Fibrous dysplasia: A tale of two syndromes.

Fibrous dysplasia (FD) is a rare, non-inherited, congenital bone disorder which may be monostotic or polyostotic. The polyostotic form may rarely present in syndromic forms when associated with extra-skeletal manifestations. Mazabraud syndrome is a rare syndrome consisting of polyostotic FD presenting with intramuscular myxomas. McCune-Albright syndrome is recognised by polyostotic FD, precocious puberty and 'café au lait' spots. This report describes an adult patient with Mazabraud syndrome and a child with McCune-Albright syndrome. Contribution: Radiographic findings are typical with bowing deformities, sclerotic, lucent or mixed lesions and bony expansion, often with endosteal scalloping. MRI is often non-contributory and may actually mimic a more aggressive process. Early detection and correct diagnosis allow for early preventative treatment and rehabilitation to prevent devastating neurological sequelae and disability.

A Rare Case of Fibrous Dysplasia Presenting With Facial Swelling and Craniofacial Deformity in a 13-Year-Old Girl.

Fibrous dysplasia (FD) is a rare benign skeletal disorder that replaces normal bone with fibrous tissue and immature woven bone. We present a case of a 13-year-old girl with right-sided facial swelling and craniofacial deformity since birth, accompanied by nasal obstruction and difficulty in breathing and swallowing. Computed tomography (CT) imaging revealed an expansile bony lesion with a ground-glass matrix involving multiple craniofacial bones. Histopathological examination confirmed the diagnosis of FD. Management involved regular monitoring and conservative measures, with surgical intervention reserved for symptomatic progression or cosmetic concerns. This case underscores the importance of considering FD in the differential diagnosis of craniofacial asymmetry and highlights the collaborative approach to patient care. Further research is needed to optimize management strategies and outcomes for pediatric patients with FD.

CT-based radiomics analysis of different machine learning models for differentiating gnathic fibrous dysplasia and ossifying fibroma.

OBJECTIVE: In this study, our aim was to develop and validate the effectiveness of diverse radiomic models for distinguishing between gnathic fibrous dysplasia (FD) and ossifying fibroma (OF) before surgery. MATERIALS AND METHODS: We enrolled 220 patients with confirmed FD or OF. We extracted radiomic features from nonenhanced CT images. Following dimensionality reduction and feature selection, we constructed radiomic models using logistic regression, support vector machine, random forest, light gradient boosting machine, and eXtreme gradient boosting. We then identified the best radiomic model using receiver operating characteristic (ROC) curve analysis. After combining radiomics features with clinical features, we developed a comprehensive model. ROC curve and decision curve analysis (DCA) demonstrated the models' robustness and clinical value. RESULTS: We extracted 1834 radiomic features from CT images, reduced them to eight valuable features, and achieved high predictive efficiency, with area under curves (AUC) exceeding 0.95 for all the models. Ultimately, our combined model, which integrates radiomic and clinical data, displayed superior discriminatory ability (AUC: training cohort 0.970; test cohort 0.967). DCA highlighted its optimal clinical efficacy. CONCLUSION: Our combined model effectively differentiates between FD and OF, offering a noninvasive and efficient approach to clinical decision-making.

Fibrous Dysplasia Polyostotic: When Radiology Clarifies the Diagnosis.

Fibrous dysplasia is a rare non-hereditary congenital condition characterized by 2 main forms: monostotic and polyostotic. Monostotic is the more common form, while polyostotic, often associated with a syndrome, is rarer. The case presented involves a 10-year-old patient who was diagnosed with polyostotic fibrous dysplasia accompanied by an endocrinopathy. This report explores the clinical and radiological aspects of this condition based on the patient's case.

Craniomaxillofacial Fibro-osseous Lesions in Children.

Craniofacial fibro-osseous lesions represent a diverse spectrum of pathologic conditions where fibrous tissue replaces healthy bone, resulting in the formation of irregular, woven bone. They are more commonly diagnosed in young people, with treatment strategies dependent on clinical behavior and skeletal maturity. This article discusses the examples of craniofacial fibro-osseous lesions, based on the latest classifications, along with their diagnostic criteria and management.

Whole Exome Sequencing as an Effective Molecular Diagnosis Tool for Craniofacial Fibrous Dysplasia with Ocular Complications.

PURPOSE: To summarize the clinical manifestations of craniofacial fibrous dysplasia (CFD) patients with ocular complications, and find effective methods to diagnose early. METHODS: Nine CFD patients with ocular complications, and their parents were recruited in this study. All patients underwent ocular and systemic examinations. Bone lesions from all patients and peripheral blood from patients and their parents were collected for whole exome sequencing (WES). According to the screening for low-frequency deleterious variants, and bioinformatics variants prediction software, possible disease-causing variants were found in multiple CFD patients. The variants were validated by Sanger sequencing. Trio analysis was performed to verify the genetic patterns of CFD. RESULTS: All patients were diagnosed with CFD, according to the clinical manifestations, classic radiographic appearance, and pathological biopsy. The main symptoms of the 9 CFD patients, included visual decline (9/9), craniofacial deformity (3/9) and strabismus (2/9), with few extraocular manifestations. The family backgrounds of all the CFD patients indicated that only the patient was affected, and their immediate family members were normal. GNAS variants were identified in all bone lesions from CFD patients, including two variant types: c.601C > T:p.R201C(6/9) and c.602G > A:p.R201H (3/9) in exon 8. The detection rate reached 100% by WES, but only 77.8% by Sanger sequencing. Interestingly, we found GNAS variants could not be detected in peripheral blood samples from CFD patients or their parents, and other potentially disease-causing gene variants related to CFD were not found. CONCLUSIONS: For CFD patients with bone lesions involving the optic canal or sphenoid sinus regions, ocular symptoms should also be considered. Furthermore, we confirmed that CFD is not inherited, somatic variants in the GNAS gene are the main pathogenic gene causing CFD. Compared to the traditional methods in molecular genetic diagnosis of CFD, WES is more feasible and effective but limited in the type of samples.

Patient-Derived Organoids Recapitulate Pathological Intrinsic and Phenotypic Features of Fibrous Dysplasia.

Fibrous dysplasia (FD) is a rare bone disorder characterized by the replacement of normal bone with benign fibro-osseous tissue. Developments in our understanding of the pathophysiology and treatment options are impeded by the lack of suitable research models. In this study, we developed an in vitro organotypic model capable of recapitulating key intrinsic and phenotypic properties of FD. Initially, transcriptomic profiling of individual cells isolated from patient lesional tissues unveiled intralesional molecular and cellular heterogeneity. Leveraging these insights, we established patient-derived organoids (PDOs) using primary cells obtained from patient FD lesions. Evaluation of PDOs demonstrated preservation of fibrosis-associated constituent cell types and transcriptional signatures observed in FD lesions. Additionally, PDOs retained distinct constellations of genomic and metabolic alterations characteristic of FD. Histological evaluation further corroborated the fidelity of PDOs in recapitulating important phenotypic features of FD that underscore their pathophysiological relevance. Our findings represent meaningful progress in the field, as they open up the possibility for in vitro modeling of rare bone lesions in a three-dimensional context and may signify the first step towards creating a personalized platform for research and therapeutic studies.

Vitamin D Attenuates Fibrotic Properties of Fibrous Dysplasia-Derived Cells for the Transit towards Osteocytic Phenotype.

Fibrous dysplasia (FD) poses a therapeutic challenge due to the dysregulated extracellular matrix (ECM) accumulation within affected bone tissues. In this study, we investigate the therapeutic potential of 1,25-dihydroxyvitamin D3 (1,25(OH)2D3) in managing FD by examining its effects on FD-derived cells in vitro. Our findings demonstrate that 1,25(OH)2D3 treatment attenuates the pro-fibrotic phenotype of FD-derived cells by suppressing the expression of key pro-fibrotic markers and inhibiting cell proliferation and migration. Moreover, 1,25(OH)2D3 enhances mineralization by attenuating pre-osteoblastic cellular hyperactivity and promoting maturation towards an osteocytic phenotype. These results offer valuable insights into potential treatments for FD, highlighting the role of 1,25(OH)2D3 in modulating the pathological properties of FD-derived cells.

Transcriptomic Signature and Pro-Osteoclastic Secreted Factors of Abnormal Bone-Marrow Stromal Cells in Fibrous Dysplasia.

Fibrous dysplasia (FD) is a mosaic skeletal disorder caused by somatic activating variants of GNAS encoding for Gαs and leading to excessive cyclic adenosine monophosphate signaling in bone-marrow stromal cells (BMSCs). The effect of Gαs activation in the BMSC transcriptome and how it influences FD lesion microenvironment are unclear. We analyzed changes induced by Gαs activation in the BMSC transcriptome and secretome. RNAseq analysis of differential gene expression of cultured BMSCs from patients with FD and healthy volunteers, and from an inducible mouse model of FD, was performed, and the transcriptomic profiles of both models were combined to build a robust FD BMSC genetic signature. Pathways related to Gαs activation, cytokine signaling, and extracellular matrix deposition were identified. To assess the modulation of several key secreted factors in FD pathogenesis, cytokines and other factors were measured in culture media. Cytokines were also screened in a collection of plasma samples from patients with FD, and positive correlations of several cytokines to their disease burden score, as well as to one another and bone turnover markers, were found. These data support the pro-inflammatory, pro-osteoclastic behavior of FD BMSCs and point to several cytokines and other secreted factors as possible therapeutic targets and/or circulating biomarkers for FD.

Wnt pathway inhibition with the porcupine inhibitor LGK974 decreases trabecular bone but not fibrosis in a murine model with fibrotic bone.

G protein-coupled receptors (GPCRs) mediate a wide spectrum of physiological functions, including the development, remodeling, and repair of the skeleton. Fibrous dysplasia (FD) of the bone is characterized by fibrotic, expansile bone lesions caused by activating mutations in GNAS. There are no effective therapies for FD. We previously showed that ColI(2.3)+/Rs1+ mice, in which Gs-GPCR signaling was hyper-activated in osteoblastic cell lineages using an engineered receptor strategy, developed a fibrotic bone phenotype with trabecularization that could be reversed by normalizing Gs-GPCR signaling, suggesting that targeting the Gs-GPCR or components of the downstream signaling pathway could serve as a promising therapeutic strategy for FD. The Wnt signaling pathway has been implicated in the pathogenesis of FD-like bone, but the specific Wnts and which cells produce them remain largely unknown. Single-cell RNA sequencing on long-bone stromal cells of 9-wk-old male ColI(2.3)+/Rs1+ mice and littermate controls showed that fibroblastic stromal cells in ColI(2.3)+/Rs1+ mice were expanded. Multiple Wnt ligands were up- or downregulated in different cellular populations, including in non-osteoblastic cells. Treatment with the porcupine inhibitor LGK974, which blocks Wnt signaling broadly, induced partial resorption of the trabecular bone in the femurs of ColI(2.3)+/Rs1+ mice, but no significant changes in the craniofacial skeleton. Bone fibrosis remained evident after treatment. Notably, LGK974 caused significant bone loss in control mice. These results provide new insights into the role of Wnt and Gs-signaling in fibrosis and bone formation in a mouse model of Gs-GPCR pathway overactivation.

Fibrous dysplasia of the head and neck in Southern Finland: a retrospective study on clinical characteristics, diagnostics, and treatment.

PURPOSE: Fibrous dysplasia (FD) is a rare genetic disease with benign bone tumors. FD can affect one (monostotic FD) or multiple bones (polyostotic FD), with craniofacial lesions being common. Because of its rarity, there are only few clinical reports on FD in the head and neck region and its clinical characteristics remain incompletely defined. This study aimed to determine patient demographics, symptoms, diagnostics, and given treatment in patients with FD of the head and neck in a Finnish population. METHODS: A retrospective review on all patients diagnosed with or treated for FD of the head and neck at the Helsinki University Hospital during 2005-2020. RESULTS: In total 74 patients were identified; 54% were male and the mean age 45 years. Overall 95% had monostotic FD. Mandibula and maxilla were the most common anatomic sites. Majority of patients had symptoms, most commonly pain and lesion growth, and 49% had extra-skeletal symptoms. For all, diagnosis was primarily based on imaging findings, biopsies were obtained from 41%. Altogether 54 patients (73%) were managed by observation only, 20 patients (27%) received treatment; ten bisphosphonates, six surgery and four both. CONCLUSION: Although highly variable in its clinical manifestations, head and neck FD lesions are often symptomatic and impose risk for extra-skeletal complications. Treatment is often conservative but should be individually tailored. Future studies are encouraged to better define the disease characteristics and hopefully offer new treatment possibilities.

Recurrent Adamantinoma With Fibrous Dysplasia-like Feature.

Adamantinoma (AD) is a rare, slow-growing primary malignant bone tumor characterized by a biphasic morphology of clusters of epithelial cells and spindle cell osteofibrous components. A strong relationship between AD and osteofibrous dysplasia (OFD) has been proposed, while fibrous dysplasia (FD) has been rarely associated with AD. We present an AD case that was followed and histologically evaluated 3 times over 6 years with different morphological patterns. The tumor in the primary biopsy and after complete resection showed classical features of AD and osteofibrous-like pattern, while the recurrent lesion presented with exclusively spindle cell morphology and was thus diagnosed as FD. However, the extensive immunohistochemical analysis in all 3 lesions revealed strong reactivity for pancytokeratin, vimentin, p63, and podoplanin, which are characteristic for AD. Although, in the FD-like section of the tumor from the first recurrence the positivity of podoplanin was stronger than pancitokeratin, which was variably positive on spindle cells. The present case highlights the problem of diagnosing AD based on a single biopsy with one tumor's component predominating over the other, and at the same time emphasizes the importance of using immunohistochemical staining for keratin and podoplanin when the histopathological features of (osteo)fibrous lesion can be linked to AD.

Diagnosis and Management of Monostotic Fibrous Dysplasia of the Tibia in an Adolescent Patient: A Case Report.

A rare benign bone condition called monostotic fibrous dysplasia (MFD) is characterized by the growth of fibrous tissue in place of a normal bone. It may lead to deformity in the affected bone, pain, and a pathologic fracture due to bone weakness. Hereunder, a case report of MFD in a 17-year-old male adolescent presenting to the hospital with localized bone pain and swelling in his right tibia is presented. After clinical examination and radiographic imaging, a provisional diagnosis of benign osteolytic lesion was considered. A magnetic resonance imaging (MRI) scan of the leg suggested the possibility of fibrous dysplasia or adamantinoma. The patient was managed with an intralesional curettage of the dysplastic bone and packing the cavity with blocks of a synthetic bone. The excised material was sent for histopathology, which established the diagnosis of fibrous dysplasia.

A Case Series and Literature Review of Craniofacial Fibrous Dysplasia.

Craniofacial fibro-osseous lesions (CFOLs) are a diverse group of relatively rare entities whose etiology ranges from reactive to dysplastic with a potential for malignant transformation. It is distinguished by the replacement of bone with fibrous tissue, that subsequently develops different degrees of calcification. Fibrous dysplasia (FD) is a component of the fibro-osseous lesion spectrum. The clinical spectrum of FD is wide, ranging from minor monostotic lesions affecting a single bone to devastating polyostotic disease involving the entire skeleton. FD produces asymmetry, which impairs face aesthetics. FD leads to bone differentiation, disintegration, and disorganization. It depicts a cellular collagenous stroma lacking mitotic figures and pleomorphism. Blood capillaries are evenly distributed, as are elongated trabeculae of woven or lamellar bone with uneven curves (often referred to as the Chinese letters pattern). Three types of FD patterns can be identified by computed tomography (CT) imaging: a cystic pattern, a homogeneously dense pattern, and a ground-glass pattern. The cornerstone of treatment is surgery, although the method varies depending on the location, size, and symptoms of the lesion. As an alternative to surgery, the use of bisphosphonates to reduce osteoclastic activity is under consideration. In this case series, we present three cases of FD involving the maxilla and mandible. We aim to correlate the clinical presentation, histological features, and radiographic findings, to promote early diagnosis, treatment, and better prognosis of the patient.

Cherubism Unmasked: A Case Report of Clinical and Histopathological Presentation.

Cherubism, an uncommon genetic disorder, manifests as painless swelling in both jaws. A 20-year-old male presented with symmetrical swelling in both the mandible and maxilla. The jaws exhibited bilateral expansion, typical of this condition. Dentofacial abnormalities associated with cherubism stem from mutations in the SH3BP2 gene, which plays a crucial role in regulating osteoblasts and osteoclasts. In summary, cherubism is a genetic disorder characterized by non-cancerous jaw bone lesions. Surgical intervention may be necessary for functional or aesthetic concerns.

Acquired Forms of Fibroblast Growth Factor 23-Related Hypophosphatemic Osteomalacia.

Fibroblast growth factor 23 (FGF23) is a pivotal humoral factor for the regulation of serum phosphate levels and was first identified in patients with autosomal dominant hypophosphatemic rickets and tumor-induced osteomalacia (TIO), the most common form of acquired FGF23-related hypophosphatemic rickets/osteomalacia (FGF23rHR). After the identification of FGF23, many other inherited and acquired forms of FGF23rHR were reported. In this review article, the detailed features of each acquired FGF23rHR are discussed, including TIO, ectopic FGF23 syndrome with malignancy, fibrous dysplasia/McCune-Albright syndrome, Schimmelpenning-Feuerstein-Mims syndrome/cutaneous skeletal hypophosphatemia syndrome, intravenous iron preparation-induced FGF23rHR, alcohol consumption-induced FGF23rHR, and post-kidney transplantation hypophosphatemia. Then, an approach for the differential diagnosis and therapeutic options for each disorder are concisely introduced. Currently, the majority of endocrinologists might only consider TIO when encountering patients with acquired FGF23rHR; an adequate differential diagnosis can reduce medical costs and invasive procedures such as positron emission tomography/computed tomography and venous sampling to identify FGF23-producing tumors. Furthermore, some acquired FGF23rHRs, such as intravenous iron preparation/alcohol consumption-induced FGF23rHR, require only cessation of drugs or alcohol to achieve full recovery from osteomalacia.

Functional outcomes and recurrence determinants in craniofacial fibrous dysplasia: Insights from 3D computed tomography and comprehensive clinical evaluation.

BACKGROUND: This study aimed to identify risk factors for postoperative lesion regrowth and to assess functional outcomes in craniofacial fibrous dysplasia, using a three-dimensional computed tomographic volumetric analysis. METHODS: A retrospective analysis was conducted on 47 patients with craniofacial fibrous dysplasia who were treated from July 2005 to December 2020. Patients were treated with either conservative shaving or radical excision followed by reconstruction. Demographic data, surgical details, lesion recurrence, and functional outcomes were assessed. Lesion volume changes and recurrence were evaluated clinically and through a computed tomographic volumetric analysis. RESULTS: Among the patients, 16 underwent conservative treatment, whereas 31 received radical treatment. The radical group showed more significant improvements in functional outcomes, particularly in orbital dystopia and facial asymmetry. Postoperative lesion volume was notably lower in the radical group (41.94 ± 38.13 cm3) compared with the conservative group (78.3 ± 47.3 cm3, p = 0.008). This reduction was maintained over an average follow-up of 3 years. Lesion growth rates were similar between the groups (8.17 ± 5.85% in radical vs. 5.84 ± 6.43% in conservative, p = 0.268). Multivariate analysis indicated that patients aged ≤20 years and those with multifocal involvement had significantly higher risks of recurrence, with adjusted odds ratios of 11.269 (p = 0.039) and 6.914 (p = 0.046), respectively. CONCLUSIONS: Our findings suggest that both conservative and radical treatments for craniofacial fibrous dysplasia provide benefits, with the radical approach notably enhancing functional outcomes. However, neither method definitively reduces lesion recurrence, highlighting the necessity for an individualized treatment strategy. This approach should balance functional enhancement with recurrence risks, tailored to each patient's specific clinical scenario.

Cystic degeneration of the fibrous dysplasia presenting with loss of vision.

Cystic degeneration of the fibrous dysplasia is a very rare clinical condition and may present with loss of vision when it involved the skull base. A 12-year-old female child presented with an enlargement of the skull. She was diagnosed as large skull base and skull vault tumor. She underwent partial removal of the tumor, and custom-made titanium implant was inserted. The diagnosis was fibrous dysplasia. Two years after the initial diagnosis, she presented with total loss of vision at her right eye. Radiological imaging confirmed the cystic degeneration within the tumor. She re-operated and the cyst fluid was evacuated in association with the removal of cyst wall. The diagnosis was the cystic degeneration of the fibrous dysplasia. Her vision was improved a few days after the surgery. Fibrous dysplasia of the skull base should be closely followed-up in order to prevent severe visual complications.

Osteofibrous dysplasia: a narrative review.

Osteofibrous dysplasia (OFD) is a rare, benign, self-limited bone disorder with a relatively low incidence, accounting for approximately 0.2% of all primary bone tumors. It was frequently found intra-cortical of the mid-shaft of the tibia. OFD can also occur in other skeletal regions, including the fibula, ulna, radius, femur, humerus, ischium, rib, tarsus, metatarsals, vertebral, and capitate. OFD can present with asymptomatic, mass, pain, swelling, deformity, and even pathological fracture. OFD might be misdiagnosed as adamantinoma (AD) and because they are three subtypes origin from the same family of bone tumors and have similar imaging features. Moreover, pathology could provide evidence for an accurate diagnosis of OFD, but misdiagnosis may occur due to small sampling materials. To date, few studies have comprehensively introduced the epidemiology, clinical manifestations, pathogenesis, radiological features, pathology, and treatment for OFD. We herein discuss clinical signs, diagnosis methods, and treatment options of OFD to improve the understanding of OFD, which is helpful for accurate diagnosis and appropriate treatment.