Review Article Aneurysmal Bone Cyst Abstract Timothy B. Rapp, MD Aneurysmal bone cysts are rare skeletal tumors that most James P. Ward, MD commonly occur in the first two decades of life. They primarily develop about the knee but may arise in any portion of the axial or Michael J. Alaia, MD appendicular skeleton. Pathogenesis of these tumors remains controversial and may be vascular, traumatic, or genetic. Radiographic features include a dilated, radiolucent lesion typically located within the metaphyseal portion of the bone, with fluid-fluid levels visible on MRI. Histologic features include blood-filled lakes interposed between fibrous stromata. Differential diagnosis includes conditions such as telangiectatic osteosarcoma and giant cell tumor. The mainstay of treatment is curettage and bone graft, with From the Department of Orthopaedic Surgery, NYU Hospital or without adjuvant treatment. Other management options include for Joint Diseases, New York, NY. cryotherapy, sclerotherapy, radionuclide ablation, and en bloc Dr. Rapp or an immediate family resection. The recurrence rate is low after appropriate treatment; member has received research or however, more than one procedure may be required to completely institutional support from AO Spine, Arthrex, the Arthritis Foundation, the eradicate the lesion. Arthritis National Research Foundation, Asterland, Biomet, DePuy, Encore Medical, Exactech, DJO, Ferring Pharmaceuticals, the neurysmal bone cysts (ABCs) cate the lesion completely while si- Geisinger Foundation, Integra Awere first described in 1942 by multaneously preserving as much of LifeSciences, Johnson & Johnson, Jaffe and Lichtenstein,1 who coined the normal host bone as possible. KCI, Medtronic, the National the term aneurysmal cyst because of Institutes of Health, OMeGA, the Orthopaedic Research and the pathologic appearance of the le- Education Foundation, the sion within bone. These bone lesions Pathophysiology Orthopaedic Trauma Association, are benign and are typically associ- the Osteosynthesis and Trauma Much debate exists regarding the na- ated with pain, swelling, or the pres- Care Foundation, Paradigm Spine, ture of ABCs. Dabska and Buraczew- Progenics Pharmaceuticals, Small ence of an expansile mass. ABCs are ski11 were among the first to com- Bone Innovations, Smith & Nephew, considered primary lesions in ap- ment on the pathophysiology and Stryker, Surgix, and Synthes, and proximately 70% of cases, with the serves as a board member, owner, natural history of the ABC. They di- officer, or committee member of the remaining 30% arising secondary to vided its progression into four 2 American Academy of Orthopaedic different primary tumors. phases, with the initial phase de- Surgeons. Neither of the following The patient with ABC most com- scribed as osteolysis of the marginal authors nor any immediate family monly presents in the first two de- member has received anything of part of the bone with discrete eleva- value from or owns stock in a cades of life. Common lesion sites in- tion of the periosteum. The growth commercial company or institution clude the femur, tibia, fibula, phase is characterized by the pro- related directly or indirectly to the humerus, skull, and posterior ele- gressive destruction of bone. Demar- subject of this article: Dr. Ward and ments of the spine. Multiple theories Dr. Alaia. cation of the lesion is poor during have been proposed regarding the this phase; bony shells and septations J Am Acad Orthop Surg 2012;20: pathophysiology of ABC, including 233-241 may not be obvious on plain radio- vascular, traumatic, and genetic graphs. The stabilization phase is de- http://dx.doi.org/10.5435/ etiologies.3-8 Primary ABC has a low JAAOS-20-04-233 fined by the classic ABC appearance: incidence rate, ranging from 0.14 to an expansile lesion with a distinct Copyright 2012 by the American 0.32 per 100,000 individuals.6,9,10 bony shell and osseous septations. In Academy of Orthopaedic Surgeons. The goal of management is to eradi- the healing phase, progressive ossifi- April 2012, Vol 20, No 4 233 Aneurysmal Bone Cyst cation of the lesion is obvious and of immunohistochemistry and in situ results in a bony mass with a some- hybridization in 19 specimens of Classification what irregular structure. ABC. They found insulin-like growth Several classification systems have Campanacci et al3 described the le- factor-I or mRNA coding for this been developed to categorize ABCs. sion as a response to local hemor- growth factor primarily localized in Enneking13 divided lesions into three rhage. An initial insult produces in- multinucleate giant cells in all of the stages: inactive, active, and aggres- traosseous bleeding, leading to the specimens. Insignificant levels of ex- sive. The inactive tumor is the most formation of a cyst. The cyst walls pression were found in normal hu- benign because the lesion is con- may house capillaries that hemor- man bone tissue. These findings sup- tained. Expansion is rare, and there rhage into the newly formed cavity, port the theory that genetic factors is minimal inflammation or perios- producing osteolytic and repair tis- may play a significant role in the de- teal reaction. An active lesion typi- sue, which may ultimately explain cally produces mild symptoms such the lesion’s predilection for rapid, ag- velopment of primary ABC. as pain, with expansion and cortical gressive expansion. Lichtenstein4 thinning as well as a layer of reactive proposed that the ABC is a reactive Clinical Presentation bone separating the lesion from nor- lesion rather than a true neoplasm mal bone visible on radiographs. Ag- and that vascular disturbances in In patients with ABC, age of onset gressive tumors are rapidly expansile bone lead to increased intraosseous ranges from 1 to 59 years, with the and destroy surrounding tissues. pressure, causing local destruction greatest prevalence between ages 12 This subtype is typically the most and distension of bone. Ratcliffe and 9,10 and 13 years. Typically, males are symptomatic. Grimer5 described the formation of affected more often than females, Capanna et al14 based their system an ABC at a fracture site in a previ- with reported ratios ranging from on five morphologic subgroups (Fig- ously normal tibia. Like Capanacci 1:1.04 to 1.8:1.9,10 In a population- ure 1). Type I lesions are centrally lo- et al3 and Lichtenstein,4 the authors based analysis of 110 surgically cated and well contained, with either postulated that the fracture altered treated ABC patients listed in the Vi- no outline or a slightly expanded the intraosseous blood flow and sub- outline. Type II lesions have marked sequently led to formation of the le- enna Bone Tumor Registry, 73 ABCs expansion and cortical thinning with sion. (66%) occurred in patients younger 9 involvement of the entire bony seg- Recently, genetics have been impli- than age 20 years. ment. Type III lesions are eccentric cated in the etiology of ABC, leading The patient with primary ABC typ- and metaphyseal and typically in- some to believe that ABC is a true ically reports pain and may present volve only one cortex. Type IV le- neoplasm rather than a reactive pro- with soft-tissue swelling or a palpa- sions are the least common subgroup cess. In a histopathologic study, Ol- ble expansile mass. As with most be- and develop subperiosteally, expand- iveira et al6 reported that gene rear- nign bony malignancies, secondary ing away from the bone. Type V le- rangements localized to t(16;17) in symptoms such as fever, weight loss, sions occur periosteally and expand 36 of 52 primary ABCs (69%) in malaise, nausea, or vomiting are not peripherally, ultimately penetrating which the ubiquitin-specific protease common. cortical bone. 6 oncogene was placed under the ABC commonly arises at sites such regulatory influence of the highly ac- as the femur, tibia, humerus, and fib- tive cadherin-11 promoter. They ula; these sites account for approxi- Imaging found no such translocations in 17 mately 52% of ABC sites.10 Other cases of secondary ABC. The authors common locations include the skull Suspected ABC can be evaluated ini- concluded that these findings con- and spinal column, with ABC being tially with plain radiography. The firm a true neoplastic etiology. Oth- one of the most common malignan- classic radiographic appearance of ers have shown that upregulation of cies (along with osteoid osteoma and ABC is a radiolucent cystic lesion ubiquitin-specific protease 6 may osteoblastoma) that affect the poste- within the metaphyseal portion of induce matrix metalloproteinase pro- rior elements of the spine. In chil- the bone. The lesion is destructive duction by activation of nuclear fac- dren, the most common sites of ex- and may expand into the surround- tor κ-light-chain-enhancer of acti- tremity ABC are the femur and ing cortical bone. The mass may ele- vated B cells, which ultimately leads tibia.2,12 ABCs in these areas are typi- vate the periosteum, but it typically to tumorigenesis.7 cally confined to the metaphyseal re- remains contained by a thin shell of Leithner et al8 reported the results gions of the bone. cortex. Typically, ABCs are eccentric 234 Journal of the American Academy of Orthopaedic Surgeons Timothy B. Rapp, MD, et al Figure 1 Illustration of the aneurysmal bone cyst classification developed by Capanna et al,14 based on morphologic changes visible on radiographs. (Redrawn with permission from Dormans JP, Hanna BG, Johnston DR, Khurana JS: Surgical treatment and recurrence rate of aneurismal bone cysts in children. Clin Orthop Relat Res 2004;[421]:205-211.) Figure 2 AP (A) and lateral (B) radiographs demonstrating an expansile metaphyseal lesion of the distal ulna with thinning of the bony cortices and internal septations in a 46-year-old man who presented with a painful mass on the distal forearm. C, Axial fat-saturated T2-weighted magnetic resonance image demonstrating fluid-fluid levels consistent with an aneurysmal bone cyst (ABC).