Other mesenchymal tumors of the bone

2022-12-01 Paola Dal Cin, PhD , Judith VMG Bovée Affiliation

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

Keywords

adamantinoma; NFATC2 gene fusion; GNAS mutations

Classification

Definition

This group of bone tumors is rather heterogeneous and includes various tumors including fibrous dysplasia, adamantinoma and undifferentiated pleomorphic sarcoma of bone. This group also includes tumors that are frequent in soft tissue but extremely rare in bone such as lipoma or leiomyosarcoma. ¹

Other mesenchymal tumors of the bone	Genetic markers(s)
Chrondromesenchymal hamartoma of the chest wall	No specific genetic findings so far
Osteofibrous dysplasia (OFD)	Trisomies 7 ,8 and 12 in a minority of spindle cells, but not on osteoblats or osteoclasts. ^2,3 MET germlilne mutation exon 14 OMIM:607278 or, occasionally, somatically acquired mutation. ⁴ No GNAS mutations ⁵
Adamantinoma of long bones	Combination of extra copies of chr.7, 8, 12, 19 and/or 21 , in classic lesions as well as in OFD -like adamantinoma. ^3,6 Recently ,NGS technologies confirmed the recurent chromosome gains; revealed a recurrent point mutations in KMT2D and KMT2D and a single EPHB4::MARCHF10 only in adamantinoma. ⁷
Simple bone cyst (SBC)	Cytogenetic analyses of 3 SBCs have been reported with inconsistent findings: t(16;20) (p11.2;q13), t(7;12) (q21;q24.3) and complex cytogenetic rearrangements. ⁸
	Recurrent FUS::NFATC2 or EWSR1::NFATC2 fusions, ^9-12 which also define a group of distinct, rare Round Cell Sarcomas with EWSR1–non-ETS fusions that predominantly arise in long bones.
Fibrocartilagenous mesenchymoma	No specific genetic findings so far
Fibrous dysplasia (FD)	GNAS (20q13.3) sporadic post-zygotic activating mutations , with p.Arg201His (66%) and p.Arg201Cys (31%) been the more commom mutations. ^13,14 GNAS mutations also associated with McCune-Albright syndrome ¹⁵ OMIM:17400 Random chromosome aberrations also reported ¹⁶
Lipoma and hibernoma of bone	No specific genetic findings so far
Leiomyosarcoma (LMS) of bone	Genomic loss and absence of phosporylated RB1,¹⁷ similar to deep soft tissue LMS
Undifferentiated pleomorphic sarcoma	Highly aneuploid by karyotypes and microrrays with several structural aberrations and marker chromosomes,¹⁸ and also homozygous deletions of CDKN2A, RB1, TP53 and ING1 overlapping with the same tumor in soft tissue. ¹⁹ Mutations of TP53 and /or chromatin-remodelling genes. ²⁰. Multiple somatic gene fusions ²¹
Bone metastases	Metastasis spread of primary malignancies elsewhere in the body

Article Bibliography

Reference Number	Pubmed ID	Last Year	Title	Authors
1	33480599	2021	The 2020 WHO Classification of Tumors of Bone: An Updated Review.	Choi JH et al
2	9242211	1997	Cytogenetic analysis of adamantinoma of long bones: further indications for a common histogenesis with osteofibrous dysplasia.	Hazelbag HM et al
3	18300815	2008	Osteofibrous dysplasia and adamantinoma in children and adolescents: a clinicopathologic reappraisal.	Gleason BC et al
4	26637977	2015	Mutations Preventing Regulated Exon Skipping in MET Cause Osteofibrous Dysplasia.	Gray MJ et al
5	11272890	2000	A comparative study of fibrous dysplasia and osteofibrous dysplasia with regard to Gsalpha mutation at the Arg201 codon: polymerase chain reaction-restriction fragment length polymorphism analysis of paraffin-embedded tissues.	Sakamoto A et al
6	11227067	2001	Extra copies of chromosomes 7, 8, 12, 19, and 21 are recurrent in adamantinoma.	Kanamori M et al
7	31021853	2019	Comprehensive Molecular Characterization of Adamantinoma and OFD-like Adamantinoma Bone Tumors.	Ali NM et al
8	22981752	2012	A simple bone cyst of the distal humerus with a t(7;12)(q21;q24.3) in a patient with hypophosphatemic rickets.	Sakai Junior N et al
9	32991339	2020	FUS-NFATC2 or EWSR1-NFATC2 Fusions Are Present in a Large Proportion of Simple Bone Cysts.	Pižem J et al
10	33316098	2021	Identification of EWSR1-NFATC2 fusion in simple bone cysts.	Hung YP et al
11	34081036	2021	Expanding the Spectrum of EWSR1-NFATC2-rearranged Benign Tumors: A Common Genomic Abnormality in Vascular Malformation/Hemangioma and Simple Bone Cyst.	Ong SLM et al
12	34089379	2021	The role of molecular diagnostics in aneurysmal and simple bone cysts - a prospective analysis of 19 lesions.	Pižem J et al
13	22245114	2012	The diagnostic utility of the GNAS mutation in patients with fibrous dysplasia: meta-analysis of 168 sporadic cases.	Lee SE et al
14	26574629	2016	GNAS Mutations in Fibrous Dysplasia: A Comparative Study of Standard Sequencing and Locked Nucleic Acid PCR Sequencing on Decalcified and Nondecalcified Formalin-fixed Paraffin-embedded Tissues.	Jour G et al
15	31673695	2020	Fibrous Dysplasia/McCune-Albright Syndrome: A Rare, Mosaic Disease of Gα s Activation.	Boyce AM et al
16	11104029	2000	Recurrent chromosome aberrations in fibrous dysplasia of the bone: a report of the CHAMP study group. CHromosomes And MorPhology.	Dal Cin P et al
17	15668899	2004	Genetic instability in primary leiomyosarcoma of bone.	Verelst SJ et al
18	10748288	2000	Frequent loss of 9p21 (p16(INK4A)) and other genomic imbalances in human malignant fibrous histiocytoma.	Simons A et al
19	21254299	2011	Array comparative genomic hybridization reveals frequent alterations of G1/S checkpoint genes in undifferentiated pleomorphic sarcoma of bone.	Niini T et al
20	30281149	2019	Genomic and transcriptomic characterisation of undifferentiated pleomorphic sarcoma of bone.	Ali NM et al
21	23637631	2013	Breakpoint analysis of transcriptional and genomic profiles uncovers novel gene fusions spanning multiple human cancer types.	Giacomini CP et al

External Links

Citation

Paola Dal Cin, PhD ; Judith VMG Bovée

Other mesenchymal tumors of the bone

Atlas Genet Cytogenet Oncol Haematol. 2022-12-01

Online version: http://atlasgeneticsoncology.org/solid-tumor/208970/other-mesenchymal-tumors-of-the-bone

Cookies