Skeletal Dysplasias

Danielle A. Katz

Polyostotic Fibrous Dysplasia and Albright’s Syndrome

Fibrous dysplasia is a condition in which there is fibro-osseous tissue in place of normal lamellar bone. Most often (85%) this process is monostotic (affecting a single bone), but it may be polyostotic (involving multiple bones). Cutaneous markings and endocrinopathies may accompany the polyostotic form, which usually has more severe skeletal involvement. This section will focus on the polyostotic form.

Pathogenesis

Etiology

Not inherited
May be due to failure of woven bone to mature to lamellar bone
G-protein gene mutations in both monostotic and polyostotic fibrous dysplasia, Albright’s syndrome, and solitary pituitary adenoma
- Activating (gain of function) mutations in GNAS1 (encodes alpha subunit of stimulatory G protein)

Epidemiology

Female predominance
Diagnosis usually made in late childhood or early adolescence
30% to 50% of patients with polyostotic fibrous dysplasia have Albright’s syndrome.

Pathophysiology

Fibro-osseous tissue within bone, most often metaphyseal
One side more involved than other

Classification

Monostotic or polyostotic
McCune-Albright (Albright’s) syndrome is:
- Polyostotic fibrous dysplasia
- Café-au-lait spots (“coast of Maine” irregular border)
- Precocious puberty or other endocrine abnormalities (Box 7.3-1)
Mazabraud’s syndrome
- Fibrous dysplasia
- Soft tissue myxomas

Diagnosis

Clinical Features

Polyostotic Fibrous Dysplasia

May be asymptomatic, although that is less common in polyostotic form
Pain
Limp (can be from pain, leg-length discrepancy, or Trendelenburg gait from “shepherd’s crook” deformity of proximal femur)
Swelling (if bone in subcutaneous location)
Angular deformity
Leg-length discrepancy
50% with craniofacial manifestations

McCune-Albright Syndrome (features in addition to the above)

Cutaneous macular pigmentation similar to café-au-lait spots of neurofibromatosis
- Irregular “coast of Maine” border (unlike smooth “coast of California” border seen in neurofibromatosis) (Fig. 7.3-1)
- Tend to cluster centrally, especially on the back
- Most frequent extraskeletal manifestation (approximately one third)
- Unusual in monostotic fibrous dysplasia
Precocious puberty or endocrinopathy
- Precocious puberty more common (20%)
  - Females > males
  - Female presentation: vaginal bleeding, premature development of sexual organs, premature secondary sex characteristics
  - Male presentation: enlarged genitals, premature secondary sex characteristics
- Endocrinopathy may include hyperparathyroidism, hyperthyroidism, Cushing syndrome, acromegaly, diabetes, rickets, osteomalacia, hyperprolactinemia.

Figure 7.3-1 Irregular “coast of Maine” border in the pigmented skin lesion associated with polyostotic fibrous dysplasia. This differs from the smooth “coast of California” border seen typically in type I peripheral neurofibromatosis and in Jaffe-Campanacci syndrome (multiple nonossifying fibromas and café-au-lait spots).

Mazabraud’s Syndrome

Myxomas with fibrous dysplasia bone lesions
Usually polyostotic (86%) over solitary fibrous dysplasia, rarely with McCune-Albright’s

Radiologic Features

Diaphyseal or metaphyseal
- Epiphyseal involvement rare
- Involvement of flat bones (skull, jaw, ribs) common
- Spinal involvement uncommon
Lucent or “ground glass” appearance (Fig. 7.3-2)
May have calcifications
Sclerotic rim typical
May expand cortex (usually does not break cortex)
May have angular deformities (e.g., “shepherd’s crook” deformity) (Fig. 7.3-3)
Increased uptake on bone scan

Histologic Features

Fibrous stroma with spindle cells
Spicules of osteoid or woven bone that have the appearance of “alphabet soup” (often described as resembling the letters C, O, J, and Y) or “Chinese characters” (Fig. 7.3-4)
Few osteoblasts (lacking osteoblastic rimming)
- Lack of osteoblastic rimming distinguishes fibrous dysplasia from osteofibrous dysplasia, more common in the tibia, which is characterized by osteoblastic rimming.
Cartilaginous foci may be present.

Treatment

Observe if asymptomatic. Endocrinologist should manage precocious puberty or other endocrinopathies.

Figure 7.3-2 Radiographs from a patient with polyostotic fibrous dysplasia show extensive involvement of the proximal femur (A) and a single lesion in the ipsilateral tibia (B). Note the characteristic loss of normal trabeculation within the lesion in the tibia, which has been referred to as a “ground glass” mineralization pattern. This less organized appearance reflects the histology, which shows a more random “Chinese character” pattern of mineralization.

Indications for Surgery

Biopsy indicated if diagnosis in question
Fracture through lesion
- If alignment unacceptable or high-risk location (e.g., proximal femur)
- In children may be able to treat pathologic fractures with casting
Progressive deformity
- If causing functional disability, unacceptable disfigurement, significantly increased risk of pathologic fracture
Pain