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.

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.

The Role of Surveillance in Predicting Fracture in Pediatric Patients With Incidentally Discovered Nonossifying Fibromas and Fibrous Cortical Defects: Is It Worth It?

BACKGROUND: Nonossifying fibroma (NOF) and fibrous cortical defect (FCDs), the most common benign pediatric bone lesions, are usually incidental x-ray findings. Surveillance of characteristic lesions has been recommended to monitor for enlargement and assess fracture risk. However, no accepted fracture risk prediction guidelines exist, so indications for prophylactic surgery are unclear. The study's purposes were to (1) characterize the timing of NOF/FCD-associated fractures, (2) quantify the resources devoted to surveillance, and (3) evaluate the potential for surveillance to prevent pathologic fracture. METHODS: A single institution retrospective review was conducted to identify pediatric patients (below 18 y old) with clinical-radiographic documentation of an NOF or FCD diagnosis from 2012 to 2020. Patients who presented with fracture were tallied but excluded from the surveillance analysis. Patients without at least one follow-up visit were also excluded. Lesional radiographic features were characterized on initial imaging. The number of visits and imaging studies devoted to surveillance were tabulated. The number of fractures and prophylactic surgeries were recorded to quantify the potential of surveillance to prevent pathologic fractures. RESULTS: The study population presenting without fracture consisted of 301 patients with 364 lesions with a mean follow-up of 20 months. By contrast, over the same period, 38 patients presented with NOF/FCD associated pathologic fractures. Surveillance included 1037 additional imaging tests over 1311 follow-up visits, or on average, 3.4 imaging studies and 4.4 visits per patient. During surveillance, only 2 (0.55%) lesions fractured. Another 10/364 (2.8%) patients underwent curettage and grafting, suggesting that-at best-the potential for preventing pathologic fracture by surveillance, assuming all 10 patients who underwent surgery would have subsequently fractured along with the 2 documented fractures, is 3.3% of lesions (12/364). CONCLUSIONS: The small number of fractures and surgeries during the follow-up period probably does not justify additional resources for surveillance beyond the initial visit, except in symptomatic patients with large lesions. However, subsequent visits may play a role in educating patients and their families regarding the natural history of these lesions. LEVEL OF EVIDENCE: Prognostic Level II-retrospective study.

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.

Fibrocartilaginous Dysplasia of the Proximal Femur in Two Pediatric Patients, Including a Pathologic Fracture in a Patient With McCune-Albright Syndrome.

Fibrocartilaginous dysplasia (FCD) is a variant of fibrous dysplasia that often involves the proximal femur in young adults. It has a similar appearance on imaging as other entities but has stippled calcifications within the lesion. The differential diagnosis often includes benign and malignant tumors such as fibrous dysplasia, chondroblastoma, enchondroma, and chondrosarcoma. Histology is required for diagnosis and treatment is typically surgical due to the potential for pain, pathologic fracture, and deformity. We report the clinical presentation, imaging findings, and management of two pediatric patients with fibrocartilaginous dysplasia of the proximal femur to (1) highlight that recognition that fibrous dysplasia may contain cartilage upon frozen section will avoid overly aggressive therapy, and (2) FCD can occur in the McCune-Albright syndrome.

[Osteosarcoma Secondary to Polyostotoic Fibrous Dysplasia of the Ribs].

Sarcomatous transformation of fibrous dysplasia is extremely rare. We present the case of a 54-yearold man with multiple rib masses, multiple enlarged lymph nodes throughout the body, and multiple osteolytic lesions on computed tomography( CT). A positron emission tomography( PET) scan showed abnormal enhancement in each. A needle biopsy of the right supraclavicular fossa lymph node revealed sarcoidosis. Considering the possibility of malignancy associated with sarcoidosis, a rib tumor resection and mediastinal lymph node biopsy were performed to confirm the diagnosis of the rib lesion. The pathology results showed that the rib mass was a low-grade central osteosarcoma and the mediastinal lymph node was sarcoidosis. The distribution of the lesions was consistent with osteosarcoma secondary to multiple fibrous bone dysplasia. As the osteosarcoma was low grade, the patient was followed up. Three years after surgery, there was no increase in residual disease.

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 6-12 months. 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.

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.

Secondary osteosarcoma associated with osteofibrous dysplasia: a case report.

Secondary osteosarcoma is a rare complication of primary malignancies and benign bone lesions. There are various types of diseases that cause secondary osteosarcoma. A 15-year-old male presented at our medical center complaining of pain and redness in the right lower leg. He had been diagnosed with osteofibrous dysplasia in the right tibia when he was 2 years old and since then had been followed up. Although he had a pathological fracture of the right tibia at the age of 7, his fracture healed with a plaster cast and did not require surgery. At the time of the patient's last visit, a radiograph revealed a periosteal reaction as well as erosion of the bone cortex. Magnetic resonance imaging revealed an infiltrative area in the soft tissue surrounding the osteofibrous dysplasia lesion in the tibia. Consequent to pathological examination (through bone biopsy), the patient was diagnosed with secondary osteosarcoma. The patient underwent chemotherapy and extensive resection with liquid nitrogen. He has been progressing satisfactorily after the operation. The present case is the first report of secondary osteosarcoma associated with osteofibrous dysplasia. During the long-term follow-up of osteofibrous dysplasia, oncologists should be aware of the possibility of secondary osteosarcoma.

Ectopic Fibrous Dysplasia Presenting As a Well-Circumscribed Orbital Mass.

The authors present the case of a middle-aged woman with subacute progressive swelling of the OD associated with pain and severely limited duction in all gazes. MRI demonstrated a ~3 cm circumscribed mass in the extraconal space, which displaced and distorted the globe and impinged upon ocular adnexa. She underwent lateral orbitotomy with bone osteotomy to remove the mass, and subsequent histopathologic examination showed woven bone set within a fibrotic background, microscopic features of fibrous dysplasia. Fibrous dysplasia is characterized by abnormal scar-like bony proliferation, typically within a preexisting structure of the skeletal system. To the authors' knowledge, this represents the first example of fibrous dysplasia presenting as an orbital mass unconnected to the craniofacial skeleton.

Intracranial Dermoid in Patients With Fibrous Dysplasia.

OBJECTIVES: Intracranial epidermoid cyst (EC) and craniofacial fibrous dysplasia (CFD) were histogenetically different rare congenital benign diseases. The coexistence of intracranial EC and CFD was extremely rare and had not been reported yet. MATERIALS AND METHODS: We retrospectively reviewed the clinical and radiologic information of 3 patients diagnosed with concomitant EC and CFD at Beijing Tiantan Hospital from January 2003 to January 2021 and summarized their clinicopathological features, treatment modalities, and outcomes. In addition, we performed a systematic review of cases of the coexisting intracranial EC and other intracranial abnormalities to explore the potential connections. RESULTS: There were 2 women and 1 man with the mean age of 31 years old. Satisfactory resection was fulfilled for all the 3 ECs. CFD, however, was managed with watchful waiting. During the mean follow-up time of 58 months, all the ECs showed no sign of recurrence, and all the CFD lesions remained stable. Two EC specimens underwent genetic study, showing no GNAS mutations and negative G s α protein expression. In the literature review of concomitant intracranial EC and other intracranial abnormalities, 23 studies were included. With 5 reported cases, the intracranial aneurysm was found to be the most common intracranial disease that coexisted with EC. CONCLUSIONS: The coexistence of intracranial EC and CFD was extremely rare. However, no convincing mechanism and evidence underlying such coexistence had been found. To provide more profound understanding about these 2 diseases and improve diagnosis and treatment strategy, further research and verification should be considered.

The Virtual Surgical Management of Facial Fibrous Dysplasia.

PURPOSE: Fibrous dysplasia (FD) is a benign condition, which is characterized by the replacement of normal bone with fibrous tissue and the deposition of woven bone in an irregular manner. Surgical resection, careful corrective osteotomies as debulking, and recontouring procedures are frequently performed, but can be complicated by postoperative regrowth of the lesion. The main aim of this study was to introduce a computer-guided technique for a predetermined technique of bone contouring of craniofacial FD involving the facial bones. METHODS: This case report was conducted on an 18-year-old girl complaining of unilateral craniofacial dysplasia. Upon clinical examination and radiographic examination, a customized computer-generated bone contouring guide was designed using virtual surgical software for accurate contouring of excess bone in the cranial vault and frontal bone. This guide was virtually designed after importing the multislice computerized tomography scans into the virtual surgical planning software. It was generated based on the mirroring option of the unaffected normal side along the median sagittal plane. In the surgery, the guide was seated in place and 5 mm implant drills were inserted through the guide depth holes. Bone removal was made using surgical burs connecting the guiding depth holes. RESULTS: At the end of the follow-up, the patient showed acceptance of her external appearance with no signs of infection or dehiscence. CONCLUSION: This patient-specific cutting guide shows a promising solution for preplanned bone removal in cases with unilateral craniofacial FD.

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.

A Rare Skeletal Disorder, Fibrous Dysplasia: A Review of Its Pathogenesis and Therapeutic Prospects.

Fibrous dysplasia (FD) is a rare, non-hereditary skeletal disorder characterized by its chronic course of non-neoplastic fibrous tissue buildup in place of healthy bone. A myriad of factors have been associated with its onset and progression. Perturbation of cell-cell signaling networks and response outputs leading to disrupted building blocks, incoherent multi-level organization, and loss of rigid structural motifs in mineralized tissues are factors that have been identified to participate in FD induction. In more recent years, novel insights into the unique biology of FD are transforming our understandings of its pathology, natural discourse of the disease, and treatment prospects. Herein, we built upon existing knowledge with recent findings to review clinical, etiologic, and histological features of FD and discussed known and potential mechanisms underlying FD manifestations. Subsequently, we ended on a note of optimism by highlighting emerging therapeutic approaches aimed at either halting or ameliorating disease progression.

Case Report Of Rib Polyostotic Fibrous Dysplasia.

Polyostotic fibrous dysplasia is a rare benign asymptomatic tumour of the ribs not requiring surgery on most occasions. We present here a case with left 10th and 11th rib fibrous dysplasia which was causing a hinderance to the Urologist for renalstone extraction. Therefore the 10th and 11th ribs were excised followed by chest wall reconstruction.

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.

[A Case of Breast Cancer Complicated by Fibrous Dysplasia That Was Difficult to Differentiate from Bone Metastasis].

A 58-year-old woman with HER2-negative hormone-sensitive postmenopausal breast cancer underwent preoperative bone scintigraphy and CT to search for distant metastasis. Bone metastasis was suspected in the spinous process of the seventh cervical vertebra. MRI revealed a mass that was hypointense on T1- and T2-weighted images and hyperintense on diffusion- weighted images, with intense contrast enhancement, indicating bone metastasis at cT1N0M1, Stage Ⅳ(M: OSS). The patient underwent partial mastectomy and sentinel lymph node biopsy. The postoperative diagnosis was pT2N0cM1, Stage Ⅳ, with the status of bone metastasis being key to staging. PET-CT showed uptake in the spinous process of the seventh cervical vertebra but no other metastatic findings. However, solitary bone metastasis to the cervical spinous process is atypical. CT-guided needle biopsy confirmed benign fibrous dysplasia, and the final diagnosis was breast cancer at pT2N0M0, Stage ⅡA. Fibrous dysplasia is characterized by impaired osteogenesis leading to fibroplasia and commonly occurs in the skull, jaw bones, ribs, and limbs. Solitary fibrous dysplasia in the cervical spinous process is rare. The lesion was asymptomatic and pathologically benign, requiring no treatment. The patient underwent postoperative radiation therapy for the conserved breast and is followed up with endocrine therapy.

GNAS mutation analysis assists in differentiating chronic diffuse sclerosing osteomyelitis from fibrous dysplasia in the jaw.

Chronic diffuse sclerosing osteomyelitis of the mandible (DSOM) and fibrous dysplasia (FD) are distinct lesions with overlapping clinicopathological features that complicate their diagnosis. This study aimed to evaluate the efficacy of GNAS mutation analysis in differentiating between these two conditions. DNA samples from patients with DSOM (n = 35) and FD (n = 29) were collected to analyze the presence of GNAS mutations in exons 8 and 9, the two previously reported hotspot regions, using polymerase chain reaction and direct sequencing. Twenty-four of 29 patients (83%) with FD showed missense mutations in codon 201 in exon 8, whereas no mutation was detected in exon 9. No mutations were found in any of the 35 cases with DSOM. We also identified one case with an uncertain diagnosis due to overlapping clinicopathological features of DSOM and FD. A Q227H mutation was detected in this case, that confirmed the diagnosis of FD. Taken together, the findings indicate that mutational analysis of the GNAS is a reliable approach to differentiate between DSOM and FD of the jaw.

Extent of Extraskeletal Manifestations of Fibrous Dysplasia/McCune-Albright Syndrome in Patients with Mazabraud's Syndrome.

Mazabraud's syndrome (MZB) is a rare condition in which fibrous dysplasia of bone/the McCune-Albright syndrome (FD/MAS) co-exists with intramuscular myxomas. Both FD and the myxomas harbor the GNAS-mutation. Recent studies have shown that extraskeletal, GNAS-related features are associated with a more severe phenotype of FD/MAS. However, patients with MZB are often only seen by orthopedic surgeons. We therefore evaluated MZB patients seen in tertiary referral centers from the Netherlands (LUMC), USA (National Institutes of Health) and France (INSERM UMR 1033 (Lyos), Hôpital Edouard Herriot). All FD/MAS patients known in these centers with an additional diagnosis of a myxoma were included. Demographic information and data on disease extent and extraskeletal manifestations of FD/MAS such as precocious puberty (PP) or café-au-lait patches (CAL) were retrieved from patient's medical records. Thirty MZB patients were included: 20 women (67%) and 10 men (33%). Patients received a diagnosis of MZB (median 42 years, range 16-19) significantly later than the diagnosis of FD/MAS (median 30 years, range 0-60), p < 0.01. Twenty-six patients were diagnosed with polyostotic disease (87%). In 97% the myxoma was located near the skeletal FD lesion. The combination of MZB and MAS was made in 13 patients in whom PP (n = 7), CAL (n = 7), GH-excess (n = 3) and hyperthyroidism (n = 3) were present. Other extraskeletal features were (multinodular) goiter (n = 2) and thyroid cysts (n = 1). Furthermore, in this cohort of patients with MZB several (pre-)malignant tumors were observed; ductal carcinoma in situ of the breast in 3 patients (10%), breast cancer in 1 patient (3.3%), intra pancreatic mucinous neoplasms in 3 patients (10%) and liver adenomas in 2 patients (6.6%). A total of 47% of patients with MZB had an additional extraskeletal feature such as an endocrinopathy. In MZB, 87% of patients suffer from polyostotic FD, 43% of patients have extraskeletal GNAS-features such as an hyperfunctioning endocrinopathy and 30% (pre-)malignant tumors. We therefore advocate that MZB patients should undergo a complete screening and long-term follow-up for extent of bone disease, but also extraskeletal GNAS features of FD/MAS.