Contemporary Surgical Management of Craniofacial Fibrous Dysplasia Using Computer-Assisted Surgery and Intraoperative Navigation.

Craniofacial fibrous dysplasia (CFD) is a rare developmental disease of bone, which typically presents as a painless, expansile mass causing deformity of the craniofacial skeleton. In rare circumstances, compression of neurovascular structures may arise, causing symptoms such as pain, visual impairment, and hearing loss. Traditionally, CFD debulking has been performed with "freehand" techniques using preoperative imaging and anthropometric norms to determine the ideal amount of tissue removal. The advent of computer-assisted surgery, computer-aided design, and computer-aided manufacturing (CAD/CAM) has revolutionized the management of CFD. Surgeons can now fabricate patient-specific osteotomy/ostectomy guides, allowing for increased accuracy in bone removal and improved cosmetic outcomes. This series of 3 cases describe our institution's technique using patient-specific ostectomy "depth guides", which allow for maximum removal of fibro-osseous tissue while sparing deep and adjacent critical structures. These techniques can be widely applied to the craniofacial skeleton to assist in the surgical management of CFD.

Craniofacial Fibrous Dysplasia: Experience at San José Hospital, Bogotá, Colombia.

INTRODUCTION: Fibrous dysplasia is a disorder in which normal bone is gradually replaced by immature fibro-osseous tissue, with an incidence of less than 7% of all benign bone tumors. The management of this disease is a challenge for plastic surgeons and neurosurgeons. GOAL: To describe the diagnostic, therapeutic, and outcome approach of patients with craniofacial fibrous dysplasia seen at the Plastic Surgery Service of the Hospital San José in Bogotá, Colombia. METHODS: This is a descriptive and retrospective case series study of patients diagnosed with monostotic and polyostotic fibrous dysplasia treated at the Plastic Surgery Department of Hospital San José during the period from January 1, 2010, to July 31, 2023. RESULTS: All (n=10) of the patients had monostotic craniofacial fibrous dysplasia. The most affected bones in patients with monostotic fibrous dysplasia were zone I bones (n=10, 100%), followed by zone II bones (n=2, 20%). Patients with zone I and II involvement manifested throbbing headaches associated with phosphenes and tinnitus (n=8, 80%) and pain during occlusion associated with edema in the affected cheek (n=5, 50%). Physical examination showed that patients with orbital wall involvement (zone I bone) had ocular dystopia (n=7, 70%).Regarding the treatment received by the patients, 90% (n=9) of the patients received surgical management as primary treatment, with orbitotomy, replacement, and/or remodeling of the roof and lateral wall of the orbit with bone graft, drilling, canthoplasty, ciliary suspension being the most frequently performed procedure (n=6, 60%). Of the patients, 20% (n=2) required reintervention. CONCLUSIONS: FD is a slowly progressive benign fibro-osseous disease that requires a timely, individualized, and multidisciplinary diagnosis and treatment to obtain favorable clinical and surgical results.The mainstay of treatment is surgery as a preventive measure since it is important to avoid future functional alterations that, depending on the location of the dysplasia, would cause a high risk of alteration of adjacent structures.

Comparison of the histopathological characteristics of diffuse sclerosing osteomyelitis of the mandible, chronic suppurative osteomyelitis, and craniofacial fibrous dysplasia.

BACKGROUND: There are relatively few reports on the histopathological characteristics of diffuse sclerosing osteomyelitis of the mandible (DSOM), which is difficult to distinguish from chronic suppurative osteomyelitis (CSO) and craniofacial fibrous dysplasia (CFD). This study aimed to summarize and compare the histopathological characteristics of DSOM, CFD, and CSO. MATERIALS AND METHODS: In this study, hematoxylin and eosin-stained sections of patients with DSOM, CSO, and CFD at the Peking University Hospital of Stomatology from 2015 to 2020 were retrieved. The histopathological characteristics were summarized, including new bone formation, inflammatory cell infiltration, bone trabecular morphology, osteoclasts, sequestrum, bacterial mass, and calcified spherules, similar to cementicles. The histopathological characteristics of DSOM, CSO, and CFD were compared, and the results were statistically analyzed. RESULTS: In total, 50, 13, and 10 patients with DSOM, CSO, and CFD were included in this study, respectively. In terms of new bone formation, both DSOM and CSO showed reactive bone formation (p = 1), whereas CFD mainly showed fiber osteogenesis (p < 0.001). The inflammatory cells of DSOM were mainly lymphocytes and plasma cells, whereas those of CSO were mainly lymphocytes and neutrophils (p < 0.001), and there was usually no inflammatory cell infiltration in the CFD specimens (p < 0.001). DSOM, CSO, and CFD showed irregular bone trabeculae (p = 0.045, p = 0.703) and active osteoclasts (p1 = 0.189, p2 = 0.256). DSOM showed a small amount of bacterial mass but no sequestrum; neither of which was found in CFD (p = 1, p = 1), but it was common in CSO (p = 0.011 and p = 0.025). DSOM and CSO showed smooth and regular basophilic lines (p = 0.308), whereas CFD showed a rough and irregular basophilic line (p < 0.001). CONCLUSIONS: The histopathological characteristics of the three diseases were partly similar, but there were evident differences. The main differences are the type of new bone formation, types and distribution of inflammatory cells, and presence of sequestrum and bacterial masses. These differences will help clinicians diagnose DSOM.

Craniofacial Fibrous Dysplasia: Clinical and Therapeutic Implications.

PURPOSE OF REVIEW: This study aims to review diagnosis, potential complications, and clinical management in craniofacial fibrous dysplasia. RECENT FINDINGS: Fibrous dysplasia (FD) is a rare mosaic disorder in which normal bone and marrow are replaced with expansile fibro-osseous lesions. Disease presents along a broad spectrum and may be associated with extraskeletal features as part of McCune-Albright syndrome (MAS). The craniofacial skeleton is one of the most commonly impacted areas in FD, and its functional and anatomical complexities create unique challenges for diagnosis and management. This review summarizes current approaches to diagnosis and management in FD/MAS, with emphasis on the clinical and therapeutic implications for the craniofacial skeleton.

Modification of LeFort I Osteotomy for Correction of Severe Maxillary Cant Associated With Fibrous Dysplasia.

Differential superior reposition of maxilla following LeFort I osteotomy in the correction of maxillary cant poses a greater challenge especially when associated with the pathology like fibrous dysplasia which completely obliterates the antrum. Purpose of this paper is to highlight the modification of LeFort I osteotomy and hypothesis is to assess its difficulty index in modifying the standard steps, in executing the maxillary separation at various to correct the gross facial asymmetry to achieve a favorable outcome. Multiphased management involved scrupulous clinical planning, advanced imaging by computed tomgraphy scans, stereolithographic models to debulk the lesion. The second phase included pre surgical orthodontic evaluation along with correction of severe maxillary cant adopting a modified LeFort 1 osteotomy technique and standard bilateral sagittal split osteotomy, thereby simultaneously attaining functional stability and esthetic harmony.

A Novel Technique for the Correction of Unilateral Craniofacial Fibrous Dysplasia Using Multiplanar Sequential Cutting Guides.

In this unique case report, the authors have described a new method for the correction of unilateral craniofacial fibrous dysplasia by using sequential cutting guides. Due to the complex 3-dimensional anatomy of zygoma, it needs to be chiseled in multiple planes to mimic the normal contralateral side. To achieve this, 3 different guides were used one after the other to perform osteotomies in different planes and remove the excess fibrous bone.

A Novel Bone Contouring Technique Using Multiple Tangential Shaving for Conservative Management of Craniofacial Fibrous Dysplasia.

This study aimed to propose a novel surgical technique, named multiple tangential shaving of bone contour, for the conservative management of craniofacial fibrous dysplasia. We retrospectively reviewed 17 patients who underwent conservative management of craniofacial fibrous dysplasia using multiple tangential shaving technique between July 2005 and December 2020. Demographics, tumor characteristics, and surgery-related factors were investigated. All patients underwent preoperative (T0) and postoperative computed tomography scans taken at least twice within 1 month for immediate assessment (T1) and at least 12 months postoperatively for long-term assessment (T2). Clinical outcomes, including tumor recurrence, perioperative complications, and physician measure of esthetic outcomes (Whitaker score), were investigated. This technique was applied for contouring of the zygomatic-maxillary and calvarial bone for patients aged between 16 and 60 years (mean age: 26 y). The mean±SD tumor volume reduction was 15.5±8.95 cm 3 , and the postoperative mean±SD tumor growth rate was 5.52±6.26% per year. Satisfactory outcome was obtained in terms of esthetics with a mean±SD Whitaker score of 1.41±0.62. Patients required a mean operation time of 1.67±0.43 hours and a mean number of shaving operations of 1.35±0.61 during the follow-up period. Five of 17 patients required reoperation because of the tumor recurrence (N=4) and to correct new-onset diplopia after surgery (N=1). In conclusion, the multiple tangential shaving technique allows an easy approach for conservative management of craniofacial fibrous dysplasia. An acceptable rate of tumor recurrence and esthetic outcomes can be obtained by selecting the appropriate candidate for a conservative approach.

PTHrP Modulates the Proliferation and Osteogenic Differentiation of Craniofacial Fibrous Dysplasia-Derived BMSCs.

Fibrous dysplasia (FD) is a skeletal stem cell disease caused by mutations in the guanine nucleotide-binding protein, alpha-stimulating activity polypeptide (GNAS) gene, which results in the abnormal accumulation of cyclic adenosine monophosphate (cAMP) and hyperactivation of downstream signaling pathways. Parathyroid hormone-related protein (PTHrP) is secreted by the osteoblast lineage and is involved in various physiological and pathological activities of bone. However, the association between the abnormal expression of PTHrP and FD, as well as its underlying mechanism, remains unclear. In this study, we discovered that FD patient-derived bone marrow stromal cells (FD BMSCs) expressed significantly higher levels of PTHrP during osteogenic differentiation and exhibited greater proliferation capacity but impaired osteogenic ability compared to normal control patient-derived BMSCs (NC BMSCs). Continuous exogenous PTHrP exposure on the NC BMSCs promoted the FD phenotype in both in vitro and in vivo experiments. Through the PTHrP/cAMP/PKA axis, PTHrP could partially influence the proliferation and osteogenesis capacity of FD BMSCs via the overactivation of the Wnt/ß-Catenin signaling pathway. Furthermore, PTHrP not only directly modulated cAMP/PKA/CREB transduction but was also demonstrated as a transcriptional target of CREB. This study provides novel insight into the possible pathogenesis involved in the FD phenotype and enhances the understanding of its molecular signaling pathways, offering theoretical evidence for the feasibility of potential therapeutic targets for FD.

Severe craniofacial fibrous dysplasia associated with decreased visual acuity: a case report.

Fibrous dysplasia is a developmental abnormality characterized by the replacement of normal bone tissue by fibrous connective tissue with poorly organized bone trabeculae. This disorder rarely occurs in the craniofacial region, but in such cases it causes facial asymmetries and has severe clinical implications for the patient. This case report describes the treatment of an 18-year-old man who presented with complaints of facial deformity and decreased visual acuity. Cone beam computed tomography revealed a diffuse bone lesion affecting the region of the maxillary, frontal, and nasal bones on the left side of the face. After microscopic examination, the diagnosis of craniofacial fibrous dysplasia was made. The patient underwent a bilateral temporal craniotomy to perform decompression of the orbital apices and correct the loss of visual acuity. In addition, surgical cosmetic contouring of the facial bones was performed. The patient has been followed up by a multidisciplinary team; at his most recent examination, 18 months after the last surgical intervention, his clinical condition remained stable.

Malignant Sarcomatous Degeneration of Craniofacial Fibrous Dysplasia.

BACKGROUND: Fibrous dysplasia (FD) is an uncommon bone disease characterized by the replacement of normal bone architecture with abnormal fibro-osseous connective tissue. Here, we discuss 2 cases of craniofacial FD, with malignant sarcomatous degeneration - a rare and morbid complication of the disease. CASE HISTORY: Two cases of craniofacial FD with malignant degeneration are presented. In the first, a 68-year-old male with a history of FD presented with acutely worsening left-sided facial pain and V2 and V3 hypoesthesia. Imaging findings suggested a large infratemporal fossa mass with biopsy demonstrating sarcomatous degeneration. Radical craniofacial resection achieved a gross total resection with likely microscopic disease. The patient was unable to tolerate adjuvant chemotherapy or radiation and succumbed to his disease 13 months following surgery.In the second case, a 36-year-old male with McCune-Albright Syndrome and craniofacial FD presented with acutely worsening left-sided headaches and midface hypoesthesia. Imaging revealed a heterogenous and expansile lesion with erosive changes in the left nasal cavity and infratemporal fossa. Pathology was suggestive of low grade sarcomatous degeneration. Given the extensive involvement of the skull base, the tumor was deemed unresectable, and the patient soon died following initiation of chemotherapy. CLINICAL RELEVANCE: Malignant sarcomatous transformation is a rare and challenging complication of craniofacial FD. Indolent onset, advanced spread at time of presentation, and close relationship with vital neurovascular structures are all hurdles for the treating clinician. The entity poses a diagnostic dilemma, as pathological analysis can be equivocal and may mimic nonmalignant processes, such as locally aggressive FD.

Surgical Correction of Craniofacial Fibrous Dysplasia Involving Orbits: A Unique Application of Patient-Specific Implants.

ABSTRACT: Craniofacial fibrous dysplasia is a slow-growing bony disorder causing asymmetry of the face; leading to aesthetic, functional, and psychological ramifications. Surgical recontouring is the most accepted form of treatment. Reconstruction of the orbit poses a serious challenge to the surgeon; hence the present study is intended to describe and evaluate a most anatomically accurate virtual treatment planning and defect-specific implant technique, enumerating postoperative functional and esthetic outcome. The study highlights a valid application of three-dimensional models and computer-guided surgical splints. The current study included 5 patients with craniofacial fibrous dysplasia involving orbits with a mean age of 19.6 years. Detailed pre- and post-operative ophthalmologic workup were documented for one year. All the participants showed improvement in eyeball position and movement. Visual acuity and intraocular pressure have returned to near normal values, and astigmatism was reduced significantly. No recurrence was noted in any of the subjects. The current technique was found helpful in reconstructing the complex orbital anatomy; however, long-term follow-up studies with a greater number of patients are recommended.

Craniofacial Fibrous Dysplasia of the Skull Assisted by Virtual Surgical Planning.

Craniofacial fibrous dysplasia (FD) involves thickening of the skull and facial bones, causing asymmetry and distortion of overlying soft tissues. Surgical contouring is often performed with rotary bur or osteotome, with the goal of matching contralateral unaffected anatomy. This is made technically challenging by having no direct visualization of contralateral structures, and the desire to control depth of resection to match the contour of the unaffected side. In our report, a 13-year-old male presented for surgical evaluation of craniofacial FD affecting the right parietal/temporal bones. A novel virtual surgical planning approach of premade drilling template with numerous pilot guide holes was used to assist bone debulking. The pilot holes allowed precise burring of the dysplastic bone. The patient achieved excellent calvarial contour symmetry without unintended intracranial extension. We believe that virtual surgical planning and drilling depth guides are effective tools in the reconstruction of craniofacial FD.

Denosumab for craniofacial fibrous dysplasia: duration of efficacy and post-treatment effects.

Denosumab has been advocated as a potential treatment for the rare skeletal disorder fibrous dysplasia (FD); however, there is limited data to support safety and efficacy, particularly after drug discontinuation. We report a case of successful treatment of aggressive craniofacial FD with denosumab, highlighting novel insights into the duration of efficacy, surrogate treatment markers, and discontinuation effects. A 13-year-old girl presented with persistent pain and expansion of a maxillary FD lesion, which was not responsive to repeated surgical procedures or bisphosphonates. Pre-treatment biopsy showed high RANKL expression and localization with proliferation markers. Denosumab therapy was associated with improved pain, decreased bone turnover markers, and increased lesion density on computed tomography scan. During 3.5 years of treatment, the patient developed increased non-lesional bone density, and after denosumab discontinuation, she developed hypercalcemia managed with bisphosphonates. Pain relief and lesion stability continued for 2 years following treatment, and symptom recurrence coincided with increased bone turnover markers and decreased lesion density back to pre-treatment levels. This case highlights the importance of considering the duration of efficacy when treating patients with FD and other nonresectable skeletal neoplasms that require long-term management.

Comparing Clinical and Radiographic Characteristics of Chronic Diffuse Sclerosing Osteomyelitis and Craniofacial Fibrous Dysplasia in the Mandible.

PURPOSE: Differential diagnosis of chronic diffuse sclerosing osteomyelitis of the mandible (DSOM) and craniofacial fibrous dysplasia (CFD) involving the mandible is challenging. The purpose of this study was to explore the differences of the clinical and radiographic characteristics between these 2 conditions. PATIENTS AND METHODS: In this retrospective cross-sectional, blinded, comparative study, clinical and imaging data of patients with DSOM and CFD at the Peking University Hospital of Stomatology from 2012 to 2018 were retrieved. Clinical characteristics, mainly pain, swelling, and trismus, and radiographic findings, including sclerosis, lysis, and subperiosteal bone formation, were evaluated. The t test, χ2 test, and Fisher-Freeman-Halton test were used to determine differences. RESULTS: Thirty-seven patients with DSOM and 32 patients with CFD were included (mean ages, 24.2 and 28.4 years, respectively); both groups showed a female predilection. DSOM (91.9%) and CFD (84.4%) were mainly unilateral. Patients with DSOM mainly presented with pain (94.6%), soft-tissue swelling (100.0%), and trismus (54.1%), whereas those with CFD did not experience pain (90.6%) and showed bone enlargement (87.5%) without trismus (6.3%). Panoramic radiographs and computed tomography scans of patients with DSOM showed subperiosteal bone formation, cortex lysis, and poorly demarcated cortex, whereas those patients with CFD mainly showed moderate-to-severe bone expansion, well-demarcated cortex, and tooth and mandibular canal displacement. CONCLUSIONS: These findings emphasize the importance of clinical and radiographic features in differentiating between DSOM and CFD. Pain, soft-tissue or bone-tissue swelling, subperiosteal bone formation, clarity of the boundary of the cortex and medulla, and continuity of the cortical bone are key points facilitating differentiation.

Extensive Polyostotic Craniofacial Fibrous Dysplasia With Optic Nerve Impingement.

ABSTRACT: Fibrous dysplasia is a benign overgrowth of metaplastic fibrous material resulting in disorganized deposition of bony matrix. Surgical intervention is the primary treatment modality. Here the authors present the case of a 36-year-old male with extensive and severe fibrous dysplasia of the calvarium, orbit, sphenoid, and facial bones causing significant facial distortion and impingement of his optic nerve. Combined operative treatment with craniofacial plastic surgery and neurosurgery was performed. Repair consisted of extensive intra- and extracranial resection and contouring of involved bones followed by reconstruction of the superior orbital rims, forehead, orbital roof, and calvarium with custom polyetheretherketone (PEEK) implant. The authors discuss the advantages of using computer assisted design/modeling, intraoperative neuronavigation, and custom prosthetic cranioplasty for surgical treatment of extensive fibrous dysplasia; a review of the current surgical literature is provided.

Malignant transformation of craniofacial fibrous dysplasia: a systematic review of overall survival.

The incidence of malignant transformation of fibrous dysplasia (FD) is very rare. Thus, the available knowledge of its characteristics, management, and survival is scarce. Here, we present a systemic review of fibrous dysplasia that had undergone malignant transformation. A comprehensive search was performed on PubMed electronic database. The survival rates and hazard ratios of age, gender, past history of previous radiotherapy, type of FD, and treatment were collected from the published articles and analyzed. Forty-eight cases were eligible for inclusion in the study. Patient's age, gender, past history radiotherapy, and type of FD did not influence the overall survival (OS). The Kaplan Meier analysis showed that the patients who had not received any treatment had poor prognosis with a median survival of 4 months. The patients that received surgery had significantly longer OS than that in the biopsy group. The prognosis of malignant transformation of FD is relatively poor, and surgery is the optimal treatment of choice. Nevertheless, the efficacy of postoperative adjuvant therapy to patient OS is still undefined.

Natural History and Progression of Craniofacial Fibrous Dysplasia: A Retrospective Evaluation of 114 Patients From Massachusetts General Hospital.

PURPOSE: The natural history of fibrous dysplasia (FD) is poorly understood. The purpose of this study was to identify differences in demographic, clinical, and radiographic characteristics among patients with craniofacial FD, including McCune-Albright syndrome (MAS), polyostotic fibrous dysplasia (PFD), and monostotic fibrous dysplasia (MFD). We hypothesized that patients with MAS would show higher disease severity, have more complications, and undergo more operations than those with PFD or MFD. PATIENTS AND METHODS: A retrospective cohort study of patients with MAS or FD, evaluated at Massachusetts General Hospital from 2000 to 2018, was implemented. Patients of all ages and genders were identified through Massachusetts General Hospital Data Registries using International Classification of Diseases, Ninth Revision (ICD-9) and International Classification of Diseases, Tenth Revision (ICD-10) codes. Those with adequate clinical and radiographic data were included. Predictor variables were diagnosis of MAS, PFD, or MFD; age; and gender. Outcome variables included severity of disease at initial presentation (aggressive, nonaggressive and slow growing, or quiescent), number of operations, and complications: pain, sensory disturbances, pathologic fracture, airway obstruction, osteomyelitis, and dental findings. Data were analyzed with descriptive statistics and assessed for significance using χ2 tests and analysis of variance (P < .05). RESULTS: A total of 229 patients were identified: 114 had craniofacial FD, and 70 of these 114 (61.4%) met the inclusion criteria (48 of whom were female patients). The average age at diagnosis was 23.5 years; mean length of follow-up, 5.8 years. Diagnoses included MAS in 9 patients, PFD in 24, and MFD in 37. Signs and symptoms at initial presentation were pain (n = 29), sensory abnormalities (n = 13), facial deformity or swelling (n = 54), and dental findings (n = 25). At presentation, the biological behavior of disease was 77.8% aggressive, 11.1% nonaggressive, and 11.1% quiescent in the MAS group; 41.7%, 41.7%, and 16.7%, respectively, in the PFD group; and 29.7%, 29.7%, and 40.5%, respectively, in the MFD group. Patients with MAS were younger and were more likely to have pain, pathologic fractures, more bones involved, bilateral disease, and visual symptoms than those with PFD or MFD. MAS patients underwent more operations (mean, 4.2 ± 4.18) than those with PFD (mean, 2.6 ± 2.31; P = not significant) or MFD (mean, 1.7 ± 1.28; P = .010). CONCLUSIONS: The results of this study indicate that patients with MAS, presumably with the same mutation, are more likely to have aggressive disease, complications, and more operations than those with PFD or MFD.

Fibrous dysplasia of the jaws: Integrating molecular pathogenesis with clinical, radiological, and histopathological features.

Fibrous dysplasia is a non-neoplastic developmental process that affects the craniofacial bones, characterized by painless enlargement as a result of bone substitution by abnormal fibrous tissue. Postzygotic somatic activating mutations in the GNAS1 gene cause fibrous dysplasia and have been extensively investigated, as well as being helpful in the differential diagnosis of the disease. Fibrous dysplasia may involve one (monostotic) or multiple bones (polyostotic), sporadically or in association with McCune-Albright syndrome, Jeffe-Lichenstein syndrome, or Mazabreud syndrome. This review summarizes the current knowledge on fibrous dysplasia, emphasizing the value of integrating the understanding of its molecular pathogenesis with the clinical, radiological, and histopathological features. In addition, we address important aspects related to the differential diagnosis and patient management.

Craniofacial fibrous dysplasia associated with McCune-Albright syndrome: challenges in diagnosis and treatment: case reports.

BACKGROUND: McCune-Albright syndrome (MAS) is a rare multisystem disorder that classically was defined by the triad of polyostotic fibrous dysplasia of bone, café-au-lait skin pigmentation, and precocious puberty. It is a condition that has a gradual onset, slow growth rate and remain painless throughout. The clinical phenotype of MAS is highly variable and no definite treatment is available. CASE PRESENTATION: This article describes two cases, a 10-year-old girl and an 11-year-old boy, both with MAS comprising deforming craniofacial FD. Challenges related to diagnosis and management included late reporting with big lesions, involvement of multiple craniofacial bones, mutilating surgeries and ultimately high degree of morbidity. CONCLUSION: Delayed diagnosis and management of MAS results in devastating physical disabilities and severe morbidity after treatment.