You are in: eMedicine Specialties > Orthopedic Surgery > NEOPLASMS Osteofibrous DysplasiaArticle Last Updated: Jul 9, 2008AUTHOR AND EDITOR INFORMATIONSection 1 of 12
  Author: Robert Mervyn Letts, MD, FRCS(C), FACS, Former Chief, Department of Surgery, Division of Pediatric Orthopedics, Children's Hospital of Eastern Ontario, University of Ottawa; Consultant Pediatric Orthopedic Surgeon, Sheikh Khalifa Medical City, UAE Coauthor(s): Darin Davidson, MD, Resident, Department of Orthopedics, University of British Columbia Editors: Lynn A Crosby, MD, FACS, Chief of Shoulder Division, Professor, Department of Orthopedic Surgery, Wright State University School of Medicine; Francisco Talavera, PharmD, PhD, Senior Pharmacy Editor, eMedicine; Sean P Scully, MD, PhD, Professor, Department of Orthopedics, University of Miami; Dinesh Patel, MD, FACS, Associate Clinical Professor of Orthopedic Surgery, Harvard Medical School; Chief of Arthroscopic Surgery, Department of Orthopedic Surgery, Massachusetts General Hospital; Harris Gellman, MD, Consulting Surgeon, Broward Hand Center, Voluntary Clinical Professor of Orthopedic Surgery and Plastic Surgery, Departments of Orthopedic Surgery and Surgery, University of Miami School of Medicine Author and Editor Disclosure Synonyms and related keywords: osteofibrous dysplasia, Campanacci syndrome, Campanacci's syndrome, fibrooseous intracortical lesion, fibro-oseous intracortical lesion, fibrous dysplasia of bone, monostotic fibrous dysplasia, polyostotic fibrous dysplasia, ossifying fibroma, congenital fibrous dysplasia, congenital fibrous defect of the tibia, intracortical fibrous dysplasia, infantile pseudarthrosis of the tibia, localized osteitis fibrosa, congenital kyphoscoliotic tibia, congenital pseudarthrosis, fibrous dysplasia, adamantinoma INTRODUCTIONSection 2 of 12
  Osteofibrous dysplasia is a rare, nonneoplastic condition of unknown etiology that affects the long bones. It frequently is asymptomatic.1 Most lesions of osteofibrous dysplasia affect the cortex of the tibia, predominantly the middle third of the diaphysis (see Image 1). The cortex often is expanded and thinned, with multiple radiolucencies mixed with intervening areas of sclerosis. The second most common site of involvement is the fibula. Numerous cases of osteofibrous dysplasia affecting the tibia have been reported. Sweet et al reported 30 cases, with ipsilateral fibular involvement in 5 cases (17%).2 In another study of 10 children with tibial lesions, one case (10%) showed ipsilateral fibular involvement. Campanacci and Laus reported 35 cases; the tibia was affected in each case, with ipsilateral involvement of the fibula in 4 cases (11%).3 Further, 22 of 35 lesions (63%) affected the middle third of the tibial diaphysis. Ishida et al found 11 of 12 lesions (92%) in the tibia, with one lesion in the ulna.4 Most of these tibial lesions affected the proximal diaphysis. Bilateral involvement is rare. However, in a study of 5 children by Ozaki et al, one child presented with bilateral lesions of both ulnae and tibiae.5 The tibia was affected in the remaining 4 children, with one having ipsilateral fibular involvement. Osteofibrous dysplasia of the mandible, which occurs exclusively in adults, commonly is referred to as ossifying fibroma. History of the ProcedureFrangenheim first described the lesion in 1921 and reported it as a congenital osteitis fibrosa.8 Subsequently, Kempson reported 2 cases affecting the tibia of young children and named the lesion ossifying fibroma.9 In 1981, Campanacci and Laus studied 35 cases and coined the term osteofibrous dysplasia of the tibia and fibula.3 They proposed this term to replace the use of ossifying fibroma because of the supposed congenital origin of the condition, the histologic resemblance to fibrous dysplasia, and the apparent exclusive involvement of the tibia and fibula.10 Osteofibrous dysplasia is occasionally referred to as Campanacci syndrome. FrequencyOsteofibrous dysplasia usually is diagnosed in children under 10 years, with a peak incidence in children aged 1-5 years. Several occurrences in newborns have also been reported.11, 12 Adults diagnosed with de novo osteofibrous dysplasia have been reported, the oldest patient being age 39 years at diagnosis.2 The reported mean age at diagnosis has been variable. Sweet et al and Ishida et al reported an average age over 10 years.2, 4 In contrast, Komiya and Inoue, Ozaki et al, and Campanacci and Laus reported an average age younger than 10 years.3, 5, 13 No significant sex preponderance has been reported consistently, although several studies have found a slight male predilection. Sweet et al reported 16 males in their 30 patients.2 Campanacci and Laus noted that 21 of 35 patients (60%) in their series were male.3 This represents the largest reported sex preponderance. In contrast, Park et al reported 38 males and 42 females in their series of 80 patients.14 EtiologyThe etiology of osteofibrous dysplasia, as well as the cell of origin, is unknown. Only one description of familial osteofibrous dysplasia has been reported.15 Osteofibrous dysplasia has been postulated to arise from a fibrovascular abnormality. Johnson proposed a relationship between osteofibrous dysplasia and adamantinoma on the basis of a common causative factor—namely, a fibrovascular defect.16 According to this theory, osteofibrous dysplasia results from an abnormality in the Haversian canals, whereas adamantinoma develops secondary to a defect of intramedullary vasculature. Komiya and Inoue reported similar findings and suggested a deficiency in blood flow within the periosteum as the etiologic factor in osteofibrous dysplasia.13 Bridge et al investigated the cytogenetics of osteofibrous dysplasia.17 They reported trisomy 12 in 2 distinct specimens from a lesion in an 11-year-old boy and trisomy 7, 8, and 22 in another boy. Studies of adamantinoma have revealed trisomy 7 and 12, suggesting a relationship between osteofibrous dysplasia and adamantinoma. Sherman et al reported the coexistence of adamantinoma and osteofibrous dysplasia in the same patient, providing additional evidence of a relationship between these 2 entities.18 Several other abnormalities have been found within adamantinoma lesions; consequently, these chromosomal anomalies may not be pathogenetic.19, 20 On the other hand, Sakamoto et al have shown mutations at the Arg 201 codon in persons with fibrous dysplasia but not in persons with osteofibrous dysplasia, suggesting a different pathogenesis for each lesion.21 ClinicalClassically, osteofibrous dysplasia has been described as painless, with a localized, firm swelling of the tibia as the presenting complaint. The tibia frequently is bowed anteriorly or anterolaterally.22 Park et al reported that of 80 patients, 25% complained of pain, 12.5% had a pathologic fracture, 8.8% presented with tibial swelling, and 6.2% presented with deformity.14 Sweet et al reported that 18 of 30 patients (60%) presented with complaints of pain, 13 (43%) with swelling, and 4 (13%) with deformity.2 One lesion was an incidental finding. Komiya and Inoue reported similar presenting complaints in a series of 10 cases.13 Ishida et al reported a duration of symptoms in 11 of 12 patients ranging from 2 months to 5 years, with an average of 14 months; one lesion was asymptomatic.4 Of 3 newborns with osteofibrous dysplasia of the tibia, 2 had swelling and 1 had pathologic fracture. Differential diagnosis The differential diagnosis of osteofibrous dysplasia includes monostotic fibrous dysplasia, nonossifying fibroma, and adamantinoma. Fibrous dysplasia can be differentiated on the basis of several characteristics. Generally, it occurs in patients older than 10 years, more commonly affects the femur and ribs, and does not resolve spontaneously. Radiographically, fibrous dysplasia appears as an intramedullary lesion with a ground-glass appearance.23 On histologic examination, fibrous dysplasia is not bordered by active osteoblasts and is cytokeratin-negative.24 Cytogenetically, fibrous dysplasia is related to anomalies affecting chromosomes 3 and 5. Sakamoto et al found that immunoreactivity for osteonectin in bone matrix is seen more commonly in osteofibrous dysplasia.25 Nonossifying fibroma can be distinguished from osteofibrous dysplasia by several typical features. Nonossifying fibroma predominantly is a metaphyseal lesion. Histologically, it is characterized by a storiform pattern of spindle cells with scattered multinucleated giant cells, is not bordered by active osteoblasts, and is cytokeratin-negative. More challenging is the distinction between osteofibrous dysplasia and adamantinoma. Accurate differentiation between these 2 lesions is essential for correct diagnosis and appropriate treatment. Adamantinoma has a similar predilection for the cortex of long bones, particularly the tibia, and may have radiologic and histologic findings similar to those of osteofibrous dysplasia.26, 27 However, adamantinoma can be distinguished from osteofibrous dysplasia by the presence of soft-tissue extension, intramedullary involvement, periosteal reaction in the absence of pathologic fracture, and the histologic finding of hyperchromatic epithelial islands. Adamantinoma typically manifests with a larger, more painful lesion and is usually found in patients older than 10 years. However, as suggested by Kuruvilla and Steiner, it is likely that osteofibrous dysplasia is part of the morphologic spectrum of adamantinoma.28 Kanamori et al found that extra copies of chromosomes 7, 8, 12, 19, and 21 recur in adamantinoma.29 These aneuploidies may be useful in differentiating adamantinoma from osteofibrous dysplasia. INDICATIONSSection 3 of 12
Due to the high recurrence rate, many authors advocate nonoperative treatment of the lesion until after skeletal maturity is reached, at which time marginal resection and bone grafting may be performed without increased risk of recurrence. For patients of any age, surgical correction of associated deformities may be required. Surgery may be indicated if the lesion is aggressive or if the patient experiences multiple pathologic fractures. Resection of large portions of the lesion usually is not necessary and only increases susceptibility to recurrent fractures. RELEVANT ANATOMYSection 4 of 12
The tibia is a tubular long bone with a triangular shape in cross section. The bone is surrounded by 4 fascial compartments. The anteromedial surface lies subcutaneously and therefore has no soft-tissue protection. The primary center of ossification appears at 7 weeks of gestation. The proximal ossific nucleus appears soon after birth and fuses with the metaphysis at approximately age 16 years. The distal ossific nucleus appears at age 2 years and fuses at age 15 years. In some, separate centers of ossification exist for the medial malleolus and tibial tubercle. The vascular supply to the tibia is provided predominantly by the posterior tibial artery, from which the nutrient artery enters the tibia at the origin of the soleus muscle along the oblique line of the tibia. The nutrient artery of the tibia has 3 ascending branches and 1 descending branch. The distal aspect of the tibia is supplied by periosteal anastomoses that enter the bone adjacent to the ankle joint. CONTRAINDICATIONSSection 5 of 12
Though nonoperative management is recommended in patients who are skeletally immature, there are no absolute contraindications to surgical intervention in children, with the exception of any underlying medical or anesthetic issues. Operative management is not recommended in patients who are skeletally immature, because of the high recurrence rate following resection and curettage and because of the predisposition to fracturing after the bone has been weakened by biopsy. Pathologic fracture does not necessarily require surgical management, since cast immobilization frequently results in good healing. WORKUPSection 6 of 12
Lab Studies
Imaging Studies
Diagnostic Procedures
Histologic FindingsDespite the characteristic radiographic appearance, Wang et al recommended that diagnosis should be based on biopsy and pathologic examination (see Image 3).6 At the time of surgery, inspection reveals an intact periosteum. The cortex is thinned and may be perforated. The lesion itself is composed of soft, granular tissue that is whitish-yellow in color. Histologic characteristics of osteofibrous dysplasia have been described well in the literature. The overall appearance is that of zonal architecture. The lesion is fibrous at its center, with immature woven bone trabeculae. Vascular channels have been described within the lesion (see Image 4). At the periphery, a prominent border of active osteoblasts rims the bony trabeculae. The presence of such a border is a differentiating factor between osteofibrous dysplasia and fibrous dysplasia, in which there is no border of active osteoblasts (see Image 5). As examination proceeds from the center of the lesion to the periphery, the bone trabeculae become larger and more lamellar in appearance. Fibroblasts in the lesion have been noted to be well-differentiated. Several studies have reported cytokeratin-positive elements on immunohistochemical staining. Occasional hemorrhagic zones, cysts, or foci of cartilaginous differentiation have been reported. Multinucleated giant cells have also been observed. TREATMENTSection 7 of 12
Medical therapyNonoperative treatment usually is recommended until skeletal maturity is reached. Recurrent pathologic fractures may be an ongoing problem in some active children. Using a tibial brace similar to those used for congenital pseudarthrosis of the tibia may minimize recurrent pathologic fractures. A lace-up leather support from just below the knee to the ankle may be used. Fractures usually are nondisplaced and can be treated in a walking patellar tendon-bearing cast. Cast immobilization is sufficient for fracture healing, though healing is slower than normal. Surgical therapyA characteristic of this lesion is the high recurrence rate following resection and curettage. Thus, many authors advocate nonoperative treatment of the lesion until after skeletal maturity is reached, at which time marginal resection and bone grafting may be performed without increased risk of recurrence.30, 31 For patients of any age, surgical correction of associated deformities may be required. Campanacci and Laus recommended wide resection with extensive bone grafting in children who are skeletally immature if the lesion is aggressive, with marked expansion and bone destruction or multiple pathologic fractures.3 Intramedullary prophylactic rodding of the tibia may also be an option in children who frequently present with fractures; this approach is similar to that used in osteogenesis imperfecta. Resection of large portions of the lesion usually is not necessary and only increases susceptibility to recurrent fractures. COMPLICATIONSSection 8 of 12
The recurrence rate after resection and curettage has been reported to be 64-100%. Goergen et al reported multiple recurrences in a 3-year-old boy and a 6-month-old boy following attempts at resection.32 Wang et al also reported multiple recurrences following surgical intervention.6 Campanacci and Laus indicated that recurrence does not occur in patients older than 10 years.3 Malignant transformation of the lesion is very rare. Ben Arush et al described the course of a boy diagnosed at age 4 years with osteofibrous dysplasia of the tibia who subsequently presented at age 14 years with synovial sarcoma of the peroneal muscles of the same leg.33 At the time of the latter diagnosis, CT scan confirmed multiple pulmonary metastases. Malignant transformation to soft-tissue sarcoma has been reported in fibrous dysplasia, most commonly in the polyostotic variation.34, 35, 36 However, the case reported by Ben Arush et al is the only report of sarcomatous degeneration of osteofibrous dysplasia. OUTCOME AND PROGNOSISSection 9 of 12
The natural history of osteofibrous dysplasia is unpredictable.37 The growth rate can vary from slow to rapid, and spontaneous resolution is possible. Campanacci and Laus reported 3 common clinical courses: (1) moderate progression, particularly during the first 5-10 years of life; (2) aggressive growth, with resulting marked deformity; and (3) spontaneous resolution. Most commonly, there is continued growth of the lesion until skeletal maturity is reached, with the most rapid period of growth occurring before age 10 years. In most cases, moderate progression is followed by gradual improvement once skeletal maturity is attained. FUTURE AND CONTROVERSIESSection 10 of 12
Osteofibrous dysplasia and adamantinoma have similar clinical presentations, as well as similar radiologic and pathologic findings. Although adamantinoma can sometimes have the appearance of a low-grade osteogenic sarcoma, osteofibrous dysplasia does not exhibit histologic characteristics of malignancy. There may be histologic gradations between osteofibrous dysplasia, benign adamantinoma, and the malignant appearance of more aggressive adamantinoma, which usually is encountered in adults. In the latter, osteoid production with cellular mitoses may give the appearance of an osteogenic sarcoma and, indeed, may progress to frank malignancy. Because the clinical course and radiologic appearance of osteofibrous dysplasia are diagnostic in children, biopsy seldom is indicated and should be avoided, if possible. In patients presenting at skeletal maturity, in whom the incidence of adamantinoma is higher, biopsy of the mid portion of the lesion may be necessary for diagnosis. Complete resection of the entire lesion of osteofibrous dysplasia is neither recommended nor necessary. Several authors have investigated the possible relationship between adamantinoma and osteofibrous dysplasia.38, 39 Dockerty and Meyerding first reported a relationship between benign fibro-osseous lesions and adamantinoma.40 Markel was the first to investigate this relationship thoroughly.41 Subsequently, 3 cases of tibial adamantinoma that mimicked osteofibrous dysplasia were reported, 2 of which occurred in children younger than 10 years.42 Several investigators have proposed that osteofibrous dysplasia represents a benign form of adamantinoma or that it is the result of a resolved adamantinoma.43 Czerniak et al described an intracortical lesion with pathologic findings similar to those of osteofibrous dysplasia, which they termed differentiated adamantinoma.44 Further, they described differentiated adamantinoma as affecting individuals younger than those with classic adamantinoma. Czerniak et al and Springfield et al reported that differentiated or osteofibrous dysplasia-like adamantinoma can progress to adamantinoma.44, 45 Thus, these lesions may represent intermediates in a continuum from osteofibrous dysplasia to adamantinoma.46, 47
Findings supporting a relationship are in conflict with an investigation by Park et al, who reported no progression from osteofibrous dysplasia to adamantinoma and who contend that osteofibrous dysplasia is distinct from adamantinoma.14 They did, however, suggest that osteofibrous dysplasia might be related to fibrous dysplasia, because 2 cases in their series transformed from osteofibrous dysplasia to monostotic fibrous dysplasia. Several reports on the pathology of adamantinoma have shown that the lesion may have areas similar in appearance to osteofibrous dysplasia.49 This finding suggests the potential for misdiagnosis in cases of inadequate biopsy. Such misdiagnosis may explain the reports of progression of osteofibrous dysplasia to adamantinoma. Thus, Springfield et al suggested that histologic diagnosis of osteofibrous dysplasia should be regarded with caution.45 Hazelbag et al advocated biopsy of the center of the lesion to avoid such an error, while Sweet et al suggested examination of the entire specimen to identify areas consistent with adamantinoma.2, 48 MULTIMEDIASection 11 of 12
REFERENCESSection 12 of 12
Osteofibrous Dysplasia excerpt Article Last Updated: Jul 9, 2008 | ||||||||||||||||||||||||||||||||||||||||
