Fibrous Dysplasia Lesions Research Articles

Concurrent fibrous dysplasia is associated with a high incidence of cystic formation in vestibular schwannomas.

Fibrous dysplasia (FD) is a rare hereditary bone disorder, typically accompanied by a seemingly-high percentage of cystic changes in central nerve system tumors. This study aimed to investigate the associations between concurrent FD lesions and the cystic formation of vestibular schwannoma (VS). Patients with VSs in our institution from January 2020 to September 2022 were retrospectively included. Based on the contrasted MRI, VSs were grouped as the cystic and solid type. Concurrent FD was diagnosed based on the radiological findings. A logistic analysis was applied to investigate the relationship between concurrent FD and cystic VSs. The effect of the interaction between gender and concurrent FD on the cystic formation of VSs was further analyzed. The current study included 1255 patients with VSs (681 females with a median age of 47 years). Of them, 142 (11.3%) were with cystic VSs. A higher percentage of cystic VSs was observed in female patients (P = 0.021), patients with concurrent FDs (P < 0.001) and those with a larger VS volume (P < 0.001). An increasing trend in percentage of cystic VSs was found among patients with from 0 to ≥ 3 FD lesions (P for trend as < 0.001). A multivariate logistic analysis identified concurrent FD (odds ratio, 6.58; 95%CI, 1.66-26.09; P = 0.007) and VS volume (odds ratio, 1.55; 95%CI, 1.66-1.70; P < 0.001) as independent risk factors related to the cystic formation. Concurrent FD is associated with a high incidence of cystic formation in VSs, which provides a new breakthrough point to investigate the underlying mechanism of cystic formation of VSs.

Dissecting the heterogeneity of craniofacial lesions in patients with fibrous dysplasia/McCune–Albright Syndrome

Fibrous dysplasia/McCune–Albright Syndrome (FD/MAS) frequently involves the craniofacial skeleton. Craniofacial fibrous dysplasia lesions exhibit diverse imaging characteristics on multimodality evaluation, utilizing radiographs, computed tomography (CT), magnetic resonance imaging (MRI), and 18F-sodium fluoride positron emission tomography (18F-NaF PET). A multimodal imaging classification of craniofacial fibrous dysplasia lesions may offer clinical insights into the types of lesions that are (1) prone to progression, (2) amenable to intervention (i.e., pharmacological or surgical), or (3) associated with symptoms such as pain. In this prospective, preliminary single site study of 15 patients with FD/MAS, the heterogeneity of craniofacial lesions (N = 35) was assessed using a combination of 18F-NaF PET, MRI, and CT. A k-means clustering algorithm was used to categorize lesions based on imaging characteristics. Clustering analysis revealed three types of lesion based on the magnitude of the regional 18F-NaF standardized uptake values (SUV), signal intensities on T1-weighted and fluid-sensitive sequences, and appearance on CT (lucent, sclerotic, and/or ground glass). This preliminary study provides a foundation for future longitudinal natural history or treatment studies, where the prognostic value of baseline craniofacial fibrous dysplasia imaging characteristics and clinical symptomatology can be further evaluated.

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.

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.

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

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. 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. In total 74 patients were identified; 54% were male and the mean age 45years. 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. 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.

RANKL inhibition reduces lesional cellularity and Gαs variant expression and enables osteogenic maturation in fibrous dysplasia

Fibrous dysplasia (FD) is a rare, disabling skeletal disease for which there are no established treatments. Growing evidence supports inhibiting the osteoclastogenic factor receptor activator of nuclear kappa-B ligand (RANKL) as a potential treatment strategy. In this study, we investigated the mechanisms underlying RANKL inhibition in FD tissue and its likely indirect effects on osteoprogenitors by evaluating human FD tissue pre- and post-treatment in a phase 2 clinical trial of denosumab (NCT03571191) and in murine in vivo and ex vivo preclinical models. Histological analysis of human and mouse tissue demonstrated increased osteogenic maturation, reduced cellularity, and reduced expression of the pathogenic Gαs variant in FD lesions after RANKL inhibition. RNA sequencing of human and mouse tissue supported these findings. The interaction between osteoclasts and mutant osteoprogenitors was further assessed in an ex vivo lesion model, which indicated that the proliferation of abnormal FD osteoprogenitors was dependent on osteoclasts. The results from this study demonstrated that, in addition to its expected antiosteoclastic effect, denosumab reduces FD lesion activity by decreasing FD cell proliferation and increasing osteogenic maturation, leading to increased bone formation within lesions. These findings highlight the unappreciated role of cellular crosstalk between osteoclasts and preosteoblasts/osteoblasts as a driver of FD pathology and demonstrate a novel mechanism of action of denosumab in the treatment of bone disease.TRIAL REGISTRATION: ClinicalTrials.gov NCT03571191

THU463 Etiology Of Hypophosphatemia In A Patient With Co-existing Mesenchymal Tumor And Fibrous Dysplasia

Abstract Disclosure: M. Patil: None. S. Wangsiricharoen: None. A. Lazar: None. T.A. Guise: None. Tumor induced osteomalacia (TIO) is a rare paraneoplastic phenomenon. Fibroblast growth factor-23 (FGF23) secretion from phosphaturic mesenchymal tumor (PMT) is implicated as the cause for hypophosphatemia and osteomalacia. Other rare conditions associated with dysregulated FGF23 production include fibrous dysplasia (FD). Coexistence of two unusual conditions which could increase FGF23 concentrations is rare. We report a case of PMT causing TIO in a patient with evidence of FD. A 79-year-old male was evaluated for worsening rib and right flank pain of more than one year duration. He also complained of generalized muscle weakness. His total alkaline phosphatase (ALP) levels were noted to be increased for many years. Computed tomography (CT) showed scattered sclerosis within ribs, and lytic lesions with cortical bone destruction in right iliac bone (4.3 x1.5 cm) and L4 vertebra. Biopsy of the right iliac lesion revealed findings compatible with PMT. Positron Emission Tomography (PET) showed fluorodeoxyglucose (FDG) avid lesion of the right anterior iliac wing, diffuse osteomalacia, insufficiency fractures of the ribs, as well as FDG avid lesions in left supra-acetabular area and in L4 vertebral body concerning for metastatic disease. Laboratory evaluation revealed ALP 306 (40-129 U/L), bone specific ALP 99 (0-20 mcg/L), phosphorus 1.5 (2.5-4.5 mg/dL), 25-(OH)-vitamin D 27 (30- 100 ng/mL), 24 hour urinary phosphorus 0.6 (0.4-1.3 g/24 hr), PTH 51.3 (15-65 pg/mL), FGF23 303 (&amp;lt;180 RU/mL), Calcium 10.3 (8.4-10.2 mg/dL), albumin 4.4 (3.5- 5.2 gm/dL), C-terminal telopeptide of type 1 collagen (CTX) 1611 (10-854 pg/mL). CT-guided cryoablation of the right iliac lesion was performed. Also, biopsy and cryoablation of the left supra-acetabular lesion was performed; pathology showed fibrous dysplasia (FD). Mutation analysis confirmed a mutation in exon 8 of GNAS gene. Post ablation, FGF23 dropped to 102 RU/mL and phosphorus increased to 3.0 mg/dL. The patient had significant improvement in bone pain and weakness. The patient with classic features of TIO improved with simultaneous cryoablation of both the PMT as well as the FD lesions. The unusual feature of the case is co-existence of PMT and FD. Malignant transformation of FD lesions is a rare complication. We confirmed that the PMT did not have GNAS mutation and is unlikely to arise from FD. And FGF23 in situ hybridization was strongly positive in the PMT and negative in the FD, ruling out FD as a contributor to patient’s hypophosphatemia. We plan to perform DOTATATE scan to differentiate PMT from FD in the L4 lesion. This is a unique case of coexistence of two separate conditions, both of which could secrete intact FGF23. Our studies suggest that PMT is the only etiology of hypophosphatemia and TIO. Presentation: Thursday, June 15, 2023

Lesion Expansion in Gnathic Fibrous Dysplasia: Natural History, Indicators of Progression, and Response to Bisphosphonates.

Fibrous dysplasia (FD) is characterized by expansile fibro-osseous lesions that may occur in association with endocrinopathies as part of McCune-Albright syndrome (MAS). Craniofacial FD is a significant source of morbidity and most commonly involves the gnathic bones. There is a critical need to understand the natural history and risk factors for gnathic FD progression to develop preventative trials and identify candidates for intervention. The purpose of this study was to characterize gnathic FD lesion expansion and to identify risk factors associated with lesion growth. Patients with gnathic FD and serial CT imaging were evaluated. Volumetric analyses of CT scans were performed using MIM Encore software. Generalized mixed model analysis was used to account for intra-subject correlation, with FD lesion volume as the dependent variable. In addition to age, effects of MAS-associated endocrinopathies, sex, disease severity, and bisphosphonate treatment were evaluated. A total of 104 total lesions in 52 patients were characterized longitudinally. Median age at initial scan was 8.8 years (range 3.4-18.8), and median age at final scan was 16.8 years (range 6.9-33.4 years). The median number of scans per subject was 4 (range 2-14). FD lesion volume increased with age (2.50 cm3 /yr, 95% confidence interval [CI] 1.95-3.04, p < 0.001). However, lesion expansion rate decreased over time (-0.05 cm3 /yr, 95% CI -0.07 to 0.04, p < 0.001). Mandibular lesions tended to expand at a greater rate than maxillary lesions (p < 0.001). Growth hormone excess was associated with accelerated expansion rate (p = 0.002). Other MAS-associated endocrinopathies, pubertal status, sex, weight, lesion density, disease severity, and bisphosphonate treatment were not associated with lesion volume or expansion. Gnathic FD lesion expansion is most rapid in younger children and declines as patients approach adulthood. The availability of quantitative natural history data will guide clinicians in identifying patients who are candidates for medical and surgical interventions and clinical trials for preventative therapies. Published 2023. This article is a U.S. Government work and is in the public domain in the USA.

Efficacy of antiresorptive agents in fibrous dysplasia and McCune Albright syndrome, a systematic review and meta-analysis.

Fibrous dysplasia (FD) is a rare skeletal disorder in which normal bone is replaced by a fibro-osseous tissue, resulting in possible deformities and fractures. The aim of this systematic review and meta-analysis was to synthesize the available evidence on the use of antiresorptive drugs in FD in terms of changes in bone turnover markers (BTMs), bone mineral density (BMD), and reducing pain. Three databases were searched in October 2022, with an update in July 2023. Of the 1037 studies identified, 21 were retained after eligibility assessment. A random-effects model was used to calculate global effect size and the corresponding standard error. Pamidronate and Denosumab were the most reported drugs in a total of 374 patients assessed. The initiation of treatments was accompanied by an average reduction of 40.5% [CI95% -51.6, -29.3] in the bone resorption parameters, and 22.0% [CI95% -31.9, -12.1] in the parameters of bone formation after 6-12months. BMD was increased in both FD lesions and in the unaffected skeleton. Pain was reduced by 32.7% [CI95% -52.7, -12.6] after 6-12 months of treatment, and by 44.5% [CI95% -65.3, -23.6] after a mean 41.2 months of follow-up. The variation in pain was highly correlated to variation in bone resorption (R2 = 0.08, p < 0.0001) and formation parameters (R2 = 0.17, p < 0.0001). This study supports the overall efficacy of antiresorptive therapies in terms of reducing bone remodeling, improving bone density, and pain in FD.

Pharmacological Interventions Targeting Pain in Fibrous Dysplasia/McCune-Albright Syndrome.

Fibrous dysplasia (FD) is a rare, non-inherited bone disease occurring following a somatic gain-of-function R201 missense mutation of the guanine-nucleotide binding protein alpha subunit stimulating activity polypeptide 1 (GNAS) gene. The spectrum of the disease ranges from a single FD lesion to a combination with extraskeletal features; an amalgamation with café-au-lait skin hyperpigmentation, precocious puberty, and other endocrinopathies defines McCune-Albright Syndrome (MAS). Pain in FD/MAS represents one of the most prominent aspects of the disease and one of the most challenging to treat-an outcome driven by (i) the heterogeneous nature of FD/MAS, (ii) the variable presentation of pain phenotypes (i.e., craniofacial vs. musculoskeletal pain), (iii) a lack of studies probing pain mechanisms, and (iv) a lack of rigorously validated analgesic strategies in FD/MAS. At present, a range of pharmacotherapies are prescribed to patients with FD/MAS to mitigate skeletal disease activity, as well as pain. We analyze evidence guiding the current use of bisphosphonates, denosumab, and other therapies in FD/MAS, and also discuss the potential underlying pharmacological mechanisms by which pain relief may be achieved. Furthermore, we highlight the range of presentation of pain in individual cases of FD/MAS to further describe the difficulties associated with employing effective pain treatment in FD/MAS. Potential next steps toward identifying and validating effective pain treatments in FD/MAS are discussed, such as employing randomized control trials and probing new pain pathways in this rare bone disease.

Fractal analysis of fibrous dysplasia and ossifying fibroma in 2D and 3D CBCT images

To assess the complexity of fibrous dysplasia and ossifying fibroma lesions by fractal dimension (FD) in 2D and 3D cone-beam computed tomography (CBCT) images. Six cases of fibrous dysplasia were compared with six cases of ossifying fibroma in different images, thicknesses and regions of interest (ROI) of 2D and 3D images. FD was determined separately in hypondense and hyperdense areas using the box-counting method. The Student t-test was applied to determine the difference in FD between lesion groups. FD of hypodense areas in 2D images ranged from 1.2566 to 1.4532 in fibrous dysplasia and from 1.1540 to 1.3601 in ossifying fibroma, while FD of hyperdense lesion areas ranged from 1.1755 to 1.4132 for fibrous dysplasia and from 1.0480 to 1.2769 for ossifying fibroma images. Panoramic reconstruction and axial images of 0.25 mm thickness revealed significant differences between lesion groups in all ROI shapes ( p < 0.05). FD of 3D images was higher in fibrous dysplasia (2.4999–2.7417) than in ossifying fibroma (1.9283–2.4144) in both hyperdense and hypodense areas, with statistical difference in almost all ROIs ( p < 0.05). FD data suggest higher complexity of structures of fibrous dysplasia lesions than of structures of ossifying fibroma.

LOW RISK OF SPONTANEOUS MEDICATION-RELATED OSTEONECROSIS OF THE JAW IN FIBROUS DYSPLASIA PATIENTS AFTER ANTIRESORPTIVE THERAPIES: A SYSTEMATIC REVIEW

<h3>Objectives</h3> The objective of this systematic review was to evaluate the risk for spontaneous occurrence of medicated-related osteonecrosis of the jaw (MRONJ) in patients with fibrous dysplasia (FD) and McCune-Albright syndrome (MAS). FD is a rare genetic disorder caused by somatic activating mutations of the GNAS locus encoding the Gsα signaling protein, resulting in reduction of GTPase activity and prolonged activation of Gsα, leading to excessive production of Cyclic adenosine monophosphate (cAMP), which disrupts the ability of bone mesenchymal stem cells to differentiate to mature osteogenic cells. With the increased use of bisphosphonates for the antiresorptive properties, the role of antiresorptives in controlling activity within FD lesions and improvement of bone quality is still inconclusive. <h3>Study Design</h3> A systematic review of the literature was performed by searching PubMed and EMBASE databases using controlled search vocabulary, namely, fibrous dysplasia, McCune-Albright syndrome, jaw, osteonecrosis, antiresorptives, antiresorptive therapy, bisphosphonate, denosumab, teriparatide, estrogen, estrogen therapy, hormone therapy, raloxifene, bazedoxifene, calcitonin, and cathepsin K inhibitor. Articles were limited to human studies, in the English language, in which patients were on antiresorptives for at least 2 years. PRISMA (Preferred Reporting Items for Systematic Reviews and Meta-Analyses) statement guidelines were used to eliminate nonrelevant studies. The patient, intervention, comparison, outcome, and time (PICOT) question asked was, "Do antiresorptives cause spontaneous occurrence of MRONJ in patients with FD/MAS monitored for at least 2 years of therapy?" <h3>Results</h3> Among the 65 records screened, only 3 articles were eligible for qualitative synthesis based on PRISMA screening criteria. There were no reported cases of spontaneous MRONJ among the patients with FD/MAS across these studies. This is a significant finding among this cohort of patients. <h3>Conclusion</h3> Patients with FD demonstrated low susceptibility to spontaneous occurrence of MRONJ, but more confirmatory studies are still needed. This systematic review was limited by the low number of FD/MAS eligible studies. This could be because of the rare genetic nature of FD/MAS, with low patient recruitment in clinical studies among factors. These pose significant challenges to implementing well-designed randomized placebo-controlled clinical trials that focus on antiresorptive-induced osteonecrosis of the jaw in FD/MAS. As more clinical studies become available, a future follow-up systematic review may provide additional insights into MRONJ complications in patients with FD/MAS treated with antiresorptives.

Central ossifying fibroma of mandible arising in association with cemento-osseous dysplasia. An unusual case presentation

<h3>Introduction</h3> Cemento-osseous dysplasia (COD) is known to develop complications including infection, necrosis, and traumatic bone cysts [1]. Neoplastic occurrence with COD has been reported, but is rare [2,3]. We report an unusual case of central ossifying fibroma (COF) of the mandibular symphysis in association with COD in a 46-yearold black female. <h3>Case Description</h3> The patient presented with a mandibular symphysis mass that was associated with difficulty of eating, speaking and paresthesia. The radiographic images showed a predominantly radiopaque mass in the symphysis region, measuring 7 × 6 × 5cm. There were discrete, minimally expansile mixed radiolucentopaque lesions in the posterior mandible and maxilla. The patient underwent mandibular resection due to the symptoms of eating and speaking difficulties as well as paresthesia. Before resection, three incisional biopsies including bilateral posterior regions of mandible and the central mass. Histopathologic examination of posterior specimens revealed similar findings of fragments consisting of cellular fibroblastic tissue intermixed with short bone spicules and cementum-like and hemorrhagic deposits associated with traumatic bone cysts. However, the central specimen showed solid tumor consisting of fibroblastic proliferation supporting spindled fibroblast-like cells. It supported cellular bone trabeculae as well as spherical cementum-like calcified deposits. This framework is interspersed with spaces lined by fibrovascular tissue supporting eosinophilic osteoid, consistent with traumatic bone cysts. <h3>Discussion</h3> COD lacks genetic abnormalities noted in fibrous dysplasia or neoplastic fibro-osseous lesions. We present an unusual association of COF with florid COD. This association has been previously reported in a patient who developed COF with COD and odontoma, and in another who developed peripheral osteoma, odontoma, COF and COD [2,3]. To the best of our knowledge, this presentation describes only the third case report of the association of COF and COD. The co-existence of COF and COD in these cases is unclear, but seems to be very rare.

Pulsatile Tinnitus Caused by Highly Vascularized Fibrous Dysplasia of Temporal Bone with Centrally Located Fibrous Cyst

To date, the management and mechanism of pulsatile tinnitus (PT) caused by fibrous dysplasia (FD) of the temporal bone have not been discussed in detail. Therefore, this study is carried out to introduce PT secondary to monostotic temporal bone FD with cystic and lytic development in simultaneity complicated by the expansile bone lesion compressing over the sigmoid sinus. A 46-year-old female patient diagnosed with FD presented with severe persistent PT seeking medical assistance. Radiologic modalities displayed a 74.3 cm3 monostotic FD with a presumably high-vascularity lytic change of the bone lesion located in the posterior portion of the mastoid cavity. The patient’s PT was non-pulse-synchronous and was irrelevant to the intracranial blood flow revealed by ultrasonographic examination. A subtotal petrosectomy was performed after a meticulous preoperative assessment. During surgery, an unprecedented elastic cystic structure with three pedicles filled with vascular fluid was appreciated at the center of the FD lesion. PT was resolved after the removal of 90.8% of the total volume of the highly vascularized low-bone mineral density fibro-osseous tissues and the fibrous cyst. There were no PT reoccurrence and no postoperative complications during a two-month follow-up. Albeit rarely encountered, caution is required as PT secondary to FD is highly associated with the vascularity of the bone lesion.

Periorbital inflammation associated with craniofacial fibrous dysplasia: Report of three cases and review of the literature

Fibrous dysplasia (FD) is a mosaic skeletal disorder in which the craniofacial bones are commonly affected. Normal structures are replaced by expansile, highly vascular, fibro-osseous tissue. The typical clinical course is a gradual, asymptomatic expansion of the osseous structures. However, in the periorbital region, even minor structural changes may cause functional impairment, such as diplopia and hyposmia. Furthermore, rapidly evolving secondary lesions, such as fluid-filled cysts, can sometimes develop. In the midface and periorbital regions, such acute change may be associated with severe pain, vision loss, and, signs of inflammation. Here we describe three patients with craniofacial FD who presented with recurrent episodes of periorbital inflammation mimicking orbital cellulitis. All presented with pain, edema, erythema, and warmth, with varying degrees of functional impairment. On imaging, all had cystic changes in the FD lesion, including two with aneurysmal bone cysts (ABCs). Two were initially diagnosed with periorbital cellulitis and treated with antibiotics; in two, the radiographic findings were misdiagnosed as osteomyelitis. Recurrent episodes were recognized as not infectious and effectively managed with corticosteroids. Given the vascular nature of FD and the association of ABCs, it is likely the findings in these patients represent inflammation associated with vascular leak in the relatively confined space of the tissues overlying the periorbital bones. Recognition of this entity can lead to more rapid and appropriate treatment.

Symptoms: Clogged Ears and Muffled Hearing

Symptoms: Clogged Ears and Muffled Hearing

Skeletal Disease Acquisition in Fibrous Dysplasia: Natural History and Indicators of Lesion Progression in Children.

Fibrous dysplasia (FD) is a rare mosaic disorder resulting in fractures, pain, and disability. Bone lesions appear during childhood and expand during skeletal growth. The rate at which FD lesions progress and the biochemical determinants of FD lesion formation have not been established, making it difficult to investigate and implement preventative therapies. The purpose of this study was to characterize FD lesion progression in children, and to identify clinical variables associated with progressive disease. Clinical data and imaging from an ongoing natural history study at the National Institutes of Health (NIH) were reviewed. 99m-Technetium methylene diphosphonate (99Tc-MDP) scans were used to determine Skeletal Burden Score (SBS), a validated quantitative scoring system. FD progression rate was determined by the change in the SBS in each patient per year. Thirty-one children had serial 99Tc-MDP scans, with a median age at first scan of 6 years (interquartile range [IQR] 4-8, range 2-10), and median follow-up 1.1 years (IQR 1.1-2.1, range 0.7-11.2). The median FD progression rate for the total group was 2.12 SBS units/year (IQR 0.81-2.94, range 0.05-7.81). FD progression rates were highest in children under age 8 years and declined with age (p=0.03). Baseline disease severity was associated with subsequent disease progression (p=0.009), with the highest FD progression rates in patients with moderate disease (baseline SBS 16-30), and lowest progression rates in those with severe disease (SBS ≥50). Serum levels of the bone formation marker osteocalcin were positively correlated with subsequent FD progression rate (p=0.01, R=0.58). There was no association between FD progression and baseline endocrinopathies, fractures, or surgery rates. FD lesions progress during childhood, particularly in younger children and those with moderate involvement. Osteocalcin may potentially serve as a biomarker for progressive disease. These findings may allow clinicians to investigate preventative therapies, and to identify children with FD who are candidates for early interventions. Published 2022. This article is a U.S. Government work and is in the public domain in the USA.

Increased Prevalence of Malignancies in Fibrous Dysplasia/McCune-Albright Syndrome (FD/MAS): Data from a National Referral Center and the Dutch National Pathology Registry (PALGA)

Malignant transformation of fibrous dysplasia lesions has been reported in patients with fibrous dysplasia/McCune-Albright syndrome (FD/MAS). Recently, we have observed an increased risk for breast cancer. In this study, the prevalence of skeletal and extraskeletal malignancies in patients with FD/MAS in the Netherlands was assessed by analyzing data from our cohort of FD/MAS patients, the Dutch Pathology Registry (PALGA), and the Netherlands Cancer Registry (NCR). We extracted data on sex, age at diagnosis of FD/MAS, type of FD/MAS, type of malignancy, and age at diagnosis of malignancy and histology of bone and malignant tissue when available, including GNAS-mutation analysis from patients' medical records. Standardized Morbidity Ratios (SMRs) with 95% confidence intervals were calculated. Twelve malignancies were identified in the LUMC FD/MAS cohort and 100 in the PALGA cohort. In this cohort, SMR was increased for osteosarcoma (19.7, 95% CI 3.5-48.9), cervical cancer (4.93, 95%CI 1.7-8.2), thyroid cancer (3.71, 95% CI 1.1-7.8), prostate cancer (3.08, 95% CI 1.8-4.6), and melanoma (2.01, 95%CI 1.2-3.1). SMRs for pancreatic cancer or hepatocellular carcinoma could not be calculated due to low numbers. The small number of malignancies identified in our FD/MAS cohort precluded the calculation of SMRs for our cohort specifically. Our findings show that patients with FD/MAS appear to have an increased risk for osteosarcoma, cervical, thyroid, and prostate cancer and melanoma. However, these data should be interpreted with caution, as true incidence rates of the identified malignancies may be influenced by the inclusion of only patients with histologically confirmed FD/MAS. The etiology of this increased risk for malignancies still needs to be elucidated.

Radiographic Follow-Up of Fibrous Dysplasia in 138 Patients.

OBJECTIVE. The purpose of this study was to explore the temporal changes in fibrous dysplasia (FD) at radiographic follow-up. MATERIALS AND METHODS. A total of 138 patients with FD who had undergone extremity radiography at least twice with a minimum 12-month interval between examinations were enrolled in this study. FD was monostotic in 99 patients and polyostotic in 39 patients. Patients were also classified according to skeletal maturity as follows: Patients 16 years old or younger were classified in the skeletally immature group (n = 34), and patients 17 years old or older were classified in the skeletally mature group (n = 104). We compared the initial and follow-up radiographs for the following findings: lesion size, opacity, sclerotic rim, calcification, and trabeculation. RESULTS. Of the 138 patients, radiographic follow-up showed no change in lesion size in 101 patients (73.2%), progression in 31 (22.5%), and regression in six (4.3%). FD in immature bones progressed more often than FD in mature bones (23/34 [67.6%] vs 8/104 [7.7%], respectively; p = 0.000), and polyostotic FD had a greater chance of regressing than monostotic FD (4/39 [10.3%] vs 2/99 [2.0%]; p = 0.032). A temporal change in FD lesion opacity was noticed in a minority of patients (19/138, 13.8%). Variable changes were observed in the sclerotic rim, calcification, and trabeculation. CONCLUSION. The radiographic follow-up of FD showed that approximately a quarter of lesions changed in size over time. Regardless of the change in lesion size, opacity and several morphologic features of FD changed during the follow-up period, which might reflect the histopathologic evolution of FD.

Monostotic Fibrous Dysplasia Mimicking Metastasis in the Femoral Neck on Bone Scintigraphy and 18F-FDG PET/CT.

A 51-year-old woman who had lung adenocarcinoma was found to have a high uptake area over the right femoral neck by means of bone scintigraphy, suggesting a suspicious bony metastasis. 18F-FDG PET/CT was arranged, and showed an FDG-avid lesion in the same region. However, after augmented CT, a well-defined ground-glass lesion with circular calcification was found, which is the favored benign lesion of fibrous dysplasia. The following imaging of bone scintigraphy and 18F-FDG PET/CT presented no apparent change. This case demonstrates that the treatment scheme should not be solely guided by abnormalities in scintigraphy. Additional imaging is recommended for accurate staging or development of an appropriate treatment plan.