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osteofibrous dysplasia

Friday 16 April 2004

Ossifying fibroma, osteofibrodysplasia, cortical osteofibrous dysplasia (COFD); differentiated adamantinoma; OFD

Digital slides

- HPC:58 : osteofibrous dysplasia

Definition: Osteofibrous dysplasia, also known as "ossifying fibroma", is a benign fibrous tumor with local aggressive behavior. It is self-limiting, deformity-producing proliferation of bone and fibrous tissue invoiving the tibia or fibule of infants and children.

Although Osteofibrous dysplasia has been considered in the past to be a variant of fibrous dysplasia, it has a quite different presentation.

Osteofibrous dysplasia (OFD) occurs almost exclusively in the tibia and/or fibula, although rarely the forearm bones are involved.

It is most often seen in young children who present with cortical tumors that may be rapidly enlarging but are usually painless.

The deformity of the involved leg may be dramatic, and clinically, the lesion initially behaves in an aggressive fashion.

However, the natural history of this lesion is that it behaves less aggressively as the child gets older.

Nosology

Although Osteofibrous dysplasia has been considered in the past to be a variant of fibrous dysplasia, it has a quite different presentation.

Osteofibrous dysplasia is a rare, clinicopathologically distinct lesion whose variable nomenclature has led to unnecessary confusion.

Osteofibrous dysplasia differs clinically and microscopically from both ossifying fibrome of the jaws and fibrous dysplasia, despite the fact that such terms as "ossifying fibroma of long bones" and "intracortical fibrous dysplasia" have been applied te these lesions.

It is unclear whether this is a benign, self-limited, occasionally regressing neoplasm, or a non-neoplastic anomaly related to bone growth, which seems far more likely, given the invariable lack of progression aller skeletal maturation.

Malignant transformation has not been reported.

The question has been raised if ossifying fibroma is a relative of fibrous dysplasia or a true neoplasm.

Epidemiology

Ossifying fibroma occurs during the first decade of life and presents clinically as a painless, enlarging mass.

Osteofibrous dysplasia is almost invariably diagnosed during the first decade of life, usually in the first 5 years, and occasionally shortly alter birth.

Resnik et al. identified 79 cases only 4 of which occurred after the age of 16 years (18 to 22 years). There maybe a slight male predilection.

Localization

The most common site in adults is the mandible.

The most common site in children is the tibia, followed by other long bones.

On long bones, osteofibrous dysplasia (OFD) occurs almost exclusively in the tibia and/or fibula, although rarely the forearm bones are involved. The great majority affect the tibia with fibular involvement being much less common. The process is almost always confined to one tibia, but occasionally the ipsilateral fibula is also involved. Rarely are both tibias or fibulas involved.

Clinical synopsis

It is most often seen in young children who present with cortical tumors that may be rapidly enlarging but are usually painless.

The deformity of the involved leg may be dramatic, and clinically, the lesion initially behaves in an aggressive fashion. However, the natural history of this lesion is that it behaves less aggressively as the child gets older.

Osteofibrous dysplasia presents as a painless enlargement of the involved bone that can lead to bowing and, occasionally, pseudoarthrosis or pathologic fracture.

Radiology

Imaging studies show that the lesion is usually extensive, involving the anterior cortex either of the diaphysis or the metaphysis of the tibia; the epiphysis is usually not affected.

Characteristic eccentric intracortical osteolysis, with distortion and thinning of the cortex, is usually evident and the cortical bone may actually be absent in places. Anterior bowing of the tibia is common, as is a multiloculated appearance. The periosteum is usually well preserved.

Ossifying fibroma has a distinctive radiologic picture. The radiographic appearance of osteofibrous dysplasie is often diagnostic, or at least highly eharacteristic.

This lytic lesion occurs in the anterior cortex of the diaphysis or metaphysis of the tibia and often causes anterior-posterior bowing. There is an expanded, lucent defect centered in the cortex and involving the diaphyseal portion of the bone. The anterior cortical surface is commonly involved.

Even when large, the lesion is separated from the medullary cavity by a rim of reactive bone of variable thickness, along the distorted inner cortical margin. The outer cortical bone may be thin or, occasionally, absent.

The reactive changes surrounding the lesion often result in considerable perilesional sclerosis.

Osteofibrous dysplasia may consist of a single lucent area, but more often there are multiple, confluent, bubble-like lucencies. Rarely, there may be multifocal or diffuse involvement of the entire tibia.

Tibial disease almost invariably produces a severe anterior bowing deformity. Anterior bowing of the tibia is common, as is a multiloculated appearance. The periosteum is usually well preserved.

In patients followed into puberty or adulthood the resultant chronic radiographic changes resemble Paget disease.

Imaging studies show that the lesion is usually extensive, involving the anterior cortex either of the diaphysis or the metaphysis of the tibia; the epiphysis is usually not affected.

Characteristic eccentric intracortical osteolysis, with distortion and thinning of the cortex, is usually evident and the cortical bone may actually be absent in places.

This well-circumscribed tumor has a multi-loculated appearance and causes distortion of the thin cortex.

Ossifying fibromas have increased uptake on bone scan.

The radiologic differential includes:

- adamantinoma of long bones
- fibrous dysplasia
- nonossifying fibroma
- osteoblastoma

Macroscopy

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.

The lesional tissue is soft, fibrous, and may be white, yellow, or red. If sufficient osteoid is present there may be a gritty consistency.

In rare, completely resected specimens the overlying, reactive periosteum is intact, even if there has been extension beyond the cortex.

Microscopy

The histologic appearance of the affected tissue is somewhat similar to that seen in fibrous dysplasia, with irregular spicules of trabecular bone and unremarkable spindle cells that produce a collagenous stroma.

However, in contrast to fibrous dysplasia, the bone spicules are characteristically lined with osteoblasts that may produce a rim of lamellar bone, even though the center of these spicules of bone may have a woven appearance.

Irregular spicules of trabecular bone are lined by osteoblasts. These osteoblasts produce a rim of lamellar bone around centers of woven bone.

The overall appearance is that of zonal architecture. The lesion is fibrous at its center, with immature woven bone trabeculae. 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.

In some areas, the surface is covered by more lamellar bone with a core of woven bone. This finding of peripheral maturation is characteristic of osteofibrous dysplasia.

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.

Vascular channels have been described within the lesion.

Foci of hemorrhage and foamy histiocytes, as well as an occasional area of cartilage (usually in the vicinity of a fracture), may be observed.

Foci of cartilage are rarely seen in the absence of fracture. Plump osteoblasts rimming bony trabeculae are conspicuous in every zone.

Osteoclasts are sometimes adjacent to the bone.

Multinucleated giant cells have also been observed. Focal collections of giant cells may be present in the fibrous stroma, probably in response to microhemorrhages, in a pattern reminiscent of giant cell reparative granuloma (GCRG).

Zonation phenomenon

Campanacci and Laos have described a "zonation phenomenon" visible in larger, well-oriented specimens obtained by wedge biopsy.

The central portion of the lesion has a predominantly fibroblastic appearance with only occasional, short, thin, immature trabeculae of woven bone.

Moving toward the periphery in any direction, there is a progressive widening of trabeculae and conversion to lamellar bone.

As the trabeculae become more numerous, they frequently anastomose and ultimately merge with the surrounding reactive cortical bone at the edge of the lesion.

Extragnathic adamantinoma (adamantinoma of long bones)

There is a well-documented but poorly understood relationship between osteofibrous dysplasia and extragnathic adamantinoma (adamantinoma of long bones).

Most recently, it has been surmised that ossifying fibroma and adamantinoma are on a continuum with osteofibrous dysplasia-like adamantinoma representing an intermediate step between the two lesions.

Findings indicate that OFD, DA, and adamantinoma, should be regarded as related conditions. However, only rarely does a case of OFD or DA eventually act in a malignant fashion.

Genetic studies have also pointed to a relationship between OFD and adamantinoma in that the tumors have been found to share recurrent trisomies (chromosomes 7, 8, 12, and 21).

OFD is certainly a distinct entity from fibrous dysplasia. Although most of the cases behave in a benign way, they may need surgery for the correction of deformity. However, it is generally held that surgery should be withheld until after puberty.

Synopsis

- cellular spindle cell stroma
- spicules of immature bone
- prominent osteoblastic rimming
- focally rimming of mature bone spicules by osteoblasts
- In some areas, the surface is covered by more lamellar bone with a core of woven bone. This finding of peripheral maturation is characteristic of osteofibrous dysplasia.
- Some cells in ossifying fibroma positive for cytokeratin.
- bony trabeculae showing prominent osteoblastic rimming
- fibrous background

  • fibrous tissue variably cellular
  • delicate collagen fiber deposition
  • more densely packed bands of collagen.

- spectrum of appearances, depending on the state of lesional maturation

Immunochemistry

Sweet and colleagues noted that single, cytokeratin-positive cells were present in 93 percent of 30 cases of osteofibrous dysplasia.

In some cases of osteofibrous dysplasia, immunoperoxidase staining shows single keratin-positive cells within the fibrous matrix.

Using immunohistochemical stains for cytokeratin, it has been shown that in some cases of OFD, it is possible to demonstrate isolated and very occasionally small nests of cytokeratin-positive cells scattered in the matrix.

In a few cases of OFD, nests of epithelial cells may be readily found without histochemical staining, and these cases have been designated as differentiated adamantinomas (DA).

Ultrastructure

Electron microscopy has demonstrated occasional cells with tonofilaments, even in the absence of cytokeratin-positive stains.

These findings indicate that OFD, DA, and adamantinoma, should be regarded as related conditions.

However, only rarely does a case of OFD or DA eventually act in a malignant fashion.

Genetic studies have also pointed to a relationship between OFD and adamantinoma in that the tumors have been found to share recurrent trisomies (chromosomes 7, 8, 12, and 21).

OFD is certainly a distinct entity from fibrous dysplasia. Although most of the cases behave in a benign way, they may need surgery for the correction of deformity.

However, it is generally held that surgery should be withheld until after puberty.

Differential diagnosis

Osteofibrous dysplasia may be confused with fibrous dysplasia or adamantinoma.

- osteofibrous lesions of bone

  • fibrous dysplasia of bone
    • Fibrous dysplasia tends to occur in older individuals, shows no predilection for the tibia or fibula, and lacks the prominent osteoblastic rimming that surrounds virtually every trabecula in osteofibrous dysplasia.
    • Radiographically, fibrous dysplasia involves the medullary portion of the bone, whereas osteofibrous dysplasia is an intracortical lesion.
  • adamantinoma
    • Both osteofibrous dysplasia and adamantinoma show a striking, if not exclusive, predilection for the diaphyseal region of the tibia and fibula.
    • Furthermore, adamantinomas may contain large osteofibrous dysplasia—like areas. In some cases, the epithelial component may be minimal and easily overlooked microscopically.
    • Conversely, as noted above, single cytokeratin¬positive cells are very common in osteofibrous dysplasia, and, in the absence of epithelial is¬lands, do not warrant a diagnosis of adamantinoma.
    • The low-grade malignancy of adamantinoma, as opposed to the self-limited nature of osteofibrous dysplasia, mandates that this distinction be made.
    • Initial diagnosis of osteofibrous dysplasia in an adolescent should be approached with caution and careful search made for any adamantinoma component.

Variants

- psammomatoid ossifying fibroma (14750354)
- cemento-ossifying fibroma

Cytogenetics

- clonal aberrations fusing breakpoints on Xq26 and 2q33 (#15022060 #)

- trisomy 7 (8156503)
- trisomy 8 (10079250, 15022060)
- trisomy 12 (8156503, 15022060)
- trisomy 20 (10079250)
- tumoral trisomy 21 (15022060, 15022060)
- tumoral trisomy 22 (8156503)

Treatment and managment

Treatment of ossifying fibroma in older patients includes conservative curettage. A thorough pathologic examination must be done for the presence of adamantinoma.

Patients who still have open growth plates are observed. If bowing of the tibia becomes an issue, bracing is recommended. Ossifying fibroma does not metastasize.

Osteofibrous dysplasia can become stationary or spontaneously regress during childhood, or slowly enlarge to involve most of the tibia.

Enlarging lesions do so primarily during the first 10 years of life; progression does not occur after skeletal maturity.

Surgical resection is rarely necessary and should be avoided, especially during childhood; attempts atsurgical treatment prior to 15years of age nearly always lead to recurrences.

Biopsy is often unnecessary, given the stereotypical clinicoradiographic features.

Fractures should be treated by cast immobilization.

The bowing deformity may be treated by an osteotomy and, if the deformity is severe, should be done as soon as feasible.

Links

- bonetumors.org
- eMedecine

See also

- osteofibrous lesions of bone (benign fibro-osseous lesions of bone)

References

- Parham DM, Bridge JA, Lukacs JL, Ding Y, Tryka AF, Sawyer JR. Cytogenetic distinction among benign fibro-osseous lesions of bone in children and adolescents: value of karyotypic findings in differential diagnosis. Pediatr Dev Pathol. 2004 Mar-Apr;7(2):148-58. PMID: 15022060

- Maki M, Saitoh K, Horiuchi H, Morohoshi T, Fukayama M, Machinami R. Comparative study of fibrous dysplasia and osteofibrous dysplasia: histopathological, immunohistochemical, argyrophilic nucleolar organizer region and DNA ploidy analysis. Pathol Int. 2001 Aug;51(8):603-11. PMID: 11564214

- Bridge JA, Dembinski A, DeBoer J, Travis J, Neff JR. Clonal chromosomal abnormalities in osteofibrous dysplasia. Implications for histopathogenesis and its relationship with adamantinoma. Cancer. 1994 Mar 15;73(6):1746-52. PMID: 8156503

- Cortical osteofibrous dysplasia of long bone and its relationship to adamantinoma. A clinicopathologic study of 30 cases. Sweet DE, Vinh TN, Devaney K. Am J Surg Pathol. 1992 Mar;16(3):282-90. PMID: 1599019

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