Quiz
Which of the following syndromes is NOT associated with Fibrous dysplasia?
- McCune Albright syndrome.
- Mazabraud syndrome
- Jaffe-Lichtenstein disease
- von-Hippel Lindau syndrome.
Click here for the answer
Answer: Von-Hippel Lindau syndrome is not associated with fibrous dysplasia.
Key facts for practice and radiology board exams
Fibrous dysplasia is a benign, non-inherited bone lesion caused by a post-zygotic GNAS mutation. It is intramedullary and expansile, with a ground glass matrix, a thinned but smooth and intact cortex, often a thick sclerotic rind, and no periosteal reaction. About 80 percent of cases are monostotic. Radiographs diagnose the classical long bone lesion; CT is the test for craniofacial disease, and MRI is non-specific.
| Feature | Detail |
|---|---|
| Cause | Post-zygotic activating missense mutation in GNAS, at codon 201 in over 95 percent of lesions. Mosaic, so it is never inherited [4] |
| Distribution | Monostotic in about 80 percent of patients, although a French cohort of 372 found 58 percent [1][8] |
| Commonest bones | Femur in 44 percent and skull in 38 percent of patients [8] |
| Radiographic triad | Ground glass matrix, thinned but smooth cortex, no periosteal reaction [1] |
| Classic margin | Rind sign, a thick sclerotic border, most often in the proximal femur [1] |
| Natural history | Expansion slows after puberty and almost no new lesions appear after age 15. Lesions stabilise but do not resolve, and some adults stay symptomatic [1] |
| Malignant change | Under 1 percent in consensus estimates, up to about 2.5 percent in referral pathology series [3][5] |
Pathophysiology
Fibrous dysplasia arises from a post-zygotic activating mutation in GNAS, at codon 201 in more than 95 percent of lesions. Constitutive Gs-alpha signalling raises intracellular cAMP and arrests skeletal stem cells before they become mature osteoblasts, so marrow is replaced by fibro-osseous tissue containing poorly mineralised woven bone [4]. The mutation is mosaic and acquired in utero, so the skeletal distribution is fixed early. The same cells overproduce FGF23, causing renal phosphate wasting and, in a subset, frank hypophosphataemia [6].
Imaging features on radiographs, CT and MRI
Slide the image for an annotated version.
| Modality | Findings |
|---|---|
| Radiograph | Intramedullary, well defined, expansile. Ground glass or hazy matrix, though some lesions are purely lucent or sclerotic. Cortex thinned with endosteal scalloping but the outer contour stays smooth. No periosteal reaction unless there is a pathological fracture [1] |
| CT | The test for the skull base, face, pelvis and spine, where plain films are not recommended for characterisation. Ground glass is the commonest craniofacial appearance; prepubertal lesions are often homogeneously dense and turn mixed after the second decade [1][3] |
| MRI | Low to intermediate T1, highly variable T2 (higher in children), and some enhancement in essentially all lesions. Non-specific: it does not reliably separate fibrous dysplasia from other lesions, and its main value is excluding a cyst [1][2] |
| Bone scan and PET | Increased uptake that is non-specific [1] |
Which imaging test to choose
- A classical ground glass intramedullary lesion with an intact cortex can be called on radiographs alone.
- An isolated monostotic lesion with no skin or endocrine findings carries a wide differential and often still needs histology [2].
- For craniofacial and skull base disease go to CT, not radiographs [1][3].
- MRI adds little diagnostically; use it to exclude a cyst or to assess a soft tissue component [1][2].
- In polyostotic or syndromic disease, refer for endocrine screening, including IGF-1, growth hormone and prolactin [2].
Differential diagnosis
| Mimic | How to separate it |
|---|---|
| Paget disease of bone | Presents decades later. On skull CT the strongest discriminators are the ground glass matrix, symmetry, paranasal sinus involvement and cranial cortical thickness [10] |
| Jaffe-Campanacci syndrome | Multiple non-ossifying fibromas with cafe-au-lait macules. Lesions are eccentric and cortically based in the metaphysis, not a central ground glass matrix |
| Neurofibromatosis type 1 | Cafe-au-lait macules have smooth ‘coast of California’ borders, against the jagged ‘coast of Maine’ borders of McCune-Albright syndrome [4] |
A lucent fibrous dysplasia lesion sits in the FOGMACHINES differential for lytic bone lesions, also written FEGNOMASCHIC: Fibrous dysplasia, Osteoblastoma, Giant cell tumour, Metastasis and myeloma, Aneurysmal bone cyst, Chondroblastoma and chondromyxoid fibroma, Hyperparathyroidism (brown tumour) and haemangioma, Infection, Non-ossifying fibroma, Eosinophilic granuloma and enchondroma, Solitary bone cyst.
Syndromes associated with fibrous dysplasia
| Syndrome | What defines it |
|---|---|
| McCune-Albright syndrome | The 2019 FD/MAS consortium defines it as fibrous dysplasia plus one or more extraskeletal feature, or two or more extraskeletal features, so fibrous dysplasia is no longer required. Cafe-au-lait macules show jagged ‘coast of Maine’ borders. Precocious puberty, the commonest endocrinopathy, affects nearly 80 percent of girls [2][4] |
| Mazabraud syndrome | Fibrous dysplasia with intramuscular myxomas, usually in the thigh and presenting in the fifth to sixth decade. It occurs with monostotic, polyostotic or McCune-Albright disease, more often polyostotic. Myxoma recurrence reaches 25 percent [1][2] |
| Jaffe-Lichtenstein disease | A historic eponym, used inconsistently. Current convention reserves it for fibrous dysplasia without extraskeletal features. The 2019 consensus drops it and classifies disease as monostotic, polyostotic or McCune-Albright syndrome [1][2] |
Complications and malignant transformation
- Fractures. In polyostotic disease and McCune-Albright syndrome, 172 fractures occurred in 35 patients, 60 percent femoral, peaking between ages 6 and 10 [9]. Progressive proximal femoral varus gives the coxa vara of the shepherd’s crook deformity [1].
- Hypophosphataemia. FGF23 driven renal phosphate wasting. Low serum phosphate tracks with more fractures, scoliosis and surgery, and children with phosphaturia fractured far earlier, at 5.1 against 16.6 years [6][9].
- Optic canal narrowing. The canal is commonly encased in craniofacial disease while vision remains normal, and only about 12 percent of completely encased optic nerves develop optic neuropathy. Prophylactic optic nerve decompression is not recommended; operate only for documented progressive visual loss [2][7].
- Malignant transformation. Under 1 percent in consensus estimates [3]. The largest pathology series found 28 sarcomas among 1,122 cases, about 2.5 percent, 19 of them osteosarcoma. Most arose in monostotic, not polyostotic, disease, and 46 percent had received radiotherapy, which with growth hormone excess are the named risk factors [1][5].
Treatment
- Most lesions need nothing beyond surveillance and simple analgesia.
- Oral bisphosphonates do not relieve fibrous dysplasia pain: the consensus finds no evidence supporting alendronate or risedronate, and reserves bisphosphonates for persistent pain above 3 out of 10 on a visual analogue scale [2].
- No bisphosphonate has been shown to reduce lesion size, lesion progression or fracture rate [2].
- Denosumab reduces lesion activity but causes rebound hypercalcaemia on withdrawal, and is not recommended outside specialist centres, preferably within a trial [2].
- Surgery is for fracture, deformity or progressive compression. Screen for and treat growth hormone excess, which raises the risk of optic neuropathy [2][7], and correct hypophosphataemia [6].
Related cases on RadioGyan
Frequently asked questions
References
- Kushchayeva YS, Kushchayev SV, Glushko TY, Tella SH, Teytelboym OM, Collins MT, et al. Fibrous dysplasia for radiologists: beyond ground glass bone matrix. Insights Imaging. 2018;9(6):1035-1056. PMID: 30484079.
- Javaid MK, Boyce A, Appelman-Dijkstra N, Ong J, Defabianis P, Offiah A, et al. Best practice management guidelines for fibrous dysplasia/McCune-Albright syndrome: a consensus statement from the FD/MAS international consortium. Orphanet J Rare Dis. 2019;14(1):139. PMID: 31196103.
- Lee JS, FitzGibbon EJ, Chen YR, Kim HJ, Lustig LR, Akintoye SO, et al. Clinical guidelines for the management of craniofacial fibrous dysplasia. Orphanet J Rare Dis. 2012;7(Suppl 1):S2. PMID: 22640797.
- Robinson C, Collins MT, Boyce AM. Fibrous dysplasia/McCune-Albright syndrome: clinical and translational perspectives. Curr Osteoporos Rep. 2016;14(5):178-186. PMID: 27492469.
- Ruggieri P, Sim FH, Bond JR, Unni KK. Malignancies in fibrous dysplasia. Cancer. 1994;73(5):1411-1424. PMID: 8111708.
- Gun ZH, Osamor C 3rd, Taylor J, Li X, Szymczuk V, Boyce AM. Serum phosphorus as a driver of skeletal morbidity in fibrous dysplasia. J Clin Endocrinol Metab. 2024;109(5):1334-1340. PMID: 37975816.
- Cutler CM, Lee JS, Butman JA, FitzGibbon EJ, Kelly MH, Brillante BA, et al. Long-term outcome of optic nerve encasement and optic nerve decompression in patients with fibrous dysplasia: risk factors for blindness and safety of observation. Neurosurgery. 2006;59(5):1011-1017. PMID: 17143235.
- Benhamou J, Gensburger D, Messiaen C, Chapurlat R. Prognostic factors from an epidemiologic evaluation of fibrous dysplasia of bone in a modern cohort: the FRANCEDYS study. J Bone Miner Res. 2016;31(12):2167-2172. PMID: 27340799.
- Leet AI, Chebli C, Kushner H, Chen CC, Kelly MH, Brillante BA, et al. Fracture incidence in polyostotic fibrous dysplasia and the McCune-Albright syndrome. J Bone Miner Res. 2004;19(4):571-577. PMID: 15005844.
- Tehranzadeh J, Fung Y, Donohue M, Anavim A, Pribram HW. Computed tomography of Paget disease of the skull versus fibrous dysplasia. Skeletal Radiol. 1998;27(12):664-672. PMID: 9921927.
Co-Authors: Dr. Bhargavi Sovani. Illustration by Dr. Disha Lokhandwala.
Improve Content And Help Your Colleagues!
Found an error in the post? Please let us know using our contact page and we will update it with due credits!
If you wish to contribute radiological images for this case (or any other article on the website), you can submit them here and you will be duly credited: Submit radiology case