Incidence

Simple bone cysts are benign tumors of childhood and adolescence. They represent approximately 3% of all primary bone tumors sampled for biopsy and nearly always occur during the first 2 decades of life, most often between 4 and 10 years of age. These cysts have a male predominance, with a 2:1 male-to-female ratio. Most cysts occur in the metaphyseal region of the proximal humerus or femur; approximately 50% of cases involve the humerus, and 18% to 27% affect the femur. The next most common sites are the proximal tibia and distal tibia. Occasionally, cysts may be found in the calcaneus, fibula, ulna, radius, pelvis, talus, lumbar spine, and other parts of the axial skeleton ( Fig. 29-1 ). *

Imaging findings in a 14-year-old boy with pain in his heel. A, Radiograph demonstrating the lucent solitary bone cyst in the calcaneus. B, A computed tomography scan showed the extent of the lesion, which is surrounded by a rim of cortical bone.

* References .

Simple cysts are often categorized as “active” or “latent” based on their proximity to the growth plate. A cyst that is juxtaphyseal (<0.5 cm from the physis) is considered active and possesses greater potential for growth. Epiphyseal involvement is rare, but if present it should be considered an aggressive form of an active lesion. A cyst that has grown away from the plate is considered latent and theoretically no longer has the capacity for growth ( Fig. 29-2 ). In reality, however, latent cysts continue to have growth potential, as proved time and again by their unexpected recurrence after treatment in the young patient. After skeletal maturity, it is uncommon for the cysts to recur or progressively worsen.

A and B, Active solitary bone cyst in the proximal left femur of a 4-year-old boy (D.J.). The cyst is juxtaphyseal. C and D, A latent solitary bone cyst has grown away from the proximal physis in the right humerus of an 8-year-old boy (D.T.). See Figure 29-4 for posttreatment results.

Etiology

The cause of simple bone cysts remains uncertain. Any theory relating to the etiology of simple bone cysts should be able to explain the following factors: (1) more than 70% are discovered in childhood, (2) more than 95% arise from or involve the metaphysis, (3) most occur in the proximal humerus or femur, (4) a cyst wall and fluid high in protein content are common, and (5) simple bone cysts represent a benign process with a significant recurrence rate after treatment.

Mirra hypothesized an intraosseous synovial cyst in which a small amount of synovial tissue became entrapped in an intraosseous position during early infant development or secondary to trauma at birth. Over time, increased pressure secondary to secretions would lead to expansion within the bone. Jaffe and Lichtenstein postulated that cysts resulted from a localized failure of ossification in the metaphyseal area during periods of rapid growth. Cohen proposed that the cause of the cyst was blockage of the circulation (venous obstruction) and drainage of interstitial fluid in rapidly growing bone. He based this theory on the finding that the chemical constituents of the fluid in simple bone cysts are similar to those of serum. Current literature further substantiates this theory of a disturbance in or occlusion of the intramedullary venous circulation.

Two genetic analyses of simple bone cysts identified single and multifocal cytogenetic rearrangements associated with the condition. These findings emphasize the need for further studies clarifying the frequency and significance of chromosomal anomalies in this type of lesion.

Drilling, trepanation, and reaming of the medullary cavity to open vascular channels between cysts and the intramedullary venous system all have been found effective in healing unicameral cysts. The cyst fluid itself may be both a factor in cyst formation and an obstacle to healing. Bone-resorptive factors, such as prostaglandins, interleukin-1, and lysosomal enzymes, are found in cyst fluid. In addition, Komiya and associates reported elevated levels of interleukin-6 and interleukin-1β in cyst fluid and the presence of tumor necrosis factor-α, interleukin-6, and interleukin-1β in cells in the cyst membrane. These findings, along with inducibility of production of nitrate and nitrite from cyst membrane cells in response to cytokine exposure, suggest that conditions within solitary bone cysts may promote production of nitric oxide. Oxygen free radicals, which are cytotoxic and known to be generated under ischemic conditions, have also been found in cysts.

Pathology

Simple bone cysts tend to expand by eroding the cortex and result in a localized bulge of the bone. Nonetheless, reactive or periosteal bone formation is not present unless a pathologic fracture occurs. Where the cortical tissue is thinnest, the wall can actually be fluctuant, and a bluish tinge from the underlying fluid can be seen. Once the affected bone has fractured, the cortical wall is thicker, and multiple bony septa may occur throughout the cyst.

The fluid found within simple bone cysts is straw colored or serosanguineous, a feature distinguishing simple bone cysts from aneurysmal bone cysts. Often, significant pressure within the cyst (which can be greater than 30 cm H ₂ O) is evident when a needle is introduced. After a fracture, however, the cyst may become filled with blood clot, granulation, or fibro-osseous tissues. The most characteristic histopathologic finding is the thin membranous lining of the cyst ( Fig. 29-3 ). Composed primarily of flattened to plump epithelium-like cells, the lining may also possess osteoclast-type giant cells, cholesterol cells, and fat cells. Hemosiderin, fibrin, calcification, and reactive bone may be seen in focal areas of the cyst.

Histologic appearance of a simple bone cyst (original magnification ×10). The thin membranous lining is composed primarily of epithelium-like cells.

Clinical Features

Clinically, cysts can be asymptomatic and may be discovered incidentally when radiographs, such as a chest film, are obtained for other reasons. More often, however, the cysts are diagnosed because of pain. The pain may be mild and reflect a microscopic pathologic fracture. More abrupt discomfort occurs when a pathologic fracture occurs after relatively minor trauma, such as a fall. These fractures occur in up to 90% of patients and heal readily, although the cysts do not. After these pathologic fractures, premature physeal closure has been reported in nearly 10% of patients.

Radiographic Findings

Simple bone cysts have several characteristic radiographic features. Approximately 50% occur in the proximal humerus and 18% to 27% in the proximal femur. The cyst is metaphyseal and usually extends to, but not across, the physis. On rare occasions it crosses the physis into the epiphysis. Typically the cyst is symmetrically expansile and radiolucent, with a thin cortical rim surrounding it. Over time the physis grows away from the cyst, thus changing from the active to the latent phase. In many newly diagnosed cases a pathologic fracture occurs with or without displacement. The one pathognomonic manifestation of a simple bone cyst is the “fallen fragment” sign. This represents a portion of fractured cortex that settles to the most dependent part of the fluid-filled cyst. However, it is seen in less than 10% of cases, and it should not be expected if the cyst has become multiloculated after a previous pathologic fracture.

On magnetic resonance imaging (MRI), simple bone cysts often have a complex appearance because of heterogeneous fluid signals and regions of nodular and thick peripheral enhancement caused by previous pathologic fracture and subsequent healing. MRI may reveal focal, thick peripheral, heterogeneous, or subcortical patterns, with focal nodules of homogeneous enhancement (diameter >1 cm) within the cyst that are associated with areas of ground-glass opacification on plain film. MRI may also detect fluid levels, soft tissue changes, and septations not seen on plain film.

Differential Diagnosis

The diagnosis can usually be established based on the presence of typical radiographic findings. Other lesions to be considered in the differential diagnosis include aneurysmal bone cyst, monostotic fibrous dysplasia, and atypical eosinophilic granuloma. All these lesions may be radiolucent. Aneurysmal bone cysts and fibrous dysplasia may be expansile and metaphyseal. However, features typically associated with these lesions usually help differentiate them from simple bone cysts.

Treatment

A common misconception in the treatment of simple bone cysts in children is that once the pathologic fracture heals, the cyst also has an excellent chance of healing spontaneously. However, most investigators examining this phenomenon have found that the likelihood of spontaneous healing of the cyst after pathologic fracture is very low, probably less than 5%. Thus if treatment of the cyst is deemed necessary, it should be undertaken as soon as the fracture has healed. However, overtreatment in skeletally mature persons should be avoided. In these individuals, if the cyst has a sufficiently thick cortex and is located in the upper extremity, periodic observation may be all that is needed. If the patient is asymptomatic, restriction of activities may not be necessary.

The treatment approach is more aggressive for all simple bone cysts in younger children and in skeletally mature individuals when the cyst is located in weight-bearing bones of the lower extremities. In these cases plans should be made for definitive treatment of the cyst to prevent future fractures and possible associated complications (e.g., shortening resulting from growth arrest and deformity). Findings by Stanton and Abdel-Mota’al suggested that the rate of growth arrest as a complication of simple bone cysts of the humerus approximates 10%, a frequency more common than is generally appreciated.

The preoperative evaluation of patients with simple bone cysts rarely requires more than good-quality radiographs of the lesion. If the diagnosis is equivocal, a bone scan will verify the presence or absence of other abnormal areas. Computed tomography (CT) may be helpful in differentiating simple bone cysts from other lesions, such as aneurysmal bone cysts or fibrous dysplasia. MRI findings of double-density fluid levels and septation associated with low signal on T1-weighted images and high signal on T2-weighted images strongly suggest the presence of an aneurysmal bone cyst rather than a simple bone cyst. The diagnosis is usually confirmed at surgery, when straw-colored fluid is aspirated through a large-bore needle introduced into the cystic cavity.

Treatment modalities include injection of corticosteroids into the cyst, injection of autologous bone marrow, multiple drilling and drainage of the cavity, and curettage of the membranous wall followed by bone grafting. A relatively high recurrence rate has been historically associated with treatment of simple bone cysts. Older forms of treatment, such as subtotal resection with or without bone grafting and total resection, have been associated with increased cyst recurrence and are rarely, if ever, used today.

Corticosteroid Injections

The successful healing of cysts after injections of methylprednisolone acetate was reported by Scaglietti and colleagues in 1979. These investigators noted favorable results in 90% of lesions and consequently concluded that treatment by curettage was seldom necessary. Healing was believed to have occurred if the cortex thickened and the cystic cavity became radiographically opaque. Filling of the cyst with “bone scar” was considered evidence of healing ( Fig. 29-4 ). Actual remodeling, with complete disappearance of the cystic cavity, often took several years. Subsequent reports have continued to substantiate the effectiveness of injecting steroids into cysts, although the success rates have been lower, ranging from 40% to 80%. ^† Ramirez and associates found that cysts in which radiographic contrast showed rapid venous outflow were less likely to heal than were cysts without this finding. This method continues to be a popular choice for the initial management of simple bone cysts. The antiprostaglandin action of steroids constitutes the rationale for their use in the treatment of cysts.

The patients whose pathologic findings are shown in Figure 29-2 underwent corticosteroid injections into the cysts. In patient D.J., Renografin injected during the first steroid treatment demonstrated filling of the cyst ( A ). Twenty months later, after a total of four injections, the cyst was healed ( B and C ). In patient D.T., the entire cyst filled during the first injection ( D ). At the time of the fourth injection 6 months later, minimal cyst cavity was seen ( E ). A venogram was obtained at the time of contrast injection. Eight months after the initial steroid treatment, the cyst had healed ( F and G ).

† References .

The patient is given a general anesthetic in the operating room, and the procedure is performed using strict aseptic techniques. Fluoroscopy with image intensification is used to locate the margins of the cyst. Two large needles with stylets (at least 14-gauge or Craig biopsy needles) are used. The first needle is introduced percutaneously, the stylet is withdrawn, and fluid is allowed to drip out. The presence of straw-colored (serosanguineous) fluid confirms the diagnosis of simple bone cyst. Vigorous aspiration must be avoided because blood may be returned, thus making it difficult to distinguish a simple bone cyst from an aneurysmal bone cyst. If straw-colored fluid is returned, contrast material (usually Renografin diluted 1:1 with normal saline) is injected to confirm the presence or absence of intracystic fibrous or osseous septa and loculation. Needles must be introduced into each separate cystic cavity to ensure delivery of the steroid; if the cyst is not filled completely, the incidence of failure of healing increases.

After the contrast material clarifies the structure of the cystic cavity, the second needle is introduced. The cavity is thoroughly flushed with normal saline solution. The operator should not aspirate when a second needle is in the cyst because air can be aspirated into the cyst from the second needle and can lead to an air embolus. When lavage with normal saline is completed, the second needle is withdrawn. Through the remaining needle, 40 to 120 mg (1 to 3 mL) of methylprednisolone acetate is introduced into the cyst, and a simple compression dressing is applied.

This procedure is usually repeated every 2 months. It requires between two and five injections, with three the usual minimal number to obtain healing. Because radiographic changes usually are not noted in the first 2 to 3 months, radiographs are not needed before then. Subsequently, radiographs are obtained every 2 to 3 months to assess healing. Evidence of healing includes diminution in the size of the cyst, cortical thickening, remodeling of the surrounding bone, and increased internal density (e.g., ground-glass ossification).

The use of serial steroid injections is the most popular treatment mode because the procedure is simple, injury to the adjacent physis is avoided, the procedure causes a minimal operative scar, little morbidity occurs, the patient is able to return promptly to a previous activity level, and the reported results are excellent. A potential disadvantage is a temporary systemic response to the steroid (Cushing syndrome). It is best not to exceed a total of 120 mg of methylprednisolone during any one injection.

Autologous Bone Marrow Injections and Other Bone Substitutes

Interest in the injection of other materials to stimulate healing led to the successful use of autologous bone marrow. In one study, Docquier and Delloye reported successful cyst regression in 15 of 17 cases after a single bone marrow injection, with recurrence in 12% of cases during a subsequent 3-year period. Collagen, demineralized bone matrix, and calcium phosphate paste are other injectable materials that are under investigation. In a small series of 11 patients, Killian and colleagues reported complete cyst healing in 9 patients after primary treatment with demineralized bone matrix, with no recurrences detected during a 2-year follow-up period. In addition, by using a combination of autologous bone marrow and demineralized bone matrix, Rougraff and Kling noted complete cyst healing in 16 of 23 patients, with 5 recurrences reported during 4 years of follow-up. At our institution, we have been encouraged with the early results using injectable bioresorbable calcium phosphate paste (alpha-BSM), and this is becoming our treatment of choice ( Fig. 29-5 ).

This 6-year 9-month-old boy underwent cyst injection with calcium phosphate (alpha-BSM) 2 months before this radiograph. He had undergone open reduction and internal fixation of a pathologic femoral neck fracture years earlier, but the cyst failed to heal.

Incidence

An aneurysmal bone cyst is a solitary, expansile, radiolucent lesion usually located in the metaphyseal region of the long bones. Seen much less often than simple bone cysts, aneurysmal bone cysts represent 1% of all primary bone tumors sampled for biopsy; the annual incidence of primary aneurysmal cysts approximates 0.1 per 10 ⁹ individuals. Nearly 70% of affected patients are between 5 and 20 years of age, and approximately half of these cysts occur in the second decade of life, although the lesion has been reported in infants. ^‡ No sex predilection is reported.

‡ References .

Approximately 20% of aneurysmal bone cysts involve the spine. They may occur anywhere between the axis and the sacrum and can cause spinal cord compression or spinal deformity. Within the vertebra itself, the cyst may be found in the body, pedicles, lamina, and spinous process ( Fig. 29-6 ). Involvement of two or more adjacent vertebrae is not uncommon. Aneurysmal bone cysts may also occur in the maxilla, frontal sinus, orbit, zygoma, ethmoid, temporal bone, mandible, sternum, clavicle, hands, and feet. ^§

Imaging findings in an 11-year-old girl with moderate back pain in the thoracolumbar spine for 6 months. Anteroposterior ( A ) and lateral spine ( B ) radiographs demonstrated an aneurysmal bone cyst of L1. C and D, Computed tomography showed that the cyst extensively involved the posterior elements on one side. E, Two years after resection and bone grafting, the radiographic appearance still was not normal.

Etiology

§ References .

Development of an aneurysmal cyst as a secondary response is supported by the association of aneurysmal cysts with other primary lesions, such as nonossifying fibromas, fibromyxomas, fibrous dysplasia, chondroblastomas, giant cell tumors, simple bone cysts, telangiectatic osteosarcomas, chondrosarcomas, and metastatic disease. Sixty-five percent of aneurysmal bone cysts have been reported to be primary, and 35% are believed to be secondary to other lesions. Thus once the diagnosis of aneurysmal bone cyst is considered, a thorough preoperative evaluation is necessary, adequate tissue must be obtained at the time of surgery, and careful pathologic studies are needed to ensure that the aneurysmal cyst is not secondary to a more serious primary neoplasm.

Pathology

Aneurysmal bone cysts vary considerably in size, with the potential to become large during the rapid, destructive growth phase. On gross inspection, the cyst consists of an encapsulated mass of soft, friable, reddish-brown tissue, usually contained within a thin subperiosteal shell of new bone. At the time of surgery, a large amount of blood may exude from a mesh of honeycomb spaces. In most cases the blood is dark red as a result of slow but continuous circulation. If the circulation to a portion of the aneurysmal cyst has been blocked, the cyst may be filled with serous or serosanguineous fluid or with focal organized blood clots.

Microscopy discloses a variable number of vascular spaces whose walls are lined with tissue composed of fibroblastic cells with collagen, giant cells, hemosiderin, and osteoid (secondary to microfractures; Fig. 29-7 ). Extensive sampling should be performed to identify possible benign or malignant precursor lesions, as well as to identify transformation into malignant lesions such as malignant fibrous histiocytoma or osteosarcoma. The histologic diagnosis of primary aneurysmal bone cyst should be made only after other possible lesions have been excluded. Fibrous tissue, bone, and giant cells are the usual elements seen in most other benign precursor lesions associated with an aneurysmal bone cyst. Any solid area that is 1 cm or larger should raise the suspicion that it may represent another lesion.

Aneurysmal bone cyst (original magnification ×10). The wall of the vascular space is lined with giant cells, collagen, and osteoid.

Another entity is a solid aneurysmal bone cyst or giant cell reparative granuloma. This solid yet radiolucent lesion appears grayish brown and often is friable. Histologic features include fibrous proliferation with giant cells, fibromyxoid areas, and bone production. Characteristically the giant cells, which are clustered in areas of recent and old hemorrhage, are found throughout the lesion. The solid aneurysmal bone cyst lacks the normally large blood-filled channels ( Fig. 29-8 ). In a review of a large series of aneurysmal bone cysts, the incidence of the solid entity was 7.5%.

Solid aneurysmal bone cyst (original magnification ×40). Clusters of giant cells are found throughout the lesion.

Clinical Features

The clinical presentation includes localized pain of several weeks’ or months’ duration, tenderness, and, if the aneurysmal bone cyst occurs in an extremity, swelling. When the cyst involves the spine, progressive enlargement may compress the spinal cord or nerve roots and result in neurologic deficits such as motor weakness, sensory disturbance, and loss of bowel or bladder control. The cysts may also cause other spinal lesions such as vertebra plana. Spinal involvement therefore mandates urgent intervention.

Radiographic Findings

The classic radiographic feature of aneurysmal bone cysts was described by Jaffe as a periosteal “blowout” or ballooned-out lesion that is outlined by a thin shell of subperiosteal new bone formation. In approximately 80% of cases the cyst involves the metaphyseal region of the long bones and, unlike simple bone cysts, is eccentric in its location. In the spine, it more often involves the posterior elements (spinous process, transverse process, and pedicles) than the vertebral body. In the shorter tubular bones of the feet, the cysts are more central and extend into the diaphysis and subarticular region (this is explained by the smaller size of the bones).

Three phases of aneurysmal cysts have been described. The incipient phase is characterized by either a small eccentric lucent lesion or a pure lifting off of the periosteum from the host bone without evidence of an intramedullary lesion. Most patients do not present with disease in this phase. Except for focal cortical thinning, the cortex may otherwise be preserved, and the periosteum may show no reaction. In this phase, the lesion can be mistaken for a simple bone cyst, nonossifying fibroma, or possibly a lytic osteosarcoma. The midphase designates the period of rapid, destructive growth and is characterized by extreme lysis of the bone, focal cortical destruction, and the development of Codman triangles (periosteal ossification at the corner of the expanded cyst). It is during this phase that the “blowout” appearance is seen on radiographs, and aneurysmal bone cysts can easily be mistaken for an aggressive malignant lesion. In the late healing or stabilization phase, the lesion grows more slowly, and the periosteum has sufficient time to lay down new bone. The cyst will exhibit the following features: eccentric (or possibly concentric), smooth-bordered expansion; a trabeculated or “bubbly” intramedullary appearance; and surrounding host bone sclerosis.

Capanna and colleagues proposed a radiographic classification system that is commonly used today. Inactive cysts have a complete periosteal shell, with the intraosseous margin defined by a sclerotic rim of reactive bone. Active cysts have an incomplete periosteal shell and a sharply defined intraosseous border. Aggressive cysts show no evidence of reparative osteogenesis, no periosteal shell, and an ill-defined endosteal margin.

Once these lesions are identified on radiographs, the tumor can be better clarified with CT, particularly if it is located in the spine. The extent of involvement of the vertebra and any encroachment of the spinal canal are readily evident. CT also demonstrates the characteristic fluid–fluid levels if the patient is able to lie still long enough for the serosanguineous fluid to separate from the blood within the chambers of the cyst that do not have active circulation. MRI is indicated if the patient has evidence of spinal cord compression or if the edges of the rapidly expanding cyst cannot be defined with CT. Fluid–fluid levels are readily evident on MRI ( Fig. 29-9 ). MRI is most valuable in the differential diagnosis because it can delineate the multicystic appearance, hypointense rim, contrast-enhancing cyst walls, double-density fluid levels, and adjacent soft tissue edema that are typical of this lesion, as well as the extent of the lesions. Gadolinium-enhanced MRI may be helpful for distinguishing the solid variant from conventional aneurysmal bone cyst. The differential diagnosis includes atypical osteosarcoma and telangiectatic osteosarcoma, which may rarely mimic aneurysmal bone cyst radiologically.

Imaging findings in a 9-year-old girl with a swollen tender first ray of the left foot. A, Anteroposterior radiograph demonstrated an expansile well-contained lesion. B to D, Magnetic resonance images better defined the lesion and showed the layering effect seen with aneurysmal bone cysts. E, Three years after curettage and bone grafting, the metatarsal was normal.

Treatment

Although spontaneous healing of aneurysmal bone cysts has been reported, it is uncommon. Thus expectant management should be considered only when the diagnosis has been made with confidence and the lesion is in a location and at a stage that do not entail any risk of fracture or further destruction. More often, when the diagnosis of aneurysmal bone cyst is made, active treatment is recommended.

Curettage and Adjunctive Therapy

Curettage followed by bone grafting of aneurysmal cysts has been the standard treatment for many years ( Fig. 29-10 ). Unfortunately, this tumor has a high incidence of local recurrence (14% to 59%) after curettage, although Gibbs and colleagues reported rates of local control approaching 90% following curettage with use of a mechanical burr in 40 patients with aneurysmal bone cyst of an extremity. In this series, very young age and open growth plates were associated with increased risk of local recurrence. Overall, however, adjunctive therapy, such as cementation, cryotherapy, or embolization, should be considered along with curettage. Cementation of the lesion with polymethyl methacrylate, followed 4 to 6 months later with replacement bone grafting, has been reported to be more effective than curettage and bone grafting alone. Cryotherapy as an adjunct to curettage and bone grafting also increases the likelihood of healing. Percutaneous sclerotherapy using absolute alcohol has also been reported with reasonable success. Steffner reported that among several techniques, the lowest rate of recurrence (7.5%) was obtained with curettage with a high-speed burr with argon beam coagulation. Embolization has been used as the sole treatment for aneurysmal bone cysts, but it is much more commonly used before surgery to interrupt the vascularity of the lesion. Embolization is useful in treating aneurysmal cysts located in areas of limited access, such as the spine and pelvis, although incidences of significant complications including fatal Ethibloc embolization of the vertebrobasilar system have been reported. Repeated embolization as the sole treatment was reported in a lesion of the pelvis in a 3-year-old child. If the cyst is located in an expendable bone, such as a rib or fibula, the surgeon should consider performing a wide or en bloc excision. Juxtaphyseal aneurysmal bone cysts may be treated satisfactorily with excision, curettage, and bone grafting, with careful preservation of the growth plate.

Imaging findings in a 3-year-old boy who presented with a painful, swollen distal forearm. Anteroposterior ( A ) and lateral ( B ) radiographs demonstrating the “blown-out” appearance of the distal radius. C, The edges of the lesion could not be seen well on computed tomography. D and E, Magnetic resonance imaging demonstrated containment of the lesion. F and G, After a biopsy confirmed the diagnosis of aneurysmal bone cyst, curettage and bone grafting were performed. H and I, Three years after surgery, the radius had healed and remodeled.

Anecdotal reports of techniques useful in the treatment of aneurysmal bone cysts include oral dexamethasone (an angiostatic agent), percutaneous intralesional injection with calcitonin and methylprednisolone, endoscopic curettage without bone grafting, and the use of multiple Kirschner pins inserted into the cyst. Garg and colleagues reported a significantly reduced rate of recurrence (0 of 8 cases) when a four-step approach of intralesional curettage, use of a high-speed burr, electrocautery, and bone grafting was used as an alternative to traditional intralesional curettage and bone grafting.

Incidence

The term fibrous dysplasia was originally proposed by Lichtenstein in 1938. He, along with Jaffe, McCune, and Albright, described this disorder of bone, as well as other extraskeletal abnormalities with which it is occasionally associated. Their descriptions remain among the best for fibrous dysplasia—a benign, nonfamilial disorder characterized by the presence of expanding intramedullary fibro-osseous tissue in one or more bones. The incidence of fibrous dysplasia is not known, but it is not an uncommon primary bone tumor. It occurs more frequently in girls than in boys, particularly the polyostotic form. Although most lesions are probably present in early childhood, they usually do not become evident before late childhood to adolescence.

Classification

In general, fibrous dysplasia can be classified into one of three categories. Monostotic fibrous dysplasia involves only one bone, and many of these patients remain asymptomatic unless a fracture or swelling occurs. The polyostotic form is more severe, involving multiple bones. Nearly any bone in the body may be affected, including the long bones of the extremities, skull, vertebrae, pelvis, scapula, ribs, and bones of the hands and feet. Often one side of the body (in particular, one of the lower extremities) is more severely affected, resulting in deformity and limb length discrepancy. Craniofacial involvement occurs in nearly 50% of patients with polyostotic disease. The third category, polyostotic form with endocrine abnormalities, is the least common form. Precocious puberty, premature skeletal maturation, hyperthyroidism, hyperparathyroidism, acromegaly, and Cushing syndrome can occur in these patients. The triad of precocious puberty (endocrinopathy), café au lait spots, and polyostotic bone involvement is commonly referred to as McCune-Albright (or Albright) syndrome.

Etiology

The exact cause of fibrous dysplasia is not known. The condition is not believed to be hereditary. Fibrous dysplasia probably results from a failure of maturation from woven to lamellar bone. Studies have reported an abnormality of a gene encoding a G protein that is important in the development of bone. Somatic activating mutations of the signal transducer Gs of the alpha chain differentiate fibrous dysplasia (particularly McCune-Albright syndrome) from other lesions, and the mutations may be responsible for the loss of control of local proliferation and growth factor expression. Elevation in the cyclic adenosine monophosphate (cAMP) level induced by the Gs-alpha mutations leads to alterations in the expression of several target genes whose promoters contain cAMP-responsive elements, such as c-fos, c-jun, II-6, and II-11. These changes affect the transcription and expression of downstream genes and result in the alterations of osteoblast recruitment and function in dysplastic bone. These mechanisms provide a cellular and molecular basis for the alterations in bone cells and bone matrix in fibrous dysplasia.

Pathology

The outer surface of expanded bone is usually smooth and covered by reactive periosteal bone. The underlying dysplastic tissue is firm and grayish white, and the proliferative tissue is fibrous. It may feel gritty when palpated, almost like sandpaper. Degenerative cystic changes resulting from cellular necrosis may be evident. Islands of hyaline cartilage may be seen.

Histologically, irregular foci of woven (nonlamellar) bone trabeculae are seen in a cellular fibrous stroma ( Fig. 29-11 ). Under the microscope, the bony spicules are often described as looking like the letters C , J , or Y or resembling Chinese characters. Osteoclastic resorption may be seen, but osteoblastic rimming of the bony spicules is uncommon. In unusual cases, as much as 95% of the lesional tissue may be fibrous. Cartilage islands, multinucleated giant cells, foamy histiocytes, and callus may be seen if a fracture has occurred. The histologic features of polyostotic lesions are identical to those of monostotic lesions.

Histologic appearance of fibrous dysplasia (original magnification ×10). Spicules of woven bone arise from the cellular fibrous stroma.

Clinical Features

The clinical manifestations are usually mild in monostotic fibrous dysplasia. Pain and a limp may be evident when the neck of the femur is involved. Local swelling may be seen when the lesion is in a superficial bone, such as the mandible, skull, or tibia. The skeletal changes are usually more severe in the polyostotic form and may result in pain, swelling, deformity, and limb length discrepancies. The classic example of this is found in the proximal femur. Repetitive microfractures can lead to a “shepherd’s crook” deformity with pain, significant varus at the femoral neck, shortening of the femur, an obvious Trendelenburg gait, and limited mobility. Deformity can occur in all the long bones, but usually not to the degree seen in the femur. In patients with polyostotic disease, the peak incidence of fractures is during the first decade of life, followed by a decrease thereafter. When the facial bones are affected, progressive deformity may become evident to the patient and family. Numerous reports of craniofacial abnormalities are found in the dental and maxillofacial literature ( Fig. 29-12 ). Spinal lesions and scoliosis may be more common in patients with polyostotic fibrous dysplasia than was previously thought. Dysplastic lesions of the spine, primarily involving the posterior elements, have been reported in 63% of patients, and scoliosis has been reported in 40% of patients. There have also been reports of vertebral collapse, angular deformity, and possible spinal cord compression.

Fibrous dysplasia. Computed tomography scans of the head demonstrate expansion of the maxilla ( A ) and replacement of a normal sinus with fibrous dysplasia ( B ). Slight facial asymmetry is noted because of the affected bone on the right side ( C ).

The most common nonskeletal manifestation associated with fibrous dysplasia is abnormal cutaneous pigmentation, or café au lait spots. These have irregular borders (“coast of Maine”), are not raised from the surrounding skin, and may be extensive, involving large areas of the trunk, face, or limbs. The café au lait spots can coexist with polyostotic fibrous dysplasia without endocrine changes or precocious puberty, or they may be absent when endocrinopathies accompany fibrous dysplasia. The pigmentation changes usually are not present in monostotic fibrous dysplasia.

When sexual precocity occurs it is most often seen in the female patient secondary to premature ovarian stimulation, and it may occur as early as 1 year of age. Most cases of McCune-Albright syndrome occur in girls and are accompanied by accelerated maturation and advanced skeletal age. In such children, abnormally rapid growth may result in tall stature at a young age. Ultimately, however, their adult stature is usually below average because of their early maturation.

Malignant transformation of fibrous dysplasia is rare but has been reported.

Radiographic Findings

Fibrous dysplasia can affect any bone. In the long bones, the lesions start in the metaphysis or diaphysis and rarely involve the epiphysis. The flat bones, ribs, jaw, and skull are commonly involved. Spinal involvement is uncommon, 12% in one study, and may produce scoliosis.

Some of the smaller lesions of fibrous dysplasia remain confined to the intramedullary region, are often surrounded by sclerosis, and may appear “bubbly” or trabeculated. Normally, however, slow replacement of the cortex is evident as expansion takes place. Larger lesions may result in an even or eccentric, smooth-bordered expansion of the bone, but they usually remain confined within a rim of periosteal bone. Angular deformity may occur in the long bones, such as the shepherd’s crook deformity in the proximal femur and occasionally in the humerus. This deformity is usually a result of remodeling of the bone after repetitive microfractures or obvious fractures through the dysplastic bone ( Fig. 29-13 ).

Imaging findings in a 9-year-old boy with polyostotic disease. A, Radiograph obtained at presentation showing fibrous dysplasia of the femur. B, Six years later, at 15 years of age, a shepherd’s crook deformity had developed as a result of repetitive microfractures of the proximal femur.

The radiographic density of the lesions depends on the amount of woven bone produced and on the amount of cortex replaced. If the lesion is small, has produced little woven bone, or has not replaced cortex, it appears radiolucent compared with surrounding normal bone. If the cortex is thinned and if the fibrous dysplasia has expanded and replaced most of the normal bone, the characteristic ground-glass appearance is seen. When this feature is extensive, it is nearly pathognomonic of fibrous dysplasia. CT clearly demonstrates this appearance.

A bone scan demonstrates increased uptake throughout the lesion and is helpful in determining the extent of the disorder if radiographs are unable to do so.

Differential Diagnosis

With monostotic fibrous dysplasia, it may be difficult to differentiate small lesions from simple bone cysts on radiographs. Less often, small lesions may be confused with histiocytosis or enchondromas. In these cases a biopsy may be necessary. Larger lesions with cortical thinning and a ground-glass appearance usually do not require a biopsy to confirm the diagnosis. Polyostotic fibrous dysplasia is readily identified on radiographs.

Treatment

Surgical Treatment

A proposed exception to the nonoperative approach in children (in the absence of fracture or deformity) is infantile fibrous dysplasia. In these children with polyostotic disease, early surgical treatment to prevent development of skeletal deformities that are difficult to correct later may provide long-term benefit. Prophylactic intramedullary nailing with nails of appropriate size was found to be most effective. In the adult, bone grafting in fibrous dysplasia has been reported to be more successful in healing the dysplastic bone.

Operative intervention is needed when repeated pathologic fractures have occurred, when lesions cause significant or progressive deformity that jeopardizes the integrity of the long bone or that results in unacceptable disfigurement, or when associated pain becomes persistent. Pathologic fractures can occur after mild trauma. These fractures are often minimally displaced, and they heal at a normal rate. Delayed union or nonunion is not a problem, but progressive deformity is. The primary goal of treatment is to realign the deformed bone, particularly in the weight-bearing lower extremities. This objective, along with ready healing of the fracture, can often be achieved with cast immobilization in the young child. If repeated fractures occur in long bones or if a fracture involves the proximal femur, surgical intervention is the preferred treatment approach. Internal fixation maintains proper alignment and can be achieved with intramedullary rods in the long bones or with compression screws with side plates in the proximal femur. Before the insertion of internal fixation, osteotomies may be required to achieve satisfactory alignment because bowing of the bone (malunions) is common after fractures. This is particularly true in the proximal femur, in which a shepherd’s crook deformity may be present. These procedures are difficult in that the lack of a well-formed bony cortex makes passage of intramedullary fixation devices challenging. Augmentation with vascularized bone, either fibula or iliac crest, has shown some promise. Alternative fixation with screw and side plate is often complicated by angulation or fracture at the end of the plate. Intraoperative blood loss may be excessive because of increased vascularity in the bone. Despite the successful use of internal fixation and nearly anatomic bone realignment, progressive deformity can still occur and can lead to the need for additional surgery.

Some authors advocate attempts to augment bone strength in addition to or in place of internal fixation. Enneking and Gearen reported that cortical strut grafting was effective in strengthening the bone in the proximal femur ( Fig. 29-14 ). In their opinion, the strength of the bone was greater if cortical rather than cancellous graft was used. Allograft cortical struts avoid the morbidity of harvesting autogenous graft and also appear to slow the resorption process by the dysplastic bone. Vascularized grafts, both fibular and iliac crest, have had some reports of success. Ultimately, however, the type of graft used may not affect the rate of recurrence.

Radiographic appearance in a 7-year-old boy with polyostotic fibrous dysplasia and a painful, progressive varus deformity. A, Radiographically, the left hip was found to be involved. B, A valgus osteotomy with allograft fibula and internal fixation was performed. C, Ten months later, the allograft fibula had been resorbed by the dysplastic bone, and varus of the proximal femur was recurring.

Treatment alternatives for skeletally mature patients are also plagued with difficulty. Total hip replacement as well as total knee replacement may provide some years of pain relief and improved function, but eventually they loosen because the bony interface lacks cortical stability.

Incidence

Osteofibrous dysplasia of the tibia and fibula has been described as a variant of fibrous dysplasia. However, molecular investigations have found that the Gs-alpha mutation at the Arg201 codon is present in fibrous dysplasia but is absent in osteofibrous dysplasia. These data suggest that the two disorders have different pathogeneses. Osteofibrous dysplasia may also have a histogenetic relationship with adamantinoma. ^¶ Cytokeratin-positive cells are found in the stroma of both osteofibrous dysplasia and adamantinomas, but not in fibrous dysplasia.

¶ References .

Osteofibrous dysplasia differs from the more common fibrous dysplasia with regard to age distribution, site, radiographic features, and clinical course. The lesion is slightly more common in boys. The symptoms almost always appear in the first decade of life. Nearly two thirds of the lesions are noted before 5 years of age, and the disorder has been noted in infants. The tibia is almost always involved, and the ipsilateral fibula may be affected. Bilateral involvement has been reported, as has involvement of the radius and ulna. Mainly the diaphysis is affected, with localization to the middle third in the tibia. Extension into the proximal or distal metaphysis is seen sometimes. Rarely, diffuse involvement of the entire shaft of the tibia occurs. When the disorder is limited to the fibula, the distal third of the bone is affected.

Etiology

The pathogenesis of osteofibrous dysplasia remains unknown ; however, several theories have been proposed: (1) it results from excessive resorption of bone with fibrous repair of the defect, (2) it is a congenital lesion or a variant of fibrous dysplasia, and (3) it results from abnormal blood circulation in the periosteum. The report of this disorder in a family may also support a genetic component to its etiology. The literature suggests that the disorder is either a reactive process secondary to adamantinoma or a precursor to adamantinoma. ^#

Pathology

# References .

Histologically, the tissue is similar to fibrous dysplasia, with irregular spicules of trabecular bone and fibrous or collagenous stroma. In contrast to fibrous dysplasia, the spicules are usually lined with osteoblasts ( Fig. 29-15 ). The finding of woven bone with juxtaposed lamellar bone (from osteoblasts) is thought to be characteristic of osteofibrous dysplasia. Immunohistochemical studies have demonstrated isolated cytokeratin-positive cells in the stroma of osteofibrous dysplasia. These cells are not seen in fibrous dysplasia but are found in adamantinomas. Based on this finding, a relationship between osteofibrous dysplasia and differentiated adamantinoma is believed to exist; however, it is not certain whether osteofibrous dysplasia represents a possible precursor of or is a secondary reaction to adamantinoma. Nests of epithelial cells are a consistent histologic finding in adamantinomas, but they are not found in osteofibrous dysplasia.

Histologic appearance of osteofibrous dysplasia (original magnification ×10). The tissue is similar to fibrous dysplasia, with irregular spicules of woven bone. In contrast to the histologic appearance of fibrous dysplasia, the spicules are usually lined with osteoblasts.

Clinical Features

The common presenting complaint is firm swelling localized over the tibia with associated mild to moderate anterior tibial bowing. Osteofibrous dysplasia is usually painless unless the patient has a coexisting pathologic fracture.

Radiographic Findings

The lesion usually is extensive, involving the anterior cortex of either the diaphysis or the metaphysis of the tibia; the epiphysis usually is not affected. Characteristic eccentric, intracortical osteolysis is found, with moderate or marked expansion of the cortex ( Fig. 29-16 ). In small areas the cortex may actually appear absent, and a “bubbled” appearance may be evident. In some areas the osteolytic areas may have a ground-glass appearance. The tibia may be bowed anteriorly or anterolaterally. If the fibula is involved, the condition is usually evident in the distal third of the bone, and it affects nearly the entire circumference of the shaft.

A and B, Osteofibrous dysplasia of the tibia and fibula in a 5-year-old girl that is associated with mild anterior bowing. C and D, Radiographs obtained at 9 years of age, when persistent discomfort was present. E and F, Bone scans showed increased uptake in the area of the lesion. G, Computed tomography showed the intracortical osteolysis. Biopsy confirmed the diagnosis of osteofibrous dysplasia.

Differential Diagnosis

The two entities that must be distinguished from osteofibrous dysplasia are monostotic fibrous dysplasia and adamantinoma. In contrast to osteofibrous dysplasia, fibrous dysplasia is characterized by the following features: (1) it is usually detected after 10 years of age; (2) it is not routinely associated with anterior or anterolateral tibial bowing; (3) it is noted to be intramedullary on radiographs, with a ground-glass appearance; (4) histologically, the bony trabeculae in the fibrous stroma are rarely surrounded by osteoblasts; and (5) it should have the Gs-alpha mutation at the Arg201 codon. Adamantinomas usually occur in patients older than 10 years of age and contain epithelial components histologically. In adolescents, an open biopsy is needed to differentiate osteofibrous dysplasia from adamantinoma. This tissue must be carefully evaluated because of the difficulty in distinguishing between the two entities.

Treatment

The natural history of osteofibrous dysplasia varies. The lesion may grow slowly or it may expand rapidly into the entire diaphysis. Spontaneous healing of the lesion has been reported. The most common clinical course is one of steady growth and expansion during the first 5 to 10 years of life. Growth then slows, and after maturity the lesion stops expanding. Treatment depends on the course of the specific lesion.

In the young child, marginal subperiosteal resection or curettage has been reported to be successful, but this form of treatment is often followed by recurrence of the lesion. A wide extraperiosteal en bloc resection will presumably achieve a cure, but such a radical procedure is rarely, if ever, indicated. Minimally invasive osteotomy and plate fixation to correct the deformity may be a useful alternative. When the deformity is mild, a conservative approach (observation) is recommended. Bracing, consisting of an ankle-foot orthosis with anterior shell, is indicated if the tibia shows a progressive angular deformity. Cast immobilization of a pathologic fracture is recommended unless angular deformity requires correction; if so, internal fixation may be needed.

Conservative management also is recommended in the treatment of adolescents with osteofibrous dysplasia. If the radiographic appearance is unchanging, the patient should probably be observed indefinitely. If the lesion grows, marginal excision followed by bone transport through distraction osteogenesis has been reported to be successful.

Incidence

Osteochondroma is the most common benign bone tumor, and it reportedly accounts for 36% to 41% of all such tumors. It is characterized by a cartilage-capped osseous projection protruding from the surface of the affected bone. The exostosis is produced by progressive enchondral ossification of the hyaline cartilaginous cap, which essentially functions as a growth plate. More than 50% of solitary osteochondromas occur in the metaphyseal area of the distal femur, proximal tibia, and proximal humerus. Other areas in which solitary osteochondromas may be found include the distal radius, the distal tibia, the proximal and distal fibula, and occasionally the flat bones such as the scapulae, ilium, and ribs. The presence of these solitary lesions within the spinal canal, with resultant neurologic compromise, has received much attention in the literature. * ^a

Etiology

References .

Unlike the more extensive hereditary (autosomal dominant) multiple exostoses, solitary osteochondromas do not appear to be genetically transmitted.

Pathology

Solitary osteochondromas may be sessile (broad based) or pedunculated (narrow based). The surface usually is lobular, with multiple bluish-gray cartilaginous caps covering the irregular bony mass. The cartilaginous caps are covered by either thin or comparatively thick perichondrium, which may adhere to the underlying irregular surface and is continuous with that of the adjacent bony cortex. When this perichondrium is removed, the shiny cartilaginous cap is exposed. The cartilaginous cap is usually 1 to 3 mm thick, but in the younger patient it may be noticeably thicker. The thickness of the cartilaginous cap may be much greater if the tumor has undergone sarcomatous change. On cut section the cartilaginous cap varies in thickness and often has an opaque yellow appearance that reflects calcification within the cartilaginous matrix.

The tumor often resembles a cauliflower; however, it may also be flat, hemispheric, or tubular with a prominent end. Its base is contiguous with the normal cortical bone, and the interior of the lesion (spongiosa bone) blends with that of the host bone.

A bursa may develop over the osteochondroma, particularly in larger lesions, where movement of the adjacent soft tissue leads to irritation. This bursal sac may contain mucinous fluid and fibrinous rice bodies.

Histologically, the cartilaginous cap is composed of bland hyaline cartilage. Variable degrees of cellularity are seen, but anaplastic cells are not characteristically evident. Normal enchondral ossification is seen at the cartilage–bone junction. In younger patients, cartilage cores may be present within the subchondral spongiosa near the physes, and these cores may be responsible for recurrence of the lesion should an incomplete resection be performed. Aside from the cartilage cores, the cancellous bone underlying the cartilaginous cap resembles that of the host, although on occasion the marrow in the interior is predominantly fatty.

The appearance of the cartilaginous cap depends on the stage of growth, becoming thinner over time. Remnants of the quiescent cap may persist well into adult life. Should increased thickness of the cartilage become evident in an adult, malignant degeneration must be considered, and the lesion should be carefully examined on histologic sections.

Clinical Features

In the majority of affected individuals, the osteochondroma becomes evident between the ages of 10 and 20 years. The condition has a slight male preponderance. An osteochondroma may be discovered as an incidental radiographic finding, or it may be detected on palpation of a protruding bump. Other factors that often draw attention to the osteochondroma include localized pain, growth disturbance of an extremity, compromised joint motion, abnormal cosmetic appearance, or secondary impingement of soft tissues (tendon, nerves, and vessels). Swelling of the lower extremity, accompanied by pain, has been reported as a result of vascular compression by an osteochondroma at the knee. On occasion, a fracture may occur through a stalk of a pedunculated (narrow-based) lesion after minor trauma. If the patient experiences progressive lower extremity weakness or numbness, MRI evaluation of the neural axis is needed, and extradural compression of the spinal cord from an osteochondroma should be given consideration.

Radiographic Findings

Several pathognomonic radiographic findings are associated with an osteochondroma ( Fig. 29-17 ):

• 1.
  

  The lesion protrudes from the host bone on either a sessile (broad-based) or pedunculated bony stalk.

  
  
• 2.
  

  It occurs either in the metaphysis or, as the main epiphyseal plate grows away from the lesion, in the diaphysis. It is never found in the epiphysis.

  
  
• 3.
  

  The cortex and cancellous bone of the osteochondroma blend with the cortex and cancellous bone of the host. This is the main radiographic finding, and any deviation from this feature should raise suspicion of a more serious lesion.

  
  
• 4.
  

  The lesion ranges in size from 2 to 12 cm.

Anteroposterior radiograph of the distal left femur in a 12-year-old boy with a solitary osteochondroma. The osteochondroma extends medially and proximally on a pedunculated bony stalk. The boy complained of discomfort when the prominence was inadvertently bumped.

Slight metaphyseal widening may occur at the site of the exostosis. Although the cartilaginous cap is not radiographically visible, partial calcification of the cartilage may be seen as small areas of radiopacity.

In the flat bones, such as the ilium or scapulae, exostoses are usually sessile and are located near the cartilaginous ends of the bone. Osteochondromas rarely develop in the carpal and tarsal bones, but they may involve the phalanges. The rare osteochondroma in the spine (occurring primarily in hereditary multiple exostoses) is rarely visualized on plain radiographs. If evidence of spinal cord compression exists, CT and MRI will clearly show the impingement.

Bursal osteochondromatosis overlying an osteochondroma of the rib has been described and, on occasion, ultrasonography may help delineate the extent of the swollen bursa. If there is concern over a progressively enlarging mass, ultrasonography may also help determine the thickness of the cartilaginous cap. Steady growth of the cartilaginous cap is acceptable during childhood and early adolescence, but growth should cease when skeletal maturity is reached. If the cartilaginous cap continues to grow after skeletal maturity, malignant transformation should be considered, and the appropriate follow-up studies should be undertaken.

Differential Diagnosis

Because of their typically distinct radiographic appearance, solitary osteochondromas are usually easily diagnosed. Occasionally they may be confused with a juxtacortical chondroma or, less commonly, with myositis ossificans with a cartilaginous cap. Juxtacortical chondromas usually have a scalloped cortical defect with a sclerotic margin. With myositis ossificans, the apparent tumor does not blend with the cortex and cancellous bone of the host bone, even though it may be attached to the periosteum. This is usually apparent radiographically, thus distinguishing the long-standing lesion of mature myositis ossificans from an osteochondroma. In the skeletally mature individual, enlargement of a solitary osteochondroma (particularly one that is associated with progressive discomfort) must alert the physician to the possibility of malignant degeneration into a chondrosarcoma.

Sarcomatous Change

Malignant degeneration of a peripheral solitary osteochondroma leads to chondrosarcoma. However, malignant degeneration of solitary osteochondromas is rare, probably occurring in less than 0.25% of lesions. Although Jaffe and Lichtenstein stated that 1% of these lesions undergo malignant change and Dahlin reported an incidence of 4.1% in solitary osteochondromas treated surgically at the Mayo Clinic (Rochester, Minn.), these figures represent select cases referred to oncology centers. Malignant change evolves very slowly, usually manifesting in adult life. When malignant changes occur, the lesions become painful and show evidence of growth.

MRI has been found useful in evaluating possible sarcomatous deterioration. The imaging modality delineates extension of the tumor mass into the adjacent soft tissues and allows proper planning of a wide resection of an underlying chondrosarcoma. Scintigraphic imaging with technetium-99m methylene diphosphonate has not been shown qualitatively to differentiate benign active exostoses from chondrosarcoma. Similarly, gallium scans cannot sufficiently distinguish between benign and sarcomatous lesions. Imaging criteria differentiating osteochondroma from chondrosarcoma are provided in Table 29-1 .

Biopsy before surgical excision of a presumed chondrosarcoma may be of limited value because of the significant chance of a nonrepresentative biopsy and the potential risk of seeding the biopsy tract. The prognosis after excision of a chondrosarcoma is excellent.

Treatment

Because a solitary osteochondroma is a benign tumor, it does not need to be surgically excised if it is asymptomatic. Excision usually is reserved for those lesions that cause pain or symptomatic impingement on neurovascular structures or that interfere with joint function. Pain usually becomes an issue when an osteochondroma is repeatedly bumped on its prominence, if a pedunculated base fractures after trauma, or if a painful bursa develops. Neurovascular impingement may include peroneal nerve compression at the knee, median nerve compression at the wrist, or, rarely, spinal cord compression from a vertebral osteochondroma. ^†a Sometimes the osteochondroma is considered cosmetically unacceptable, and the adolescent will ask to have it removed because he or she prefers a scar to a bump. Finally, surgical excision is indicated any time the possibility of malignant transformation of an underlying osteochondroma exists, as demonstrated by an increase in the size of the lesion or in symptoms after skeletal maturity.

†a References .

Occasionally a peripheral nerve (e.g., the peroneal nerve at the fibular head or the radial nerve along the humerus) may be close to the underlying lesion. Preliminary dissection of the nerve above the lesion can help avoid inadvertent injury to the nerve during excision of the osteochondroma. This anatomic situation, however, is more likely to occur with multiple hereditary exostoses than with a solitary osteochondroma.

Incidence

Hereditary multiple exostoses comprise an autosomal dominant condition affecting numerous areas of the skeleton that have been preformed in cartilage. The overall prevalence approaches 1 in 50,000, double the previously reported prevalence of 1 in 100,000. The disorder is known by a variety of terms: multiple hereditary osteochondromas, cartilaginous exostosis, diaphyseal aclasis (stressing abnormality of the modeling process), multiple osteochondromatosis, chondral osteoma, chondral osteogenic dysplasia of direction, deforming chondrodysplasia, hereditary deforming chondrodysplasia, and multiple cancellous exostoses. The term most commonly used today, hereditary multiple exostoses, was proposed by Jaffe in 1943.

The median age at the time of diagnosis in affected individuals is approximately 3 years. Hereditary multiple exostoses have a penetrance of 50% by 3 years of age. By the end of the first decade of life, 80% of affected persons will have exostoses. By 12 years of age, nearly all affected individuals have evidence of exostoses because penetrance of the disorder has been found to reach 96% to 100% ( Fig. 29-18 ). Although some studies reported that incomplete penetrance preferentially affects girls, other investigations showed no such reduction.

Hereditary multiple exostoses in a 12-year-old boy. Extensive involvement of the femora, tibiae, and fibulae was evident clinically and radiographically.

Several studies showed that the disorder may have a “profound” impact on the quality of life, both for children and adults. The reports emphasize difficulties with occupational and sporting activities, as well as frequent issues with pain and emotional self-esteem. Adult height was lower than the 25th percentile in 58% of patients in one study.

Etiology

The disorder is one of autosomal dominant inheritance, with penetrance approaching 96%. If a person whose family is affected by hereditary multiple exostoses has not had an exostosis by 12 years of age, it is unlikely that exostoses will develop later. However, a small risk remains that a particular individual will have affected children because the gene is nonpenetrant in approximately 4% of carriers. Approximately 10% of affected individuals have no family history of hereditary multiple exostoses.

Numerous genetic studies have found anomalies on chromosomes 8, 11, and 19, thus making this a genetically heterogeneous disorder. ^‡a Specifically, the three loci are 8q23-24.1 ( EXT1 ), 11p11-13 ( EXT2 ), and 19p ( EXT3 ). The EXT1 and EXT2 genes encode glycosyltransferases involved in the biosynthesis of heparan sulfate proteoglycans. These proteoglycans, synthesized by chondrocytes and secreted to the extracellular matrix of the growth plate, play critical roles in growth plate signaling and remodeling necessary for normal endochondral ossification with the growth plate. Mutations of the EXT1 and EXT2 genes lead to absence of heparan sulfate (and thus abnormal cell signaling) in the chondrocyte zones of exostosis growth plates. The chondrocyte disorganization results in the development of the exostoses. The most severe forms of this disorder and malignant transformation of exostoses to chondrosarcomas are associated with the EXT1 mutations. A multigenerational study of patients with hereditary multiple exostoses reported a novel mutation, nt112delAT, in the EXT2 gene. Another gene, EXTL (or EXT-like ), has been identified that shows a striking sequence similarity to both EXT1 and EXT2 .

‡a References .

Pathology

The gross pathologic and microscopic features of hereditary multiple exostoses are similar to those described for solitary osteochondromas.

Clinical Features

Multiple exostoses usually manifest during early childhood (although rarely before 2 years of age) with several knobby, hard, subcutaneous protuberances near the joints. Numerous sites can be involved. On presentation, five or six exostoses typically may be found, involving both the upper and lower extremities. The “knobby” appearance of the child is so characteristic that one can usually make the diagnosis by clinical inspection alone. Over time, the upper and lower extremities may appear short in relation to the trunk. Shortening of the limbs is usually disproportionate. Approximately 10% of affected individuals have a lower limb length inequality. Patients are not considered dwarfs, and the trunk–limb growth difference usually does not become obvious until the pubertal growth spurt. The local presence of osteochondromas is consistently associated with growth disturbance. In particular, an inverse correlation between osteochondroma size and relative bone length exists, suggesting that the growth retardation in this condition may result from the local effects of enlarging osteochondromas rather than a skeletal dysplasia effect. On occasion, concerned affected parents may bring in their normal-appearing child for screening. One report found that discomfort related to the multiple osteochondromas has been underestimated and that pain is often a problem that needs attention during care of these patients.

Of patients affected with hereditary multiple exostoses, 70% have involvement of the distal femur, 70% the proximal tibia, and 30% the proximal fibula ( Fig. 29-19 ). The likelihood of involvement near the knee in at least one of these three locations is approximately 94%. The proximal humerus is affected in 50% of cases, the scapula and ribs in 40%, the distal radius and ulna in 30%, the proximal femur in 30%, the phalanges in 30%, the distal fibula in 25%, the distal tibia in 20%, and the bones in the foot in 10% to 25%. Tibiofibular synostosis often develops from chronic apposition of osteochondromas proximally or distally but rarely causes symptoms or functional impairment. As the lesions enlarge, they may cause discomfort secondary to pressure on adjacent soft tissues, and they may hinder normal joint mobility.

Osteochondromas are seen involving the femur, tibia, and fibula.

Osteochondromas of the proximal humerus are often readily palpable but rarely cause neurologic dysfunction ( Fig. 29-20 ). However, because of their proximity to major nerves, great care must be taken if resection is necessary. The scapula is involved in 40% of affected individuals, with osteochondromas located on the anterior or the posterior aspect of the scapula. The presence of osteochondromas on the anterior aspect of the scapula may lead to discomfort during scapulothoracic motion. Winging of the scapula secondary to the presence of osteochondromas has been described.

This exostosis on the medial aspect of the proximal humerus was minimally symptomatic.

Obvious deformity in the forearm is seen in 39% to 60% of patients. The ulna is shorter than the radius, and the radius is bowed laterally, with its concavity toward the short ulna ( Fig. 29-21 ). Often the distal end of the ulna is more severely affected than the distal end of the radius, thus leading to this discrepancy in length. A mild flexion deformity of the elbow is usually present. Loss of forearm pronation and supination occurs with increasing age. Dislocation of the radial head occurs and is usually associated with a negative ulnar variance. The resulting forearm deformities are usually asymmetric. The patient’s main complaint often is an undesirable cosmetic appearance. The natural history of these deformities has been described as progressive, with variable weakness, functional impairment, and worsening cosmetic deformity of the extremity. Some authors, however, report that the deformities are well tolerated and lead to little loss of function. One study evaluating the forearm in untreated adults with hereditary multiple osteochondromatosis found that most were employed in careers of their choice, participated in recreational activities, and were free of pain. Objective measurement of function demonstrated greater disability than that found from subjective reporting.

Two wrist deformities in a brother and sister. A, In the boy, the distal radius exhibited growth arrest on the ulnar aspect with associated compensation at the wrist joint. B, In the girl, the distal ulna was short as a result of growth arrest.

Deformity of the hand is uncommon. The main area of involvement appears to be around the metacarpophalangeal joint, but the proximal interphalangeal joint is the most common site of deformity. Metacarpal shortening usually does not cause functional problems and does not need to be treated. Angular deformity, although uncommon, does cause problems and requires surgical intervention. No evidence indicates that deformity can be prevented by early excision of the osteochondromas.

In the lower extremity, valgus of the proximal tibia is frequently present and is nearly always found in the proximal metaphyseal region of the tibia. The valgus progressively increases during growth spurts. Occasionally some angulation occurs distally at the femur, and the patient may have recurrent dislocation of the patella.

Osteochondromas of the proximal femur may lead to progressive hip dysplasia, which occasionally requires corrective varus osteotomy ( Fig. 29-22 ). Adverse effects on femoral growth are less with proximal involvement than with distal involvement.

A, Anteroposterior pelvic radiograph showing abnormal proximal femora resulting from hereditary multiple exostoses. B, Computed tomography scans of the hip region clearly demonstrated the 10-cm sessile osteochondroma on the left femur.

Although osteochondromas near the ankle are not uncommon, the reported prevalence of ankle deformities ranges widely, from 2% to 54%. The characteristic ankle valgus deformity is often accompanied by decreased ankle motion. This deformity is caused either by retardation of the normal distal fibular growth or by deficient growth of the lateral half of the distal tibial epiphysis. The severity of the ankle valgus varies because the distal fibular physis progressively rises in relation to the tibiotalar articular space. Ankles with lesions at both the lateral distal tibia and the distal fibula have more progressive valgus than do ankles with tibial lesions only. A natural history study of the lower extremity in patients with multiple exostoses found measurable decreases in ankle function and suggested that correction or prevention of excessive tibiotalar tilt may be warranted to improve outcome.

There have been numerous reports of spinal cord impingement by vertebral osteochondromas. ^§a The cervical, thoracic, and lumbar region can be affected. Roach and colleagues found that 68% of their patients with hereditary multiple exostoses had exostoses arising from the spinal column, and 27% had lesions within the canal by MRI studies. Many of these lesions were not evident on plane radiographs, and few were symptomatic. Some cases with neurologic compromise have been reported, but the exact frequency of these events has yet to be determined.

§a References .

Radiographic Findings

Unlike solitary osteochondromas, hereditary multiple exostoses involve a significantly greater portion of the metaphysis or diaphysis and are generally more irregular in shape. Over time, lesions that begin in the metaphyseal region migrate into the diaphysis of the long bones. The exostoses vary in number, size, and configuration. Like solitary osteochondromas, they may be sessile or pedunculated, cauliflower-like, or even narrow with a pointed end. They nearly always point away from the physis. In nearly 95% of cases, evidence of the osteochondroma is found around the knee. Thus the disorder can often be confirmed with radiographs of the knee. Irregular zones of calcification may be present, particularly in the cartilaginous cap. In older individuals, however, extensive calcification with changes in the shape of the cartilaginous caps suggests possible malignant degeneration.

Differential Diagnosis

The numerous lesions associated with hereditary multiple exostoses make the radiographic findings pathognomonic of the disorder. If painful growth of an osteochondroma becomes evident in a skeletally mature individual with hereditary multiple exostoses, chondrosarcomatous transformation must be excluded.

Sarcomatous Change

Transformation of a lesion in hereditary multiple exostoses to chondrosarcoma during childhood is exceedingly rare. In general, transformation in adulthood remains uncommon; current reports indicate the risk to be 0.9% to 5%. The apparent risk of malignant degeneration may become greater as the duration of follow-up increases. In the 1994 study by Schmale and associates, two thirds of the individuals with transformation were younger than 40 years of age when the authors reported an incidence of 0.9%. At this time, the lifetime risk of chondrosarcoma is estimated to be approximately 1% to 2%. The genetic abnormalities found on chromosomes 8 and 11 ( EXT1 and EXT2 ) may play a role in the development of chondrosarcomas. Malignant transformation is more frequently associated with the EXT1 mutations.

The most frequent sign of sarcomatous change is a painful, enlarging mass, usually one of long duration. The relative frequency of chondrosarcomas is reported to be highest with osteochondromas of the pelvis or shoulder girdle. The clinical course of the tumor is slow, and metastasis, usually to the lungs, occurs late.

If the cartilaginous cap of the exostoses exceeds 1 cm in thickness, malignancy should be suspected. Inadequate surgical removal almost always results in recurrence. The prognosis is good if metastasis has not occurred. Radiation therapy has no effect on the tumor.

Treatment

The only treatment for hereditary multiple exostoses is surgery. Because the exostoses are numerous and many are asymptomatic, a cautious approach is warranted. The mere presence of an osteochondroma is not an indication for surgery. Reasonable indications include (1) pain from external trauma or irritation of surrounding soft tissues, (2) growth disturbance leading to angular deformity or limb length discrepancy, (3) joint motion compromised by juxtaarticular lesions, (4) soft tissue (tendon, nerve, or vessel) impingement or tethering, (5) spinal cord compression, (6) false aneurysm produced by an osteochondroma, (7) painful bursa formation, (8) obvious cosmetic deformity, and (9) a rapid increase in the size of a lesion. During childhood, numerous operations may be necessary, and this prospect should be discussed in detail with the parents soon after the disorder is diagnosed. Life expectancy is normal unless malignant degeneration of an osteochondroma has occurred and metastases have developed.

Osteochondromas involving the forearm frequently lead to surgical intervention. Early excision of the lesions on the radius and ulna does not alter or correct existing deformity, but it may delay progression of the deformity. If ulnar shortening has occurred with bowing of the radius, lengthening of the ulna combined with distal radial hemiepiphyseal stapling has been found effective in correcting the deformity. Ulnar lengthening is best done gradually by distraction osteogenesis. Spontaneous regression of an osteochondroma of the radius after lengthening of the ulna has even been reported. Reduction of the ulnar inclination of the radius to normal values by corrective distal radial osteotomy may restore a more physiologic range of motion and decrease wrist pain. Creation of a “one-bone forearm” has been successful as a salvage procedure for severely affected forearms. Deformities of the forearm should be treated early and aggressively in an effort to prevent further progression and to reduce disability. A prominent, symptomatic, dislocated radial head can be safely excised after skeletal maturity.

Marked shortening of the humerus may result from a proximal physeal growth disturbance. If the discrepancy is significant, distraction osteogenesis has been successful in increasing the length of the humerus.

For skeletally mature individuals with significant genu valgum, varus osteotomy of the proximal tibia can result in an improved appearance. However, if an osteochondroma is present in the proximal fibula, any osteotomy of the proximal tibia or fibula carries a significant risk of peroneal nerve palsy. In the skeletally immature patient, stapling along the medial side of the proximal tibial physis or distal femoral physis may be sufficient to correct the valgus. If correction is achieved by this method, the staples should be left in longer (slight overcorrection) to prevent recurrence of the deformity after staple removal.

Ankle valgus is treated either by medial distal tibial physeal arrest in the skeletally immature patient or by a varus corrective osteotomy in the more mature individual ( Fig. 29-23 ). Guided growth procedures provide gradual correction, and staples, plates, and screws may be used. Tibiofibular synostoses frequently occur distally, but usually no symptoms or functional impairments result from this occurrence, and the condition does not need to be surgically treated.

A, Excessive ankle valgus accompanied by a distal tibiofibular synostosis led to discomfort. B to D, A varus closing wedge osteotomy in the distal tibiofibular region resulted in improved alignment and resolution of the patient’s discomfort.

Incidence

Intramedullary cartilaginous solitary enchondromas are relatively common and account for approximately one fourth of all benign tumors. Unlike multiple enchondromatosis, which is frequently diagnosed during childhood, solitary enchondromas are usually diagnosed after the second decade of life. The peak age of presentation is approximately 35 years.

Pathology

Enchondromas appear as glistening white, grayish-white, or pearly tissues that have a gritty feel on palpation resulting from the intrinsic calcification. The tumor is easily cut with a knife, as if it were soft chalk.

Histologically, enchondromas are proliferating nests of cartilage cells that lack obvious atypia. Foci of calcification are present. Plates of lamellar bone surround the lobules of cartilage in a partial to complete circumferential manner. Invasive infiltration of the bone marrow spaces is not characteristic of benign solitary enchondromas.

Although mitotic figures within the dysplastic cartilaginous lesions may be found in specimens from growing children, the likelihood of malignancy is low. In the adult, however, it may be difficult to differentiate an enchondroma from a low-grade sarcoma. In general, small peripheral cartilage tumors are usually benign, whereas the large axial tumors in the adult are more likely to be malignant. A malignant change of a solitary enchondroma in childhood or adolescence would be a rare event.

Clinical Features

Nearly 50% of diagnosed solitary enchondromas occur in the hand, the phalanges in particular. The carpal bones are occasionally affected. Of the long tubular bones, the femur and humerus are frequent sites of localization. Occasionally the ribs, sternum, innominate bones, and vertebral column may also be affected.

Clinically, enchondromas in the fingers are usually diagnosed after local trauma. Some patients, however, present with a firm, local swelling in the region of the affected phalanx or metacarpal without a fracture or local pain. Nearly 75% of patients with enchondromas involving the hands or feet have a solitary lesion. The remaining patients have multiple enchondromatosis. When the solitary enchondroma involves the femur or humerus, it is usually quiescent, with no clinical signs evident until adulthood.

Radiographic Findings

Solitary enchondromas usually appear as well-delineated, lucent defects in the metaphyseal region of long bones. In the phalanges of the hand or foot, the entire shaft may be involved. The cortical rim is usually intact unless a fracture has occurred through the weakened bone ( Fig. 29-24 ). Calcification is usually present within the lesion and appears as fine punctate stippling. In the larger long bones, calcification may be more pronounced, and this feature can make the differentiation between enchondroma and bone infarct difficult. Most lesions are 3 to 4 cm, with a range of 1 to 8 cm. Usually no evidence of focal cortical erosion, scalloping of the cortex, significant cortical thickening, or bone expansion is present. In the older symptomatic adolescent, cortical thinning and expansion in the larger long bones can be troubling because these radiographic findings may represent features of low-grade chondrosarcoma.

A solitary enchondroma in the middle phalanx of the ring finger. Radiographs showed a well-delineated lucent lesion with an intact cortical rim. It was noticed because of mild, painless swelling of the digit.

CT is useful for evaluating cartilaginous tumors, especially in the long bones, pelvis, and spine. Technetium bone scanning generally is not necessary when evaluating a child with presumed enchondroma.

Differential Diagnosis

Confusion between an enchondroma and a bone infarct may occur when the radiolucent lesion has a significant amount of calcification. However, in general, the calcification seen with bone infarcts is more peripherally located. In the phalanges of the hand and foot, solitary enchondromas may be difficult to differentiate from epithelial inclusion cysts. In a metacarpal, it may be difficult to distinguish a solitary enchondroma from a small solitary bone cyst, a nonossifying fibroma, or a focus of fibrous dysplasia.

Treatment

For solitary enchondromas in the hand, complete curettage followed by autogenous bone grafting usually results in cure. However, recurrences may occur many years after excision and go undetected until they cause widening or cortical erosion of the phalanx or metacarpal. Similar treatment is undertaken for solitary enchondromas in the long bones, in which the recurrence rate remains low. If an en bloc wide excision were performed, the recurrence rate would be even lower. However, the possibly unacceptable postoperative functional deficit makes this more aggressive approach unnecessary.

The risk of malignant degeneration of an isolated enchondroma is rare in childhood. However, these lesions should have regular radiographic follow-up. Enchondromas in the pelvis, scapulae, sternum, vertebrae, and proximal areas of the large long bones have a greater likelihood of malignant transformation in adulthood.

Pathology

On gross inspection of the lesions, the bones show numerous islands of glistening cartilage, which are usually located in the diaphyseal and metaphyseal regions. Infrequently, abnormal cartilage may also be seen in the epiphyseal region. This close proximity of the tumor to the physis can lead to profound inhibition of growth that results in severe limb length discrepancies or angular deformities. As longitudinal growth continues, the abnormal enchondroma cartilage derived near the epiphyseal plate forms long, linear masses within the shaft. This phenomenon is seen only in Ollier disease and explains the pathognomonic “fanlike” metaphyseal septation seen on radiographs. The dense lines represent bone formed by normal enchondral ossification, and the intervening columns of lucency represent the epi­physeally derived areas of abnormal cartilage.

The histologic features in multiple enchondromatosis generally resemble those of a solitary enchondroma. However, in multiple enchondromatosis the appearance may be that of a highly cellular lesion with ominous nuclei mimicking a low-grade chondrosarcoma. Eventual malignant transformation into chondrosarcomas has been reported to occur in 20% to 33% of those affected. Therefore communication among the surgeon, pathologist, and radiologist is imperative when making the diagnosis in the older adolescent or adult. In general, aggressive histologic findings are likely to represent a benign lesion if the biopsy site is the hand rather than the long bones or the pelvis. Conversely, if the biopsy site is the pelvis or larger bones, suspicion of low-grade sarcomas is higher. The atypical cellular features in Ollier disease may explain the relatively high incidence of chondrosarcomatous transformation in older individuals who are moderately or severely affected.

Clinical Features

Multiple enchondromatosis is an uncommon, nonhereditary disorder. The physical signs related to this condition commonly begin in childhood and vary with the extent of the lesions and their effect on the weakened bones. The number of bones affected can vary greatly, with the phalanges, femur, and tibia most commonly affected ( Fig. 29-25 ). Because of the tendency toward unilateral involvement, severe lower limb length discrepancies and angular deformities result, with a noted increased incidence of varus angulation in the lower femur. Discrepancies may be in the range of 10 to 25 cm by maturity. Deformity and enlargement of fingers may impair normal function. Forearm abnormalities such as bowing, limited rotation, and ulnar deviation of the hand may be evident.

A young boy with Ollier disease. A, Anteroposterior radiograph. All the metacarpals and phalanges in the hand were affected. B, After curettage of the proximal phalanx of the little finger, glistening white tumor was evident. C, Histologic examination demonstrated the proliferative nests of cartilage cells.

Maffucci syndrome is a condition of enchondromatosis associated with multiple hemangiomas involving soft tissue. These lesions may be associated with superficial phleboliths, which can appear on radiographs as roundish opacities in the soft tissues. Hemangiomas have also been noted to occur within internal organs. Because of this, total-body MRI has been recommended to detect asymptomatic lesions that will thus alter the diagnosis to Maffucci syndrome and change the prognosis. Multiple pigmented nevi and vitiligo are other occasional nonskeletal manifestations. An abnormality in neuropeptides appears to stimulate growth of abnormal blood vessels.

Another related entity, generalized enchondromatosis, represents a more severe expression of the disorder. Nearly all the metaphyseal regions in all the long and short tubular bones are affected.

Radiographic Findings

Bone abnormalities are usually more extensive than the physical examination would suggest. In the long bones, enchondromatosis is recognized as radiolucent longitudinal streaks that involve the metaphysis and extend down into the diaphysis. Epiphyses are usually not affected but may be involved. The cortex overlying the enchondroma is usually thin, and calcification within the lesion is common. Significant shortening and angular deformity are frequently noted in the involved long bones, whether in the hands, feet, or limbs.

CT is useful for evaluating multiple enchondromatosis, particularly in the long bones and pelvis. CT clarifies cortical and osteal scalloping better than plain radiography and allows precise comparisons to be made over time.

Sarcomatous Change

The incidence of secondary chondrosarcoma in patients with Ollier disease is approximately 25% to 30% by 40 years of age. ^‖a Those patients with Maffucci syndrome have a similar or higher likelihood of development of malignant degeneration. Schwartz and associates reported a nearly 100% expectation of malignant degeneration. Over the long term, periodic surveillance of the brain and abdomen for occult malignant lesions is indicated in patients who have enchondromatosis. Increased localized growth of a lesion in an extremity accompanied by pain is the hallmark of possible malignancy. In such a situation, biopsy of the lesion is indicated. Hematopoietic malignant diseases (acute lymphoid leukemia and chronic myeloid leukemia) have been described in association with both Ollier disease and Maffucci syndrome.

Treatment

‖a References .

Findings in a 4-year-old boy with Ollier disease. A, Radiograph demonstrating unilateral left lower extremity involvement. B, A valgus osteotomy of the distal femur was performed to correct the notable genu varum. C, Two years later, the genu varum recurred because of the abnormal growth at the distal femoral physis. Another osteotomy was planned; future limb lengthening will be needed.

Incidence

Chondroblastomas are uncommon benign cellular cartilage tumors that are most often located in the epiphyses of the long bones of the extremities. Chondroblastomas are twice as common in male as in female patients. The peak age of occurrence is in the second decade, and most patients present before 30 years of age.

Chondroblastoma was first described in detail by Codman in 1931. He called the lesion an epiphyseal chondromatous giant cell tumor. Before his description, the tumors were often thought to represent chondrosarcomas. Chondroblastomas are still occasionally referred to as Codman tumor.

Etiology

Jaffe and Lichtenstein conjectured that the lesion arises from cartilage “germ cells” or cells of the epiphyseal cartilage. However, because of reports of the lesion involving the skull or rib (where cartilage “germ cells” would not likely be found), this hypothesis is difficult to confirm.

The biologic nature of chondroblastomas and their histogenetic origin continue to be a matter of debate. Abnormalities in chromosomes 5 and 8 have been reported in chondroblastoma; however, specific locations have not been clearly identified. Cytogenetic and spectral analyses of chondroblastomas have revealed diploid karyotypes with relatively simple karyotypes. Recurrent breakout points have been found at 2q35, 3q21-23, and 18q21. Another study reported that a receptor activator of NF-κB ligand (RANKL), which is a key molecule essential for regulating osteoclast formation and activity, may be involved in the formation of chondroblastomas.

Pathology

Gross specimens obtained at curettage are often characterized by pieces of gray-pink or hemorrhagic tissues intermixed with gritty, calcified, cholesterol-laden tissues. Small islands of bluish to white chondroid may be visible. Because chondroblastomas are often found to contain cystic or degenerative areas, the amount of tissue removed may be less than expected based on the radiographic appearance.

Histologically, the tumor is characterized by polygonal cells (chondroblasts), giant cells, islands of chondroid or hyaline cartilage, “chicken-wire” calcification, and nodules of calcification in the stroma ( Fig. 29-27 ). The chicken-wire calcification results when lacelike deposits of calcium are intermixed on the intercellular chondroid matrix.

Histologic evaluation of chondroblastoma shows polygonal cells (chondroblasts), giant cells, islands of chondroid or hyaline cartilage, and “chicken-wire” calcification.

A small percentage of chondroblastomas may be primarily cystic or hemorrhagic, thus making differentiation from aneurysmal bone cysts difficult histologically. Another, more worrisome tumor, clear cell chondrosarcoma, may histologically resemble chondroblastoma. However, clear cell chondrosarcomas occur in adults with closed physes, and the radiographic appearance and clinical presentation of these tumors is not consistent with chondroblastomas.

Clinical Features

The most common locations are the proximal humerus, distal femur, and proximal tibia. Chondroblastomas have also been found in the skull, maxilla, temporal bone, ribs, pelvis, hands, proximal femur, patella, talus, calcaneus, and throughout the spine. Multifocal benign chondroblastomas have been reported. Nonepiphyseal locations in the long bones have been described.

Symptoms usually are mild, consisting of pain and localized tenderness. The discomfort is often present for 6 months to several years before diagnosis. Because the lesion is epiphyseal, the adjacent joint may be swollen and have limited range of motion. If tumor is present in a lower extremity, an antalgic limp may be evident. Pathologic fractures are uncommon. Neurologic deficits can occur if the vertebrae are involved.

Radiographic Findings

Chondroblastomas are usually located in the epiphyses, but they may extend into the metaphyseal region ( Fig. 29-28 ). They are usually eccentric, involving less than one half of the entire epiphysis. The lesion is rimmed by a border of host bone sclerosis, and small punctate calcifications are present in the tumor. Commonly, the physis adjacent to the lesion is present at the time of diagnosis. If all these features are present, this radiographic appearance is pathognomonic for chondroblastoma.

Chondroblastoma. Anteroposterior ( A ) and lateral ( B ) radiographs of the left hip in a 16-year-old girl showing a subchondral radiolucent lesion in the femoral head (epiphyseal region) that is rimmed by a border of host bone sclerosis. C, Bone scan shows significant uptake in the left femoral head. D, Computed tomography of the hips shows calcification within the lesion.

CT clearly demonstrates the extent of the lesion within the epiphyseal region and its proximity to the physis or subarticular surface.

MRI findings associated with chondroblastoma have been reported. Adjacent bone marrow edema and soft tissue edema, as well as periosteal reactions, are more dramatically demonstrated on MRI than on plain radiographs. Bone marrow edema is common. Knowledge of the MRI findings of chondroblastoma may allow for more accurate diagnosis and help to avoid confusion with infection or aggressive neoplasms.

Fine-needle aspiration yields satisfactory material for interpretation and confirmation of the diagnosis.

Differential Diagnosis

The differential diagnosis includes giant cell tumors, enchondromas, synovial lesions (e.g., pigmented villonodular synovitis [PVNS], rheumatoid arthritis), and atypically located eosinophilic granuloma. An epiphyseal osteoblastoma-like osteosarcoma with strong similarities to chondroblastoma has been reported.

Treatment

Complete curettage and excision of the lesion (using a high-speed burr) are often successful. The surgeon should avoid interfering with the joint surface or disturbing the physes in the immature skeleton. The defect is filled with either autogenous or allograft bone. Although a definite risk of recurrence exists after intracapsular curettage, one study reported local control in approximately 80% of cases. Preservation of the physis should be considered a secondary concern compared with complete and thorough excision of the chondroblastoma. If the tumor is beneath articular cartilage, adequate excision may occasionally require removal of some of the joint cartilage. Allografting and vascularized fibular grafting have been done to prevent joint surface collapse. A large series from France with a mean of 5 years of follow-up showed a 32% recurrence rate after curettage. Radiofrequency ablation was used in a report of 13 patients, with relief of symptoms in 12 patients and collapse of the articular surface in the remaining patient. Arthroscopy has been used as an adjunct in the excision of lesions in the proximal tibia and proximal femur.

Occasional chondroblastomas require wide marginal resection, especially those tumors that have recurred locally. Reconstruction after marginal or wide en bloc resection usually requires a partial or full osteoarticular allograft.

Chondroblastomas have been known to undergo benign pulmonary metastasis. When found in the lung, these metastases are usually rimmed with bone. When identified, these lesions should be surgically removed to ensure proper diagnosis.

Incidence

Chondromyxoid fibromas are rare, benign tumors representing less than 0.4% of primary bone tumors sampled for biopsy. They consist mainly of cartilaginous tissue intermixed with areas of myxomatous and fibrous elements. The myxomatous components are probably caused by degeneration of chondroid tissue, whereas the fibrous component may result from repair of the degenerated areas.

Etiology

Cytogenetic analysis of chondromyxoid fibromas has found an unbalanced reciprocal translocation between the short arm of chromosome 3 and the long arm of chromosome 6. Two known cartilage-related genes are located in the regions affected by this unbalanced rearrangement. These genes function to control growth and maturation of endochondral bone, the site of origin of cartilaginous tumors. A specific matrix composition, not seen in other mesenchymal neoplasms, has been found in chondromyxoid fibroma.

Pathology

Most chondromyxoid fibromas are smaller than 5 cm. The tissue is firm, grayish white, and often covered on the outer surface with a thin rim of bone or periosteum. Cysts or areas of hemorrhage may be found within the lesion ( Fig. 29-29 ). Histologically, chondromyxoid fibromas have a lobulated pattern, with some of these lobules sparsely cellular and others more cellular. Those lobules that have few cells are composed of a myxoid or chondroid matrix. Microscopic areas of cystic degeneration may contribute to the myxoid appearance. Other features of chondromyxoid fibroma include osteoclast-like giant cells, intermixed fibrous tissue, and occasionally cholesterol, hemosiderin, and lymphocytes. Distinct calcification is rare but has been reported.

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