# Fatal giant craniofacial fibrous dysplasia in a very young child

Kevin Perge, Sara Cabet, Solene Bergignat, Deborah Gensburger, Roland Chapurlat, Marc Nicolino

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Kevin Perge, Sara Cabet, Solene Bergignat, Deborah Gensburger, Roland Chapurlat, et al. Fatal giant craniofacial fibrous dysplasia in a very young child. Journal of Stomatology, Oral and Maxillofacial Surgery, 2025, 126 (1), pp.101996. 10.1016/j.jormas.2024.101996. inserm-05028849

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Submitted on 10 Apr 2025

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Short Communication

# Fatal giant craniofacial fibrous dysplasia in a very young child

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CrossMark

Kevin Perge<sup>a,b,e,*</sup>, Sara Cabet<sup>c,b</sup>, Solene Bergignat<sup>a</sup>, Deborah Gensburger<sup>d,e</sup>, Roland Chapurlat<sup>d,b,e</sup>, Marc Nicolino<sup>a,b,e</sup>

A 36-month-old ivorian girl was transferred to our reference center for a voluminous right hemifacial craniofacial fibrous dysplasia (FD). This diagnosis was mentioned at 18 months due to the appearance of a large right maxillary and sphenoidal bone mass responsible for a distinct orbital asymmetry and confirmed by CT scan and bone biopsy. She had no other bone involvement. At 36 months, she was referred to our center because of a significant increase in bone swelling. On examination, there was an obvious nontender, asymmetric right maxillary and sphenoidal growth. The girl also presented with skin café-au-lait spots typical of McCune Albright syndrome. Hormonal assessment did not reveal any hormonal hypersecretion. An osteotomy and contouring surgery was attempted due to the rapid growth of FD. The result was globally satisfactory despite the persistence of facial asymmetry. Genomic study of DNA extracted from bone biopsy identified the most frequent missense pathogenic variant in the *GNAS1* gene (p. R201H). Two months later, the girl presented a very rapid increase in bone deformity responsible for right proptosis, mouth and nose deviations (Figure). Breathing, chewing, and phonation became difficult.

CT exploration showed asymmetrical craniofacial FD responsible for craniofacial asymmetrical deformity and, compression of several structures (Fig. 1). A sarcomatous dedifferentiation was highly suspected on the exophytic heterogeneous lytic component obliterating the right maxillary sinus because of bone cortex ruptures and rapid growth. Angiography showed no marked increased arterialization and no early venous outflow. In the hypothesis of sarcomatous degeneration, a new bone biopsy was performed and showed a recurrence of the previously described FD, with no signs of sarcomatous transformation. The evolution was fatal following bleedings despite treatment with bisphosphonates, anti-angiogenic chemo-

therapies which were discontinued due to tumor progression. Thus, we report an exceptional case of craniofacial FD with fatal rapid growth. Craniofacial FD usually exhibits slow growth rate with growth arrest after puberty [1]. However, several reports have documented lesions manifesting rapid growth in adult but no such young presentation has been reported [2]. Our case underlines that giant facial FD as previously described, seem to preferentially affect African ethnic group suggesting associated aggravating genetic factors [2]. Differential diagnosis is a malignant transformation of FD. This last was described as a rare complication, affecting, according to a recent systematic review, 1.67 % of adults, especially after 30-40 years [3]. However, the prevalence is difficult to accurately determine due to rarity of FD and potential referral bias in tertiary care centers [3,4]. Atypical radiographic features such as cortical destruction and extension of the lesion into the adjacent soft tissue are suggestive of malignancy [5]. Malignant transformation should also be considered if a patient presents a rapidly expanding lesion associated with new focal pain [4]. The risk of malignancy is increased in case of prior irradiation therapy [3], polyostotic form, McCune-Albright or Mazabraud syndromes [4]. Finally, in the case of FD with severe cosmetic disfigurement and functional disturbance of the affected and adjacent structures, surgical treatment appears to be the only therapeutic option despite a risk of recurrence. Indeed, the surgery, particularly recontouring procedures may lead to recurrence, sometimes even with a rebound effect [6]. Other drug options such as denosumab, a RANKL inhibitor, not used in our patient, may be effective in improving lesion activity and mineralization and could thus avoid or in these rare cases be combined with surgical treatment [7]. However further studies are needed to determine the potential usefulness of this and other novel therapies, particularly in children with FD.

<footnote><sup>a</sup> Hospices Civils de Lyon, Hôpital Femme Mère Enfant, Service d'Endocrinologie Pédiatrique et Pédiatrie Générale, 59 Boulevard Pinel, 69500 Bron, France</footnote>

<footnote><sup>b</sup> Université Claude Bernard, Lyon 1, Lyon, France</footnote>

<footnote><sup>c</sup> Hospices Civils de Lyon, Hôpital Femme Mère Enfant, Service d'Imagerie Médicale, 59 Boulevard Pinel, 69500 Bron, France</footnote>

<footnote><sup>d</sup> Hospices Civils de Lyon, Hôpital Edouard-Herriot, Service de rhumatologie, 5 place d'Arsonval, 69003 Lyon, France</footnote>

<footnote><sup>e</sup> Centre national de référence de la dysplasie fibreuse des os, Hôpital E Herriot, 69437 Lyon, France</footnote>
<figure><img src="image_5.png" /><figcaption>**Fig. 1.** A giant craniofacial fibrous dysplasia Photograph of patient (A), Coronal CT images (B,C) showed asymmetrical craniofacial location of fibrous dysplasia with a component with ground-glass homogeneous appearance (loss of the normal bony corticomedullary differentiation, arrow in B), crossing sutures and involving skull and facial bones such as sphenoid (* in B), zygomatic, temporal or maxilla (arrowhead in B) bones. The content of the right orbit (arrow in C) as well as ethmoid and maxillary right sinuses were compressed by the bony expansion. A sarcomatous dedifferentiation was highly suspected on the exophytic heterogeneous lytic component (* in C,D,E) that obliterated paranasal sinuses (C), ruptured the bone cortex (arrowhead in C) and destroyed roots and teeth (C). Imaging follow-up showed a rapid growth of the exophytic bony component of the lesion (D and E are 10-months apart sagittal CT images).</figcaption></figure>

**Patient consent for publications**

Permission was obtained from the parents of the patient to pub-
lish images in Figure.

Funding

No funding was received.

Declaration of competing interest

The authors have declared that no competing interests exist.

CRediT authorship contribution statement

**Kevin Perge:** Writing – review & editing, Writing – original draft, Validation, Investigation, Data curation, Conceptualization. **Sara Cabet:** Writing – review & editing, Writing – original draft, Validation, Investigation, Data curation, Conceptualization. **Solene Bergignat:** Writing – review & editing, Validation, Resources. **Deborah**

**Gensburger:** Writing – review & editing, Validation. **Roland Chapur-**
**lat:** Writing – review & editing, Validation. **Marc Nicolino:** Writing –
review & editing, Writing – original draft, Validation, Data curation,
Conceptualization.

References

[1] Pan KS, Taylor J, Szymczuk V, Boyce AM. Lesion expansion in gnathic fibrous dysplasia: natural history, indicators of progression, and response to bisphosphonates. J Bone Miner Res 2023.

[2] Chen Y, Ding X, Yang Y, Yan W, Chen D, Li Z. Craniofacial fibrous dysplasia associated with McCune-Albright syndrome. J Oral Maxillofac Surg 2009;67(3):637-44.

[3] Furmah P, Aminoshariae A, Mupparapu M, Syed AZ. Frequency of spontaneous osteosarcomatous transformation of craniofacial fibrous dysplasia: a systematic review. Oral Surg Oral Med Oral Pathol Oral Radiol 2023;135(5):678-85.

[4] Hartley I, Zhadina M, Collins MT, Boyce AM. Fibrous dysplasia of bone and McCune-Albright syndrome: a bench to bedside review. Calcif Tissue Int 2019;104:517-29.

[5] Qu N, Yao W, Cui X, Zhang H. Malignant transformation in monostotic fibrous dysplasia. Medicine (Baltimore) 2015;94:e369.

[6] Kim DY. Current concepts of craniofacial fibrous dysplasia: pathophysiology and treatment. Arch Craniofac Surg 2023;24(2):41-51.

[7] De Castro LF, Michel Z, Pan K, et al. Safety and efficacy of denosumab for fibrous dysplasia of bone. N Engl J Med 2023;388:766-8.