Polyostotic fibrous dysplasia (PFD) is caused by somatic activating mutations in the GNAS gene in the skeletal stem cells. This leads to the proliferation of immature osteogenic cells and replacement of the normal bone marrow with a fibro-osseous tissue. The lesions can result in deformity of the bones and fractures.

PFD may be mono- or polyostotic. Any part of the skeleton can be affected. The most commonly affected sites are the skull base and proximal parts of the femur. The femoral lesions are responsible for the most functional impairment [1] [2]. The lesions can be isolated or associated with hyperfunctioning endocrinopathies and café-au-lait skin spots called McCune-Albright syndrome [3] [4].

The spectrum of involvement in PFD ranges from two bones to 75% or more of the skeleton. In general, PFD is found in the tibia, femur, pelvic bones and the foot. Other sites may also be affected but less commonly, for example, the skull, ribs, and bones of the upper extremity. The lumbar spine, cervical spine, and clavicle are uncommonly affected.

Typical deformities observed in PFD include leg length discrepancies, rib deformities, and facial asymmetry.

The most common complication of PFD is fracture and it is detected in more than half of the cases with the polyostotic type of the disease [5]. The majority of patients (75%) with PFD have symptoms, including pain, deformities, and pathologic fractures [6].

Malignant transformation can occur but it is rare and the reported prevalence ranges from 0.4% to 4% [5]. The most common malignant tumors are chondrosarcoma, fibrosarcoma, and osteosarcoma. Most of the patients with malignancies are older than thirty years at the time of diagnosis. Generally, the craniofacial region is affected with the femur, tibia, and pelvis following. Polyostotic lesions have a higher rate of malignant transformation than monostotic lesions.

• Precocious Puberty

  Albright's syndrome is characterized by the combination of polyostotic fibrous dysplasia, precocious puberty and café-au-lait spots. [ncbi.nlm.nih.gov]

  Clinical findings Precocious puberty, polyostotic (cystic fibrous dysplasia) spontaneous fractures at young age, café-au-lait spots on skin, ovarian cysts. [medical-dictionary.thefreedictionary.com]

  Puberty — Albright's Syndrome with Precocious Puberty — Albright-Mccune-Sternberg Syndrome — Albright-Sternberg Syndrome — Albright's Syndrome — Syndrome, Albright's — Albright's Disease of Bone [mesh.kib.ki.se]

• Goiter

  A toxic multinodular goiter was also associated, but unique was the spontaneous normalization of the thyroid function. [ncbi.nlm.nih.gov]

  Osteodystrophia fibrosa combined with precocious puberty and exophthalmic goiter. Am. J. Dis. Child. 63: 748, 1942. CrossRef Google Scholar 5. Moldawer M., Rabin E.R. Polyostotic fibrous dysplasia with thyrotoxicosis. Arch. Intern. [link.springer.com]

  These include sexual precocity, espeCially in females (3, 4), goiter and/or hyperthyroidisr:n (4, 5), growth hormone (GH) hypersecretion (6), Cushing' disease (7) and ac-celerated skeletal growth (8). [docslide.com.br]

  The thyroid gland, a butterfly-shaped organ at the base of the neck, may become enlarged (a condition called a goiter) or develop masses called nodules. [ghr.nlm.nih.gov]

  Patients with McCune-Albright Syndrome may have other thyroid abnormalities, including thyroid enlargement (called a goiter), cysts, and nodules. [magicfoundation.org]

• Wheelchair Bound

  Two of the five children had been wheelchair-bound before treatment. All children are now community ambulators. In 5 of 10 hips, there was a significant decrease in the neck-shaft angle over time compared with the immediate postoperative angle. [ncbi.nlm.nih.gov]

  A 5-point score was used: 0, bed-wheelchair-bound; 1, walking with aids possible, but nonfunctional; 2, household walker, with/without aids; 3, neighborhood walker with/without aids; and 4, independent walker ( 17 ). [academic.oup.com]

• Respiratory Insufficiency

  Subtotal resection of this benign tissue mass ameliorated the respiratory insufficiency and led to sustained improvement in exercise tolerance, increase in pulmonary reserve, and decrease in signs of heart failure and pulmonary hypertension. [ncbi.nlm.nih.gov]

• Osteoporosis

  Osteoporosis International. 2003, 14 (6): 507-514. 10.1007/s00198-003-1399-y. View Article PubMed Google Scholar Solomon DH, Rekedal L, Cadarette SM: Osteoporosis treatments and adverse events. [ijpeonline.biomedcentral.com]

  Calcium metabolism and 4 7 calcium kinetics before and after long-term thyrocalcitonin treatment in senile osteoporosis. Clin. Sci. 1970: 38, 397–407. Google Scholar 21. Ryan, W. G., Schwartz, T. B. [link.springer.com]

  Primary and secondary osteoporosis, symptomatic Paget disease of bone, osteogenesis imperfecta both in children and adults and fibrous dysplasia are currently the major indications for bisphospho-nates. [indianpediatrics.net]

  Osteoporosis may be caused by or worsened by hyperthyroidism. In some cases, hyperthyroidism cannot be controlled by medication. [rarediseases.org]

• Back Pain

  This 25-year-old woman with polyostotic fibrous dysplasia (McCune-Albright syndrome) suffered low-back pain after a minor traumatic injury. Neurological examination demonstrated normal status. [ncbi.nlm.nih.gov]

  Case 2: A 20-year-old female was seen at another hospital for low back pain of two years duration and had X-rays of lumbosacral spine which were reported as metastatic malignancy. She was referred to this department. [ijcasereportsandimages.com]

  27740949 ) Hennessy G....Mansberg R. 2016 46 Two-Stage Surgical Treatment of Complex Femoral Deformities with Severe Coxa Vara in Polyostotic Fibrous Dysplasia. ( 30237924 ) Ippolito E...Fichera A 2016 47 Polyostotic fibrous dysplasia presenting with back [malacards.org]

• Neck Pain

  The patient had remarkable improvement in clinical relief of neck pain and improvement of myelopathic symptoms at 1-year follow-up. [ncbi.nlm.nih.gov]

• Bowing of The Long Bones

  Bowing of the long bones occurs frequently in the polyostotic form, and stress fractures often result. Shepherd's crook deformity is a characteristic feature of fibrous dysplasia. [ncbi.nlm.nih.gov]

• Coxa Valga

  RESULTS: Six reproducible patterns of deformity were identified in both untreated and operated femurs: type 1 (24%), normal neck-shaft angle with altered shape of the proximal femur; type 2 (6%), isolated coxa valga with neck-shaft angle 140 ; type 3 [ncbi.nlm.nih.gov]

• Cafe-Au-Lait Spots

  When melanotic pigmentation (cafe-au-lait spots) and multiple endocrine hyperfunction are additionally associated it is referred to as albright syndrome ICD-9-CM Volume 2 Index entries containing back-references to 756.54 : [icd9data.com]

  McCune-Albright syndrome ( MAS ) is a genetic disorder characterized by the association of: endocrinopathy: precocious puberty polyostotic fibrous dysplasia: more severe than in sporadic cases cutaneous pigmentation: coast of Maine ' cafe au lait ' spots [radiopaedia.org]

  Other symptoms include: Bone fractures Deformities of the bones in the face Gigantism Irregular, large patchy cafe-au-lait spots There is no specific treatment for McCune-Albright syndrome. [medlineplus.gov]

  It is characterized by a typical phenotype which includes polyostotic fibrodysplasia, precocious puberty independent from gonadotropins, cafe-au-lait spots and a series of endocrine abnormalities. [bone-abstracts.org]

  When melanotic pigmentation (cafe-au-lait spots) and multiple endocrine hyperfunction are additionally associated it is referred to as albright syndrome. [icd10data.com]

• Hyperpigmentation

  It is characterized by deformities and fractures of the bones, endocrine abnormalities including early puberty, and skin hyperpigmentation Fibrous dysplasia of bone affecting several bones. [icd9data.com]

  INTRODUCTION: Fibrous dysplasia (FD) is a disorder involving either one (monostotic) or several bones (polyostotic FD [PFD] and sometimes is associated with cafe- au -lait hyperpigmentation of the skin and one or more hyperfunctioning endocrinopathies [ncbi.nlm.nih.gov]

  THE McCUNE ALBRIGHT SYNDROME: THE McCUNE ALBRIGHT SYNDROME POLYOSTOTIC FIBROUS DYSPLASIA CUTANEOUS HYPERPIGMENTATION ENDOCRINE HYPERFUNCTION The Classic TRIAD ... [slideee.com]

  It is characterized by deformities and fractures of the bones, endocrine abnormalities including early puberty, and skin hyperpigmentation. Fibrous dysplasia of bone affecting several bones. [icd10data.com]

  Introduction McCune-Albright Syndrome (MAS) is a rare disease presenting with the classical triad of polyostotic fibrous dysplasia (FD), skin hyperpigmentation (café-au-lait spots) and endocrine dysfunction, usually seen as precocious puberty in females [ijpeonline.biomedcentral.com]

• Facial Pain

  Significant correlations were not found for headache/facial pain or recurrent/chronic sinusitis. Thirty-one subjects met the criteria for longitudinal analysis (follow-up mean, 6.3 years; range, 4.4-9 years). [ncbi.nlm.nih.gov]

  […] contain spicules of woven bone with typical osteoblasts embedded within fibrous component.[ 5 ] Clinically FD result to pain, deformity, fracture, and nerve entrapments,[ 4 ] but it usually depends on which bone is involved and consist of: Propetosis, facial [surgicalneurologyint.com]

• Myelopathy

  In the spine, PFD may lead to pathologic fracture and myelopathy even after adolescence. Vertebroplasty with or without decompression and fixation may be the appropriate option for cases with myelopathy. [ncbi.nlm.nih.gov]

  Considering the advanced radiographic findings in multiple vertebrae and possibility of impending paraplegia, the patient was referred to UK for confirmation of the diagnosis and for prophylactic surgical fusion, to prevent compressive myelopathy. [ijcasereportsandimages.com]

  Wu FL, et al: Polyostotic fibrous dysplasia involving the thoracic spine with myelopathy: case report and review of the literature. Spine J 2014;14:e11-e15. [karger.com]

• Radiculopathy

  A 35-year-old man with McCune-Albright syndrome and severe polyostotic fibrous dysplasia of C2 and C3 vertebrae presented with severe neck pain, radiculopathy, quadriparesis and myelopathy. [ncbi.nlm.nih.gov]

The cornerstones of diagnosis in PFD are imaging, and if needed, histological evaluation.

The first line in the workup is a plain radiograph. The diagnosis is straightforward in the presence of typical findings. Computed tomography (CT) scans are necessary to assess complex parts of the skeleton like the pelvis, spine, chest, and facial bones [7] [8] [9] [10].

Bone scintigraphy is of limited use in detecting subtle pathologic fractures. The features of a bone scan in fibrous dysplasia are non-specific. Magnetic resonance imaging (MRI) is required for the assessment of cord compression if the spine is involved [11] [12] [13].

On plain radiography, fibrous dysplasia is observed as a well-defined, intramedullary and expansile lesion in the metaphysis or diaphysis. Lesions can range from completely radiolucent to sclerotic, although, most lesions have the characteristic ground-glass appearance [6]. The underlying histopathology of the lesion correlates directly with the amount of haziness shown radiographically. Radiolucent parts are mainly composed of fibrous elements whereas radiopaque lesions have a larger proportion of woven bone.

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2. Leet AI, Wientroub S, Kushner H, et al. The correlation of specific orthopaedic features of polyostotic fibrous dysplasia with functional outcome scores in children. J Bone Joint Surg Am. 2006;88(4):818-23.
3. Albright F, Butler AM, Hampton AO, Smith PH. Syndrome characterized by osteitis fibrosa disseminata, areas of pigmentation and endocrine dysfunction, with precocious puberty in females, report of five cases. N Engl J Med. 1937;216:727-46.
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