Cysts of the jaws
2025-11-24 Paola Dal Cin, PhD Affiliation1.Brigham and Women's Hospital , Harvard Medical School, Boston , MA (USA)
Keywords
osseous lesion, osteoclast like giant cells,MAPK pathway mutationsClassification
Definition
A group of different osseous lesions, sharing an abundance of osteoclast like giant cells and overlapping clinical and morphological features e.g. central giant cell granuloma (CGCG), peripheral giant cell granuloma, cherubism and aneurysmal bone cyst, 1-3
Multiple giant cell lesions that microscopically are indistinguishable from CGCG occur in several syndromes, most of which are known to be caused by mutations in the MAPK pathway. 4
| Giant cell lesions and bone cysts | Genetic marker(s) |
|---|---|
| Central giant cell granuloma (CGCG) | TRPV4, KRAS and FGFR1 gain-of-function mutations of the MAPK signaling pathway, have recently been identified in CGCG suggesting a pathogenetic relationship to non-ossifying fibroma of bone.5 In rare cases , KRAS and TRPV4 were both mutated, in contrast FGFR1 mutations were mutually exclusive with both of them.5 H3-3A muation was not detected in CGCG.6 |
| Multiple CGCG lesions have been described ind rarer forms of RASopathies. 7,8 A novel polysystemic syndrome due to germline TRPV4 p.Leu619Pro and further extend the spectrum of TRPV4 channelopathies. 9 | |
| Cherubism | Cherubism is a rare craniofacial disorder in children characterized by destructive jaw bone expansion OMIM:118400, predominantly resulting from SH3BP2 mutations in 80% of cases and inherited in an autosomal dominant fashion.10 SH3BP lies at at 4p16.3 in an area on chromosome 4 deleted in Wolf–Hirschhorn syndrome, a disorder without cherubism findings. 11 |
| Aneurysmal bone cyst (ABC) | Cytogenetic rearrangements of the USP6 at 17p13 in 70% of the cases, mainly with CDH11 , several other partners gene have been treported .12 Demonstration of USP6 rearrangement bshould be used to confirm the diagnosis in cases where histology may be inconclusive. ABC-like areas can be observed in other bone tumors of the jaw and are referred to as secondary ABC.13 Differentiating primary from secondary ABC sometimes requires additional molecular testing e.g. USP6 rearrangement. |
| Simple bone cyst (SBC) | Simple bone cysts show a predilection for the mandibular body. So far, no NFATC2 fusions were detected in simple bone cyst of the jaw. 14 More than half of SBCs in the peripheral skeleton have been shown to harbour either FUS::NFATC2 or EWSR1::NFATC2 fusion 15,16 |
Article Bibliography
| Reference Number | Pubmed ID | Last Year | Title | Authors |
|---|---|---|---|---|
| 1 | 31838586 | 2020 | Molecular findings in maxillofacial bone tumours and its diagnostic value. | Cleven AHG et al |
| 2 | 34742488 | 2021 | Giant Cell-Rich Tumors of Bone. | Hartmann W et al |
| 3 | 35312978 | 2022 | Update from the 5th Edition of the World Health Organization Classification of Head and Neck Tumors: Odontogenic and Maxillofacial Bone Tumours. | Vered M et al |
| 4 | 31705763 | 2020 | Making sense of giant cell lesions of the jaws (GCLJ): lessons learned from next-generation sequencing. | Gomes CC et al |
| 5 | 30385747 | 2018 | TRPV4 and KRAS and FGFR1 gain-of-function mutations drive giant cell lesions of the jaw. | Gomes CC et al |
| 6 | 27499898 | 2015 | Diagnostic value of H3F3A mutations in giant cell tumour of bone compared to osteoclast-rich mimics. | Presneau N et al |
| 7 | 35382488 | 2022 | Giant Cell Lesions of the Jaws Involving RASopathy Syndromes. | Luna M et al |
| 8 | 38347383 | 2024 | Multiple central giant cell granuloma of the jaws: diagnostic signposts of Noonan syndrome and RASopathy. | Friedrich RE et al |
| 9 | 33685999 | 2022 | De novo TRPV4 Leu619Pro variant causes a new channelopathy characterised by giant cell lesions of the jaws and skull, skeletal abnormalities and polyneuropathy. | Ragamin A et al |
| 10 | 33941395 | 2022 | SH3BP2-related fibro-osseous disorders of the maxilla and mandible: A systematic review. | Kueper J et al |
| 11 | 30236129 | 2018 | Molecular and cellular characterizations of human cherubism: disease aggressiveness depends on osteoclast differentiation. | Kadlub N et al |
| 12 | 32011035 | 2020 | Novel ASAP1-USP6, FAT1-USP6, SAR1A-USP6, and TNC-USP6 fusions in primary aneurysmal bone cyst. | Šekoranja D et al |
| 13 | 40606728 | 2025 | Recognition and Recurrence of Aneurysmal Bone Cyst Secondary to Giant Cell Tumor: A Case Series and Review Of The Literature. | Salduz A et al |
| 14 | 36939112 | 2023 | No NFATC2 fusion in simple bone cyst of the jaw. | Ong SLM et al |
| 15 | 32991339 | 2020 | FUS-NFATC2 or EWSR1-NFATC2 Fusions Are Present in a Large Proportion of Simple Bone Cysts. | Pižem J et al |
| 16 | 33316098 | 2021 | Identification of EWSR1-NFATC2 fusion in simple bone cysts. | Hung YP et al |
Citation
Paola Dal Cin, PhD
Cysts of the jaws
Atlas Genet Cytogenet Oncol Haematol. 2025-11-24
Online version: http://atlasgeneticsoncology.org/solid-tumor/209349/cysts-of-the-jaws
