Tuesday, November 3, 2009

FIBROUS DYSPLASIA

Fibrous Dysplasia

• originally described by Lichtenstein in 1938 and by Lichtenstein and Jaffe in 1942
• represent approximately 5% to 7% of benign bone tumors
• A sporadic disorder of osseous and fibrous tissue development characterised by postzygotic mutation of GNAS1 gene coding for stimulatory G protein.
• Analysis of the Gs α subunit in patients with fibrous dysplasia, as well as in those with McCune-Albright syndrome, reveals a missense point mutation at the arginine 201 codon, which results in an arginine-to-histidine or arginine-to-cysteine substitution in the end protein product
• This result in autonomous function in bone, skin and various endocrine glands dependent on c-AMP -protein kinase, a signal transduction pathway.
• It is postulated that elevated levels of cAMP could then lead to the expression of proto-onco genes such as c-fos in affected osteoblasts.
• The proto-onco gene c-fos has been implicated in the process of osteoblastic differentiation and proliferation that may lead to the formation of fibrous dysplasia lesions
• In bones areas of trabecular origin, bone is replaced by cellular fibrous tissue containing flecks of osteoid and woven bone.
• Tumour progression occurs during pregnancy indicating the presence of oestrogen receptors
• It can be monostotic, polyostotic or monomelic.
• McCune-Albright syndrome-polyostotic fibrous dysplasia plus café-au-lait spots (Coast of Maine appearance) and hyperfunction of endocrine systems like precocious puberty.
• Mazabraud’s syndrome: in this syndrome skeletal lesions of fibrous dysplasia are combined with intramuscular myxomas.

Clinical features:

• Pain and deformity are signs that microfractures are developing in a lesion and should be
addressed.
• Localized pain may be the presenting symptom in patients with fatigue fractures in high-stress areas in dysplastic bone, especially in the femoral neck.
• Can occur at any age but mostly seen around the age of 30.
• Female patients can experience an increase in the pain level during pregnancy and at
particular times during their menstrual cycle because of estrogen receptor
• Polyostotic form involves maxilla and other craniofacial bones, ribs, metaphyseal or diaphyseal portions of proximal femur and tibia (MC site: proximal femur).
• Weight bearing bones may be deformed, e.g. shepherd’s crook deformity of proximal femur.
• Pathological fractures may occur and are more frequently seen in polyostotic disease
• Sarcomatous degeneration (osteosarcoma) of femur or facial bone is a rare complication.
• Rarely renal wasting of phosphate leading onto rickets coexists.
• In McCune Albright syndrome the lesion tend to be larger, more persistent, and associated with more complications
• Polyostotic disease may have deformities, which include: coxa vara, the shepherd’s crook deformity, bowing of the tibia, the Harrison groove (a horizontal depression along the lower border of the thorax, corresponding to the costal insertion of the diaphragm), and protrusio acetabuli
• Malignant transformation is seen in 0.4 to 4 % of tumors and includes osteosarcoma, fibrosarcoma, and chondrosarcoma.(3)
• Malignant transformation is seen in adults over 30 years of age and the most common site of involvement is the craniofacial area, followed by femur, tibia and pelvis and also tends to occur more frequently in Mazabraud’s syndrome(1,2).

Gross pathology:• Yellowish white tissue with a distinctive gritty feel, imparted by the small trabeculae of bone scattered throughout the lesion
• The lesion can be easily peeled away from the encircling shell of reactive bone by blunt dissection
• The tissue can be cut with a scalpel and may bleed briskly when cut, as a result of its concentration of small vessels.
Histology: there is fibroblast proliferation that produces collagen matrix along with metaplastic woven bone. The woven trabeculae are disorganized and have been described as having a ‘Chinese letter’ appearance. Areas of cartilage formation are commonly present

X-ray:
• Radiolucent cystic areas, which are expansile with deep endosteal scalloping and ‘ground glass appearance’ or ‘shower door glass appearance’ in the metaphysis or shaft with medullary calcification.
• Lesion is bounded by a distinct rim or shell of reactive bone that is defined more sharply on its inner border than on its outer border, where it may fade gradually into normal cancellous bone
• Can grow eccentrically or concentrically and can resemble simple bone cyst.
• Endosteal scalloping maybe present, the periosteal surface is smooth and without reaction.
• Monostotic lesions mature after skeletal growth ceases., whereas polyostotic lesions continue to grow
• A well-defined sclerotic rim is usually seen.
• Radiologically facial bone involvement present as radiodense lesions (leonine ossea- leonine appearance)
• When a fatigue fracture is present in the proximal femur there are two humps of reactive bone on the medial cortex separated by a thin radiolucent line resembling a “parrot’s beak”

Bone scans are useful to evaluate the extent of the disease. A bone scan that does not show increased uptake does not exclude the diagnosis of fibrous dysplasia

CT scans are useful to evaluate the thickness and extent of lesion, also endosteal reaction, periosteal new bone reaction, and homogeneity of the poorly mineralized lesional tissue

MRI:
• T1-images show low signal intensity, T2-weighted images have a higher-intensity signal
that is not as bright as the signal of malignant tissue, fat, or fluid.
• Cysts demonstrate high signal intensity on T2-weighted images secondary to high water content.
• It is also useful in evaluating suspected malignant degeneration of known fibrous dysplasia lesions by showing the extent of the lesion and/or the surrounding soft tissues and its soft-tissue extension, if present.

Treatment
No effective treatment is available.
1. Monostotic asymptomatic small lesions require no surgery especially in patients who have attained skeletal maturity. In newly identified cases, a bone scan is needed to exclude a diagnosis of polyostotic disease. When polyostotic disease is found, a referral to an endocrinologist for endocrine and metabolic testing is paramount
2. I.v pamidronate therapy may cause radiographic resolution in polyostotic disease (4). Dose:
60mg/day for 3 days, which is repeated every 6 months, supplemented with calcium (500 to 1500 mg/day) and vitamin D (800 to 1200 IU/ day).
Monitoring markers of bone turnover (N-telopeptide and alkaline phosphatase) at six-month intervals and bone mineral density yearly during treatment is a means of assessing the efficacy of bisphosphonate therapy.
3. Large painful, fracture prone lesions can be curetted and grafted. A cortical graft may be useful to bridge the defect, especially a cortical allograft since it is reabsorbed slowly.
– Suitable osteotomies to correct deformities may be employed.
– Treatment may be postponed until skeletal maturity since recurrence is very common
– Fixed-angled internal-fixation devices, like intramedullary nails should be employed to correct the deformity.
– Collins et al devised an insturment for measuring the skeletal burden of fibrous dysplasia and predicting the functional outcome (5). Decision and type of surgery can be attained from this score.
– Irradiation is contraindicated because of the risk of radiation induced sarcoma later in life

Ref:
1. Yabut SM Jr, Kenan S, Sissons HA, Lewis MM. Malignant transformation of fibrous
dysplasia. A case report and review of the literature. Clin Orthop Relat Res.
1988;228:281-9.
2. Lopez-Ben R, Pitt MJ, Jaffe KA, Siegal GP. Osteosarcoma in a patient with Mc-Cune-Albright syndrome and Mazabraud’s syndrome. Skeletal Radiol. 1999;28:522-6.
3. Harris WH, Dudley HR Jr, Barry RJ. The natural history of fibrous dysplasia. An orthopaedic, pathological, and roentgenographic study. Am J Orthop. 1962; 44:207-33.
4. Chapurlat RD, Delmas PD, Liens D, Meunier PJ. Long-term effects of intravenous pamidronate in fibrous dysplasia of bone. J Bone Miner Res. 1997;12:1746-52.
5. Collins MT, Kushner H, Reynolds JC, Chebli C, Kelly MH, Gupta A, Brillante B, Leet AI, Riminucci M, Robey PG, Bianco P, Wientroub S, Chen CC. An instrument to measure skeletal burden and predict functional outcome in fibrous dysplasia
of bone. J Bone Miner Res. 2005;20:219-26.

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