Aneurysmal Bone Cyst

Aneurysmal bone cyst (ABC) is a benign, locally aggressive bone lesion made of blood-filled cavities separated by fibrous septa that contain fibroblasts and osteoclast-like giant cells. Despite the name it is not a true cyst: there is no epithelial lining.

Who. Three quarters of patients are under 20, with the peak between 10 and 20 years. The lesion is rare under 5 and over 50.

Where. Long-bone metaphyses account for half of cases:

• Long bones - 50%. Metaphyseal and eccentric; femur, tibia and humerus most often
• Spine - 15-20%. Posterior elements, with the neurological risk that follows
• Pelvis - 10%. Often large at presentation; embolisation is useful here
• Flat bones - 10%. Scapula, ribs, clavicle
• Small bones - 10%. Hands and feet; talus and calcaneus

Primary or secondary. About 70% arise de novo and carry the USP6 rearrangement. The remaining 30% are conventionally quoted as arising within a pre-existing bone lesion, and it is that lesion which then needs treating. Read the 30% as a pathology-referral proportion rather than a surgical one: in Mankin's 150 consecutive patients only one lesion was considered secondary. The clinical instruction does not depend on the percentage, and solid areas are biopsied to exclude malignancy whatever the figure.

The USP6 rearrangement. Understanding of ABC was transformed by the discovery that primary lesions carry a rearrangement of the USP6 (Tre2) gene on chromosome 17p13, found in 36 of 52 primary ABC (69%, quoted as 70%). The commonest fusion partner is CDH11 (cadherin-11), through t(16;17)(q22;p13): the highly active, bone-restricted CDH11 promoter is juxtaposed to the USP6 coding sequence and drives its over-expression, which leads to increased MMP production and osteoclast activation.

Which cell is neoplastic. The rearrangement is confined to the spindle (stromal) cells and absent from the giant cells. That identifies the stromal cell as the neoplastic one and confirms ABC as a true neoplasm, not a reactive process.

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Secondary ABC arises within a pre-existing bone lesion and carries no USP6 rearrangement. The precursors:

• Giant cell tumour (most common)
• Chondroblastoma
• Osteoblastoma
• Fibrous dysplasia
• Osteosarcoma, above all telangiectatic osteosarcoma, which must be excluded

Histology. Blood-filled cavities without an endothelial lining, separated by fibrous septa of spindle-shaped fibroblasts, osteoclast-type giant cells, reactive woven bone and haemosiderin. Blue reticulated chondroid material, a basophilic calcified matrix, is characteristic. There is no cytological atypia; atypia is the finding that points to malignancy.

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By morphological pattern. The solid variant is the difficult one for the pathologist: it must be distinguished from giant cell reparative granuloma and low-grade malignancy.

By radiological stage. Enneking's stages run from a contained lesion to a destructive one:

• Stage 1 (latent) - small, well-contained lesion
• Stage 2 (active) - progressive growth, thin cortex
• Stage 3 (aggressive) - cortical destruction, soft-tissue extension

Pain. Local pain is the presenting complaint in 80%. It comes on gradually, progresses and may worsen with activity; night pain is uncommon, unlike malignancy.

Swelling. A visible or palpable mass, which may be warm because the lesion is vascular. Rapid enlargement can occur.

Pathological fracture. Roughly 8-12% present with a fracture through the thinned, expanded cortex: about 8% in a systematic review of the literature (PMID 38731012) and 11.6% of 258 consecutive primary ABCs (PMID 40640436). It may be the presenting complaint.

The spinal lesion. Posterior elements are most commonly affected, and neurological symptoms are reported in about half of paediatric spinal ABC: lower-limb weakness in 8 of 17 (47%) in a 20-year children's-hospital series, against pain in 16 of 17 (94%) (PMID 38252929). Radiculopathy or myelopathy may require urgent decompression. Spinal stability was compromised in 15 of 17 (88%), requiring instrumented fusion, so plan for stabilisation rather than curettage alone.

Examination. Local tenderness over the lesion, swelling or mass effect, reduced range of motion if the lesion lies near a joint, and a neurological deficit with spinal lesions.

Red flags. Features that should make you doubt a benign diagnosis:

• Systemic symptoms (fever, weight loss)
• Rapid progression
• Severe night pain
• Very young or very old patient

X-rayMRICT

What you see. An eccentric, expansile lytic lesion, usually metaphyseal in a long bone, with a soap-bubble or honeycomb appearance from the internal septations and a pencil-thin periosteal shell, the eggshell cortex of a blown-out bone. The pattern is geographic with a narrow zone of transition and a trabeculated internal architecture, and there is no periosteal reaction unless the lesion has fractured.

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Aggressive features. Cortical breach or soft-tissue extension require careful evaluation, because they may indicate a secondary ABC within a malignant lesion. Plain radiographs are the first-line imaging but cannot reliably distinguish ABC from other lesions.

Fluid-fluid levels. Present in 70-90% and the most useful diagnostic feature: blood products at different stages of degradation layer out within the cystic spaces, and are best seen on T2-weighted axial sequences.

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Signal. T1 and T2 signal vary with the age of the blood products; the cystic areas are high signal with low-signal septa, and a peripheral low-signal rim on all sequences marks the fibrous capsule. With gadolinium the septa enhance and the cystic contents do not.

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Not pathognomonic. Fluid-fluid levels also occur in giant cell tumour (14%), telangiectatic osteosarcoma, chondroblastoma and occasionally a simple bone cyst. MRI is essential for surgical planning and for assessing extent, but always consider malignancy.

Primary ABC

Age

Under 20 years

Key Features

Eccentric, expansile, USP6 positive

Management

Curettage + adjuvant

Secondary ABC

Age

Any age

Key Features

Within other lesion (GCT, chondroblastoma)

Management

Treat underlying lesion

Giant Cell Tumour

Age

20-40 years

Key Features

Epiphyseal, subarticular, RANK-L+

Management

Curettage + cement or denosumab

Telangiectatic osteosarcoma

Age

10-25 years

Key Features

Aggressive, cortical destruction, atypical cells

Management

Neoadjuvant chemo + resection

Simple bone cyst (UBC)

Age

Under 20 years

Key Features

Central, metaphyseal, fallen leaf sign

Management

Steroid injection, curettage

Differential of Expansile Lytic Lesions with Fluid-Fluid Levels

Diagnosis	Age	Key Features	Management
Primary ABC	Under 20 years	Eccentric, expansile, USP6 positive	Curettage + adjuvant
Secondary ABC	Any age	Within other lesion (GCT, chondroblastoma)	Treat underlying lesion
Giant Cell Tumour	20-40 years	Epiphyseal, subarticular, RANK-L+	Curettage + cement or denosumab
Telangiectatic osteosarcoma	10-25 years	Aggressive, cortical destruction, atypical cells	Neoadjuvant chemo + resection
Simple bone cyst (UBC)	Under 20 years	Central, metaphyseal, fallen leaf sign	Steroid injection, curettage

Bone detail. CT shows the well-defined expansile lytic lesion, the thin but intact cortical shell and the honeycomb of internal septations; fluid-fluid levels are visible but less sensitively than on MRI. It is used to assess cortical integrity, plan bone grafting, guide the biopsy approach and evaluate fracture risk.

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CT angiography may be useful before embolisation, to identify feeding vessels and assess vascularity. CT provides excellent bone detail; MRI is superior for soft-tissue characterisation.

Biopsy. Required for diagnostic confirmation, to rule out malignancy (especially a secondary ABC) and before definitive treatment. A CT-guided core needle biopsy is preferred, and it must sample the solid areas rather than purely cystic regions. Send tissue for histology and for cytogenetics: the USP6 rearrangement is detectable by FISH or RT-PCR. The report should confirm ABC histology and exclude telangiectatic osteosarcoma by the absence of cellular atypia; a USP6 rearrangement confirms a primary ABC.

Algorithm

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The decision. Biopsy comes first, to confirm ABC and exclude a secondary lesion or a malignant mimic. What follows depends on:

• Location and accessibility
• Patient age and activity level
• Presence of a pathological fracture
• Secondary versus primary ABC
• Risk of functional impairment

Spinal ABC. The options are embolisation followed by surgery, curettage with stabilisation, and radiation, which is controversial and reserved for inaccessible lesions. Denosumab is showing promise.

The pathological fracture. Immobilise or splint first and, if possible, allow the fracture to heal before definitive treatment; curettage with internal fixation may proceed instead. A fracture at presentation raises the recurrence rate (Complications and Prognosis).

Local recurrence. The complication that matters most. Beyond the adjuvant, the 258-patient series (PMID 40640436) puts numbers on the other risk factors:

• Age under 5 years: 34.4% versus 19.0% (p = 0.046). The discriminator is very young age, not simply an open physis
• Pathological fracture at presentation: 40.0% versus 18.4% (p = 0.006)
• No adjuvant use
• Inadequate surgical margins or incomplete curettage
• Solid ABC variant

When it recurs. Usually within the first 2 years: mean time to first recurrence was 24.2 months, but the median disease-free survival was only 10 months, so surveillance must start early. Soft-tissue oedema and fluid-fluid levels predict a faster recurrence (median 5 and 6 months respectively, against 12 months without).

Managing recurrence. Re-curettage is usually effective. Resection may be considered after multiple recurrences, and embolisation or denosumab for difficult locations.

Treatment-related complications. The operation carries its own risks:

• Pathological fracture, intra- or post-operative
• Infection
• Joint stiffness with periarticular lesions, and osteoarthritis later
• Growth disturbance in children, the risk of a physeal-crossing lesion
• Neurological injury in spinal ABC

Malignant transformation. Extremely rare, usually to a secondary osteosarcoma, and often after radiation therapy.

Prognosis. ABC is benign, with zero metastatic potential and no mortality from the disease. Local control is achieved in most cases, 70-90% with adjuvant therapy, and 10-year disease-free survival is greater than 90%. Most patients return to full activity with minimal long-term disability; functional outcomes are excellent, with MSTS scores of 85-95%, and limb salvage is greater than 99%.

Observation is rarely appropriate. A small asymptomatic lesion may stabilise, but the risk of progression and pathological fracture means close monitoring is required.

Global Epidemiology

• Incidence: Approximately 0.14 per 100,000 population per year (roughly 1.4 per million); ABC accounts for around 1-6% of primary bone tumours
• Age: Peak 10-20 years; about 75-80% occur before age 20, consistent across populations
• Sex: Slight female predominance in most series
• Site distribution: Long-bone metaphysis (most common), spine and pelvis next; this pattern is stable worldwide

Side-by-Side Guidance and Consensus

Where guidelines genuinely differ, the divergence is mainly in first-line modality for accessible lesions (curettage in most US/UK practice versus greater early use of sclerotherapy/embolisation in several European and high-volume Asian centres) rather than in oncological principles.

Registry and Trial Evidence

• No implant joint-registry (NJR/AJRR/AOANJRR) directly tracks ABC because reconstruction is usually graft or cement, not arthroplasty
• Evidence is driven by bone-tumour centre series and the single randomised trial comparing sclerotherapy with curettage (Varshney 2010)
• Multi-institutional sarcoma networks (e.g. EMSOS, regional bone-tumour registries) provide the pooled outcome data underpinning recurrence estimates

High- vs Limited-Resource Practice

• Optimal first-line modality: extended curettage remains standard, but the only randomised trial showed sclerotherapy with comparable healing, fewer complications and lower hospital burden. Practice varies by region and lesion site rather than by high-level consensus.
• Denosumab: effective for inaccessible or recurrent ABC, but the evidence is case-series level; the concerns are the rebound after cessation, treatment duration and the open physis, and it is not first-line for accessible lesions.
• Adjuvant choice: phenol, cryotherapy, argon beam and high-speed burring all reduce recurrence, but no adjuvant has been shown superior in randomised comparison.
• Solid ABC variant: its true recurrence risk is debated.
• Radiotherapy: historically used for inoperable lesions but largely abandoned because of the small but real risk of post-radiation sarcoma.
• Spinal ABC stabilisation: timing and extent of instrumentation versus embolisation-led management remain individualised, with no trial-level guidance.

Key References

1. Oliveira AM, Hsi BL, Weremowicz S, et al. USP6 (Tre2) fusion oncogenes in aneurysmal bone cyst. Cancer Res. 2004;64(6):1920-1923.

2. 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. 2004;165(5):1773-1780.

3. Campanacci M, Capanna R, Picci P. Unicameral and aneurysmal bone cysts. Clin Orthop Relat Res. 1986;(204):25-36.

4. Mankin HJ, Hornicek FJ, Ortiz-Cruz E, et al. Aneurysmal bone cyst: a review of 150 patients. J Clin Oncol. 2005;23(27):6756-6762.

5. Varshney MK, Rastogi S, Khan SA, et al. Is sclerotherapy better than intralesional excision for treating aneurysmal bone cysts? Clin Orthop Relat Res. 2010;468(6):1649-1659.

6. Rossi G, Mavrogenis AF, Facchini G, et al. How effective is embolization with N-2-butyl-cyanoacrylate for aneurysmal bone cysts? Int Orthop. 2017;41(8):1685-1692.

7. Pelle DW, Ringler JW, Peacock JD, et al. Targeting receptor-activator of nuclear kappaB ligand in aneurysmal bone cysts: verification of target and therapeutic response. Transl Res. 2014;164(2):139-148.

8. De Cristofaro R, Biagini R, Boriani S, et al. Selective arterial embolization in the treatment of aneurysmal bone cyst and angioma of bone. Skeletal Radiol. 1992;21(8):523-527.

Suggested Reading

• WHO Classification of Tumours: Soft Tissue and Bone Tumours (5th Edition)
• Greenspan's Orthopedic Imaging
• Dahlin's Bone Tumors (6th Edition)