo M et al
10	24412018	2013	Bizarre parosteal osteochondromatous proliferation: a new cytogenetic subgroup characterized by inversion of chromosome 7.	Broehm CJ et al
11	2198255	1990	Genetic and behavioral analysis of flagellar switch mutants of Salmonella typhimurium.	Magariyama Y et al
12	26170993	2015	Recurrent 12q13-15 chromosomal aberrations, high frequency of isocitrate dehydrogenase 1 mutations, and absence of high mobility group AT-hook 2 expression in periosteal chondromas.	Panagopoulos I et al
13	21536235	2011	Cytogenetic findings in 14 benign cartilaginous neoplasms.	Sakai Junior N et al
14	21598255	2011	IDH1 and IDH2 mutations are frequent events in central chondrosarcoma and central and periosteal chondromas but not in other mesenchymal tumours.	Amary MF et al
15	31728625	2020	Mutation-driven epigenetic alterations as a defining hallmark of central cartilaginous tumours, giant cell tumour of bone and chondroblastoma.	Venneker S et al
16	32253147	2020	Multiple hereditary exostoses and enchondromatosis.	Jurik AG et al
17	9576285	1998	Clonal karyotypic abnormalities of the hereditary multiple exostoses chromosomal loci 8q24.1 (EXT1) and 11p11-12 (EXT2) in patients with sporadic and hereditary osteochondromas.	Bridge JA et al
18	21703028	2011	Breakpoint characterization of large deletions in EXT1 or EXT2 in 10 multiple osteochondromas families.	Jennes I et al
19	24162739	2013	Distinct H3F3A and H3F3B driver mutations define chondroblastoma and giant cell tumor of bone.	Behjati S et al
20	26844533	2016	The H3F3 K36M mutant antibody is a sensitive and specific marker for the diagnosis of chondroblastoma.	Amary MF et al
21	19903358	2009	A balanced t(5;17) (p15;q22-23) in chondroblastoma: frequency of the re-arrangement and analysis of the candidate genes.	Romeo S et al
22	20696777	2010	Heterogeneous and complex rearrangements of chromosome arm 6q in chondromyxoid fibroma: delineation of breakpoints and analysis of candidate target genes.	Romeo S et al
23	24658000	2014	GRM1 is upregulated through gene fusion and promoter swapping in chondromyxoid fibroma.	Nord KH et al
24	10973256	2000	Mutations of the gene encoding the protein kinase A type I-alpha regulatory subunit in patients with the Carney complex.	Kirschner LS et al
25	28008382	2016	Osteochondromyxoma: Review of a rare carney complex criterion.	Golden T et al
26	12550753	2003	Chromosome 6 abnormalities are recurrent in synovial chondromatosis.	Buddingh EP et al
27	31273315	2019	Synovial chondromatosis and soft tissue chondroma: extraosseous cartilaginous tumor defined by FN1 gene rearrangement.	Amary F et al
28	31589790	2020	A molecular study of synovial chondromatosis.	Agaram NP et al
29	21804604	2012	Secondary peripheral chondrosarcoma evolving from osteochondroma as a result of outgrowth of cells with functional EXT.	de Andrea CE et al
30	25644707	2015	Cell cycle deregulation and mosaic loss of Ext1 drive peripheral chondrosarcomagenesis in the mouse and reveal an intrinsic cilia deficiency.	de Andrea CE et al
31	1179337	1975	[Haukeland project. Information and views].	Heimann P et al
32	10502300	1999	Characterization of fertilization-modulated myelin basic protein kinases from sea star: regulation of Mapk.	Lefebvre DL et al
33	19336518	2009	Genomic profiling of chondrosarcoma: chromosomal patterns in central and peripheral tumors.	Hallor KH et al
34	21596255	2011	Evaluation of Scheimpflug imaging parameters in subclinical keratoconus, keratoconus, and normal eyes.	Uçakhan ÖÖ et al
35	25648524	2015	Periosteal chondrosarcoma: a histopathological and molecular analysis of a rare chondrosarcoma subtype.	Cleven AH et al
36	22674453	2012	Genetic characterization of mesenchymal, clear cell, and dedifferentiated chondrosarcoma.	Meijer D et al
37	15133857	2004	Signal pathways involved in emodin-induced contraction of smooth muscle cells from rat colon.	Ma T et al
38	22034177	2012	Identification of a novel, recurrent HEY1-NCOA2 fusion in mesenchymal chondrosarcoma based on a genome-wide screen of exon-level expression data.	Wang L et al
39	23185413	2012	Whole-transcriptome sequencing identifies novel IRF2BP2-CDX1 fusion gene brought about by translocation t(1;5)(q42;q32) in mesenchymal chondrosarcoma.	Nyquist KB et al
40	3314733	1987	Disseminated cicatricial pemphigoid in a child and in an adult. Ultrastructural diagnostic criteria and differential diagnosis with special reference to acquired epidermolysis bullosa.	Hausser I et al

External Links

OMIM database

Citation

Judith VMG Bovée ; Paola Dal Cin

Chondrogenic tumors

Atlas Genet Cytogenet Oncol Haematol. 2022-03-02

Online version: http://atlasgeneticsoncology.org/solid-tumor/208941/chondrogenic-tumors