Benign 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

APC mutations,EXT1/EXT2 mutation, FOS rearrangement,H3F3A /H3F3B mutation,GRM1 fusions

Classification

Definition

Bone and cartilage tumors	Genetic markers
Benign maxillofacial bone and cartilage tumors
Osteoma	Osteoma is a benign bone-forming tumor.Sporadic osteomas tend to be solitary , with no specific molecular markers. Multiple osteomas should raise the possibility of Gardner syndrome with APC mutations. ¹ In rare cases of osteoma morphologically mimicking osteoblastoma, additional IHC or FISH testing for FOS can rule out osteoblastomas.²
Osteochondroma	Multiple osteochondromas are developed in the context of multiple hereditary exostoses (HME), mutations in either EXT1 or EXT2, located on chromosome 8q24 or chromosome 11p11-12 , respectively, detected in about 90% of the HME cases.³ Malignant transformation is more frequent in HME than solitary osteochondromas. Heterozygous EXT1 mutations are detected equally in solitary osteochondromas and HME, while EXT2 mutation are infrequent in solitary osteochondromas. ⁴
Osteoblastoma	Osteoblastoma are associated with FOS rearrangement and rarely FOSB in th he vast majority of cases. c-FOS nuclear expression is detected in most osteoblastoma limited to osteoblastic component. FOS gene rearrangement (detected by FISH) would strongly support the diagnosis of osteoblastoma over osteosarcoma. ⁵
Chondroblastoma	95% of chondroblastomas harbour a p.K36M mutation on H3-3A (chromosome 1) , or , mainly, H3-3B (chromosome 17) .The histone mutant-specific antibody K36M. has been used as a molecular test to differentiate from other bone tumor mimics. ^6,7
Chondromyxoid fibroma (CMF)	The genetic driver even 90% of tumors involves rearrangement on 6q, resulting in upregulating glutamate metabotropic receptor 1 (GRM1) gene through gene fusion and promoter swapping with active gene promoters, such as COL12A1, BCLAF1, or MEF2A It seems to be unique for CMF, while it is rarely present in other cartilagineous tumors . ^8,9 GRM1 immunohistochemistry can be a surrogate marker for GRM1 rearrangement .¹⁰
Desmoplastic fibroma of bone	Desmoplastic fibroma is a locally aggressive neoplasm., and is historically considered as the intraosseous counterpart of desmoid-type fibromatosis. Trisomy 8 and 20 have been reported in some cases by cytogenteic analysis. ¹¹ Additional molecular testing is helpful in differentiating desmoplastic fibroma from low-grade osteosarcoma e.g., MDM2 amplification ¹² and fibrous dysplasia e.g., GNAS mutation. Rare cases of CTNNB1 mutation has been also reported. ^12-14

Article Bibliography

Reference Number	Pubmed ID	Last Year	Title	Authors
1	31070935	2019	Familial Adenomatous Polyposis Syndrome: An Update and Review of Extraintestinal Manifestations.	Dinarvand P et al
2	31490237	2019	FOS Expression in Osteoid Osteoma and Osteoblastoma: A Valuable Ancillary Diagnostic Tool.	Amary F et al
3	28466453	2017	Hereditary Multiple Exostoses: New Insights into Pathogenesis, Clinical Complications, and Potential Treatments.	Pacifici M et al
4	33622860	2021	Osteochondromas: An Updated Review of Epidemiology, Pathogenesis, Clinical Presentation, Radiological Features and Treatment Options.	Tepelenis K et al
5	34742480	2021	Benign Bone-Forming Tumors.	Amary F et al
6	26844533	2016	The H3F3 K36M mutant antibody is a sensitive and specific marker for the diagnosis of chondroblastoma.	Amary MF et al
7	28557595	2017	Chondroblastoma: An Update.	Chen W et al
8	24658000	2014	GRM1 is upregulated through gene fusion and promoter swapping in chondromyxoid fibroma.	Nord KH et al
9	38890779	2024	Detection of GRM1 gene rearrangements in chondromyxoid fibroma: a comparison of fluorescence in-situ hybridisation, RNA sequencing and immunohistochemical analysis.	Torrence D et al
10	35650682	2022	GRM1 Immunohistochemistry Distinguishes Chondromyxoid Fibroma From its Histologic Mimics.	Toland AMS et al
11	10079250	1999	Trisomies 8 and 20 characterize a subgroup of benign fibrous lesions arising in both soft tissue and bone.	Bridge JA et al
12	30159138	2018	Low-grade central fibroblastic osteosarcoma may be differentiated from its mimicker desmoplastic fibroma by genetic analysis.	Song W et al
13	31838586	2020	Molecular findings in maxillofacial bone tumours and its diagnostic value.	Cleven AHG et al
14	31901437	2020	A case of desmoplastic fibroma of bone with CTNNB1 point mutation.	Kadowaki H et al

External Links

Citation

Paola Dal Cin, PhD

Benign maxillofacial bone and cartilage tumors

Atlas Genet Cytogenet Oncol Haematol. 2025-11-24

Online version: http://atlasgeneticsoncology.org/solid-tumor/209348/benign-maxillofacial-bone-and-cartilage-tumors