Fibrous Dysplasia and McCune-Albright Syndrome
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Direct answer
Fibrous dysplasia is a benign skeletal lesion in which normal bone is replaced by fibro-osseous tissue, caused by somatic activating GNAS mutations. McCune-Albright syndrome is the combination of polyostotic disease, café-au-lait skin spots and endocrine hyperfunction, most often precocious puberty. Lesions often show a ground-glass appearance on X-ray and may deform weight-bearing bones.
What you must remember
- Cause: a postzygotic activating GNAS mutation increases cAMP signalling in osteoblast precursors.
- Distribution: most cases are monostotic, while polyostotic disease is more extensive and more often linked with endocrine features.
- Radiology: an expansile, well-defined lesion with a ground-glass appearance and sometimes a sclerotic rim.
- Classic deformity: shepherd's crook deformity of the proximal femur from coxa vara.
- McCune-Albright triad: polyostotic fibrous dysplasia, café-au-lait macules and precocious puberty.
- Endocrine hyperfunction: growth hormone excess, hyperthyroidism and Cushing syndrome from adrenal hyperplasia can occur.
- Treatment: observation for small asymptomatic lesions, surgery for fracture or deformity, and bisphosphonates for bone pain.
A stepwise approach to a lytic bone lesion in a child
A child with an expansile bone lesion and pigmented skin spots needs the skeleton and the endocrine system checked together. The steps below show how the diagnosis is reached and treated.
- Image the lesion: plain radiographs show the ground-glass pattern, and CT or MRI defines the extent and fracture risk.
- Examine the skin: the number and shape of café-au-lait macules matter, because unilateral macules with irregular borders favour McCune-Albright syndrome.
- Screen the endocrine axes: look for signs of precocious puberty in girls and boys, acromegalic or thyrotoxic features, and Cushingoid change, and check LH, oestradiol, IGF-1, TSH and cortisol.
- Confirm when uncertain: biopsy is reserved for lesions that are unclear on imaging, and histology shows woven bone in fibrous stroma with a Chinese letter pattern.
- Treat the bone: small asymptomatic lesions are observed, while orthopaedic stabilisation is planned for fracture or progressive deformity.
- Treat the endocrine disease: an aromatase inhibitor such as letrozole is used in some patients with precocious puberty, and other hyperfunction is managed by endocrinology.
Where students lose marks
These are common traps in bone pathology and endocrine questions.
- Trap: calling a ground-glass lesion malignant by appearance. Correct: fibrous dysplasia is benign, and the ground-glass appearance is typical, so biopsy is needed only when the picture is unclear.
- Trap: taking café-au-lait spots alone as neurofibromatosis. Correct: irregular, unilateral spots favour McCune-Albright, whereas NF1 spots have regular borders and are accompanied by neurofibromas.
- Trap: looking only at the bone and missing endocrine disease. Correct: the GNAS mutation affects several glands, so precocious puberty and hyperthyroidism must be checked.
Frequently asked questions
What is the characteristic radiological appearance of fibrous dysplasia?
Fibrous dysplasia typically shows a ground-glass appearance on plain radiographs, with an expansile lesion in the affected bone. The lesion usually has a well-defined margin and may have a sclerotic rim. A lytic or permeative pattern would suggest a different diagnosis.
Why does McCune-Albright syndrome cause precocious puberty?
McCune-Albright syndrome causes precocious puberty because GNAS activation in ovarian or testicular cells produces gonadotrophin-independent oestrogen or androgen secretion. This is peripheral precocious puberty, so LH is suppressed. Puberty may therefore appear early without any pituitary activation.
Which skin finding helps identify McCune-Albright syndrome?
Unilateral café-au-lait macules with irregular, jagged borders, often described as coast of Maine borders, help identify McCune-Albright syndrome. They are usually unilateral and do not cross the midline. Their irregular outline distinguishes them from the regular spots of neurofibromatosis.
Which drug is used for bone pain in polyostotic fibrous dysplasia?
Bisphosphonates reduce bone pain in fibrous dysplasia and may limit progression in patients with painful or active disease. Their use is decided individually by specialists. Surgery is reserved for deformity, fracture or nerve compression.