Case 1 -

Aneurysmal Bone Cyst Carrie Y. Inwards, M.D.

Case History: A 17 year old male complained of 5 months of back pain. As the name implies, aneurysmal bone cyst (ABC) is an expansile ("aneurysmal") lesion composed of numerous blood filled cystic spaces. It was first recognized in 1942 by Lichtenstein and Jaffe who mentioned it in a paper describing solitary bone cysts. Since that time it was widely regarded as a reactive process with the propensity to behave in a locally aggressive fashion. Many different theories have been proposed for the pathogenesis of ABC. One of the most widely accepted was that a local circulatory abnormality led to increased venous pressure and resultant dilation of the local vascular network. The reactive nature of ABC was initially challenged in 1999 by the work of Panoutsakopoulos et al, who demonstrated that some primary ABCs exhibited the chromosomal translocation t(16;17)(q22;p13) as a recurrent cytogenetic abnormality. These initial observations by Panoutsakopoulos et al were later confirmed by Dal Cin et al. Oliveira et al extended these studies by showing that the t(16;17)(q22;p13) fuses the promoter region of the osteoblast cadherin 11 gene (CDH11) on chromosome 16q22 to the entire coding sequence of the ubiquitin protease USP6 gene (also known as TRE2 or TRE17) on chromosome 17p13, suggesting that the pathogenesis of most primary ABCs involves upregulation of USP6 transcription driven by the highly active CDH11 promoter. In a subsequent study, Oliveira et al also found rearrangements of CDH11 and/or USP6 in almost 70% of 52 primary ABCs examined. Rearrangements of these genes were restricted to the spindle cells in the cyst wall and were not found in multinucleated giant cells, inflammatory cells, endothelial cells, or osteoblasts. The results of these studies support characterization of ABC as a clonal neoplastic disorder rather than a reactive process. Aneurysmal bone cyst can also be associated with other tumors and tumor-like conditions. This type of ABC is often referred to as secondary ABC. The precursor lesions are almost always benign and most commonly include giant cell tumor, chondroblastoma, and fibrous dysplasia. Aneurysmal bone cyst is usually a minor component of the process. However, at times the lesion may be predominantly cystic and obscure the underlying primary lesion. The incidence of secondary ABC is difficult to assess since cystic degenerative change may be misinterpreted as secondary ABC. Oliveira et al investigated CDH11and USP6 rearrangements in 17 secondary ABCs. The negative results of this study indicated that secondary ABCs may represent a nonspecific morphologic pattern in a diverse group of neoplasms. Pain and swelling are the most common clinical manifestations of ABC. Patients with involvement of the vertebrae may show neurological symptoms. There is a slight predilection for females and approximately 80% of the patients are in the first two decades of life. Aneurysmal bone cyst may occur in any portion of the skeleton. However the region around the knee, including the distal femur and the proximal tibia, constitute the single most common site. Aneurysmal bone cysts frequently involve the spine where the cervical vertebrae are more frequently involved than the others. In the long bones, aneurysmal bone cysts tend to involve the metaphysis, whereas in the spine they tend to involve the posterior elements. A typical roentgenographic appearance of an aneurysmal bone cyst is an area of lucency situated eccentrically in the medullary cavity in the metaphysis of a long bone. However, the lesion may be central, cortical, or even on the surface of bone. It can also occur as a primary lesion in soft tissue. Most aneurysmal bone cysts are completely lytic but faint traces of mineral may be found. The lesion often extends through the cortex to form a soft tissue mass. Typically the soft tissue mass is well demarcated and may show a rim of ossification or calcification. This peripheral shell may be better visualized on CT scan. In a small number of cases, the roentgenographic features may suggest a malignant neoplasm. CT scans usually show fluid-fluid levels which are highly characteristic, but not diagnostic of ABC. Magnetic resonance images show internal septations that produce a honeycomb appearance and fluid-fluid levels. Most often the gross specimen is received in fragments. The tissue is in the form of red granular material. Occasional foci of calcification may be seen. One characteristic aspect is that the gross specimen is considerably smaller than would be expected from the radiographic appearance. If the lesion is resected intact, spaces separated by thin walled septa are found. Case 1 - Slide 1 Click to view with ImageScope Click to view with a Web-Based Viewer Microscopically, under low magnification an ABC has the appearance of multiple variably sized spaces separated by septa. The spaces are either empty or contain blood. The septa consist of loosely arranged slender spindle cells, capillaries, scattered multinucleated giant cells and varying amounts of matrix. The spindle cells are mitotically active but do not show cytological features of malignancy. Oftentimes a very thin strand of osteoid, frequently referred to fiber osteoid, is present in the septum just beneath the lining. In more solid areas, thicker seams of woven bone and reactive osseous trabeculae are present. Calcification is another common finding. It may be finely dispersed in a lace-like pattern or more condensed with an amorphous or powdery appearance. Some aneurysmal bone cysts will show very thick septa, giving rise to solid areas composed of more closely packed spindle cells. At times, ABCs will be almost entirely solid with little in the way of septa formation. These lesions are composed of more densely packed spindle cells, prominent reactive new bone formation, and a sprinkling of lymphocytes. The term solid aneurysmal bone cyst or giant cell reparative granuloma has been employed for this histologic variant. Despite the predominately solid nature of these lesions, most will show at least small foci of cyst formation. The differential diagnosis primarily involves giant cell tumor and osteosarcoma. Giant cells may be prominent in an aneurysmal bone cyst but they usually lack the concentrated uniform appearance seen in a typical giant cell tumor. Giant cell tumors, almost without exception, involve the end of a bone whereas aneurysmal bone cysts are metaphyseal. In the spine, aneurysmal bone cysts tend to involve the posterior elements whereas giant cell tumors involve the body. Telangiectatic osteosarcoma is the most important differential diagnosis. Aneurysmal bone cysts and telangiectatic osteosarcomas share clinical, radiographic, gross, and low power microscopic appearances. The only distinction is made by recognizing cytological features of malignancy in the septa and lining in telangiectatic osteosarcoma. Relatively solid aneurysmal bone cysts can be mistaken for osteosarcoma of the ordinary type. Low grade osteosarcomas are not nearly as cellular as an aneurysmal bone cyst. The loose arrangement of the tissue is in contrast to the compact arrangement of tumor cells in an osteosarcoma. An ABC with solid areas and abundant new bone formation with prominent osteoblastic rimming may resemble osteoblastoma. Treatment is surgical removal. This is usually accomplished with curettage followed by insertion of bone graft or polymethylmethacrylate. Occasionally resection is indicated if the lesion is very large or located in a bone that can be easily resected. Recurrences may develop. The rate of recurrence varies in the literature from 5% to greater than 40%. However, the prognosis is excellent with most recurrence rates being closer to 20% or less. There is only one case report of malignant transformation of an ABC. References Campanacci M, Capanna R, Picci P: Unicameral and aneurysmal bone cysts. Clin Orthop Relat Res 204:25-36, 1986 Dal Cin P, Kozakewich HP, Goumnerova L, et al: Variant translocations involving 16q22 and 17p13 in solid variant and extraosseous forms of aneurysmal bone cyst. Genes Chromosomes Cancer 28:233-234, 2000 Dorfman HD, Czerniak B: Cystic lesions, in Dorfman HD, Czerniak B (eds): Bone Tumors. St. Louis, MO, Mosby, 1998, pp 855-912 Dormans JP, Hanna BG, Johnston DR, et al: Surgical treatment and recurrence rate of aneurysmal bone cysts in children. Clin Orthop Relat Res 421:205-211, 2004 Jaffe HL: Aneurysmal bone cyst. Bull Hosp Joint Dis 11:3-13, 1950 Jaffe, H.L., Lichtenstein, L.: Solitary Unicameral Bone Cyst. 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