Nonossifying Fibroma

Nonossifying fibroma (NOF) is one of the most common benign bone lesions in children and adolescents. It is also known as metaphyseal fibrous defect, cortical desmoid, or fibrous cortical defect. While historically considered a reactive and non-neoplastic lesion, it is now recognized as a true neoplasm driven by activating mutations in the MAPK pathway (commonly involving the KRAS, FGFR1, and/or NF1 genes). Typically occurring in the metaphysis of long bones (especially the distal femur and proximal tibia), NOFs are generally asymptomatic and often discovered incidentally via imaging.  Very large lesions may rarely present with mechanical pain or pathological fracture. These lesions are self-limiting and tend to resolve spontaneously before or during growth plate closure in most individuals. As such, surgery is limited to large lesions causing mechanical pain or those presenting with pathological fracture.

Epidemiology

Nonossifying fibromas are the most common benign bone tumors in children and adolescents, accounting for 30-40% of all pediatric bone lesions. They display a slight male predominance, with a male-to-female ratio of approximately 1.5:1. NOFs are typically diagnosed between ages 4-14, with peak incidence during periods of rapid skeletal growth. Population studies suggest that up to 30% of children may develop these lesions, though the true prevalence is likely higher due to the asymptomatic and often undetected nature of many cases. Multiple NOFs (typically defined as three or more lesions) occur in approximately 5% of individuals and may be associated with specific syndromes.

Clinical Features

Nonossifying fibromas typically originate in the metaphysis of long bones, adjacent to the growth plate. As the growth plate grows away from the lesion, the NOF extends along the long axis of the bone and gradually becomes encased by sclerotic bone. In the course of external remodeling, the lesion that was initially metaphyseal and intra-medullary becomes meta-diaphyseal and intra-cortical as the cortex grows into the lesion. Once the lesions are intra-cortical, most go on to heal.  Most NOFs are discovered incidentally during imaging for unrelated issues, as they are usually asymptomatic. Larger lesions, typically those involving over 50% of the diameter of the bone, may cause symptoms such as mechanical pain, localized stress reaction, or, in some cases, a pathologic fracture due to structural weakening of the affected bone.

Radiologic Features

On plain x-rays, nonossifying fibromas appear as lytic lesions with well-defined, sclerotic margins (Figure 1). They typically measure less than 3 cm in their greatest dimension, though larger lesions can occur. The classic appearance is described as having a geographic margin with a lobulated pattern and surrounding sclerosis.

NOFs typically originate in an eccentric position within the metaphysis, adjacent to the growth plate. Over time the lesion ceases to grow but with external remodeling, the cortical bone “grows” into the lesion, as the lesion shifts from a metaphyseal intramedullary position to a metadiaphyseal intracortical one (Figure 2). This remodeling process follows Wolff’s law where bone grows along lines of mechanical stress. During the remodeling phase, there can be a period of mechanical weakening as the cortex thins over the lesion. This increases the risk of stress reactions or fracture, particularly when the lesion involves >50% of the bone diameter.

Centrally located NOFs are less common and demonstrate different remodeling patterns. A centrally positioned lesion may take longer to reach the cortex, if it does at all. In some centrally located NOFs, bone formation appears just proximal to the lesion (indicating healing), while sclerosis is seen extending away from the lesion, reflecting its original adjacency to the growth plate.

Magnetic resonance imaging (MRI) and computed tomography (CT) are generally unnecessary for diagnosing NOFs, as plain x-rays typically provide sufficient radiologic detail.  Biopsies are usually not needed as the diagnosis can typically be made via x-rays of the lesion. MRI may be helpful if the patient is symptomatic and the possibility of a superimposed stress reaction or stress fracture must be considered.

Pathology

Grossly, NOFs appear as well-circumscribed, yellow to brown lesions with a firm, fibrous consistency. Microscopically, the lesion is characterized by an irregular distribution of giant cells within a proliferative backdrop of fibroblastic cells (Figure 3). The fibroblastic cells are arranged in a characteristic storiform (whorled) pattern and display spindle-shaped nuclei. These cells often contain cytoplasmic hemosiderin, which contributes to the lesion’s brown coloration, and are separated by varying amounts of collagen deposition. The osteoclast-like giant cells typically contain fewer nuclei (3-8 per cell) than those seen in giant cell tumor of bone. Additionally, in nonossifying fibroma, the nuclei of the giant cells are round, in contrast to the long, spindled nuclei of the background stromal cells. This is unlike giant cell tumor of bone, where  the nuclei of the giant cells and the stromal cells are both round.

Differential Diagnosis

Nonossifying fibroma is rarely mistaken for other lesions. It is thus considered one of the ‘do not touch’ lesions – tumors whose radiographic appearance is so distinctive (in the context of patient age and lesion location) that biopsies and other tests are unnecessary.

In rare instances, small NOFs can mimic fibrous dysplasia, while large tumors in the proximal tibia can mimic chondromyxoid fibroma. Fibrous dysplasia typically shows a more homogeneous ‘ground-glass’ appearance without the well-defined sclerotic borders characteristic of NOF, while chondromyxoid fibroma tends to have a more lobulated appearance and, unlike NOF, may cross the growth plate to involve the epiphysis. In cases where the diagnosis is uncertain, biopsy is usually needed for confirmation.

Disease Course: Treatment and Prognosis

Since nonossifying fibromas are benign and self-limiting, observation is the mainstay of treatment. The natural history is spontaneous resolution, typically occurring before or during growth plate closure. Asymptomatic lesions require only periodic radiographic monitoring until resolution. However, patients presenting with mechanical pain should be evaluated for stress reaction using MRI, particularly with fat-suppressed T2 sequences. If stress reaction is present (indicated by increased signal around the tumor), a short period of restricted weight-bearing typically allows for healing.

Large lesions (those involving more than 50% of the bone’s transverse diameter) may require intervention in specific circumstances. Persistent mechanical pain unresponsive to restricted weight-bearing may warrant intralesional  curettage and bone grafting. In the rare case of displaced pathologic fracture, fracture management is required; however, the fracture healing process usually generates sufficient new bone that specific treatment of the underlying NOF may become unnecessary.

Key Test Topics

• Nonossifying fibromas appear as eccentric, metaphyseal, lobular lesions with a sclerotic border. X-rays are usually sufficient to make a diagnosis and they do not require further imaging or biopsy, given their characteristic radiographic appearance and that they often resolve spontaneously as the patient reaches skeletal maturity.
• Lesions involving more than 50% of the transverse diameter of the bone may require intervention with curettage and bone grafting. If there is a pathologic fracture, it can often be managed with standard age-appropriate fracture care without specific treatment of the NOF.