Moderators: Dr. K. Krishnan Unni and Dr. Franco Bertoni
Case 1 -
Aneurysmal Bone Cyst
Carrie Y. Inwards, M.D.
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
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
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
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
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.
- 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. With Emphasis on the Roentgen Picture, the Pathologic Appearance, and the Pathogenesis. Arch Surg 44:1004-1025, 1942.
- Kyriakos M, Hardy D: Malignant transformation of aneurysmal bone cyst, with an analysis of the literature. Cancer 68:1770-1780, 1991
- Leithner A, Windhager R, Lang S, et al: Aneurysmal bone cyst: A population-based epidemiologic study and literature review. Clin Orthop Relat Res 363:176-179, 1999
- Levy WM, Miller AS, Bonakdarpour A, et al: Aneurysmal bone cyst secondary to other osseous lesions: Report of 57 cases. Am J Clin Pathol 63:1-8, 1975
- Lichtenstein L: Aneurysmal bone cyst: A pathological entity commonly mistaken for giant cell tumor and occasionally for hemangioma and osteogenic sarcoma. Cancer 3:279-289, 1950
- Lichtenstein L: Aneurysmal bone cyst: Observations on 50 cases. J Bone Joint Surg 39A:873-882, 1957
- Mankin HJ, Hornicek FJ, Ortiz-Cruz E, et al: Aneurysmal bone cyst: A review of 150 patients. J Clin Oncol 23:6756-6762, 2005
- Marcove RC, Sheth DS, Takemoto S, et al: The treatment of aneurysmal bone cyst. Clin Orthop Relat Res 311:157-163, 1995
- Martinez V, Sissons HA: Aneurysmal bone cyst: A review of 123 cases including primary lesions and those secondary to other bone pathology. Cancer 61:2291-2304, 1988
- Nielsen,G.P.,Fletcher, CDM, Smith,MA, Rybak,L, Rosenberg,AE: Soft Tissue Aneurysmal Bone Cyst: A Clinicopathologic Study of Five Cases. Am J Surg Pathol 26(1): 64-69, 2002.
- Oliveira AM, Hsi BL, Weremowicz S, et al: USP6 (Tre2) fusion oncogenes in aneurysmal bone cyst. Cancer Res 64:1920-1923, 2004
- Oliveira AM, Perez-Atayde AR, Dal CP, et al: Aneurysmal bone cyst variant translocations upregulate USP6 transcription by promoter swapping with the ZNF9, COL1A1, TRAP150, and OMD genes. Oncogene 24:3419-3426, 2005
- Oliveira AM, Perez-Atayde AR, Inwards CY, et al: USP6 and CDH11 oncogenes identify the neoplastic cell in primary aneurysmal bone cysts and are absent in so-called secondary aneurysmal bone cysts. Am J Pathol 165:1773-1780, 2004
- Panoutsakapoulos, G., Pandis, N, Kyriazoglou, I. et.al.: Recurrent t(16:17)(q22:p13) in aneurysmal bone cysts. Genes, Chromosomes, Cancer 26:265-266, 1999.
- Papagelopoulos PJ, Choudhury SN, Frassica FJ, et al: Treatment of aneurysmal bone cysts of the pelvis and sacrum. J Bone Joint Surg 83A:1674-1681, 2001
- Rodriguez-Peralto,JL, Lopez-Barea,F, Sanchez-Herrera, S., Atienza, M: Primary Aneurysmal Cyst of Soft Tissues (Extraosseous Aneurysmal Cyst). Am J Surg Pathol 18(6): 632-636, 1995.
- Rosenberg, A.,Nielsen,G.P., Fletcher, J.A.: Aneurysmal Bone Cyst. In: Fletcher, C.D.M., Unni,K.K., Mertens, editors. World Health Organization Classification of Tumors. Pathology and Genetics of Tumors of Soft Tissue and Bone. Lyon: IARC Press: 2002, 338-339.
- Sanerkin, NG, Mott,MG, Roylance,J: An Unusual Intraosseous Lesion with Fibroblastic, Osteoclastic, Osteoblastic, Aneurysmal and Myxoid Elements: "Solid" Aneurysmal Bone Cyst. Cancer51:2278-2286, 1983
- Sullivan RJ, Meyer JS, Dormans JP, et al: Diagnosing aneurysmal and unicameral bone cysts with magnetic resonance imaging. Clin Orthop Relat Res 366:186-190, 1999
- Tillman BP, Dahlin DC, Lipscomb PR, et al: Aneurysmal bone cyst: An analysis of ninety-five cases. Mayo Clin Proc 43:478-495, 1968
- Vergel De Dios AM, Bond JR, Shives TC, et al: Aneurysmal bone cyst: A clinicopathological study of 238 cases. Cancer 69:2921-2931, 1992