The road to an FD diagnosis is often long and ambiguous. Many clinicians have never encountered this disease before. Below we describe the typical diagnostic path - step by step - to help you ask the right questions and know what to expect.
Educational content, not a substitute for a medical consultation. Before any clinical decision, please consult a clinician experienced with FD/MAS.
The histopathological picture of fibrous dysplasia (FD) can closely resemble other bone lesions, in particular Juvenile Ossifying Fibroma (JOF) - a benign tumor which is however treated surgically, by radical excision. FD in children without pain or functional impairment is not operated on - observation until skeletal maturity.
Confusing these two diagnoses can lead to an unnecessary, extensive operation in a child. That is why after any biopsy with a result suggesting FD or JOF, a GNAS gene mutation test should be ordered. It is the only way to unambiguously confirm fibrous dysplasia.
A dentist, primary-care physician, or parent notices the lesion. It may be a bone thickening, facial asymmetry, bone pain, or an incidental finding on an X-ray. Not every lesion hurts - many FD cases are discovered incidentally.
The clinician orders a computed tomography scan (CT) or CBCT (for jaw lesions). FD has a characteristic ground-glass appearance. MRI may be needed for soft-tissue assessment. The imaging is suggestive but not enough on its own for diagnosis.
A bone sample is collected and examined under a microscope. The pathologist looks for FD-typical patterns: irregular bone trabeculae in a fibrous stroma (the "Chinese characters" pattern). The problem: the same picture can be produced by other lesions, including JOF.
Genetic testing of the biopsy material for GNAS mutations. The most common mutation is c.601C>T (p.Arg201Cys) - responsible for about 60% of cases. The second most common is c.601C>A (p.Arg201Ser). A positive result = confirmed FD. The test can be ordered from a paraffin block.
A bone scintigraphy (bone scan) checks whether FD affects a single bone or many. This matters for determining the disease type and the monitoring plan. If FD is polyostotic, the clinician should also order hormonal tests for McCune-Albright syndrome.
Once the diagnosis is confirmed: a monitoring plan (periodic CT/MRI, endocrine follow-up), assessment of pharmacological treatment indications, and a decision on possible surgery - usually deferred until skeletal maturity.
FD treatment options →"Minor histological features consistent with fibrous dysplasia" - that was the opinion of Prof. Mara Riminucci of Sapienza University in Rome after analyzing slides that had previously been described as Juvenile Ossifying Fibroma. Expert histological verification confirmed FD.
Prof. Natasha Appelman-Dijkstra of Leiden University Medical Center, in a consultation with our family, clearly stated: "advice against surgery" - in a child without pain or functional impairment, with confirmed FD, surgery is not indicated.
These opinions illustrate how much depends on proper diagnostics. A histopathology result without a GNAS test can lead to a misdiagnosis and an unnecessary surgical intervention.
Make sure the biopsy material will be preserved in a paraffin block. From the same material you can later order a GNAS genetic test - no need to repeat the biopsy.
If the histopathology suggests FD or JOF, tell your doctor: "I would like to order a GNAS gene mutation test from the biopsy material, to confirm or rule out fibrous dysplasia." The test is performed using Sanger sequencing or NGS.
The GNAS test can be ordered from biopsy material (paraffin block) or from peripheral blood - though sensitivity from blood is lower due to mosaicism. A list of specific Polish laboratories performing this test is in the section below.
This is the most common GNAS mutation in FD - responsible for about 60% of cases. The second is c.601C>A (p.Arg201Ser). Both affect codon 201 of the GNAS gene and lead to constitutive activation of the Gs-alpha protein, resulting in abnormal bone development.
Below are four laboratories that publicly advertise testing for somatic GNAS mutations. The test is performed from a paraffin block (preferred) or from peripheral blood. Price, turnaround time, and ordering procedure can change - check current details on the chosen laboratory's website. The test usually requires a referral from the treating physician.
Somatic GNAS mutation testing via sequencing. Material: paraffin block. Turnaround: about 10 working days. This is where we ran our son's test - efficiently, with good service.
ul. Mogilska 86/3, Kraków · biuro@oncogene.pl · +48 12 410 58 73
Somatic GNAS mutation testing. Material: paraffin block. Turnaround: about 10 days. Sample drop-off and result pickup possible in Poznań (ul. Dąbrowskiego 77A) and Zielona Góra (ul. Towarowa 20).
cgm@genesis.pl · +48 61 62 63 436
A test within McCune-Albright syndrome diagnostics (includes GNAS mutation analysis). Performed by Warsaw molecular diagnostics provider Genomed. Check the website for current pricing and required documents.
Central Clinical Hospital of the Medical University of Łódź. Services of the Clinical Genetics Department and Outpatient Clinic, including selected molecular tests. Check the current price list and ordering path.
The list is not exhaustive. If you run or know of another Polish laboratory performing this test, write to us - we will gladly extend the list.
Javaid M.K., Boyce A., Appelman-Dijkstra N., …, Collins M.T. (2019). "Best practice management guidelines for fibrous dysplasia/McCune-Albright syndrome: a consensus statement from the FD/MAS international consortium", Orphanet Journal of Rare Diseases, 14(139). Open-access. A consensus of 51 experts from 13 countries; cited by Leiden, Sapienza, and UCSF as the foundation of contemporary clinical care. The full publication can be printed and brought to a consultation - together with the diagnostic flowcharts.
Open publication (Orphanet J Rare Dis) → Download flowcharts (FD/MAS Alliance) →
Coming soon: a Polish version of the flowcharts - with ICD-10 codes, a list of Polish laboratories performing the GNAS test, and NFZ reimbursement pathways. This is the first concrete use case for our Live Guidelines platform.