Polyostotic Fibrous Dysplasia Research Articles (Page 1)

Skeletal and endocrine manifestations of McCune-Albright syndrome in patients with fibrous dysplasia.

Polyostotic fibrous dysplasia in an adult with middle ear cholesteatoma and ipsilateral visual impairment

Recovery of neurological deficit after posterior total en-bloc resection of locally aggressive polyostotic fibrous dysplasia

McCune-Albright Syndrome (MAS) is a non-inherited disorder caused by missense point mutations in the GNAS1 gene located on the long arm of chromosome 20. It is a sporadic disease characterised by polyostotic Fibrous Dysplasia (FD), café-au-lait lesions, and a variety of endocrine disorders, including gonadal hyperfunction, hyperfunction of the thyroid and adrenal cortex, as well as excessive Growth Hormone (GH) secretion. The diagnostic triad includes polyostotic FD, precocious puberty, and café-au-lait lesions. When at least two of these are present, the diagnosis of MAS is confirmed. We present a case of an 18-year-old girl who presented with abdominal distension and a history of ovarian cystectomy. A detailed history revealed precocious puberty with vaginal bleeding at age three. Imaging showed a large, well-defined ovarian cyst with no solid component or septation. Magnetic Resonance Imaging (MRI) and Computed Tomography (CT) revealed multiple expansile lytic lesions with a ground-glass matrix in the pelvic bones, skull, and sphenoid, suggestive of polyostotic FD. Café-au-lait macules and hormonal findings pointed towards MAS. This case highlights the importance of considering MAS in young females with recurrent ovarian cysts, skeletal abnormalities, and early pubertal changes, as ovarian cysts with bony lesions do not always indicate metastasis and require careful evaluation to avoid misdiagnosis.

Objective: To investigate the clinicopathological and genetic characteristics of malignant transformation of polyostotic fibrous dysplasia (FD) in long bone. Methods: A retrospective analysis of clinical characteristics and morphological features was conducted from 4 cases of malignant transformation of FD diagnosed at Beijing Jishuitan Hospital from January 2016 to December 2023. Hotspot mutations for GNAS gene were tested in 4 cases by Sanger sequencing, in which both FD and malignant tissues were detected in 3 cases respectively. Results: There were 2 female and 2 male patients, aged 46 to 53 years [mean (49±3.2) years], and the course of the disease spanned from 2 months to 36 years. The tumor involved the femur (n=2), tibia (n=1) and humerus (n=1). Three of them were diagnosed with FD before surgery. Single photon emission computed tomography showed multiple increases in bone metabolism, CT showed poorly margin, cortical destruction and soft tissue mass with uneven enhancement. Three cases had both FD and sarcoma components, while the remaining case exhibited exclusively sarcoma. The sarcomas displayed significant morphological variation, with 1 case diagnosed as osteosarcoma and 3 cases classified as low to high grade spindle cell sarcoma. Immunohistochemical results did not provide any indications for clear classification. Sanger sequencing demonstrated GNAS mutations of p.R201H (c.CGT>CAT, n=2) and p.R201C (c.CGT>TGT, n=2). All 4 cases were followed-up for 18 to 76 months, and received chemotherapy after surgery; 2 cases maintained disease-free, one case was diagnosed with invasive breast cancer through a core needle biopsy 3 months after chemotherapy, and another one was found to relapse 18 months after surgery. Conclusions: Some cases of polyostotic FD occur in association with café-au-lait macules and/or endocrine hyperfunctioning in McCune-Albright syndrome (MAS); polyostotic FD and MAS have more malignant potential than monostotic FD, but they are not the risk factors for FD malignancy. GNAS mutations may be involved in the occurrence and development of FD. The histologic types of malignant transformation of polyostotic FD in long bone are diverse, the sarcoma components of FD also present the GNAS mutation, suggesting potential involvement in the pathogenesis of FD malignancy.

Noonan syndrome (NS) is a developmental malformation condition in the RASopathies group, characterized by variable clinical and molecular features. The syndrome is genetically heterogeneous, with the most frequent mutation found in approximately 50% of cases occurring in the PTPN11 gene. NS is reported to be associated with neurogenic, hematopoietic, melanocytic and other visceral malignancies, but osteosarcoma development has not been reported in association with NS. Therefore, we report the first case of a male with NS who developed osteosarcoma of the mandible in a background of long-standing polyostotic fibrous dysplasia (FD) of the craniofacial bones.

BACKGROUND: Primary hyperparathyroidism is the leading cause of hypercalcemia, usually caused by a parathyroid adenoma and potentially leading to metabolic bone disorders. Fibrous dysplasia is a rare skeletal disorder that can coexist with hyperparathyroidism, although it is rarely found without McCune-Albright syndrome. CASE: A 31-year-old woman with a history of hemodialysis presented with progressive swelling of the upper and lower jaw over the past two years, accompanied by bone pain and fatigue. Laboratory tests revealed elevated parathyroid hormone levels, serum creatinine, and hypocalcemia. Magnetic resonance imaging (MRI) of the neck identified an isointense lesion in the left thyroid gland but failed to localize the parathyroid adenoma. 99mTc-Sestamibi parathyroid scintigraphy showed multiple adenomas in the lower poles of both thyroid lobes. 99mTc-MDP bone scintigraphy demonstrated a metabolic superscan pattern, leading to a diagnosis of primary hyperparathyroidism with polyostotic fibrous dysplasia. The patient underwent minimally invasive parathyroidectomy, which was histopathologically confirmed as bilateral inferior parathyroid adenomas. Postoperatively, the patient experienced significant symptom improvement, including reduced bone pain and improved quality of life. CONCLUSION: The coexistence of primary hyperparathyroidism and fibrous dysplasia without McCune-Albright syndrome is rare but important to recognize. Parathyroid and bone scintigraphy play a crucial role in diagnosis, assessing bone involvement, and planning appropriate therapy. A multimodal imaging approach enables early detection and more effective surgical strategies, improving clinical outcomes for patients.

Synchronous polyostotic fibrous dysplasia and meningiomatosis: a case report on the challenging treatment for severe intracranial hypertension

McCune-Albright syndrome is characterized by a triad of café au lait macules, polyostotic fibrous dysplasia (FD), and endocrine abnormalities. Bilateral and extensive presentation of FD is rarely reported. We report an interesting case of 24-year-old woman presenting with multiple episodes of slip and fall, sustaining multiple fractures with history of precocious puberty and skin complaints. On evaluation with 99m Tc-MDP bone scan, all the long bones, ribs, pelvic bones, frontal bone, and maxilla showed deformities and increased osteoblastic activity, suggesting extensive polyostotic FD. Thus emphasizing the crucial role of 99m Tc-MDP bone scan in the diagnosis of extensive FD and guides in understanding of the polyostotic involvement.

Abstract Background: Fibrous dysplasia (FD) is a rare benign bone disorder characterized by the replacement of normal bone with fibro-osseous tissue, often resulting in structural deformities and fractures. Polyostotic FD affecting weight-bearing bones like the femur may present with significant functional impairment. Case Presentation: An 18-year-old female presented with left hip pain and limited mobility. Radiographs revealed polyostotic FD with coxa vara and femoral Shepherd’s crook deformity. She had previously undergone subtrochanteric valgus osteotomy with plate fixation, which failed, leading to a recurrence of the deformity within a year. Intervention: A salvage procedure was performed involving extensive curettage of the lesion, corticocancellous iliac crest bone grafting with a bone graft substitute, and corrective valgus osteotomy fixed using a proximal femoral locking compression plate. Histopathology confirmed the presence of fibrous dysplasia. Outcome: At the 7-year follow-up, the patient remained asymptomatic with improved mechanical alignment, increased bone density at the femoral neck, and no recurrence of deformity. Functional outcomes were excellent, with the Harris Hip Score improving from 27 to 97. Conclusion: This case highlights the effectiveness of a combined approach involving deformity correction, curettage, bone grafting, and stable fixation in the management of complex femoral deformities in polyostotic FD. Early mechanical correction and structural reconstruction are essential to prevent recurrence and ensure long-term functional success.

A clinical observation of a 27-year-old patient with polyostotic fibrous dysplasia, skin manifestations and prolactin+HGH-secreting pituitary adenoma - McCune-Albright syndrome - without GNAS gene mutation is described. The patient had a rapidly increasing formation in the left temporoparietal region, which reached 18×20×15 cm, accompanied by local pain and fever 4 months prior to hospitalization. Diagnosis of osteosarcoma was verified by biopsy. Neoadjuvant chemotherapy in the presence of intracranial hypertension and giant tumor has been refused. Preoperative embolization of tumor vessels with polyvinyl alcohol emboli was moderately effective. Tumor node has been removed, blood loss amounted to 5500 ml, blood autodonation, cell saver, 1 dose of donor erythrocytes were used. On the 1st day, the patient was transferred to the clinical unit, pain and fever ceased. He was discharged on the 8th day in satisfactory condition. Nevertheless, chemotherapy in the home area was not performed and the patient died from the disease progression in 1.5 months. The algorithm of care in osteosarcoma - neoadjuvant chemotherapy, tumor resection and adjuvant treatment. The possibility of malignant neoplasms development from fibrous dysplasia in McCune-Albright syndrome must be taken into consideration. The development of an algorithm for care in such patients requires accumulation of material and its analysis.

Polyostotic fibrous dysplasia: A case-based discussion

Fibrous dysplasia/McCune-Albright syndrome (FD/MAS) is a rare and complex condition caused by somatic variants in the GNAS gene that lead to a wide clinical spectrum. The diagnostic process and therapeutic pathway vary per centre and therefore international harmonisation of data collection should be pursued. To understand the diagnostic pathways and clinical outcomes of patients with FD/MAS reported on an electronic-reporting tool (e-REC) across European centres to guide the develop a condition-specific module within the European Registries for Rare Endocrine and Bone conditions. Centres that reported new cases on e-REC between October 2019 and May 2021 were approached to complete a survey in May 2021. Fifty-eight cases were included. Median age at presentation was 20 years (range, 0, 72). Of the 58 included cases, the presentation type was isolated craniofacial FD in 19 (33%), monostotic FD in 15 (26%), polyostotic FD in 10 (17%), and MAS in 13 (13%). Standardised questionnaires to assess pain and quality of life were used routinely in 21/58 patients (36%). The majority of patients had more than one healthcare provider, with great diversity in the specialty of the coordinating physician. A standardised dataset module for FD/MAS was developed through collaboration with the FD/MAS study group, incorporating expert consensus and clinical insights. Key variables were identified to capture essential diagnostic, clinical, and patient-reported outcomes. The diagnostic path for patients with FD/MAS across European expert centres is variable. The outcomes of this study allowed the building of the first international FD/MAS-specific data collection.

Fibrous dysplasia (FD) accounts for 5-7% of all benign bone tumors. It presents in two main forms - monostotic, which is more common affecting a single bone and presenting usually in 3rd decade of life; polyostotic, affecting several bones, is less common, and is seen mainly in the 1st decade of life. These usually present as bone pain or pathological fracture. It may also be part of McCune-Albright syndrome. Since the femur is an important weight-bearing bone in the human body, most cases of FD affecting the femur present as pathological fracture more early than other sites. The mainstay of management includes treatment of pathological fracture and prevention of bony deformity until skeletal maturity. The aim of this study was to analyze a series of cases of FD of femur affecting the pediatric population. A retrospective study was conducted at two tertiary-level centers of urban India, wherein all case records of FD under follow-up between January 2015 and December 2023 were analyzed. In all, there were 13 cases. Definitive management was decided on a case-by-case basis. We grouped the cases into 2 categories based on recurrence. Out of 13 cases, 11 were males while 2 patients were females. The mean age at presentation was 10.5 years (range 4-12 years). Two cases were of polyostotic FD, while 11 cases were of monostotic FD. In 11 cases, the intertrochanteric region of the femur was affected, while in 2 cases the affection extended into the proximal shaft of the femur as well. The mean follow-up period was 48 months (Range 15-84 months). In category one (no recurrence) there were 10 patients, while in category two (recurrence of FD) there were 3 patients. The recurrence rate in our series was 23%. Although FD is also seen in the adult population, its implications are more pronounced in a growing skeleton. The series of cases where surgical intervention has been done with a long follow-up in the pediatric population are limited. In literature, clinical classification of FD, anatomical location in the proximal femur, variation in neck-shaft angle and osteocalcin levels have been found to be significant in predicting causes of fractures and their recurrences. Internal fixation is preferable to prevent deformities where there are high chances of a pathological fracture as is evident by the natural history of FD. Long-term follow-up is important as there are chances of recurrence in childhood until puberty.

Malignant transformation of craniofacial fibrous dysplasia: A clinicopathological, immunohistochemical and molecular analysis of 15 cases in one single institution

Fibrous dysplasia (FD) is a rare disorder of bone in which normal bone is replaced by abnormal fibro-osseous tissue. It more commonly involves the long bones, craniofacial bones, ribs, and pelvis. The involvement of single bone is called as monostotic type of FD and if multiple bones are involved it is called polyostotic type of FD. Its occurrence is predominantly observed in teenagers, and it usually becomes static after adulthood. The incidence of monostotic FD (MFD) is four times more than that of polyostotic FD (PFD). The posterior region of the jaw bone is more prone and rarely crosses the midline. The malignant potential is 0.5% for cases that remain untreated. Here, we present a case of MFD involving the posterior region of the right side of the mandible in a 37-year-old female patient. The clinical diagnostic approach, different imaging modalities, and histological examination methods for definitive diagnosis have been elaborated. During the regular follow-up, the MFD lesion showed no obvious signs of progression or malignancy features.

INTRODUCTION/BACKGROUNDFibrous Dysplasia is a rare developmental bone disorder in which fibro-osseous tissue replaces normal bone tissue. It can manifest either monostotic or polyostotic associated with McCune-Albright syndrome. Bisphosphonates such as pamidronate and alendronate have been used to improve bone mineral density due to antiresorptive properties. However, the literature on the use of zoledronate is limited. CASEA 10-year-old female presented with a fracture of the right midshaft of the femur following a trivial fall. She had a history of precocious puberty and limping gait since the age of four years old. On examination, she was tall for her age and there was thoracolumbar scoliosis with huge cafe au lait patches at her lower back. Biochemically, she had elevated alkaline phosphatase level and low serum vitamin D. Skeletal survey revealed multiple patchy areas of lucency with irregular margins in the long bones, skull and pelvis. Bone mineral density was low suggestive of osteoporosis. Her fracture of the right midshaft of the femur was due to polyostotic fibrous dysplasia with underlying McCuneAlbright syndrome. As bisphosphonate is required in fibrous dysplasia, she was treated with multiple doses of intravenous zoledronate starting at 0.0125 mg per kg which she tolerated well and then increased to 0.025 mg per kg. Her response was good, evidenced by reduced alkaline phosphatase level and improved bone mineral density. Her fracture healed with no complications or incidence of new fracture. CONCLUSIONThe administration of intravenous zoledronate enhances bone mineral density and demonstrates improvements in bone biomarkers. It was well tolerated and should be used in McCune-Albright syndrome with fibrous dysplasia of the bone.

Rare case of polyostotic fibrous dysplasia of bilateral tibia with pathological fracture and associated endocrinopathy managed conservatively

Fibrous dysplasia (FD), commonly known as Lichtenstein-Jaffe disease, is a benign fibro-osseous bone disease. Clinical symptoms often include bone pain, deformities, pathological fractures, or nerve compression. Fibrous dysplasia (FD) in the cranio-facial region presents major management concerns because to the risk of deformity, loss of function, and recurrence. The purpose of this study is to demonstrate a single institution's experience managing cranio-facial FD with zolendronic acid, as well as an extensive review of the available literature on the subject. This retrospective study was conducted in the Orthopedic Oncology unit of the Department of Surgical Oncology with a study duration between January 1, 2019, and January 1, 2022. There were seven patients with cranio-facial fibrous dysplasia in the current study. The effects of zolendronic acid were evaluated using clinical assessment, data, radiological findings, biochemical indicators. Furthermore, a comprehensive literature review was conducted in order to compile the current data of cranio-facial FD. The study included seven individuals (five men and two females), four with polyostotic FD and three with cranio-facial FD. The average follow-up duration was 18.75months. The study found that all parameters improved: the mean VAS score increased from 7 to 1, mean serum calcium levels increased from 8.75 to 8.46mg/dL, mean serum phosphorus levels increased from 4.46 to 4.17mg/dL, and serum alkaline phosphatase levels increased from 152 to 93.25IU/L.A comprehensive literature review was conducted using PubMed and Google Scholar with the following keywords: "Fibrous dysplasia," "Cranio-facial bones," "Bisphosphonate," and "Zolendronic acid." The search included 24 studies published between 2000 and 2022, incorporating all relevant studies available to date. Our study demonstrated the effectiveness of zolendronic acid in the treatment of cranio-facial fibrous dysplasia. Zolendronic acid offers potential as a feasible treatment options in treating cranio-facial FD, with possible advantages including alleviating symptoms, disease progression stabilisation, and morbidity reduction. However, multi-centre prospective randomised study with larger sample numbers and longer follow-up periods are needed in future.

Hypercalciuria is the most common metabolic risk factor in people with kidney stone disease. Its etiology is mostly multifactorial, although monogenetic causes of hypercalciuria have also been described. Despite the increased availability of genetic diagnostic tests, the vast majority of individuals with familial hypercalciuria remain unsolved. In this study, we investigated a consanguineous pedigree with idiopathic hypercalciuria. The proband additionally exhibited severe skeletal deformities and hyperparathyroidism. Whole-exome sequencing of the proband revealed a homozygous ultra-rare variant in TRPV5 (NM_019841.7:c.1792G>A; p.(Val598Met)), which encodes for a renal Ca2+-selective ion channel. The variant segregates with the three individuals with hypercalciuria. The skeletal phenotype unique to the proband was due to an additional pathogenic somatic mutation in GNAS (NM_000516.7:c.601C>T; p.(Arg201Cys)), which leads to polyostotic fibrous dysplasia. The variant in TRPV5 is located in the TRP helix, a characteristic amphipathic helix that is indispensable for the gating movements of TRP channels. Biochemical characterization of the TRPV5 p.(Val598Met) channel revealed a complete loss of Ca2+ transport capability. This defect is caused by reduced expression of the mutant channel, due to misfolding and preferential targeting to the proteasome for degradation. Based on these findings, we conclude that biallelic loss of TRPV5 function causes a novel form of monogenic autosomal recessive hypercalciuria, which we name renal Ca2+-wasting hypercalciuria (RCWH). The recessive inheritance pattern explains the rarity of RCWH and underscores the potential prevalence of RCWH in highly consanguineous populations, emphasizing the importance of exploration of this disorder within such communities.