Disclaimer: The information contained within the Grand Rounds Archive is intended for use by doctors and other health care professionals. These documents were prepared by resident physicians for presentation and discussion at a conference held at Baylor College of Medicine in Houston, Texas. No guarantees are made with respect to accuracy or timeliness of this material. This material should not be used as a basis for treatment decisions, and is not a substitute for professional consultation and/or peer-reviewed medical literature.

Fibrous Dysplasia
May 20, 1999
Carrie A. Roller, M.D.

YM is a 12-year-old girl who has had facial asymmetry that has progressed throughout her childhood. She was diagnosed with fibrous dysplasia at an outside institution. After a number of surgical recontouring procedures, she was referred to the Texas Childrens Hospital for further treatment. The anterior projection of the maxillary lesion could be seen as a fullness of the left cheek and a displacement of left nasal ala. A coronal non-contrast CT revealed her most cosmetically obvious lesion. There was an expansion of the left maxillary bone that impinged on the orbit and lateral nasal wall.

These axial views reveal the posterior extent of the maxillary lesion, as well as the involvement of the sphenoid. Although sphenoid involvement is not as cosmetically obvious or problematic, skull base lesions and any attempts to surgically treat these lesions, threaten such vital structures as cranial nerves and large vessels. The patient is therefore limited to conservative surgical procedures designed to alleviate symptoms and minimize cosmetic deformity. It is hoped that the disease process will slow or even stop when she reaches puberty.

Fibrous dysplasia is a non-neoplastic, primary disorder of bone. The disease process replaces normal medullary bone with a variable amount of abnormal and structurally weak fibrous and osseous tissue.

Fibrous dysplasia is described in terms of three major types: monostotic, involving a single bone; polyostotic, having multiple lesions involving multiple bones; and McCune Albright syndrome, a polyostotic form of fibrous dysplasia that also involves endocrine abnormalities.

The monostotic form of fibrous dysplasia is the most common, comprising 70% of cases. There is an equal male to female ratio, and this form is the most likely to quiesce at puberty. A typical monostotic lesion will involve the femur, tibia or ribs, with 25% occurring in the bones of the skull.

Twenty-five percent of fibrous dysplasia involves two or more bones. These lesions may be localized to one region of the body or they may be disseminated, involving virtually every bone. There is a female predilection in polyostotic fibrous dysplasia, and up to 50% may involve bones in the head and neck. These lesions are more likely to continue to progress even after puberty.

In 1937, Albright and associates described a syndrome consisting of disseminated bony lesions, hyperpigmented skin lesions, and endocrine dysfunction with precocious puberty in females. This syndrome is now known as Albright Syndrome or McCune-Albright syndrome and is responsible for 3% of cases of fibrous dysplasia. Endocrine abnormalities typically include hyperthyroidism and precocious puberty in females, but may also involve any of a multitude of other endocrine abnormalities, including acromegaly, gigantism, and hyperprolactinemia.

The café au lait spots of McCune-Albright syndrome rarely cross the midline and tend to be in the same region as the bony lesions. The buttocks and lumbosacral areas are the most common sites. These lesions have irregular borders described as "Coast of Maine." The café au lait spots associated with von Recklinghausen's disease have smoother borders likened to the "Coast of California."

Onset of fibrous dysplasia typically occurs by the age of 30, and is most often found during childhood. It manifests as one or more slowly enlarging, painless bony masses and may involve virtually any bone in the body. Lesions can become quite disfiguring and can lead to functional impairment.

Deformity is progressive and by mass effect there may be impingement on other structures and functional impairment.

These lesions tend to be structurally weak and are therefore prone to pathologic fracture. Alkaline phosphatase may be elevated in up to 30% of patients with polyostotic fibrous dysplasia, and a dramatic rise may herald malignant degeneration. Calcium and phosphorus tend to be normal.

Malignant degeneration occurs in less than 1% of cases of fibrous dysplasia. Malignancies are almost exclusively osteosarcoma. For unknown reasons, monostotic and craniofacial lesions have the greatest potential for malignant degeneration, and radiation therapy has been found to increase the risk by 400-fold. Pain, rapid growth of a lesion and a dramatic elevation of alkaline phosphatase may herald malignant transformation.

Aside from the aforementioned endocrine abnormalities and gross deformity, there are manifestations of this disease specific to the head and neck. Cranial nerve compromise from compression is an obvious example. But there have also been a number of reported cases involving the temporal bone, and these can give rise to quite a variety of problems.

Conductive hearing loss was a complaint in 80% of those with temporal bone involvement. This may be due to obstruction of the external auditory canal, or, more infrequently, involvement of the middle ear system. Seventh nerve compromise may occur if the fallopian canal is encroached upon, and erosion of the otic capsule can lead to sensorineural hearing loss and vertigo.

Histologically, fibrous dysplasia replaces lamellar bone with an abnormal metaplastic version of immature woven bone. The fibrous portion resembles the fibrous stroma of normal immature bone, but the osseous component is an irregular and poorly oriented version of woven bone. The trabeculae also differ in that they lack the osteoblastic rimming typical of normal bony trabeculae. Mature lamellar bone consists of parallel and concentric rings of collagen with few osteocytes. Immature woven bone consists primarily of a random configuration of collagen fibers, with numerous osteocytes and osteoblasts rimming spicules of bone. In fibrous dysplasia, there is a matrix of whorls of fibrous tissue surrounding irregular spicules of immature or woven bone.

There are histologic differences between normal woven bone and fibrous dysplasia. The spicules of woven bone are lined with osteoblasts and have regular borders. The bony portion in fibrous dysplasia has irregular borders that are not rimmed with osteoblasts. The fibrous components are similar.

The irregular, misshapen trabeculae form odd geometric patterns and are described as "Chinese letters."
Three types of radiographic appearance have been described for fibrous dysplasia. The first and most common is "Pagetoid," due to its similarity of appearance to Paget's disease of bone. These lesions have in common a characteristic "Ground Glass" appearance with coexisting radiodense and radiolucent areas. Pagetoid lesions often involve the calvarium. Spicules of new bone are responsible for the well-known "ground glass" appearance of the fibrous regiona.

Twenty-five percent of fibrous dysplasia lesions have a sclerotic appearance. CT reveals a non-homogeneous thickening of bone, and T1 MRI reveals a non-homogeneous lesion of intermediate signal intensity. CT is the preferred mode of imaging in these bony lesions. On T1 MRI, fibrous dysplasia appears as non-homogeneous with intermediate signal intensity. On T2 weighted MR, the lesions are non-homogeneous with low to intermediate signal intensity. The turbinate swelling is incidental.

Number one on the differential diagnosis is ossifying fibroma. However, fibrous dysplasia may also clinically or radiographically resemble Paget's disease of bone, aneurysmal bone cyst, giant cell tumor, or the brown tumor of hyperparathyroidism. The distinction is made based on the combination of clinical picture, radiographic findings, and histology

Histologically, ossifying fibroma is characterized by a mixture of mature-appearing lamellar bone and fibrous stroma, as opposed to the immature woven bone of fibrous dysplasia. The osseous components here are rimmed with osteoblasts, unlike fibrous dysplasia that lacks normal osteoblastic rimming.

Plain radiographs depict an ossifying fibroma of the left fronto-orbital region. Note the thick hyperostotic "cap." This lesion's appearance differs from cystic lesions of fibrous dysplasia in that the margins are severely hyperostitic and the central portion is isodense with normal bone, rather than radiolucent as expected in fibrous dysplasia.

Paget's disease is an essentially benign process of disordered bone production and resorption. It is found within the axial skeleton and occurs in 11% of persons over 80 years of age. It creates osteoblastic and osteolytic lesions that radiographically are virtually indistinguishable from fibrous dysplasia. Histologically it is characterized by lamellar bone surrounded by numerous osteoblasts and few osteoclasts.

Dr Robert Fechner from the Pathology Department at the University of Virginia considers fibrous dysplasia and ossifying fibroma to be on a continuous spectrum of histopathology. Often specimens will not fall easily into a category and a pathologist will return a diagnosis of "benign fibro-osseous lesion." Clinical information is very important in making the distinction. Age of onset is before 25 years in 90% of fibrous dysplasia patients, and over 25 in 90% of ossifying fibroma patients. There is a significant female predilection with ossifying fibroma, and lesions tend to be smaller in ossifying fibroma. Mandibular involvement is much more common in ossifying fibroma; however, it is far from uncommon in fibrous dysplasia.

GNAS1 is the gene that is responsible for the alpha subunit of the G protein that activates adenylyl cyclase. This gene is found on chromosome 20. Activating mutations of this gene are responsible for cellular proliferation of endocrine tissues and the bony lesions of fibrous dysplasia. Inactivating mutations create resistance to hormonal signals in such diseases as Albright's Hereditary Osteodystrophy.

In response to a hormone ligand, the alpha subunit of the G protein activates adenylate cyclase to form cyclic amp that then activates a number of intracellular processes. The mutation of GNAS1 found in fibrous dysplasia constitutively activates the alpha subunit. Depending on the involved tissue this can create endocrine hyperfunction or the bony lesions of fibrous dysplasia.

It is thought that mutations in this gene which occur early in embryological development lead to diffuse disease and that later mutations cause such limited disorders as fibrous dysplasia and may be responsible for some pituitary and thyroid tumors. This mutation has been found in blood, liver and heart in some patients, and, while uncommon, cardiac arrhythmia and hepatic disorders have been reported in conjunction with fibrous dysplasia.

Radiation is contraindicated as it has been found to increase the rate of malignancy arising from fibrous dysplasia by 400 times.

Expectant management is based on the possibility that the disease process will slow or subside at the onset of puberty.

Conservative surgical management consists of shaving, reshaping and excising lesions as they become problematic. Indications are progressive deformity, compromise of function, pain or suspicion of malignancy. An example would be optic canal unroofing from compression or threatened compression of the optic nerve.

Radical resection is based on the principle that this is a localized disease process. Theoretically, removal of all involved tissue should be curative. Chen and Noordhoff's Zone 1 consists of the frontal, orbital, nasal, ethmoid, zygomatic and upper maxillary areas. It is the most evident part of the face. Zone 1 lesions are considered to be amenable to radical excision and reconstruction with autogenous bone graft. In 1990, Chen reported successful resection for cure and reconstruction of Zone 1 lesions in five of 14 patients.

Zone 2 is the hair-bearing cranium. This area is also amenable to radical resection. However, deformities of this region are less cosmetically obvious, so conservative surgical shaving is the modality recommended by Chen.

Zone 3 comprises the base of skull region including the mastoid, petrous and pterygoid regions. This is a dangerous area for exploration due to the presence of cranial nerves and large vessels. Treatment is conservative, with surgery only as symptoms arise or in cases of where some structures, such as the optic nerve are endangered.

Zone 4 is the tooth-bearing bones, the maxillary alveolar bone and the mandible. Treatment is conservative, based on the principle that resection will necessitate dentures, which are not as functional as natural teeth. Surgical shaving is therefore preferred.

YM is a 12-year-old girl who has had progressive, slow, non-painful enlargement of her left cheek since early childhood. She was diagnosed with fibrous dysplasia at an outside hospital and after numerous procedures was referred to the Texas Childrens Hospital for further care. Over the past year she has noticed a slightly decreased rate of enlargement of her left maxillary lesion.

On physical examination she has a fullness of her left maxilla which displaces her left nasal ala anteriorly and medially. The lesion in visible as a fullness of the left lateral nasal wall. The maxillary branch of her trigeminal nerve is non-functional. She has well-healed scarring of her left maxillary gingiva from previous surgical procedures. No other abnormalities are noted on physical examination.

Maxillofacial CT reveals a left maxillary lesion extending from the anterior maxillary wall, involving the entire area of the expected maxillary sinus and encroaching upon the inferior aspect of the left orbit. There is a second lesion involving the left side of the sphenoid bone.

Due to the involvement of the sphenoid, it was determined that the patient would not be a good candidate for resection for cure. She underwent a recontouring procedure involving multiple osteotomies. Based on the apparent slowing of growth of her lesions, it is hoped that with the onset of puberty her disease will quiesce.

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Last modified: November 19, 2005