Malignant maxillofacial bone and cartilage tumors

2025-11-24 Paola Dal Cin, PhD Affiliation

1.Brigham and Women's Hospital , Harvard Medical School, Boston , MA (USA)

Keywords

osteosarcoma, chromoanagenesis, co-amplification of MDM2 and RASAL1,IDH mutations, HEY1, TFCP2

Classification

Definition

Bone and cartilage tumors	Genetic marker(s)
Malignant maxillofacial bone and cartilage tumors
Osteosarcoma of the jaw (JOS)	Osteosarcma developping mainly in the mandible differs from long-bone osteosarcomas. ^1,2 The presence of mandibular osteosarcoma in a young patient should raise the suspicion of an underlying TP53 germline mutation,.³, or radiation after retionablastoma or Page disease of the bone. In gemeral, the hallmark of osteosarcoma is chromosomal instability resulting in highly complex chromosomal aneuploidy and both intertumoural and intratumoural heterogeneity, likely caused by chromoanagenesis (chromothripsis/chromoplexy).⁴ There have been few reports to date of the molecular alterations that occur in JOS. Immunohistochemical studies have found a high positivity for p53 in JOS samples,⁵ MDM2 amplification with/without CDK4 by immunohistochemistry/FISH analysis was used to distinguish osteosarcoma from benign fibro-osseous lesions in the head and neck. ¹ Co-amplification of MDM2 and RASAL1 could constitute an early signature for the risk of transformation of JOF into high-grade JOS.^6,7
The chondrosarcoma family of tumors	Finding of an IDH1/IDH2 mutation is diagnostic for chondrosarcoma and excludes chondroblastic osteosarcoma.⁸ However the finding of wild-type IDH1/ IDH2 does not exclude chondrosarcoma, since not all chondrosarcomas harbour such mutations. In the head and neck area , IDH mutations have a higher detection rate in skull base tumors, infrequent in in laryngeal and tracheal cartilages , and absenti n tumors of the facial skeleton. ⁹
Mesenchymal chondrosarcoma	Almost all cases harbour a specific HEY1::NCOA2 fusion gene, or (much more rarely) IRF2BP2::CDX1. ¹⁰ Other additional genetic changes have been also repoted e.g.TP53 loss, RB1 pathway alterations, and CDKN2A homozygous loss.¹¹
Rhabdomyosarcoma with TFCP2 (TFCP2-RMS)	TFCP2 gene at 12q12.12 fused with either EWSR1 or FUS typically results in a spindle cell and/or epithelioid variant of rhabdomyosarcoma.e.g. TFCP2-RMS. The most commonly occur in young adults and aminly arise in craniofacial bones. Intragenic ALK deletions are present in roughly half of all cases, preserving the kinase domain of the protein, and correlate with ALK upregulation at the transcript and protein levels. Complex genetic profiles were observed by array CGH and recurrent CDKN2A deletions, which may contribute to its aggressive pathogenesis. ^12,13 Occasional alterations were reported, including MDM2 amplification,¹² TP53 mutation ¹³ and chromothripsis in 1p and 3p. ¹⁴
	Interesting, rare cases of TFCP2-RMS have been reported with a MEIS1::NCOA2 fusion .However the none of these tumors were located on the head and neck region. ¹⁵

Article Bibliography

Reference Number	Pubmed ID	Last Year	Title	Authors
1	32026294	2020	The Utility of MDM2 and CDK4 Immunohistochemistry and MDM2 FISH in Craniofacial Osteosarcoma.	Limbach AL et al
2	33113487	2020	Osteosarcoma of the jaws: An overview of the pathophysiological mechanisms.	Bertin H et al
3	29420387	2018	High-Grade Conventional Osteosarcoma of the Mandible Associated With P53 Germline Mutation.	Ginat D et al
4	40563473	2025	Chromoanagenesis in Osteosarcoma.	Li G et al
5	12747978	2003	Clinicopathological and immunohistochemical analysis of twenty-five head and neck osteosarcomas.	Junior AT et al
6	24925056	2015	Chromosome 12 long arm rearrangement covering MDM2 and RASAL1 is associated with aggressive craniofacial juvenile ossifying fibroma and extracranial psammomatoid fibro-osseous lesions.	Tabareau-Delalande F et al
7	26997440	2016	A new subtype of high-grade mandibular osteosarcoma with RASAL1/MDM2 amplification.	Guérin M et al
8	23598960	2013	Molecular distinction of chondrosarcoma from chondroblastic osteosarcoma through IDH1/2 mutations.	Kerr DA et al
9	30296521	2019	IDH mutation status in a series of 88 head and neck chondrosarcomas: different profile between tumors of the skull base and tumors involving the facial skeleton and the laryngotracheal tract.	Tallegas M et al
10	29582189	2018	Mesenchymal Chondrosarcoma: a Review with Emphasis on its Fusion-Driven Biology.	El Beaino M et al
11	37760551	2023	Mesenchymal Chondrosarcoma from Diagnosis to Clinical Trials.	Dudzisz-Śledź M et al
12	31383960	2020	A subset of epithelioid and spindle cell rhabdomyosarcomas is associated with TFCP2 fusions and common ALK upregulation.	Le Loarer F et al
13	33382123	2021	Head and neck rhabdomyosarcoma with TFCP2 fusions and ALK overexpression: a clinicopathological and molecular analysis of 11 cases.	Xu B et al
14	30477883	2019	Rhabdomyosarcoma with FUS re-arrangement: additional case in support of a novel subtype.	Wong DD et al
15	37668330	2023	Intraosseous Spindle Cell Rhabdomyosarcoma with MEIS1::NCOA2 Fusion - Case Report with Substantial Clinical Follow-up and Review of the Literature.	Smith BF et al

External Links

Citation

Paola Dal Cin, PhD

Malignant maxillofacial bone and cartilage tumors

Atlas Genet Cytogenet Oncol Haematol. 2025-11-24

Online version: http://atlasgeneticsoncology.org/solid-tumor/209350/malignant-maxillofacial-bone-and-cartilage-tumors