Current concepts of craniofacial fibrous dysplasia: pathophysiology and treatment

Abstract

Fibrous dysplasia is an uncommon genetic disorder in which bone is replaced by immature bone and fibrous tissue, manifesting as slowgrowing lesions. Sporadic post-zygotic activating mutations in GNAS gene result in dysregulated GαS-protein signaling and elevation of cyclic adenosine monophosphate in affected tissues. This condition has a broad clinical spectrum, ranging from insignificant solitary lesions to severe disease. The craniofacial area is the most common site of fibrous dysplasia, and nine out of 10 patients with fibrous dysplasia affecting the craniofacial bones present before the age of 5. Surgery is the mainstay of treatment, but the technique varies according to the location and severity of the lesion and associated symptoms. The timing and indications of surgery should be carefully chosen with multidisciplinary consultations and a patient-specific approach.

Keywords: Bone neoplasms; Fibrous dysplasia; Fibrous dysplasia, monostotic; Fibrous dysplasia, polyostotic; Pathophysiology.

Fig. 1

Distribution of fibrous dysplasia according to its classification. MAS, McCune-Albright syndrome.

Fig. 2

Pathophysiology of fibrous dysplasia and current treatment targets. BMSC, bone marrow stromal cell; IL-6, interleukin-6; PDGF-B, platelet-derived growth factor subunit B; FGF-23, fibroblast growth factor-23; NFG, nerve growth factor; GTP, guanosine triphosphate; cAMP, cyclic adenosine monophosphate; PKA, protein kinase A; CREB-P, cAMP response element-binding protein; CREM-P, cAMP response element modulator protein; AP-1, activator protein 1.

Fig. 3

Histologic features of craniofacial fibrous dysplasia (all images are in hematoxylin and eosin stain). (A) Typical low-power appearance. Irregular, curvilinear, and immature bony trabeculae surrounded by fibrous background (zygoma, ×40). (B) Osteoclast activity and focal osteoblastic rimming is observed at high-power field (zygoma, ×200). (C) Relatively preserved continuity and lamination of bony trabecula. (skull, ×40) (D) Absent of osteoblastic rimming (skull, ×200) (E) Hypercellular lesion with abundant fibrous tissue (mandible, ×100).

Fig. 4

Presentation of café-au-lait spots. (A) Café-au-lait spots in fibrous dysplasia show more complex margins. (B) Café-au-lait spots in neurofibromatosis tend to have smoother borders.

Fig. 5

Surgical management of craniofacial fibrous dysplasia. (A-D) Simple shaving of the maxillary alveolar bone lesion with preservation of normal dentition. (E-I) Decortication with a maxillary anterior wall bone graft. (J, K) Radical excision of a frontal bone lesion and reconstruction with a polyetheretherketone patient-specific implant was done, while the periorbital and maxilla areas were recontoured with shaving.

Fig. 6

Four zones of craniofacial dysplasia. Redrawn from Chen et al. Plast Reconstr Surg 1990;86:835–44 [47].