Fibrous Dysplasia Lesions Research Articles

Bone-Grafting in Polyostotic Fibrous Dysplasia.

Polyostotic fibrous dysplasia is a skeletal disease that results from somatic activating mutations in the gene GNAS in skeletal stem cells, leading to proliferation of immature osteogenic cells with replacement of normal marrow and bone with fibro-osseous tissue. Lesions may cause bone deformity or fracture. In the surgical care of polyostotic fibrous dysplasia, the role of grafting and the optimal grafting material are not clear. The purpose of this study was to evaluate the long-term survival of bone-grafting procedures in subjects with polyostotic fibrous dysplasia over time. The operative reports and radiographs of a cohort of subjects with polyostotic fibrous dysplasia followed in a natural history study were reviewed. Twenty-three subjects (mean age at the time of enrollment, thirteen years [range, two to forty years]) with fifty-two bone-grafting procedures had a mean follow-up time of 19.6 years (range, twenty-nine months to forty-seven years). Kaplan-Meier life table estimates, Cox proportional hazard models, and t tests comparing means were performed to assess various aspects of graft survival. Kaplan-Meier curves showed a 50% estimate of survival of 14.5 years. Cox proportional hazards models showed no advantage comparing allograft with autograft or structural with nonstructural graft materials. The mean age of the patients was significantly greater (p < 0.001) in the subgroup of subjects in whom grafts were maintained over time (20.9 years) compared with the subgroup of patients whose grafts were resorbed over time (9.8 years). Bone-grafting, including both allograft and autograft, is of limited value in ablating the lesions of fibrous dysplasia. The expectations of patients and surgeons should include the high probability of graft resorption over time with return of bone characteristics of fibrous dysplasia, particularly in younger patients. This suggests the maintenance of normal bone mechanics with implant support should be the priority of any surgical intervention.

Benign and Malignant Proliferative Fibro-osseous and Osseous Lesions of the Oral Cavity of Dogs.

Ossifying fibroma (OF) and fibrous dysplasia (FD) are benign, intraosseous, proliferative fibro-osseous lesions (PFOLs) characterized by replacement of normal bone by a fibrous matrix with various degrees of mineralization and ossification. Osteomas are benign tumors composed of mature, well-differentiated bone. Clinical, imaging, and histologic features of 15 initially diagnosed benign PFOLs and osteomas of the canine oral cavity were evaluated. Final diagnoses after reevaluation were as follows: OF (3 cases), FD (4 cases), low-grade osteosarcoma (LG-OSA) (3 cases), and osteoma (5 cases). Histology alone often did not result in a definitive diagnosis for PFOL. OF appeared as a well-circumscribed, radiopaque mass with some degree of bone lysis on imaging. Most lesions of FD showed soft tissue opacity with bone lysis and ill-defined margins. Low-grade OSA appeared as a lytic lesion with a mixed opacity and ill-defined margins. Osteomas were characterized by a mineralized, expansile, well-circumscribed lesion. Although histologic features of PFOLs were typically bland, the lesions diagnosed as LG-OSA had some features of malignancy (eg, bone invasion or a higher mitotic index). Treatment varied widely. Of the 10 dogs with benign PFOL or osteoma with known outcome (10/12), 9 showed either complete response (6/10) or stable disease (3/10) after treatment. Of the 2 dogs with LG-OSA with known outcome, 1 showed complete response after curative intent surgery, but 1 patient had recurrence after partial maxillectomy. Definitive diagnosis of mandibular/maxillary PFOL is challenging via histopathologic examination alone, and accurate diagnosis is best achieved through assimilation of clinical, imaging, and histopathologic features.

Craniofacial Fibrous Dysplasia in an Elderly Patient: A Case Report with a Review of Literature.

Fibrous dysplasia is a benign fibro-osseous disorder, characterized by fibrous connective tissue containing abnormal bone which replaces normal bone. It represents 2 to 5% of all bone tumors and 7% of all benign tumors. Most commonly it affects younger age groups, with a higher prevalence in the maxilla than the mandible. It is a lesion of unknown etiology, uncertain pathogenesis, and diverse histopathology. Fibrous dysplasia can involve multiple bones (polyostotic) or a single bone (monostotic). The lesions of fibrous dysplasia can be surgically recontoured for esthetic or functional purposes once the growth ceases. Here we report a case of craniofacial fibrous dysplasia in an 83-year-old elderly male patient with emphasis on radiographic features.

CT and MR Imaging in a Large Series of Patients with Craniofacial Fibrous Dysplasia.

SummaryBackgroundIn this retrospective review of patients with craniofacial fibrous dysplasia (FD), the clinical and radiological findings of CT and MR scan were analyzed.Material/MethodsThe study material included 32 patients, at 9 to 68 years of age that were directed for differential diagnostics of several disorders in the head. We recorded CT and MRI data related to the lesion number, location, sidedness, appearance, and sex of the cases with craniofacial FD.ResultsOf 32 patients involved in this study, 17 had monostotic and 15 had polyostotic involvement pattern. Bones most commonly involved by monostotic involvement in females were, in descending order, mandibular, maxillary, and sphenoid bones, while the sphenoid bone was involved the most in males. Leontiasis ossea was observed in 2 patients. Sclerotic and mixed lesion types were more common in both females and males. In T1- and T2-weighted MRI sequences, hypointensity was more common compared to hyperintensity or heterogeneous intensity. The type of enhancement of lesions was found similar after contrast medium administration.ConclusionsIn the presence of craniofacial FD during CT or MRI imaging of the head, a detailed description of FD lesions may provide an important clinical benefit by increasing radiological experience during the diagnostics of this rare disorder.

An atypical monomelic presentation of Mazabraud syndrome.

Mazabraud syndrome is a rare condition characterized by a combination of fibrous dysplasia and intramuscular myxomas. In Mazabraud syndrome, the distribution of fibrous dysplasia is mostly polyomelic and frequently located in the femur, with myxomas adjacent to the fibrous dysplasia lesion of bone (mostly in the quadriceps muscle). However, when presented as atypical clinical features, patients of Mazabraud syndrome is either misdiagnosed or difficult to diagnose. We report an atypical monomelic case of Mazabraud syndrome in the right upper arm and discuss the difficulties in making an accurate diagnosis.

Oral Rehabilitation With Dental Implants for Teeth Involved in a Maxillary Fibrous Dysplasia

Introduction: Fibrous dysplasia (FD) is a rare but important benign lesion affecting the maxillofacial region that presents bone pain, deformities, and fracture. Although FD presents radiographic patterns, it has to be analyzed histologically for a final diagnosis. Currently, there is no universally accepted guide for FD treatment. This case report describes a successful case of excision of the entire lesion in the upper left maxilla and the placement of two dental implants for oral rehabilitation, followed by guided bone regeneration.Case Presentation: A 49‐year‐old female patient presented with a growth on the left side of the maxilla that developed 4 years previously. Cone‐beam computed tomography was used to analyze the lesion and clinical features, and the FD was confirmed by histologic analysis. Extraction of the teeth involved with the lesion and excising the lesion was suggested. This was followed by two‐implant placement for oral rehabilitation, grafting the cavity with an osteoconductive material. Both implants were successfully integrated, as confirmed by clinical examination and a resonance frequency test.Conclusion: Dental implant and related guided bone regeneration can be successfully obtained in a patient with an FD lesion.

Intramedullary rod fixation of fibrous dysplasia without use of bisphosphonates

Controversy exists regarding approach to treatment of pediatric patients with fibrous dysplasia. We retrospectively reviewed medical records of seven patients who were treated at our institution for fibrous dysplasia by intramedullary rod fixation without bisphosphonate supplementation. Seven patients with a total of ten fibrous dysplasia lesion sites surgically treated by intramedullary rod fixation were included. Of these ten lesion sites, eight demonstrated pathologic fracture at the time of fixation. Complete fracture healing was observed in all eight sites, with no incidence of recurrent pathologic fractures examined radiographically. There were no major infections or neurologic deficits, and lesions appeared to stabilize. In this series, intramedullary rod fixation proved to be successful in treatment of acute pathologic fracture and incompletely healed fibrous dysplasia lesions. We observed partial resolution of fibrous dysplasia lesions at all ten sites without significant long-term complications. Following treatment, there were no refractures. Level IV, case series.

Dental perspectives in fibrous dysplasia and McCune–Albright syndrome

McCune-Albright syndrome (MAS) is a rare multisystem disorder characterized by the triad of polyostotic fibrous dysplasia (FD), endocrine disorders, and café-au-lait skin pigmentation. Ninety percent of MAS patients have FD lesions in the craniofacial area, resulting in significant orofacial deformity, dental disorders, bone pain, and compromised oral health. Maxillomandibular FD is also associated with dental developmental disorders, malocclusion, and high caries index. There are limited data on the outcomes of dental treatments in maxillomandibular FD/MAS patients, because clinicians and researchers have limited access to patients, and there are concerns that dental surgery may activate quiescent jaw FD lesions to grow aggressively. This report highlights current perspectives on dental management issues associated with maxillomandibular FD within the context of MAS.

Diagnostic value of investigating GNAS mutations in fibro-osseous lesions: a retrospective study of 91 cases of fibrous dysplasia and 40 other fibro-osseous lesions

GNAS (guanine nucleotide-binding protein/α-subunit) mutations that induce the activation of G-protein α-subunit participate in the pathogenesis of fibrous dysplasia. The aim of this study was to evaluate the sensitivity and specificity of GNAS mutations in fibrous dysplasia and other fibro-osseous lesions, to assess the value of investigating this mutation in the diagnosis of fibro-osseous lesions. We studied 91 cases of fibrous dysplasia. The quality and/or quantity of genomic DNA were suitable for molecular analysis for 51 cases of fibrous dysplasia. GNAS mutations were investigated by three techniques: high-resolution melting (exon 8), allele-specific PCR (exons 8 and 9) and/or direct DNA sequencing (exons 8 and 9). Fibrous dysplasia samples were classified blind to the GNAS mutation status into six histological subtypes as conventional, fibro-involutive, osteosclerosing, cementifying, osteocartilaginous and with prominent aneurysmal cystic changes. We also studied 14 cases of low-grade osteosarcoma, 21 cases of ossifying fibroma, 3 cases of osteofibrous dysplasia, 1 case of osseous dysplasia of the jawbone and 1 post-traumatic lesion of the ribs. Twenty-three cases of fibrous dysplasia (45%) showed mutations of codon 201 (exon 8, p.R201H or p.R201C). No mutation was found on codon 227 (exon 9). GNAS mutations in conventional fibrous dysplasia were detected in the same proportion (47%) as in the other histological subtypes (47%, P=0.96), regardless of sex (P=0.44), age (P=0.90) and location (P=1). GNAS mutations were not detected in any other fibro-osseous lesions. The GNAS mutation was thus specific to fibrous dysplasia in the context of fibro-osseous lesions. The particular mosaicism of mutant and non-mutant cells within the lesion or the existence of other mutations not already described could explain the lack of GNAS mutation in cases of fibrous dysplasia. Investigating this mutation may constitute a valuable complementary diagnostic tool, despite its low sensitivity, particularly in unconventional morphologically different subtypes of fibrous dysplasia.

Resection of orbito-cranial fibrous dysplasia lesion and reconstruction with titanium

To discuss the method and opportunity of operation for orbito-cranial fibrous dysplasia, and further to summarize our experience in repairing the bony defect with titanium after excision and assess the surgical outcomes. A retrospective study was performed in 21 patients with visual function damage and/ or orbital malformation, who treated surgically. All patients were underwent CT examinations (coronal, horizontal, sagittal and three-dimensional scans) before surgery. CT image data of patients with serious orbital skull lesions were analyzed by computer to produce the three-dimensional, solid titanium mesh prostheses used to repair the lesions; for smaller lesions solid titanium mesh prostheses were shaped artificially during surgery according to the normal orbit and the cranium. All the patients were treated surgically via craniofacial approach. After removing the diseased tissue, the defective area was repaired by titanium plate and nets. Of the 21 patients, tumor removal was complete in 18 patients, and incomplete in 3 patients due to extensive invasion into the sious cavernosus. Of the 13 patients with vision impairment before surgery, vision was improved in 11 cases (range from 3 to 5 lines) following surgery. All orbital malformations were healed in these 11 patients. Patients with fibrous dysplasia should undergo surgical treatment as soon as possible. Where this results in visual dysfunction or orbital-cranial deformities, repairing the bony defect with titanium material has many advantages: it is solid, easily molded, and easily fastened.

Rapidly Enlarging Orbital Tumor in a Facial Fibrous Dysplasia Lesion

Malignant change in fibrous dysplasia (FD) is a well-described phenomenon in the literature. When rapid enlargement is observed in an FD lesion, malignant change should be considered first. We present a case with McCune-Albright syndrome in which a rapidly enlarging orbital tumor developed in a facial FD lesion, which was subsequently proven to be a metastasis from an incidental esophageal carcinoma. Although metastasis of a malignant tumor to an FD lesion is quite rare and has been neglected as a differential diagnosis in the literature, it should be included in the important differential diagnosis because hematogenous metastasis could readily occur in FD due to its abundant blood flow. The importance of systemic examinations, such as positron emission tomography, is also emphasized.

Characteristic Radiological and Histological Patterns of Fibrous Dysplasia and Ossifying Fibroma of the Jaws at University of Nairobi Dental Teaching Hospital

Objective: To characterize the diagnostic features of ossifying fibroma (OF) and fibrous dysplasia (FD) of the jaw bones. Study Design: A histopathological and radiological analysis with full clinical documentation. Setting: University of Nairobi Dental Teaching Hospital (UNDH). Study Population: All archival cases diagnosed as FD and OF from 1992-2006 were retrieved from the UNDH Oral Pathology Laboratory records. New cases were included as they pre-sented over a 6-month period from January to June 2007. Methodology: Information regarding the histological type of a fibro-osseous lesion (FOL) including the clinical features, demographic and radiographic data was documented for analysis; and comparison between pathological parameters and the final diagnosis was evaluated with the chi-square test. Results: FD lesions constituted 40 (27.2%) cases while 107 (72.8%) were OF. The age ranged from 1 - 72 years (mean = 24.19 ± SD 13 years). The differences in the gender distribution were not statistically significant. Radiographic analyses showed statistically significant differences between the appearances of the body (p = 0.012) and the margins (p = 0.003) of FD and OF. The microscopic differences between the two lesions were not statistically significant. Conclusion: Differentiation between FD and OF is only possible after critically analyzing the clinical, radiological and histological criteria.

Mc Cune Albright syndrome: estimation of bone strength parameters and response to treatment using peripheral Quantitive Computed Tomography (pQCT) of the tibia

Methods We present a 14y old girl with polyostotic fibrous dysplasia (right humerus, femur, tibia, skull), precocious puberty and cafe au lait skin spots, diagnosed as MAS with a confirmed heterozygous c.601C>T mutation of the GNAS1 gene. Due to initial bone pain and continuously increasing bone turnover, the patient was treated with iv bisphosphonates for 4 years. We used pQCT to estimate bone strength parameters at the site of fibrous dysplasia lesion of the right tibia (38% of tibia length) vs the same site of the left (healthy) tibia at baseline and after treatment. A Stratec XCT-2000 scanner was used (Stratec Medizintechnik, Pforzheim, Germany) and we specifically assessed for the 38% site cortical BMC (Cort_CNT), cortical BMD (Cort_DEN), cortical area (Cort_A),cortical thickness (Cort_THK) and Stress Strain Index (SSI) as an indicator of bending/torsional strength.

Bilateral Tibial Adamantinomas Simulating Stress Fractures on Scintigraphy

A 35-year-old woman presented with continued tenderness in the left leg for more than 2 months. The patient was sent to the nuclear medicine department for evaluation. Three phase blood flow imaging followed by a whole body bone scan were performed. Scintigraphy revealed metabolically active lesions in both tibiae. The lesion was larger in size on left side. Scintigraphy per se raised suspicion of bilateral tibial stress fracture. Slightly increased uptake of tracer in the medial condyle of the right femur was because of old trauma. Evaluation of the whole body bone scan showed another lesion in the left pubic bone. Correlation of the CT scan findings of both tibiae (diaphyseal involvement, areas of lucency, breach of cortex, soft tissue component extending into medullary region) with the whole body bone scan raised the suspicion of adamantinoma, which ultimately proved to be multifocal adamantinomas. Differential diagnosis includes fibrous dysplasia, eosinophilic granuloma, polyostotic osteomyelitis, and skeletal metastatic lesions. (Lädermann et al, Orthopedics. 2008;31:282; Daffner et al, Am J Roentgenol. 1982;139:943–948; Desai et al, J Surg Oncol. 2006;93:429–433; Papagelopoulos et al, Orthopedics. 2007;30:211–215; Siblerstein et al, Diagnostic Patterns in Nuclear Medicine. Reston, VA: Society of Nuclear Medicine; 1998:199–210). This is a rare case of multifocal adamantinomas. This case emphasizes that nuclear medicine physicians should not block their minds to a single entity, and always keep options open. Whenever feasible and possible, the whole body should be scanned. Careful review of the whole set of data and correlation with other imaging modalities helps most of the time to reach a proper diagnosis. Adamantinoma should be included in the gamut/differential diagnosis of tibial stress fractures.

The surgical and orthodontic management of cherubism in a growing child

Cherubism is a rare non-neoplastic disease that affects the jaws causing significant destruction and disfigurement. The disease also affects the normal eruption, occlusion and function of the dento-alveolar complex. Cherubism may radiographically and histologically resemble central giant cell granuloma, fibrous dysplasia and other giant cell lesions. The case of a 15-year 4-month-old girl with no obvious facial swelling or signs of cherubism is described in this report. The patient presented with a dental malocclusion that included the ectopic eruption and displacement of teeth caused by the lesion. The radiographic findings derived from Cone Beam Computed Tomography (CBCT) technology are described. This case report details the orthodontic and surgical diagnosis and management of a teenager during the post growth period.

Quantitative Analysis of Activating Alpha Subunit of the G Protein (Gsα) Mutation by Pyrosequencing in Fibrous Dysplasia and Other Bone Lesions

Benign fibro-osseous lesions (BFOLs) frequently display overlapping histological features. The differentiation of fibrous dysplasia (FD) from other BFOLs can be difficult, even for experienced orthopedic pathologists. Accurately distinguishing FD from other BFOLs may have significant clinical and treatment implications. A somatic mutation in gene GNAS encoding the α subunit of the G protein (Gsα) involving the codon corresponding to Arg 201 has been identified in FD and is specifically absent in other BFOLs. We have developed a quantitative assay by pyrosequencing that has a detection sensitivity of 95%. The test allows the identification of the two most common types of mutation (Arg→His and Arg→Cys) in a single reaction, with the ability to analyze other rare mutations. Of the 24 FD cases in this series, 23 (96%) were positive for GNAS/Gsα mutation. Nineteen of 23 positive cases exhibited a G→A mutation (Arg→His), whereas four had a C→T mutation (Arg→Cys). One of three BFOL, not otherwise specified cases was positive for G→A mutation. None of the osteofibrous dysplasia, ossifying fibromas, or other bone lesions were positive for this mutation. Our experience is that pyrosequencing is an easy and accurate quantification method for Gsα mutation detection in fibrous dysplasia. Mutation analysis of the Gsα by pyrosequencing has significant potential for improving discrimination between FD and other BFOLs in problematic cases.

Fibro-osseous lesion of maxilla. Report of two cases in a family with review of literature

Fibrous dysplasia is a disturbance of bone metabolism that is classified as a benign fibro-osseous lesion. Fibrous connective tissue containing abnormal bone, replaces normal bone. The etiology of fibrous dysplasia is unknown. The radiographic appearance of the irregularly shaped trabeculae aids in the differential diagnosis. Occurring most commonly in the second decade of life, the lesions of fibrous dysplasia can be surgically recontoured for esthetic or functional purposes once they become dormant.

Endoscopic transphenoidal approach for fibrous dysplasia of clivus, tuberculum sellae, and sphenoid sinus; report of three cases

Fibrous dysplasia is a benign disease in which medullary bone is replaced by fibro-osseous tissue, and causes distortion and overgrowth of the involved bone and represents about 3% of all bone tumors. There is variability in the manifestation of Fibrous Dysplasia lesions with imaging techniques due to their proportional variations of fibrous to osseous tissue. Radiological differential diagnoses include meningioma, chordoma on MRI and Paget disease on CT imagings. We report three cases of monostotic fibrous dysplasia, affecting clivus, tuberculum sellae, and sphenoid sinus through the pterygopalatine fossa. We performed pure endoscopic transphenoidal approach for those three cases with the guide of neuronavigation. Extended approach was used via binostril for fibrous dysplasia of clivus and Tuberculum sellae. Radiologic report revealed chordoma and meningioma for the two cases and fibrous dysplasia for the last case. Total resection of tuberculum sellae, subtotal resection of clivus and partial resection of sphenoid sinus lesions were performed. Pathology diagnosis were fibrous dysplasia in all three patients. Histopathological sampling provided by surgical approach should be obtained to establish the final diagnosis. Endoscopic approaches are convenient for skull base lesions even for biopsy or curative resections providing panoramic view and avoid brain retraction.

Transfer, analysis, and reversion of the fibrous dysplasia cellular phenotype in human skeletal progenitors

Human skeletal progenitors were engineered to stably express R201C mutated, constitutively active Gs alpha using lentiviral vectors. Long-term transduced skeletal progenitors were characterized by an enhanced production of cAMP, indicating the transfer of the fundamental cellular phenotype caused by activating mutations of Gs alpha. Like skeletal progenitors isolated from natural fibrous dysplasia (FD) lesions, transduced cells could generate bone but not adipocytes or the hematopoietic microenvironment on in vivo transplantation. In vitro osteogenic differentiation was noted for the lack of mineral deposition, a blunted upregulation of osteocalcin, and enhanced upregulation of other osteogenic markers such as alkaline phosphatase (ALP) and bone sialoprotein (BSP) compared with controls. A very potent upregulation of RANKL expression was observed, which correlates with the pronounced osteoclastogenesis observed in FD lesions in vivo. Stable transduction resulted in a marked upregulation of selected phosphodiesterase (PDE) isoform mRNAs and a prominent increase in total PDE activity. This predicts an adaptive response in skeletal progenitors transduced with constitutively active, mutated Gs alpha. Indeed, like measurable cAMP levels, the differentiative responses of transduced skeletal progenitors were profoundly affected by inhibition of PDEs or lack thereof. Finally, using lentiviral vectors encoding short hairpin (sh) RNA interfering sequences, we demonstrated that selective silencing of the mutated allele is both feasible and effective in reverting the aberrant cAMP production brought about by the constitutively active Gs alpha and some of its effects on in vitro differentiation of skeletal progenitors.

Bilateral fibrous dysplasia of the mandible in a 7-year-old male patient-A rare case

Fibrous dysplasia is a disturbance of bone metabolism that is classified as a benign fibro-osseous lesion. Fibrous connective tissue, containing abnormal bone, replaces normal bone. The etiology of fibrous dysplasia is unknown. The radiographic appearance of the irregularly shaped trabeculae aids in the differential diagnosis. Occurring most commonly in the second decade of life, the lesions of fibrous dysplasia can be surgically recontoured for esthetic or functional purposes once they become dormant. Here, we report a case of bilateral fibrous dysplasia in a 7 year old male patient and its diagnostic work-up.