Chronic diffuse sclerosing osteomyelitis of the mandible (DSOM) and fibrous dysplasia (FD) are distinct lesions with overlapping clinicopathological features that complicate their diagnosis. This study aimed to evaluate the efficacy of GNAS mutation analysis in differentiating between these two conditions. DNA samples from patients with DSOM (n = 35) and FD (n = 29) were collected to analyze the presence of GNAS mutations in exons 8 and 9, the two previously reported hotspot regions, using polymerase chain reaction and direct sequencing. Twenty-four of 29 patients (83%) with FD showed missense mutations in codon 201 in exon 8, whereas no mutation was detected in exon 9. No mutations were found in any of the 35 cases with DSOM. We also identified one case with an uncertain diagnosis due to overlapping clinicopathological features of DSOM and FD. A Q227H mutation was detected in this case, that confirmed the diagnosis of FD. Taken together, the findings indicate that mutational analysis of the GNAS is a reliable approach to differentiate between DSOM and FD of the jaw.
Your institute does not have access to this article
Subscribe to Journal
Get full journal access for 1 year
We are sorry, but there is no personal subscription option available for your country.
Get time limited or full article access on ReadCube.
All prices are NET prices.
The datasets used and/or analyzed during the current study are available from the corresponding author on reasonable request.
Suei Y, Tanimoto K, Taguchi A, Yamada T, Yoshiga K, Ishikawa T, et al. Possible identity of diffuse sclerosing osteomyelitis and chronic recurrent multifocal osteomyelitis. One entity or two. Oral. Surg. Oral. Med. Oral. Pathol. Oral. Radiol. Endod. 80, 401–408 (1995).
Timme M, Bohner L, Huss S, Kleinheinz J, Hanisch M. Response of Different Treatment Protocols to Treat Chronic Non-Bacterial Osteomyelitis (CNO) of the Mandible in Adult Patients: A Systematic Review. Int. J. Environ. Res. Public Health. 17, 1737 (2020).
Suei Y, Taguchi A, Tanimoto K. Diagnosis and classification of mandibular osteomyelitis. Oral. Surg. Oral. Med. Oral. Pathol. Oral. Radiol. Endod. 100, 207–214 (2005).
Patel R, Jacob R, Lee K, Booth TN. Parotid swelling and chronic recurrent multifocal osteomyelitis of mandible in children. Int. J. Pediatr. Otorhinolaryngol. 79, 47–52 (2015).
Javaid MK, Boyce A, Appelman-Dijkstra N, Ong J, Defabianis P, Offiah A, et al. Best practice management guidelines for fibrous dysplasia/McCune-Albright syndrome: a consensus statement from the FD/MAS international consortium. Orphanet. J. Rare Dis. 14, 139 (2019).
Slootweg PJ. Maxillofacial fibro-osseous lesions: classification and differential diagnosis. Semin. Diagn. Pathol. 13, 104 (1996).
Eversole R, Su L, ElMofty S. Benign fibro-osseous lesions of the craniofacial complex. A review. Head Neck Pathol. 2, 177–202 (2008).
Jacobsson S. Diffuse sclerosing osteomyelitis of the mandible. Int. J. Oral. Surg. 13, 363–385 (1984).
Boyce AM, Collins MT. Fibrous dysplasia/mccune-albright syndrome: a rare, mosaic disease of gα s activation. Endocr. Rev. 41 (2020).
Pan KS, Heiss JD, Brown SM, Collins MT, Boyce AM. Chiari I malformation and basilar invagination in fibrous dysplasia: prevalence, mechanisms, and clinical implications. J. Bone Miner. Res. 33, 1990–1998 (2018).
Boyce AM, Burke A, Cutler Peck C, DuFresne CR, Lee JS, Collins MT. Surgical management of polyostotic craniofacial fibrous dysplasia: long-term outcomes and predictors for postoperative regrowth. Plast. Reconstr. Surg. 137, 1833–1839 (2016).
Jia K, Li T, An J. Is operative management effective for non-bacterial diffuse sclerosing osteomyelitis of the mandible? J. Oral. Maxillofac. Surg. 79, 2292–2298 (2021).
Beck C, Morbach H, Beer M, Stenzel M, Tappe D, Gattenlöhner S, et al. Chronic nonbacterial osteomyelitis in childhood: prospective follow-up during the first year of anti-inflammatory treatment. Arthritis Res. Ther. 12, R74 (2010).
Wipff J, Costantino F, Lemelle I, Pajot C, Duquesne A, Lorrot M, et al. A large national cohort of French patients with chronic recurrent multifocal osteitis. Arthritis Rheumatol. 67, 1128–1137 (2015).
Jansson A, Renner ED, Ramser J, Mayer A, Haban M, Meindl A, et al. Classification of non-bacterial osteitis: retrospective study of clinical, immunological and genetic aspects in 89 patients. Rheumatology (Oxford). 46, 154–160 (2007).
Girschick H, Finetti M, Orlando F, Schalm S, Insalaco A, Ganser G, et al. The multifaceted presentation of chronic recurrent multifocal osteomyelitis: a series of 486 cases from the Eurofever international registry. Rheumatology (Oxford). 57, 1203–1211 (2018).
Otto S, Troeltzsch M, Burian E, Mahaini S, Probst F, Pautke C, et al. Ibandronate treatment of diffuse sclerosing osteomyelitis of the mandible: Pain relief and insight into pathogenesis. J. Craniomaxillofac Surg. 43, 1837–1842 (2015).
Otto S, Burian E, Troeltzsch M, Kaeppler G, Ehrenfeld M. Denosumab as a potential treatment alternative for patients suffering from diffuse sclerosing osteomyelitis of the mandibled-A rapid communication. J. Craniomaxillofac Surg. 46, 534–537 (2018).
Hallmer F, Korduner M, Møystad A, Bjørnland T. Treatment of diffuse sclerosing osteomyelitis of the jaw with denosumab shows remarkable results-A report of two cases. Clin. Case Rep. 6, 2434–2437 (2018).
Jia K, Li X, An J, Zhang Y. Comparing clinical and radiographic characteristics of chronic diffuse sclerosing osteomyelitis and craniofacial fibrous dysplasia in the mandible. J. Oral Maxillofac. Surg. 79, 1053–1061 (2021).
Lumbroso S, Paris F, Sultan C. Activating Gs alpha mutations: Analysis of 113 patients with signs of McCune-Albright syndrome—A European collaborative study. J. Clin. Endocrinol. Metab. 89, 2107–2113 (2004).
Idowu BD, Al-Adnani M, O’Donnell P, Yu L, Odell E, Diss T, et al. A sensitive mutation-specific screening technique for GNAS1 mutations in cases of fibrous dysplasia: the first report of a codon 227 mutation in bone. Histopathology. 50, 691–704 (2007).
Renapurkar S, Pasternack MS, Nielsen GP, Kaban LB. Juvenile mandibular chronic osteomyelitis: role of surgical debridement and antibiotics. J. Oral. Maxillofac. Surg. 74, 1368–1382 (2016).
Tabareau-Delalande F, Collin C, Gomez-Brouchet A, Decouvelaere AV, Bouvier C, Larousserie F, et al. Diagnostic value of investigating GNAS mutations in fibro-osseous lesions: a retrospective study of 91 cases of fibrous dysplasia and 40 other fibro-osseous lesions. Mod. Pathol. 26, 911–921 (2013).
Shi R-R, Li X-F, Zhang R, Chen Y, Li T-J. GNAS mutational analysis in differentiating fibrous dysplasia and ossifying fibroma of the jaw. Mod. Pathol. 26, 1023–1031 (2013).
Johannsen A. Chronic sclerosing osteomyelitis of the mandible. Radiographic differential diagnosis from fibrous dysplasia. Acta Radiol. Diagn. (Stockh). 18, 360–368 (1977).
Jour G, Oultache A, Sadowska J, Mitchell T, Healey J, Nafa K, et al. 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. Appl. Immunohistochem. Mol. Morphol. 24, 660–667 (2016).
Shin SJ, Lee SJ, Kim SK. Frequency of GNAS R201H substitution mutation in polyostotic fibrous dysplasia: Pyrosequencing analysis in tissue samples with or without decalcification. Sci. Rep. 7, 2836 (2017).
Liang Q, Wei M, Hodge L, Fanburg-Smith JC, Nelson A, Miettinen M, et al. Quantitative analysis of activating alpha subunit of the G protein (Gsα) mutation by pyrosequencing in fibrous dysplasia and other bone lesions. J. Mol. Diagn. 13, 137–142 (2011).
Isobe Y, Takahashi K, Kiso H, Nakao K, Ikeno M, Koyama N, et al. Direct evidence for the age-dependent demise of GNAS-mutated cells in oral fibrous dysplasia. Arch. Oral. Biol. 93, 133–140 (2018).
Lee SE, Lee EH, Park H, Sung JY, Lee HW, Kang SY, et al. The diagnostic utility of the GNAS mutation in patients with fibrous dysplasia: meta-analysis of 168 sporadic cases. Hum. Pathol. 43, 1234–1242 (2012).
Ferguson PJ, Bing X, Vasef MA, Ochoa LA, Mahgoub A, Waldschmidt TJ, et al. A missense mutation in pstpip2 is associated with the murine autoinflammatory disorder chronic multifocal osteomyelitis. Bone. 38, 41–47 (2006).
Grosse J, Chitu V, Marquardt A, Hanke P, Schmittwolf C, Zeitlmann L, et al. Mutation of mouse Mayp/Pstpip2 causes a macrophage autoinflammatory disease. Blood. 107, 3350–3358 (2006).
Hurtado-Nedelec M, Chollet-Martin S, Chapeton D, Hugot JP, Hayem G, Gérard B. Genetic susceptibility factors in a cohort of 38 patients with SAPHO syndrome: a study of PSTPIP2, NOD2, and LPIN2 genes. J. Rheumatol. 37, 401–409 (2010).
This work was supported in part by Research Unit of Precision Pathologic Diagnosis in Tumors of the Oral and Maxillofacial Regions, Chinese Academy of Medical Sciences (2019RU034). We would like to thank Dr. Ruirui Shi, Ms. Xuefen Li, and the Central Laboratory of Peking University School and Hospital of Stomatology for their support. This work was supported by CAMS Innovation Fund for Medical Sciences (2019-12M-5-038).
The regional Ethical Review Board of Peking University School and Hospital of Stomatology approved this study (PKUSSIRB-202272025), and the study was performed in accordance with the Declaration of Helsinki. The authors declare no competing interests.
Ethics approval and consent to participate
The regional Ethical Review Board of Peking University School and Hospital of Stomatology approved this study (PKUSSIRB-202272025), and the study was performed in accordance with the Declaration of Helsinki.
Publisher’s note Springer Nature remains neutral with regard to jurisdictional claims in published maps and institutional affiliations.
About this article
Cite this article
Xue, J., Jia, K., Li, T. et al. GNAS mutation analysis assists in differentiating chronic diffuse sclerosing osteomyelitis from fibrous dysplasia in the jaw. Mod Pathol (2022). https://doi.org/10.1038/s41379-022-01103-w