Aneurysmal Bone Cyst​

Aneurysmal Bone Cyst

Aneurysmal bone cysts (ABCs) are benign bone lesions that can nonetheless be locally aggressive and destructive. ABCs consist of blood-filled spaces within bone that can become large and multi-chambered. Both primary and secondary aneurysmal bone cysts exist, with secondary lesions denoting those that arise within another preexisting tumor. Aneurysmal bone cysts typically have an aggressive appearance on radiographs and, therefore, can be mistaken for malignancy. Although aneurysmal bone cysts are usually treated with intra-lesional surgery, local recurrence rates can be high.

An aneurysmal bone cyst was given its name due to its appearance on imaging studies, even though it is neither a true aneurysm nor a cyst. The term “aneurysmal” refers to the distended appearance of the lesion, resembling an aneurysm of an artery wall. However, ABCs do not involve blood vessels. The term “cyst” is used because the lesion appears cyst-like on imaging, with fluid-filled cavities or spaces within the bone. However, ABCs are not true cysts, as they lack an epithelial lining which defines a cyst.

Epidemiology

Aneurysmal bone cysts usually occur in the first two decades of life. About 80% of lesions occur in the long bones at the metaphysis or in flat bones such as the pelvis; the remaining 20% of lesions occur within the posterior elements of the spine.

Clinical Features

Most patients present with mild pain and swelling. In weight-bearing bones such as the femur or tibia, patients may describe worsening mechanical pain. In bones with thin, soft-tissue coverage such as the proximal fibula, patients may report an enlarging prominence. Aneurysmal bone cysts may present with a pathologic fracture but are not usually associated with systemic symptoms such as lethargy, fever, or chills.

Radiologic Features

Aneurysmal bone cysts are usually located in the metaphysis but have been reported throughout the skeleton. Aneurysmal bone cysts are lytic, expansile, eccentric lesions that cause the bone to take on an appearance similar to an aneurysm of a blood vessel.

ABCs have a thin, sclerotic border characterized by cortical thinning and remodeling, expansion of the bone (Figure 1). The medullary edges of the lesion are well-defined; this is described as “geographic margins.” (The term “geographic” stands in contrast to descriptions such as “moth-eaten” or “permeative,” which indicate more aggressive and poorly defined edges.)

Figure 1: An AP radiograph of the tibia, demonstrating an aneurysmal bone cyst. As shown, the lesion is an eccentric and radiolucent, with expansile remodeling of bone. (Image reproduced courtesy J Pathol Transl Med. 2023 Mar 14;57(2):81–87. doi: 10.4132/jptm.2023.02.23).

Additionally, there is no mineralized matrix within the lesion. In children, aneurysmal bone cysts can expand to the point where they cross and damage the adjacent growth plate.

Magnetic resonance imaging (MRI) demonstrates classic “fluid-fluid” levels, which represent the separation of the cellular component of blood from the supernatant (Figure 2). In the context of an ABC, this occurs because the lesion contains blood products at varying stages of degradation and protein content. The heavier, more cellular, or protein-rich components settle at the bottom of the cyst whereas the lighter, serum-like component remains at the top, creating a clear line of separation between the two densities. (This finding is a hallmark of ABCs, though it is not pathognomonic.)

Figure 2: An anteroposterior radiograph of the tibia shows an eccentric, well-defined, juxtaphyseal, lytic and expansile lesion (asterisk) involving the proximal tibial metadiaphysis [left]. An axial fat-suppressed T2-weighted magnetic resonance image of the leg [right] shows fluid-fluid levels throughout the lesion (arrows). The fluid-fluid level is created when two distinct substances with different densities separate within the cyst or tumor, creating a horizontal interface due to gravity. ( Image reproduced courtesy of Restrepo, R., Zahrah, D., Pelaez, L. et al. Update on aneurysmal bone cyst: pathophysiology, histology, imaging and treatment. Pediatr Radiol 52, 1601–1614 (2022))

Multiple septations can be seen within the lesion. Areas of nodular enhancement are not visible in primary aneurysmal bone cysts, but are visible in secondary aneurysmal bone cysts, which occur within a solid tumor.Areas of secondary ABC can occur in any vascular tumor in bone such as Osteosarcoma, Ewing Sarcoma, giant cell tumor of bone, metastatic renal cell carcinoma, etc. Finding these solid areas and sampling them via biopsy is important in distinguishing secondary from primary ABC. The “donut” sign can be seen on bone scans, characterized by central photopenia with peripheral uptake.

Pathology

Macroscopic evaluation of aneurysmal bone cysts reveals a large cavity filled with bloody fluid. The cyst walls are lined with fibrous tissue (but no epithelium, as would be seen in a true cyst). Bony septations can also be seen.

Histology reveals giant cells, blood, and woven reactive bone, but no mitoses or atypical cells (Figure 3).

Figure 3: High-power H&E stain of an aneurysmal bone cyst, demonstrating lakes of blood containing hundreds of red blood cells, as well as septae comprised of benign stromal cells (thin arrow) and multinucleated giant cells (thick arrow. The tumor stains positively for USP6. ( Image courtesy of Dr. Gord Zhu)

In primary aneurysmal bone cysts, a t(16;17) translocation involving fusion of the USP6 gene with the CDH11 (Cadherin-11) gene has been identified. This translocation is diagnostic of primary aneurysmal bone cysts, as it is not expressed by secondary aneurysmal bone cysts. In secondary aneurysmal bone cysts, tissue from the primary tumor may be present, such as that from a giant cell tumor of bone or osteoblastoma. If mitoses or atypical cells are visible, concern should be raised for a telangiectatic osteosarcoma.

Differential Diagnosis

Unicameral Bone Cyst (UBC): UBCs can have a similar appearance to ABCs on X-ray, presenting as a well-defined, expansile, lytic lesion in the metaphysis of a long bone. However, UBCs typically lack the septations and fluid-fluid levels often seen in ABCs. Also, UBC’s are full width central lesions where the expansion is usually not wider than the widest part of the metaphysis, whereas ABCs are eccentric within the cross-section of the bone and very expansile.

Giant Cell Tumor (GCT): GCTs can also present as an expansile, lytic lesion, often in the metaphyseal/epiphyseal region of long bones. They may have a more aggressive appearance than ABCs, with significant cortical destruction and soft tissue extension.

Telangiectatic Osteosarcoma: This aggressive bone tumor can mimic the appearance of an ABC, with a lytic, expansile lesion and possible fluid-fluid levels on imaging. Distinguishing between these two entities is crucial, as telangiectatic osteosarcoma requires more aggressive, multi-modality treatment. Again, look for areas of solid tumor in the osteosarcoma which will not be present in a primary ABC.

Fibrous Dysplasia: In the early stages, fibrous dysplasia can appear as a well-defined, somewhat expansile, lytic lesion, potentially mimicking an ABC. However, fibrous dysplasia typically has a ground-glass appearance and is a solid tumor without areas of cystic change in most cases. In its later stages in older patients, fibrous dysplasia can spontaneously regress leaving areas of fluid in the prior lesion.

Secondary Aneurysmal Bone Cyst: The imaging characteristics of secondary ABCs are predominantly those of the primary bone lesion with the addition of typical fluid-fluid levels seen on MRI.

Disease Course: Treatment and Prognosis

The tentative diagnosis of an aneurysmal bone cyst can be made with radiographs and MRI, but a biopsy of the lesion is still required for histologic confirmation, especially if nodular enhancement is visible on MRI. The biopsy should focus on sampling the solid components, if they are present.

Intralesional curettage with bone grafting remains the gold standard for treatment and is successful in most patients. Adjuvant treatments used with curettage include phenol, argon beam coagulation, and liquid nitrogen. However, local recurrence rates can be as high as 40%; recurrence rates are highest in skeletally immature patients. In the case of multiple local recurrences or debilitating disease, wide resection with reconstruction offers the greatest local control. Less invasive techniques can be used to manage aneurysmal bone cysts in difficult-to-reach locations, such as the pelvis or spine. Direct injection of sclerosing agents or bone fillers, serial embolization of the tumor, and radiation have been employed with varying degrees of success.

Key Test Topics

A high index of suspicion for telangiectatic osteosarcoma must be demonstrated when evaluating a presumed aneurysmal bone cyst.
An aggressive intramedullary border on x-ray, nodular enhancement on MRI, and/or atypical mitoses on biopsy should raise concern.
Lesions treated with appropriate intralesional curettage that still exhibit rapid local recurrence should increase the index of suspicion for a malignant process.
A t(16;17) translocation involving fusion of the USP6 gene with the Cadherin-11 gene is diagnostic