Continuing Education Activity

Fibrous dysplasia is a typically benign bone lesion characterized by intramedullary fibro-osseous proliferation secondary to altered osteogenesis. The polyostotic form often presents in childhood. Malignant transformation is rare, and remote radiation therapy has been reported as a risk factor. McCune-Albright syndrome is a relatively rare condition featuring polyostotic fibrous dysplasia (often unilateral) with skin pigmentation lesions and endocrine dysfunction (often female precocious puberty). This activity examines how to properly evaluate fibrous dysplasia and highlights the role of the interprofessional team in caring for patients with this condition.

Objectives:

• Review the history and physical exam of a patient with fibrous dysplasia.
• Summarize the treatment of fibrous dysplasia.
• Describe the evaluation of a patient suspected of having fibrous dysplasia.
• Explain how the facilitation of interprofessional team education and discussion can optimize the effective detection of fibrous dysplasia and inform the need for subsequent evaluations.

Introduction

Fibrous dysplasia is a typically benign bone lesion characterized by intramedullary fibro-osseous proliferation secondary to altered osteogenesis.[1] First introduced by Lichtenstein and Jaffe in 1942 and originally termed Jaffe-Lichtenstein syndrome, fibrous dysplasia can occur in monostotic form (single bone) or polyostotic form (multiple bones).[1] Fibro-osseous tissue replacing normal bone can result in complications including fractures or compression of adjacent soft tissues including neurovascular structures.[2] Monostotic fibrous dysplasia is often an asymptomatic clinical entity. The polyostotic form often presents in childhood. Adult presentation often occurs incidentally during imaging for an unrelated indication.[2] Fibro-osseous replacement of bone can lead to pathologic fracture, especially in weight-bearing bones or the upper extremities in athletes.[3] Malignant transformation is rare, and remote radiation therapy has been reported as a risk factor.[4] McCune-Albright syndrome is a relatively rare condition featuring polyostotic fibrous dysplasia (often unilateral) with skin pigmentation lesions and endocrine dysfunction (often female precocious puberty). Mazabraud syndrome is a very rare polyostotic variant that features coexistent single or multiple intramuscular myxomas.[5]

Etiology

The etiology of fibrous dysplasia has been linked with a missense mutation in the GNAS1 gene on chromosome 20. Abnormal proliferation of fibrous tissue ensues following an activating mutation.[6]

Epidemiology

Incidence has been estimated at 1 in 5,000 to 10,000.[7] Most commonly fibrous dysplasia is first diagnosed in children or young adults. There is not a gender predilection. Overall, fibrous dysplasia constitutes 5% of all benign bone lesions.[2] The monostotic form is the most frequent, accounting for 75% to 80% of fibrous dysplasia cases.[8]

Histopathology

Fibrous dysplasia has histologic elements of immature collagen and immature bone trabeculae forming a fibrocellular matrix.[9] Trabeculae are not rimmed by osteoblasts secondary to osteoblast maturation arrest and histologic transition from normal to abnormal bone is usually abrupt.[9]

History and Physical

Patients with monostotic fibrous dysplasia are often asymptomatic.  Occasionally patients may present with bone pain. Pathologic fracture with minor inciting trauma can also be a first presentation.[10] Pregnancy can increase disease activity and therefore increase the risk of pain and pathologic fracture.[11] History and physical examination may contribute little to disease evaluation in cases of asymptomatic osseous involvement. History should address the characteristics of bone tenderness, bony protuberance, osseous asymmetry, endocrine disturbance, and dermatologic complaints. A family history of bone lesions may be present in hereditary forms of fibrous dysplasia such as cherubism. Although malignant transformation is rare, it does occur in less than 1% of cases.[12] In a patient with known fibrous dysplasia, periodic evaluation for aggressive lesion growth should be performed.[13] McCune-Albright syndrome should be considered in the setting of hyperfunctioning endocrinopathy.

Physical exam has a minor role in evaluating lesions. In the setting of pain, focal palpation may increase pain with fractures. Visual inspection for skeletal deformities and asymmetries can provide clues to sites of involvement. Leg length discrepancy may indicate disease such as the classic shepherd’s crook deformity at the proximal femur.[14] Facial involvement can result in orbital asymmetry.[15] Other potential face complications include proptosis, frontal bossing, or enlargement of the mandible.[16]

Common sites of involvement subject to deformity are the ribs, long bones, and craniofacial structures. Less common sites include the hands, sternum, and spine.[17][18] In the setting of McCune-Albright syndrome, the physical examination should include an evaluation of the skin to asses for cafe au lait skin pigmentation. Skin acne may be a feature of endocrinopathy (Cushing syndrome).[19] A thorough physical examination to assess the endocrine system should be performed. This also includes the cardiopulmonary, gastrointestinal as well as thyroid evaluation.[20] Assessment of vision and hearing in the setting of craniofacial manifestation of fibrous dysplasia is also important.[2]

Evaluation

Imaging plays a chief role in the diagnosis and evaluation of the disease extent. Radiography should be utilized first in an evaluation. Advanced imaging such as computerized tomography (CT) and magnetic resonance imaging (MRI) can exclude other bone lesions; evaluate for soft tissue complications occurring from fractures, craniofacial neurovascular complications; and assess lesions for rare malignant transformation.[21] CT and MRI also have a role in the evaluation of adrenal hyperplasia, thyroid nodules, and pituitary tumors.[22][23] Classically, bone lesions have an internal ground glass matrix on radiographs and CT, but appearance can be varied with lytic and/or sclerotic components, possible bone expansion, and cortical thinning [12] Bowing deformities (including the femoral shepherd's crook deformity), discrepant limb length, and short stature secondary to premature fusion of growth plates can be characterized with imaging.[21] Bone scan demonstrating increased Technetium-99m radiotracer uptake may have a role in polyostotic cases to assess disease extent.[24] Finally, biopsy with histologic evaluation may be necessary in select cases when imaging features mimic malignant lesions.[14]

Treatment / Management

Monostotic fibrous dysplasia cases are often asymptomatic. Patients in this category can be followed periodically with assessment for new symptoms and radiographs.[25] Treatment is not required in asymptomatic cases. Adult medication therapy with bisphosphonates can alleviate bone pain and disease-associated osteoporosis.[10] Bisphosphonates inhibit osteoclastic bone resorption, preserving cortical bone mass and thereby reducing fracture risk.[26][27] Surgery may have a role in symptomatic fibrous dysplasia management. Surgical management includes internal fixation following pathologic fractures or prophylactic internal fixation in lesions weakening weight-bearing bones.[14] Additional surgical interventions include correction of extremity and spine deformities and limb length discrepancies.[14] Craniofacial surgery can play an important role in alleviating nerve compression symptoms.[28] Surgery may involve bone lesion curettage, bone grafting, and insertion of metallic fixation rods, plates, and screws.[14]

Differential Diagnosis

In the setting of polyostotic McCune-Albright syndrome, accurate assessment of the cafe au lait skin pigmentation lesions is important. Associated skin lesion borders have been described as serrated, which is in contrast to smooth skin lesion borders in neurofibromatosis.[11]

Fibrous dysplasia often has varied imaging presentation and osseous sites of involvement and therefore other bone diseases must often be considered. Monostotic radiologic appearance can mimic simple bone cyst, giant cell tumor, fibroxanthoma, osteoblastoma, hemangioma, osteofibrous dysplasia, and Paget disease.  Polyostotic appearance can mimic neurofibromatosis, hyperparathyroidism (Brown tumors), enchondromatosis, and eosinophilic granuloma.[25][11] Patient age, bone location (fibrous dysplasia has a predilection for the long bone diaphysis), presence of ground glass matrix, and non-aggressive appearance may be lesion features that favor fibrous dysplasia.[11] Bone biopsy does have a role if malignancy cannot be excluded following clinical and imaging work up.[14]

Complications

Usually fibrous dysplasia is monostotic and asymptomatic. In the cases of severe bone deformity, bowing may result in musculoskeletal dysfunction or accelerate development of osteoarthritis.[29] Spine lesions may predispose to scoliosis and subsequent functional limitations.[30] Craniofacial cases may have associated cranial nerve deficits including vision and hearing loss.[31][32] Malignant transformation to sarcoma is rare but can occur with a prior history of radiation therapy.[33]

Consultations

• Pediatric orthopedics
• Orthopedics
• Genetics

Deterrence and Patient Education

Patient education regarding the risk of fracture is important.[34] In cases of craniofacial disease, patients should be coached to monitor for evolving cranial nerve deficits including vision and hearing loss. In the setting of McCune-Albright syndrome, parents and the patient should be educated on the various manifestations of the syndrome and genetic counseling should be performed.[35] Routine visits to an endocrinologist should be incorporated to monitor for symptoms of endocrine dysfunction.

Enhancing Healthcare Team Outcomes

Managing fibrous dysplasia involves an interprofessional team approach, primarily with pediatrics/primary care, orthopedics, and radiology.  Genetics and endocrinology should be added for cases of McCune-Albright syndrome. Craniofacial involvement should prompt neurology, ophthalmology, audiology, and possible neurosurgery consultation.[3][36] Additional support from physical therapy and psychiatry in cases of disability or deformity may be warranted.[3]