Continuing Education Activity

Osteofibrous dysplasia (OFD) is a rare disease. It is considered a benign non-neoplastic condition of unknown cause, characterized by a fibrovascular defect. Common sites of involvement are the two leg bones, the tibia, and the fibula. This activity reviews the evaluation and treatment of osteofibrous dysplasia and highlights the role of the interprofessional team in the care of patients with this condition.

Objectives:

• Identify the etiology of osteofibrous dysplasia.
• Review the appropriate steps in the evaluation of osteofibrous dysplasia.
• Outline the management options available for osteofibrous dysplasia.
• Summarize interprofessional team strategies for improving care coordination and communication to advance the care of osteofibrous dysplasia.

Introduction

Osteofibrous dysplasia (OFD) is a benign fibro-osseous developmental condition of bone which commonly occurs in the cortical bone of the anterior mid-shaft of the tibia in children.[1] First described by Frangenheim in 1921, it is also called congenital fibrous dysplasia and ossifying fibroma of the long bones.[2] 

The term "osteofibrous dysplasia of the tibia and fibula" was coined by Camanacci and Laus, thereby including the histological similarity to fibrous dysplasia and the occurrence of the disease in the tibia in the term.[3] However, lesions may also affect the fibula, the radius, and the ulna. Osteofibrous dysplasia should be distinguished from adamantinoma, which is a malignant biphasic tumor characterized by different morphological patterns, clusters of epithelial cells, surrounded by a spindle-cell.[4]

OFD can be classified as monostotic, polyostotic, and McCune Albright syndrome. Most cases of monostotic lesions present with no significant symptoms and are often found incidentally on x-ray. The condition mainly affects patients in their third decade.[5]

Etiology

Osteofibrous dysplasia is a rare form of fibrous dysplasia that primarily affects the tibia and is confined to the cortices. OFD comprises 0.2% of all primary bone tumors. It is most commonly detected during infancy and childhood, and the most frequent site is the cortical bone of the anterior mid-shaft of the tibia.[1] Cytogenetic studies show that it may occur with trisomy 7, 8, 12, 22.

Epidemiology

Osteofibrous dysplasia is a rare condition usually found in younger children < 10 years old. It affects males more than females. It most frequently occurs in the first two decades of life. OFD is usually localized to the tibia, but the ipsilateral fibula is occasionally involved. Within the tibia, the mid diaphysis is the most commonly affected area. The involvement of the radius and ulna have also been reported. The progression of the lesion generally halts with the achievement of skeletal maturity.[6]

Pathophysiology

Osteofibrous dysplasia is limited mostly to the cortex, and its color is mainly yellow to white with a gritty, fibrous consistency. Microscopically, the characteristic finding is distinct osteoblastic rimming of woven bone trabeculae. A central osteolytic area characterizes it, the tissue being mainly fibrous with some scanty, thin, immature trabeculae of woven bone. Proceeding from the center to the periosteal and medullary spaces, the bone trabeculae became progressively more massive, more numerous, mature, and lamellar, until they join with each other and finally merge with the bone. Osteoblastic rimming shows features of fibrous dysplasia.[7]

Histopathology

Histology is similar to fibrous dysplasia, except in OFD, osteoblastic rimming is present. Fibroblast proliferation surrounding islands of woven bone with osteoblastic rimming and mitotic figures may have giant cells. OFD is characterized by the osteoid tissue, fibrous tissue, and a small number of epidermoid cells. An immunohistochemical assay is mandatory in some cases to detect epidermoid cells, which are not visible on standard hematoxylin and eosin staining because of their small number.[8]

It is sometimes difficult to histologically differentiate between OFD and adamantinoma (AD). A large tissue specimen is required for differentiation. The fibrous and epithelial component amounts can vary widely even within the same tumor, and sampling error is a significant concern with percutaneous or other limited biopsy specimens. Several cases have been published in which lesions initially diagnosed as OFD on small biopsy were finally diagnosed as AD after adequate diagnostic tissue was taken.[9]

OFD is characterized by a loose, often storiform fibrous background containing spicules of woven bony trabeculae lined by a layer of osteoblasts. Although this histologic appearance is quite similar to fibrous dysplasia (hence, their similar names), fibrous dysplasia typically lacks the distinctive osteoblastic rimming of the bony trabeculae. Additionally, OFD demonstrates a zonal architecture, in which more immature woven bone trabeculae are located centrally. However, moving outwards toward the periphery of the lesion, the trabeculae become more numerous, larger, and more mature and lamellar.[10]

History and Physical

Osteofibrous dysplasia is mostly asymptomatic and presents with a painless swelling on the anterior or anterolateral part of the tibia. The physical exam may reveal local tenderness over the tibia. Patients initially present with lower leg swelling, which may be painless, or with anterior bowing. Rarely, patients may present with a pathological fracture. Occasionally, the lesion is noted incidentally on x-rays taken for other reasons, often after trauma.[6]

OFD and adamantinoma may both present with pain, swelling, and deformity. Anterior bowing of the tibia is the most common symptom. Both typically occur in the tibial diaphysis, with OFD being limited to the cortex. OFD has also been reported in the fibula, ulna, and radius. However, adamantinoma may also occur in the fibula and has been reported in the calcaneum, femur, ulna, radius, humerus, olecranon, ischium, rib, spine, metatarsals, and capitate. Pathological fracture is more common than swelling or deformity in patients with OFD.[4]

Evaluation

The recommended x-ray views are anteroposterior and lateral views of the affected area. Usually, the findings are anterior eccentric lytic tibial lesions in children that often lead to tibial bowing. The location is usually in the diaphysis of the tibia with no periosteal reaction. It is usually confined to the anterior cortex. The essential radiographic priority is to differentiate OFD from adamantinoma.

Osteofibrous dysplasia is mostly found in the diaphysis of the tibia in patients aged <20 years. It usually involves the anterior cortex of the tibia and may cause anterior bowing of the tibia. OFD mainly manifests as an intracortical lytic lesion in the tibia, which has well-circumscribed edges and is occasionally surrounded by a zone of sclerosis. Multiple lucencies may be present within the cortex and in between some sclerotic areas. The involved cortex of the tibia may be expanded or thickened. Periosteal reaction is very rare, but if present, it is thick and solid appearing. OFD rarely progresses radiographically during childhood, and progression stops when the child reaches skeletal maturity.[6]

The typical radiographic findings of OFD show eccentric, well-circumscribed osteolytic lesions with a sclerotic border in the anterior cortex of the tibial diaphysis. As the tumor progresses, it shows a longitudinal spread to the metaphysis. Cortical expansion and intramedullary extension may occur and can lead to an anterior bowing deformity of the tibia. While radiographic findings of OFD are well-known, magnetic resonance imaging (MRI) findings of OFD have not been fully described in the literature.[10][11]

OFD typically appears as an osteolytic lesion with lobular loculations and a bubbly appearance with well-circumscribed sclerotic edges. It usually involves the anterior diaphyseal cortex of the tibia or fibula with nearby cortical expansion. Intramedullary involvement and anterior bowing deformity are common complications as the lesion progresses.[12][13]

On MRI, the signal intensity of OFD is intermediate on T1 and intermediate to high on T2- weighted images. The cells, collagen density, and degree of mineralization in the osteoid matrix may cause the signal intensity. Additional hemorrhagic or cystic, myxoid change and even cartilaginous differentiation can modify the signal intensity and contribute to a heterogeneous signal intensity on T2-weighted images. However, OFD does not always show such different signal intensity patterns and is similar to other tumors with fibroblastic stroma. The relatively well-enhanced pattern is likely a reflection of rich fibrovascular stroma, and it is similar to other fibrous tumors.[14][15]

MRI may help in differentiating other tumors or tumor-like lesions, which can simulate OFD in radiological features. Regarding small and unilocular OFD, osteoid osteoma, intracortical abscess, and intracortical hemangioma are the primary differential diagnoses. Regarding multilocular OFD, the differential diagnosis includes adamantinoma, an aneurysmal bone cyst, intracortical fibrous dysplasia, and osteoblastoma.

Osteoid osteoma: Compared to OFD, osteoid osteoma shows more extensive marrow and soft tissue edema concerning its nidus size. An intracortical abscess shows peripheral rim enhancement compared with the diffuse enhancement pattern of OFD on contrast-enhanced MR images. 

Intracortical hemangioma contains lattice-like coarse trabeculations and fatty components.  

Aneurysmal bone cyst commonly shows fluid levels and marginal septal enhancement, while OFD shows diffuse enhancement.

Osteoblastoma, which involves the long bones, frequently accompanies extensive perilesional marrow and soft tissue edema.

Cortical-based fibrous dysplasia is common, especially in the tibia. Fibrous dysplasia is known to have hyper- or hypointense signals in T2 images depending on the components and exhibit a central or rim enhancement pattern. 

Adamantinoma has nearly the same signals as OFD on the x-ray. However, MRI findings may provide further information to differentiate both lesions.[16][17]

OFD exhibits different imaging features from lesions restricted to the cortex to more aggressive lesions with full intramedullary involvement or perilesional marrow edema. The variable MRI findings of OFD may provide the basis for differentiating OFD from adamantinoma and other bone lesions simulating as OFD.[11]

Treatment / Management

OFD is rare, and because most of the published literature is limited to case reports and small case series, definitive management recommendations are difficult to establish, and the management continues to be controversial. Because it is a benign lesion that seldom progresses during childhood and never progresses after skeletal maturity, some surgeons recommend observation without surgical intervention other than obtaining a biopsy. Bracing may be indicated to minimize deformity and prevent fracture. Surgical intervention in OFD (e.g., curettage or excision) before puberty may result in a high recurrence incidence. Surgical intervention is reserved for massive or deforming lesions or pathological fractures.[10] 

Many lesions behave in a benign manner and may remain asymptomatic. As noted, pathological fractures may occur, or the deformity may be significant enough to interfere with walking. Some progressive cases may lead to bone defects, requiring surgical intervention. Among surgical options, both curettage and localized subperiosteal excision carry the risk of recurrence, while radical excision and reconstruction may create additional morbidity such as pseudarthrosis. Furthermore, pathologic fractures may need surgical intervention.[18]

Any correction of deformity will, of course, require surgical intervention and is usually performed after skeletal maturity. The surgical options for OFD mainly include focused curettage and bone grafting with or without external fixation. Curettage is considered the most standard treatment method for benign lesions, as well as aggressive lesions. However, the bone cavity created after curettage often needs to be filled with graft, such as acrylic cement or bone grafts, to restore its mechanical stability.[5] OFD may become aggressive after an operation has been performed. Curettage or en-bloc excision with bone grafting can be used in the treatment of this lesion, but frequent recurrence has been reported. It has been noted that any progression of the lesion in OFD comes to an end after puberty and that surgery should be delayed for as long as possible and should be limited to extensive lesions.[19]

A more aggressive surgical approach for OFD is extraperiosteal resection. In one review of 16 patients diagnosed with OFD on initial biopsy, three ultimately were diagnosed with OFD-like AD or classic AD based on evaluation of the resection specimen. Thus, the authors' concluded that because of the risk of sampling error and the theory that OFD could progress to AD, all OFD lesions should be treated aggressively. An extraperiosteal approach was recommended because intralesional treatment usually is inadequate, resulting in local recurrence. However, others feel that a larger biopsy would have shown AD allowing differentiation of OFD from AD. Most authors think that the benign nature of OFD is well established and that as long as the diagnosis is correct, observation and symptomatic treatment are adequate.[10][20]

The treatment for OFD-like adamantinoma is not well established due to the scarcity of cases. Careful observation and symptomatic treatment have been suggested. Surgery does not increase the risk of recurrence or the development of metastases. The aggressive nature of OFD-like adamantinoma compared to OFD is noticed not only histologically and radiologically but also clinically, especially the degree of pain.[4]

Differential Diagnosis

The differential diagnosis of a cortical, lytic, expansile lesion can be extensive. In addition to OFD and AD, differential diagnoses include:

• Fibrous dysplasia
• Unicameral bone cyst
• Osteomyelitis
• Nonossifying fibroma
• Aneurysmal bone cyst
• Chondromyxoid fibroma
• Langerhans cell histiocytosis (i.e., eosinophilic granuloma)
• Osteosarcoma
• Chondrosarcoma
• Hemangioendothelioma
• Angiosarcoma
• Metastatic carcinoma[21] 

Clinical information, including patient age and history, as well as the location of the lesion in the tibial diaphysis, may help to narrow the differential.

Staging

Diagnosis and staging start with a detailed history and examination. The surgeon should obtain plain radiographs of the affected bone in AP and lateral views. A computed tomography (CT) scan can provide more information on the degree of cortical destruction and may reveal an occult pathologic fracture. MRI of the lesion is necessary for diagnosis and planning treatment. Extension of the lesion into the medullary canal or extraosseous soft tissues can be detected and would suggest a diagnosis of AD as opposed to OFD, in which the lesion is generally contained within the cortex. MRI is also critical in demonstrating the full proximal and distal extent of the lesion, allowing the surgeon to plan a proper operation with tumor-free margins in cases of AD.

MRI can also aid in identifying the presence of multifocal disease, such as occult involvement of the ipsilateral fibula. A well-planned biopsy should be considered to confirm the diagnosis, even if the lesion is radiographically typical for OFD. The lesion may represent early AD. Alternatively, OFD may be a precursor to AD. In either case, a biopsy would facilitate a search for an epithelial component to the tumor. A large diagnostic tissue specimen is required for an accurate diagnosis.

The biphasic nature of classic AD (i.e., benign fibrous and malignant epithelial) can lead to sampling error and to an erroneous diagnosis of a malignant AD as OFD. Therefore a large biopsy of the lesion's most radiolucent area is recommended. Immunohistochemical staining for keratin can help in identifying the scattered epithelial cells in OFD-like AD and the nests of epithelial cells in classic AD. When the biopsy shows malignant AD, the patient should be evaluated for metastatic disease. The commonest sites for metastasis are the lungs, regional lymph nodes, and other bones. Physical examination for lymphadenopathy should be performed, and a high-resolution CT scan of the thorax and nuclear bone scan should be performed.[6][22]

Prognosis

Lesions usually disappear and do not cause problems in adulthood. OFD is a benign lesion, and thus it has an excellent prognosis. However, there is evidence of a link between OFD and AD. However, several large series of patients with OFD with excellent follow-up have failed to show any case of OFD that has progressed to AD. Isolated cases have reported the progression of OFD to AD, but these may represent biopsy sampling error and initial misdiagnosis.[23][24]

Long-term surveillance is required for survivors of this low-grade, slowly progressing tumor. Local recurrence usually occurs 5 to 15 years after diagnosis, but it has been reported as late as 24 and 36 years after diagnosis. Metastases can also occur many years later, even after initial resection with wide margins and a disease-free interval of more than 10  years. Metastases are managed with surgical resection.[6]

As there is no clear evidence of progression from OFD to adamantinoma, conservative management with observation or curettage is often successful for patients with OFD and OFD-like adamantinoma. Resection with clear margins is required for patients with adamantinoma. Late tumor recurrence is not uncommon in adamantinoma, and prolonged follow-up should be considered.[4]

Complications

The most important complication of OFD is the pathological fracture, which usually occurs after mild trauma. Other complications include bone deformity, recurrence, malignant transformation, and severe pain.

Deterrence and Patient Education

Osteofibrous dysplasia is a type of benign bone tumor that is usually located in the tibial bone. It presents with painless swelling in the leg in children and is diagnosed by radiograph. Parents should be educated that it may cause a pathological fracture or bony deformity. Parents should also be counseled that a large biopsy should be obtained to differentiate between OFD and adamantinoma.

Enhancing Healthcare Team Outcomes

Osteofibrous dysplasia is seen in the first or second decades of life. More than half of all the patients are under 5 years of age. Even neonates may be affected. Osteofibrous dysplasia has a characteristic natural course. The lesion grows progressively until the patient reaches the age of 15 years. After the cessation of skeletal maturation, the lesion becomes stable or may even regress spontaneously. It is infrequent to see a patient with osteofibrous dysplasia over the age of 35 years. Management should include an interprofessional team approach with clinicians, radiologists, nurses, and possibly an oncologist, to improve outcomes.