As defined by the World Health Organization (WHO), the aneurysmal bone cyst (ABC) is a benign tumorlike lesion that is described as "an expanding osteolytic lesion consisting of blood-filled spaces of variable size separated by connective tissue septa containing trabeculae or osteoid tissue and osteoclast giant cells."[1] It most often affects individuals during their second decade of life and may occur in any bone in the body.[2, 3, 4, 1, 5, 6, 7, 8, 9] Although benign, the ABC can be locally aggressive. Its expansile nature can cause pain, swelling, deformity, disruption of growth plates or joint surfaces, neurologic symptoms (depending on location), and pathologic fracture.[2, 3, 4]
View Image | Aneurysmal bone cyst of the upper arm. Courtesy of Johannes Stahl, The Virtual Radiological Case Collection. |
Jaffe and Lichtenstein first described ABC as its own entity in 1942, when they noted "a peculiar blood-containing cyst of large size."[10] Two cases were reported in which a lesion with a "soap-bubble" appearance on radiographs was found on the superior pubic ramus of a 17-year-old male and on the second vertebra of an 18-year-old male. The lesions were expansile and showed evidence of erosion of the surrounding bone and encroachment of the surrounding tissues. Upon surgical exposure of the lesions, a thin, bony wall that contained bloody fluid was found.
Jaffe and Lichtenstein suggested that ABCs may have been mistaken for other benign and malignant bone tumors in the past.[10] Although ABC is a separate entity, in some situations, distinguishing an ABC from a giant cell tumor of bone or a telangiectatic osteosarcoma is difficult.
The true etiology and pathophysiology remain a mystery, but the mainstay of treatment has been intralesional curettage.[11] Recurrence is not uncommon.[2, 12] Other surgical options include en-bloc resection or wide excision, selective arterial embolization, and curettage with locally applied adjuvants such as liquid nitrogen, argon beam photocoagulation, or phenol.
Because ABCs may affect any bone in the body, the relevant surgical anatomy necessarily varies with location. The long tubular bones are the most common sites for ABCs, followed by the spine and the flat bones. These three areas account for 80% of all ABCs. When present in long tubular bones, ABCs tend to be eccentrically located in the metaphysis.
ABCs least commonly involve a subperiosteal location, where they may form a predominant soft-tissue mass. However, ABCs can occur in any location, including the diaphysis and epiphysis.
Rarely, ABCs have also been known to affect an adjacent bone; however, spinal ABCs are associated with a higher incidence of contiguous lesions. Almost all ABCs of the spine involve the posterior elements, and a high incidence of neurologic symptoms is observed, as well as more local aggressive behavior.
The pelvis accounts for approximately 50% of lesions occurring in the flat bones.[13] Secondary lesions tend to have a predilection for the areas of the body in which the primary lesion typically arises.
In a published review of 897 cases of ABC, the following rates of occurrence were reported[14] :
The true pathophysiology of ABCs is unknown.[11]
Different theories about several vascular malformations exist; these include arteriovenous fistulas and venous blockage. The vascular lesions then cause increased pressure, expansion, erosion, and resorption of the surrounding bone. The malformation is also believed to cause local hemorrhage that initiates the formation of reactive osteolytic tissue. Findings from a study in which manometric pressures within the ABCs were measured support the theory of altered hemodynamics.
Most primary ABCs demonstrate a t(16;17)(q22;p13) fusion of the TRE17/CDH11-USP6 oncogene. This fusion leads to increased cellular cadherin-11 activity that seems to arrest osteoblastic maturation in a more primitive state.[15] This process may be the neoplastic driving force behind primary ABCs as opposed to secondary ABCs, which seem to occur reactively as a result of another underlying disease process.[16]
The true etiology of ABCs is also unknown. Most investigators believe that ABCs are the result of a vascular malformation within the bone; however, the ultimate cause of the malformation is a topic of controversy. Three commonly proposed theories are as follows:
A certain percentage of primary ABCs may be truly neoplastic—as opposed to vascular, developmental, or reactive—phenomena. It has been shown that as many as 69% of primary ABCs demonstrate a characteristic clonal t(16;17) genetic translocation[17] leading to upregulation of the TRE17/USP6 oncogene,[15, 16] whereas no secondary ABCs demonstrate this cytogenetic aberration.
ABCs are generally considered rare, accounting for only 1-6% of all primary bony tumors. A group from Austria reported an annual incidence of 0.14 ABCs per 100,000 people[18] ; however, the true incidence is difficult to calculate because of the existence of spontaneous regression and clinically silent cases.
A biopsy-proven incidence study from the Netherlands showed that ABCs were the second most common tumor or tumorlike lesion found in children.[19]
Most studies have also found a slightly increased incidence in women. Although the ABC can appear in persons of any age, it is generally a disease of the young (albeit a rare one in the very young). About 50-70% of ABCs occur in the second decade of life, with 70-86% occurring in patients younger than 20 years. The mean patient age at onset is 13-17.7 years.
The prognosis for an ABC is generally excellent, though some patients need repeated treatments because of recurrence, which is the most common problem encountered when treating an ABC.
The overall cure rate is 90-95%.[20, 21] A younger age, open growth plates, and a metaphyseal location all have been associated with an increased risk of recurrence.[20] The stage of the ABC has not been shown to influence the rate of recurrence; however, most clinicians believe that Enneking/Musculoskeletal Tumor Society (MSTS) stage 3 lesions have the highest recurrence rate, other factors being equal. Capanna morphologic types I and II recur more often than types III, IV, and V.
Reported primary recurrence rates have varied greatly. Small studies have shown a benefit to using selective arterial embolization, and some authors advocate it as a first-line treatment. Other authors argue that not enough data on selective embolization exist and that surgery is the first-line treatment. Intralesional excision has the most data to suggest that it is a safe and effective method.
Recurrence rates for different techniques have varied. Some studies have reported recurrence rates as high as 59% with intralesional excision[22] and as low as 0% with resection.[14] In a summary of studies of different treatment methods, the following rates of recurrence were reported[14] :
Patients with an aneurysmal bone cyts (ABC) usually present with pain, a mass, swelling, a pathologic fracture, or a combination of these symptoms in the affected area. The symptoms are usually present for several weeks to months before the diagnosis is made, and the patient may also have a history of a rapidly enlarging mass. Neurologic symptoms associated with ABCs may develop secondary to pressure or tenting of the nerve over the lesion, typically in the spine.
Pathologic fracture occurs in about 8% of ABCs, but the incidence may be as high as 21% in ABCs that have spinal involvement.
Other findings may include the following:
Alkaline phosphatase levels may be increased, but laboratory studies are generally of no benefit in the workup of a patient with an aneurysmal bone cyst (ABC).
Radiographic findings usually consist of an eccentric or, less commonly, a central or subperiosteal lesion that appears cystic or lytic. Images may show expansion of the surrounding bone with a blown-out, ballooned, or soap-bubble appearance. Some views may show an eggshell-appearing bony rim surrounding the lesion. One may see the cystic spaces and, rarely, partially ossified septa.[23] Unlike unicameral bone cysts (UBCs), ABCs tend to expand the bone wider than the adjacent physis (see the image below).
View Image | Aneurysmal bone cyst of distal radius in 11-year-old male. Note multiple septations, lytic cyst cavity, and extensive cortical thinning and expansion .... |
Capanna et al described the following five morphologic types of ABC on the basis of radiographic findings[24] :
The same characteristics are demonstrated on computed tomography (CT) as on plain radiography; however, CT scans also show internal septation (ie, calcified rim, eggshell appearance), which may be completely or partially intact. Fluid-fluid levels can also be seen[25] ; these are most often found in the ABC, but they are not exclusive to it. The fluid-fluid levels are caused by the separation of cellular material and serum within the cystic spaces.
For optimal visualization of these levels, patients must remain in the position in which they are imaged for at least 10 minutes so that enough separation of the materials of different attenuation can be obtained. The CT views then must be acquired in a plane that is perpendicular to the fluid levels.
Findings from magnetic resonance imaging (MRI) are similar to those from CT, but MRI can more specifically reveal blood within the lesion, as well as expansion into the soft tissues.[23] (See the image below.)
View Image | Axial and sagittal T2-weighted MRI of distal femoral aneurysmal bone cyst. Note multiple fluid-fluid levels throughout lesion consistent with multiple.... |
MRI can distinguish ABCs from telangiectatic osteosarcoma (TOS), in that TOS has thick, nodular enhancement of tissue surrounding the cystic spaces on gadolinium-enhanced contrast MRI corresponding with sarcomatous tissue. TOS may also demonstrate necrosis, whereas ABC has no necrosis and a thin peripheral rim with septal enhancement without nodularity.[26]
The appearance on imaging studies has been divided into phases of progression: initial or incipient, growth, stable, and healing.
The initial or incipient phase is characterized as follows:
The growth phase is characterized as follows:
The stable phase is characterized as follows:
The healing phase is characterized as follows:
On bone scans, increased uptake is observed around the lesion. Findings often demonstrate a halo or "donut" effect of increased radionuclide uptake surrounding an area of little uptake.
In some cases, angiography reveals a hypervascular area around the ABC. An intense diffuse area of persistent contrast accumulation may be visualized without main afferent or efferent vessels observed. It may be helpful to plan selective arterial embolization as the primary treatment or as a preoperative method to help control intraoperative blood loss.
Some investigators believe that pathognomonic findings on radiography, CT, and MRI may be used to confirm a diagnosis of ABC. However, if any doubt exists, an open biopsy must be performed because of the high frequency of accompanying tumors. Other authors believe that a histologic diagnosis based on an open biopsy should be routinely determined because it is necessary to confirm the diagnosis of ABC and to ensure that another lesion (eg, a malignancy) does not coexist with the ABC.
When biopsy is performed, the sample should include material from the entire lesion; a limited biopsy could easily cause a coexisting lesion to be missed, leaving the patient with a morbid prognosis.
As with all orthopedic oncology-related diseases, biopsy is part of the treatment, not the workup. The surgeon performing the biopsy must be able to handle the definitive care for either a benign or a malignant diagnosis; therefore, the biopsy must occur in the surgical plane of definitive resection. A well-thought-out referral is preferred to a poorly planned biopsy.
The gross appearance of the ABC is that of a blood-soaked sponge. A thin subperiosteal shell of new bone surrounds the structure and contains cystic blood-filled cavities. The tissue within shows brownish intertwining septa. The stroma contains proliferative fibroblasts, spindle cells, areas of osteoid formation, and an uneven distribution of multinucleated giant cells that tend to surround the fluid-filled cavities in a “pigs at the trough” formation.
The tissue within the septations includes cavernous channels that do not contain a muscular or elastic layer in their walls. Areas of new and reactive bone formation can also be found in the ABC. Mitotic figures are common to ABCs, but no atypical figures should be evident. Finally, the entire lesion should be removed and examined completely to ensure that no other underlying lesions exist.
A solid variant of the ABC has also been described; the histologic findings are similar to those of the cystic lesions, but the solid variant has a solid gross appearance.[27]
The staging of benign musculoskeletal neoplasms was described by Enneking in 1986, who classified benign lesions into the following three broad categories[28, 24] :
This system has been adopted by the Musculoskeletal Tumor Society (MSTS). Part of the Enneking classification contains the Lodwick radiographic grading system (see below).[29, 30, 31]
Latent (inactive) musculoskeletal neoplasms have the following characteristics:
Active musculoskeletal neoplasms have the following characteristics:
Aggressive musculoskeletal neoplasms have the following characteristics:
Lodwick grade IA is characterized as follows[29, 30, 31] :
Lodwick grade IB is characterized as follows:
Lodwick grade IC is characterized as follows:
Lodwick grade II is characterized as follows:
Lodwick grade III is characterized as follows:
Aneurysmal bone cysts (ABCs) generally are treated surgically.[32] Rarely, asymptomatic ABCs may be seen in which there is clinically insignificant destruction of bone. In such cases, close monitoring alone of the lesion may be indicated because of the evidence that some ABCs spontaneously resolve. When a patient is monitored in this manner, the diagnosis must be certain, and the lesion should not be increasing in size.
Some anatomic locations may be difficult to access surgically. If this situation is encountered, other methods of treatment, such as intralesional injection and selective arterial embolization, may be successful. In the future, advances in osteoinductive materials (eg, genetically engineered bone morphogenic protein) may offer a less invasive treatment of ABC.
Impending pathologic fracture, especially a fracture of the hip, is a challenging problem and an indication for intervention, which often includes curettage, adjuvant treatment, and internal fixation.
Selective arterial embolization has shown much promise for ABCs in small studies. However, the number of cases treated with this therapy is not large, both because ABCs are rare and because selective arterial embolization has been available only since the 1980s.[33, 34]
With the use of angiography, an embolic agent is placed at a feeding artery to the ABC, cutting off the nutrient supply and altering the hemodynamics of the lesion. Various materials, such as springs and foam, have been used to create the emboli.
Selective arterial embolization has the advantage of being able to reach difficult locations, being able to save joint function when subchondral bone destruction is present, and making the complications that are associated with invasive surgery (eg, bleeding) less likely to occur. Selective arterial embolization may be performed within 48 hours before surgery to reduce the amount of intraoperative hemorrhage.
Some of the literature suggests that selective arterial embolization can be a primary treatment for ABC if the following conditions are met:
Contraindications for selective arterial embolization include the following:
Only case evidence exists for intralesional injection, but the injection may be attempted for cases in which surgical access is difficult and for those in which other modalities are contraindicated.[35] (Note: Do not use this approach if the patient has allergies to the injection components, a pathologic or impeding fracture, neurologic symptoms, or unbearable symptoms such as pain. Do not use intralesional injection if a more proven treatment is indicated.)
There has also been case evidence for the use of calcitonin[36] and methylprednisolone injections in the regression of ABCs. This is thought to combine the inhibitory angiostatic and fibroblastic effects of methylprednisolone with the osteoclastic inhibitory effect and the trabecular bone-stimulating properties of calcitonin. The injections are performed under computed tomography (CT) guidance and anesthesia. Growth of the ABC must be closely monitored, and the treatment may need to be repeated several times. Years may pass before the ABC resolves.
ETHIBLOC (Ethicon, Norderstedt, Germany) injection is also performed under CT guidance and anesthesia.[37] The injected solution is a mixture of zein, oleum papaveris, and propylene glycol and acts as a fibrosing agent, and an inflammatory reaction may occur after its administration. Bony healing may take months to years. Side effects (eg, localized thrombosis, pulmonary embolus, osseocutaneous fistula formation, and severe surrounding tissue necrosis) make it a poor first-line choice in the absence of an obvious surgical contraindication.[9]
Some case evidence also suggests healing improvement when systemic calcitonin treatment is used as an adjuvant to other treatment modalities.
An Australian study by Clayer in 15 patients with pathologically confirmed ABC suggests that percutaneous aspiration and injection of ABCs using an aqueous solution of calcium sulfate may have value.[2] All patients except one who have reported pain before the procedure were completely without symptoms at 4 weeks post injection. The calcium sulfate was reabsorbed within 8 weeks.
During the minimum 2-year follow-up period, two patients developed local recurrence of the lesion, one of whom later developed a pathologic fracture. Two other patients sustained pathologic fractures at 12 and 22 months post injection, respectively. Clayer concluded that this procedure has "early clinical and radiological responses and a low complication rate in a consecutive group of patients with ABC."[2]
In several series, intralesional percutaneous injection of doxycycline has been reported to be beneficial in inducing stromal cell necrosis, reversing bone destruction, and preserving neighboring anatomy including physes and subchondral bone.[38, 39, 40, 41, 42] The principal proposed mechanisms of action for the success seen include the following[39] :
Contraindications for intralesional injection are as follows:
Radiotherapy has been used in the past, but this treatment is generally contraindicated, because of the risk of sarcoma induction, gonadal damage, and growth-plate disruption. Substantial risk is associated with treating a benign lesion with a therapy that can have damaging adverse effects, though radiation therapy is still occasionally used at low doses to treat surgically inaccessible lesions.
Extensive preoperative planning should be completed with the use of cross-sectional imaging. Embolization as a treatment or preoperative technique should be considered. When possible, a tourniquet should be used. Thought should also be given to what possible methods and materials may be needed to provide stability after ABC excision or resection.
Depending on the size and nature of the lesion, the patient's fluid volume and blood loss may have to be monitored closely.
The unusual stage 1 ABC can be treated with intralesional curettage[43] ; the more common stage 2 ABC is treated by intralesional excision. The difference between curettage and excision is that excision involves wide unroofing of the lesion through a cortical window by careful abrasion of all the surfaces with a high-speed burr and, possibly, local adjuvants such as phenol, methylmethacrylate (MMA), or liquid nitrogen. These adjuvants are controversial because firm evidence that they are effective is lacking, and their use entails considerable risk.
En-bloc or wide excision is typically reserved for stage 3 ABCs that are not amenable to intralesional excision (eg, extensive bony destruction); the recurrence rate after en-bloc excision is about 7%. Reconstructive options after wide excision include structural allografting and reconstruction with either endoprostheses or allograft-prosthetic composites.
In the past, intralesional excision was the mainstay of treatment. The ABC is accessed, a window is opened in the bony wall, and then the contents of the ABC are removed. Excision of the walls with curettes, rongeurs, or high-speed burrs has been described. The intralesional method leaves more bony structure intact than en-bloc or regional resection.
Intralesional excision may also be used around joints and other vital areas to try to preserve function. The defect may then be filled with bone chips, bone strut, or other supporting material to add strength and to enhance healing of the excised area.
Concerns for local resection include the following:
Concerns for en-bloc excision of a deep lesion include the following:
Concerns for intralesional removal include the following:
The surgeon may also use adjuvant therapy, which extends the area of treatment beyond that which can be physically excised. The use of liquid nitrogen, phenol, argon beam gas plasma photocoagulation, and polymethylmethacrylate (PMMA) may achieve an extended area of treatment.
The adjuvants involve the use of chemical, freezing, or thermal means to cause bone necrosis and microvascular damage to the walls of the physically excised cyst, disrupting the possible etiology. Compared with en-bloc and regional resection, the use of adjuvants leaves more bone intact, and an increased area is treated compared with the area treated with intralesional resection alone.
Liquid nitrogen is the most popular adjuvant, and it is often described in the literature. After the ABC is exposed and a window is opened, liquid nitrogen may be applied by pouring it into the cyst through a funnel or by using a machine that is designed to spray the liquid onto the walls of the lesion. The surgeon should be sure to leave the window open, allowing the gas to escape.
A total of two or three cycles of freezing and thawing should be used to obtain maximum bone necrosis. The surrounding tissue, especially the neurovascular bundles, must be protected to ensure these structures are not damaged. Avoiding the use of a tourniquet with cryotherapy is suggested to keep the surrounding tissue vascularized, making it more resistant to freezing.
Phenol is much less often used as an adjuvant. Some authors have questioned the effectiveness of phenol because of its poor penetration of bony tissue compared with that of liquid nitrogen. However, phenol has had some success in certain studies, and it has the benefit of being easy to use. Phenol is simply applied to the mechanically removed walls by using soaked swabs. Any remaining phenol is removed with suction, and the cavity is filled with absolute alcohol. Finally, the cavity is irrigated with isotonic sodium chloride solution.
PMMA may also be used, though the effectiveness of its thermal properties in causing bone necrosis has been questioned in the literature. However, PMMA does have the benefit of rendering a large lesion mechanically sound and making it easier to recognize a local recurrence. If PMMA is used in a subchondral location, the joint surface should be protected by placing cancellous grafts or Gelfoam (Pharmacia & Upjohn Co, Kalamazoo, MI) before cementation. It is not clear that removing the cement and replacing it with a bone graft is necessary.
Argon beam coagulation has also been used in several studies, with some promising results.[44, 45, 46] One study noted that surgical treatment with curettage and adjuvant argon beam coagulation is an effective treatment option for ABC; the primary complication was postoperative fracture.[45]
An additional study found that argon beam photocoagulation, while avoiding the toxic effects of phenol, yielded statistically equivalent recurrence rates, functional outcomes, and complication rates in the treatment of benign-aggressive bone tumors.[46] However, the authors also noted an increased fracture rate in the argon beam photocoagulation cohort as compared with the phenol cohort.
Concerns for adjuvant intralesional therapy include the following:
NOTE: Special consideration is necessary in dealing with ABCs that are near open physes. The reader is referred to the literature for general considerations when operating around physes. The reported rate of physeal injury is significant, and patients and their families must be made aware of this possibility. Furthermore, it has been shown that attempts to spare the adjacent physes by performing a less-than-aggressive curettage of ABCs have resulted in increased risk of local recurrence in patients with open growth plates.[47, 48]
Spinal ABCs usually cause neurologic symptoms and pose treatment challenges. The details of surgical excision can be found elsewhere. There is evidence to support an attempt at one or two trials of selective arterial embolization before surgical excision.
A group in Japan developed an endoscopic approach to the treatment of ABC.[49] They successfully treated four patients with ABCs that lacked the aneurysmal component. The technique was completed with a variety of curettes, ball forceps, Kirschner wires (K-wires), an arthroscope, and a drill. The method may leave a more stable structure and is minimally invasive.
Treatment for a secondary ABC is that which is appropriate for the underlying lesion.
Activity modification should be as tolerated to the fitness of the patient, the anatomic location of the surgery, and the extent of the surgery and reconstruction. Mechanical or chemical prophylaxis against deep vein thrombosis may also be indicated.
Complications can vary with the location in which the ABC arises. Many of these are related to the proximity of the surrounding tissues.
Universal complications that have been described with surgery include the following:
Additional complications that have been shown with spinal locations include the following:
Complications that are associated with liquid nitrogen include the following:
A complication that is associated with phenol is necrosis of the surrounding tissue exposed to the phenol (eg, neurovascular bundles, physis).
A complication that is associated with selective arterial embolization is unintentional embolization of a vital area.
Finally, fracture risk may be elevated in those adjuvantly treated with argon beam photocoagulation, particularly in weightbearing bones.
When the diagnosis of ABC is suspected or confirmed, consultation with an orthopedic oncologist should be obtained.
Recurrence usually happens within the first year after surgery, and almost all episodes occur within 2 years.[50, 51, 52] However, patients should still be monitored on a regular basis for 5 years. It is beneficial to detect recurrence early when the lesion is still small and easier to treat. Children should be monitored until they have reached maturity to ensure that any possible recurrence does not cause deformity or interfere with their growth. Any patients who have received radiation should be monitored for life because of the risk of secondary sarcoma.
In this histologic image, the septum contains fibroblasts, mononuclear histiocytelike cells, multinucleated giant cells, and capillaries. The lining of the large vascular spaces may be indistinct or consist of a single layer of attenuated stromal cells, as seen here. Used with permission from the American Registry of Pathology. Courtesy of Armed Forces Institute of Pathology.