A 42-year-old man with rapidly progressive vision loss
Christine James, D.O., Darnell Josiah, M.D., and Kymberly Gyure, M.D
A 42-year-old man with a past medical history of fibrous dysplasia presented to the emergency department with a five-day history of progressive vision loss in his left eye. The patient had symptoms of a sinus infection two days prior to presentation and had suffered a nose bleed that required packing in the emergency room (ER) one day earlier.
An MRI was obtained (Figure 1).
The patient subsequently underwent a left frontotemporal craniotomy, left posterior orbitotomy, and left clinoidectomy to decompress the optic nerve. A soft tissue mass was discovered growing medial to the optic nerve and involving the medial orbit. The mass was debulked and submitted for pathologic evaluation (Figures 2-3).
Figure 1. MR imaging reveals expansion of the frontal bones typical of fibrous dysplasia as well as a midline destructive lesion with an associated soft tissue mass.
Figure 2. The lesion is composed of sheets of spindle-shaped cells (original magnification – 100x).
Figure 3. At higher magnification, the cells are pleomorphic with numerous mitotic figures. There is focal osteoid formation (original magnification – 400x).
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Fibrous dysplasia, also known as Lichtenstein-Jaffe disease, is a rare condition in which fibrous tissue develops in the medullary cavity of bone and replaces the normal bone. This results in weakening of the underlying bone, sometimes causing deformation and pathologic fractures. If one bone is affected, the condition is referred to as monostotic fibrous dysplasia. This type is most common (70-80%) and is usually asymptomatic and only found incidentally. Polyostotic fibrous dysplasia involves multiple bones, the most common of which are the femur, tibia, pelvis, ribs, skull, and humerus. The lumbar and cervical spine, as well as the clavicle, are typically spared. Monostotic fibrous dysplasia does not typically evolve into polyostotic fibrous dysplasia. Fibrous dysplasia of the facial bones of the skull can cause very visible external deformities of the face and cause vision and hearing loss due to nerve compression. Lesions in the anterior face can cause obstruction leading to otitis media, sinusitis, mouth breathing, and sleep apnea. One clinical hallmark of fibrous dysplasia is the “Shepherd crook”, a coxa varus angulation of the proximal femur due to multiple fractures. Another symptom is bone pain due to the expansion of the medullary cavity.
Most individuals are diagnosed during their teenage years or in early adulthood. Fibrous dysplasia is associated with McCune-Albright syndrome, and those affected may experience precocious puberty and café-au-lait spots. Endocrine derangements are caused by involvement of the pituitary, adrenal, parathyroid, or thyroid glands. Fibrous dysplasia also has an association with neurofibromatosis type II. When fibrous dysplasia is found in association with soft tissue myxomas, the diagnosis of Mazabraud syndrome can be made. Pregnancy may cause a hormonal imbalance that favors more rapid growth of the lesions and aneurysmal bone cyst formation.
Imaging studies reveal expanded bones with a “ground glass” appearance of the medullary cavity. The lesions are often classified as sclerotic, cystic/lytic, or mixed. Sclerotic fibrous dysplasia is found in 35% of cases and occurs frequently at the skull base and in thick bones. Mixed lesions comprise 40% of cases, and the cystic/lytic type is most rare. Fibrous dysplasia tends to occur in the diaphysis or metaphysis of long bones. A thick layer of reactive, sclerotic bone, termed the “rind”, may surround the lesions. Bone scans can be used to assess the extent of the disease. The uptake may become less intense as the lesions age.
The histologic hallmark is randomly oriented, “alphabet soup” or “Chinese character” trabeculae of woven bone that lack osteoblastic rimming. Multinucleated giant cells may be seen along the trabecular borders. No lamellar bone is seen. Fibrocartilaginous dysplasia, cystic changes, and hemorrhage can also be seen. Transcription factor c-fos is elevated. The patient’s serum will have elevated levels of alkaline phosphatase, and the urine may have increased levels of hydroxyproline. Neither of these laboratory results is sensitive or specific for fibrous dysplasia.
The differential diagnosis for fibrous dysplasia includes Paget disease of the bone, osteofibrous dysplasia, ossifying fibroma, and sarcoma. Paget disease spares the orbits, nasal cavities, and maxilla and lacks the “ground glass” appearance on CT. Osteofibrous dysplasia occurs only in the tibia and fibula and has a mean age of diagnosis of 24 years. Cherubism is a similar disease that causes fibrous replacement of the bone of the maxilla and mandible. This condition causes painless swelling and often spontaneously regresses at puberty.
A somatic gene mutation has recently been linked to fibrous dysplasia and McCune-Albright syndrome. The GNAS1 gene is located on chromosome 20q13.2-13.3 and encodes the alpha subunit of the stimulatory G protein, Gsα. The mutated Gsα protein stimulates adenylate cyclase which upregulates cAMP of osteoblastic cells and, in turn, triggers excessive growth of fibrous bone without proper mineralization. There is also increased production of the cytokine IL-6, which is involved in upregulating osteoclast differentiation. The extent of the disease depends on the time of the mutation, with a worse prognosis stemming from mutations during early embryonic development.
Cancer arises in less than 0.5% of patients with fibrous dysplasia not associated with McCune-Albright syndrome. The rate tends to be higher with the polyostotic type. When the association is present, the risk increases to approximately 4%. Malignant transformation occurs usually in the third and fourth decade and may be associated with prior radiation treatment of the fibrous dysplasia. The most common malignancies include osteosarcoma, fibrosarcoma, chondrosarcoma, and so-called malignant fibrous histiocytoma. The facial bones are most commonly affected followed by the lower extremity bones and pelvis. Of the facial bones, the most common location is the maxilla, followed by the mandible and zygomatic bone. Prognosis tends to be worse in malignant transformation than with a primary sarcoma of the same type.
Treatment includes pain management and the use of bisphosphonates. Intravenous pamidronate is the agent of choice and has been shown to decrease bone pain. The use of calcitonin is controversial. Surgical intervention is often necessary to treat displaced fractures, refractory hairline fractures, progressive deformation, encroachment on the foramen magnum, and for cancer. When vision loss is present, high dose steroids should be started prior to optic nerve decompression. Post-operative vision recovery is not predictable, as visual acuity may improve, stabilize, or deteriorate further. Radiation should not be used in treatment protocols because of its association with increased malignant transformation.
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