Fibrous Dysplasia

Fibrous dysplasia is a benign condition in which normal bone is replaced by fibrous tissue and abnormal bone. It is a disorder of the bone-forming cells called osteoblasts which produce immature woven bone in a nonsensical “alphabet soup” pattern instead of normal mature bone. Fibrous dysplasia is often found incidentally although it occasionally presents with symptoms of bone weakness such as mechanical pain and impending pathological fracture. Fibrous dysplasia is caused by an activating missense mutation in the GNAS1 gene on chromosome 20, which encodes the Gsα protein. Although most cases are monostotic, asymptomatic, and do not require treatment. There exists a polyostotic form of fibrous dysplasia that can cause skeletal deformity or increased risk of fracture, necessitating surgical intervention. Malignant transformation is rare but usually results in the transformation of the lesion to high grade osteosarcoma.

Epidemiology

Fibrous dysplasia usually arises in childhood and adolescence and slowly grows into adulthood. Although any bone can be affected, it tends to involve long bones preferentially. Fifty to sixty percent of cases occur in the femur and tibia, 10-25% in the facial bones, and 10% in the ribs. Seventy-five percent of cases are monostotic. Fibrous dysplasia should be on the differential diagnosis for any benign appearing lesion in bone and especially for any “long lesion in a long bone.”

Clinical Features

Most cases of fibrous dysplasia are found incidentally. If the lesion causes significant cortical thinning or occurs in a weightbearing bone, patients may report mechanical pain and difficulty performing activities. If the lesion is polyostotic, patients may exhibit facial deformity due to the expansion of the facial and cranial bones. Endocrine abnormalities exist in 2-3% of patients. For example, McCune-Albright syndrome is an endocrine disorder characterized by polyostotic fibrous dysplasia, café-au-lait spots, and precocious puberty. The café-au-lait spots of McCune-Albright as having irregular, jagged borders (“coast of Maine”) in contrast to the smooth borders of neurofibromatosis (“coast of California”), and do not cross the midline. A complete medical history and thorough skin evaluation are required for this diagnosis.

Mazabraud syndrome is a rare benign disorder characterized by the association of polyostotic fibrous dysplasia with one or more intramuscular myxomas.

Radiologic Features

Fibrous dysplasia is commonly described as a “long lesion in a long bone” yet it has a very variable appearance. It can present as a small benign appearing lesion in bone similar in appearance to a nonossifying fibroma or it can be a very large, long lesion in a long bone. It is often found in the metaphysis and/or diaphysis of long bones and usually has a geographic margin with sclerotic borders. The loss of trabecular lines on x-ray is due to the replacement of trabecular bone with discontinuous trabeculae in the fibrous tissue within the marrow cavity. This gives rise to the classic “ground glass appearance” as each punctate trabeculum is a point on an x-ray and all of these points together form a ground glass appearance. Fibrous dysplasia can also result in cortical thinning and expansion (Figure 1 and 2). MRI is not a primary imaging modality for fibrous dysplasia bur rather is reserved for specific clinical questions such evaluating soft tissue extension or cortical breakthrough when malignant transformation is suspected (Figure 3). Polyostotic fibrous dysplasia occurs when the disease is present in more than one bone and often does so unilaterally. Repeated microfractures combined with repeated attempts at healing can result in deformity. For example, a varus deformity in the proximal femur, called a “shepherd’s crook deformity,” (Figure 4) can arise due to the fatigue failure of the weakened bone.

Figure 1A and 1B: X-ray of the right leg in anteroposterior (A) and lateral (B) views showing an osteolytic lesion in the proximal tibia. (Image courtesy Diagnosis and Management of Monostotic Fibrous Dysplasia of the Tibia in an Adolescent Patient: A Case Report. Cureus 16(3): e56052. doi:10.7759/cureus.56052)

Figure 2: X-ray of the left hip showing fibrous dysplasia of the proximal femur. (Image courtesy of Yi-Jin Kuok, https://radiopaedia.org/cases/17974)

Figure 3A and 3B: MRI of the right leg in anteroposterior (A) and lateral (B) views showing the lesion in the proximal tibia seen in Figure 1. (Image courtesy Diagnosis and Management of Monostotic Fibrous Dysplasia of the Tibia in an Adolescent Patient: A Case Report. Cureus 16(3): e56052. doi:10.7759/cureus.56052)

Figure 4: Shepherd’s crook deformity (courtesy https://radiopaedia.org/cases/shepherd-crook-deformity-polyostotic-fibrous-dysplasia)

Pathology

Histologic evaluation of the lesion reveals a fibrous background with woven, immature bone occurring as disconnected “alphabet soup” trabeculae (See Figures 5 and 6). Osteoblastic rimming, namely, osteoblasts lining the edges of newly formed bone trabeculae, is notably absent. (Osteoblastic rimming is a feature of osteofibrous dysplasia, a rare benign tumor-like condition that primarily affects the cortices of the tibia in patients 10 years of age or younger, presenting with painless anterior shin swelling.)

Although the spindle cell stroma can show increased cellularity, the cells are bland and benign in appearance (i.e., small, uniform, no mitoses or atypia). The convoluted shapes of the woven bone spicules have been described as “Chinese characters” and are arranged haphazardly like an “alphabet soup”. When repeated microtrauma is present, secondary reactive changes such as macrophages, foamy histiocytes, and even callus formation can be seen. Cartilage can also be seen on biopsy due to the intrinsic nature of the lesion and/or secondary reactive changes. Care should be taken to ensure that these lesions are not mistaken for a chondrosarcoma.

Figure 5: H&E stain of fibrous dysplasia at higher power, showing the fibrous stromal spindle cells and scattered woven bone trabeculae in detail. Note the absence of cytologic atypia.

Figure 6: H&E stain of fibrous dysplasia at low power, showing the classic architectural pattern of irregular, curvilinear woven bone trabeculae set in a fibrous stroma, variously described as ‘Chinese characters’ or ‘alphabet soup.’

Differential Diagnosis

The differential diagnosis of fibrous dysplasia includes unicameral bone cysts; chondromyxoid fibroma; osteo (cortical) fibrous dysplasia; and non-ossifying fibroma.

Disease Course: Treatment and Prognosis

Monostotic fibrous dysplasia is usually treated with observation and surveillance. Given the rare but real possibility of malignant transformation, an annual radiographic evaluation is reasonable, but there is no generally agreed upon follow-up schedule for this disease. Patients should be counseled that the onset of pain is a potential sign of impending fracture or malignant transformation. Patients who are in pain or at risk for pathologic fracture require intralesional curettage with bone grafting and internal fixation. Allografts, especially cortical allografts, are thought to provide the best long-term grafting result. This is because cancellous autografts are resorbed and replaced by dysplastic woven bone leading to diffuse recurrence and a high rate of failure. The successful use of polymethyl methacrylate bone cement and hydroxyapatite preparations has also been reported. Patients with polyostotic fibrous dysplasia tend to have a more aggressive disease course characterized by deformity, pain, and fracture. Surgical intervention can range from intralesional curettage with or without internal fixation for benign disease to multi-modality treatment for malignant transformation. Intramedullary nail fixation is the gold standard for weight-bearing lesions due to its load-sharing properties, and that long nails protecting the entire bone are preferred to prevent construct failure. Medical management with bisphosphonates has been shown to decrease bone turnover activity as well as the rate of fracture in small cohort studies.

Key Test Topics

Fibrous dysplasia is caused by a somatic, non-heritable mutation in the G1 alpha subunit of the G_s
Structural or cancellous bone allografts are preferred over autografts (autologous bone is rapidly absorbed).
Fibrous dysplasia should be on the differential diagnosis for any benign lesion in bone or any “long lesion in a long bone.”
Polyostotic fibrous dysplasia is associated with McCune-Albright syndrome (café au lait spots, precocious puberty).