Aneurysmal Bone Cyst

Definition

Aneurysmal bone cyst (ABC) is a benign, locally aggressive bone lesion characterised by blood-filled cavities separated by fibrous septa containing fibroblasts and osteoclast-like giant cells. Despite the name, it is not a true cyst as it lacks an epithelial lining.

Key Epidemiology

Age Distribution:

• 75% occur in patients under 20 years old
• Peak incidence 10-20 years
• Rare in children under 5 years and adults over 50 years

Location:

• Long bone metaphysis (50%) - most commonly femur, tibia, humerus
• Spine (20%) - typically posterior elements
• Pelvis (10%)
• Flat bones and small bones (20%)

Types:

• Primary ABC (70%): De novo lesion with USP6 rearrangement
• Secondary ABC (30%): Arises within pre-existing bone lesion

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Genetic Basis

The understanding of ABC has been transformed by discovery of the USP6 gene rearrangement.

Primary ABC:

• 70% harbour USP6 (Tre2) gene rearrangement on chromosome 17p13
• Most common fusion partner is CDH11 (cadherin-11)
• USP6 overexpression leads to increased MMP production and osteoclast activation
• This confirms ABC is a true neoplasm, not a reactive process

Secondary ABC:

• Arises within pre-existing bone lesion
• No USP6 rearrangement
• Common precursor lesions:
  • Giant cell tumour (most common)
  • Chondroblastoma
  • Osteoblastoma
  • Fibrous dysplasia
  • Telangiectatic osteosarcoma (must exclude)

Histological Features

Characteristic Findings:

• Blood-filled cavities (not lined by endothelium)
• Fibrous septa containing:
  • Spindle-shaped fibroblasts
  • Osteoclast-type giant cells
  • Reactive woven bone
  • Hemosiderin deposits
• Blue reticulated chondroid material - characteristic basophilic calcified matrix
• No cytologic atypia (important to exclude malignancy)

ABC Classification Systems

EtiologyMorphologyLocation

Classification by Origin:

Type	Frequency	Characteristics	USP6 Status
Primary ABC	70%	De novo lesion, no underlying pathology	Positive (70%)
Secondary ABC	30%	Within pre-existing bone lesion	Negative

Common Precursor Lesions for Secondary ABC:

• Giant cell tumour (most common)
• Chondroblastoma
• Osteoblastoma
• Fibrous dysplasia
• Telangiectatic osteosarcoma (must exclude)
• Osteosarcoma

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Classification by Morphological Pattern:

Type	Description	Clinical Significance
Classic ABC	Multiple blood-filled cystic cavities with septa	Most common presentation
Solid ABC Variant	Predominantly solid with minimal cysts	Higher recurrence, needs careful pathology
Mixed ABC	Combination of solid and cystic areas	Evaluate solid areas for malignancy

Radiological Classification (Enneking):

• Stage 1 (Latent): Small, well-contained lesion
• Stage 2 (Active): Progressive growth, thin cortex
• Stage 3 (Aggressive): Cortical destruction, soft tissue extension

Classification by Anatomic Location:

Location	Frequency	Special Considerations
Long bones	50%	Metaphyseal, eccentric; femur, tibia most common
Spine	15-20%	Posterior elements; neurological risk
Pelvis	10%	Often large at presentation; embolisation useful
Flat bones	10%	Scapula, ribs, clavicle
Small bones	10%	Hands, feet; talus, calcaneus

Skeletal Maturity Consideration:

• Open physes: Higher recurrence risk (37% vs 21%)
• Physeal-crossing lesions: Growth disturbance risk

Presenting Symptoms

Local Pain:

• Most common presentation (80%)
• Gradual onset, progressive
• May worsen with activity
• Night pain uncommon (unlike malignancy)

Swelling:

• Visible or palpable mass
• May be warm due to vascularity
• Rapid enlargement can occur

Pathological Fracture:

• Occurs in 10-15%
• Due to cortical thinning and expansion
• May be the presenting complaint

Neurological Symptoms (Spine ABC):

• Present in 60-70% of spinal ABC
• Radiculopathy, myelopathy
• May require urgent decompression
• Posterior elements most commonly affected

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Physical Examination

Findings:

• Local tenderness over lesion
• Swelling or mass effect
• Decreased range of motion if near joint
• Neurological deficit (spinal lesions)

Red Flags for Malignancy:

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

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Imaging

X-rayMRICT

Plain Radiographs

Classic Features:

• Eccentric expansile lytic lesion
• Soap-bubble or honeycomb appearance
• Pencil-thin periosteal shell (eggshell cortex)
• Internal septations creating multiloculated appearance
• Usually metaphyseal in long bones

Zone of Transition:

• Geographic pattern with narrow zone of transition
• No periosteal reaction (unless fractured)
• Trabeculated internal architecture

Aggressive Features (require careful evaluation):

• Cortical breach
• Soft tissue extension
• May indicate secondary ABC in malignant lesion

Plain radiographs are the first-line imaging but cannot reliably distinguish ABC from other lesions.

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MRI Features

Hallmark Finding:

• Fluid-fluid levels in 70-90% of cases
• Represent layering of blood products at different stages of degradation
• Best seen on T2-weighted axial sequences
• Most useful diagnostic feature

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Signal Characteristics:

• Variable T1 signal (depending on blood product age)
• Variable T2 signal
• High signal cystic areas with low signal septa
• Peripheral low signal rim on all sequences (fibrous capsule)

Contrast Enhancement:

• Septa enhance with gadolinium
• Cystic contents do not enhance

Important Limitations:

• Fluid-fluid levels are NOT pathognomonic
• Also seen in:
  • Giant cell tumour (14%)
  • Telangiectatic osteosarcoma (must exclude)
  • Chondroblastoma
  • Simple bone cyst (occasionally)

MRI is essential for surgical planning and assessing extent but always consider malignancy.

CT Features

Bone Detail:

• Well-defined expansile lytic lesion
• Thin but intact cortical shell
• Internal septations with honeycomb pattern
• Fluid-fluid levels visible (but less sensitive than MRI)

Role of CT:

• Assess cortical integrity
• Surgical planning for bone grafting
• Guide biopsy approach
• Evaluate fracture risk

CT Angiography

May be useful for:

• Pre-operative embolisation planning
• Identifying feeding vessels
• Assessing vascularity

CT provides excellent bone detail but MRI is superior for soft tissue characterisation.

Biopsy

When Required:

• Diagnostic confirmation
• Rule out malignancy (especially secondary ABC)
• Before definitive treatment

Technique:

• CT-guided core needle biopsy preferred
• Sample solid areas - avoid purely cystic regions
• Send for histology AND cytogenetics (USP6 FISH)

Interpretation:

• Confirm ABC histology
• Exclude telangiectatic osteosarcoma (cellular atypia)
• USP6 rearrangement confirms primary ABC

Genetic Testing

USP6 Rearrangement:

• Present in 70% of primary ABC
• Detectable by FISH or RT-PCR
• Useful for diagnostic confirmation
• Absent in secondary ABC and other tumours

Algorithm

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Treatment Algorithm

Factors Influencing Treatment:

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

Surgical Management

Extended CurettageEn Bloc ResectionNon-Surgical Options

Extended Curettage with Adjuvant

Gold Standard Treatment for accessible ABC:

Technique:

1. Adequate surgical exposure
2. Create cortical window
3. Thorough curettage of all cyst contents
4. High-speed burr to extend margins (2-3mm)
5. Adjuvant therapy:
   • Phenol (3 minutes)
   • Liquid nitrogen cryotherapy
   • Argon beam coagulation
   • High-speed burr alone
6. Reconstruct defect

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Reconstruction Options:

• Autograft (iliac crest)
• Allograft (chips or structural)
• PMMA cement (provides immediate stability)
• Combination graft and cement

Outcomes:

• Local recurrence 10-30%
• Most recurrences within 2 years
• Better outcomes with adjuvant use

Extended curettage preserves bone stock and function while achieving local control.

En Bloc Resection

Indications:

• Expendable bones (fibula head, distal ulna, rib, clavicle)
• Multiple recurrences after curettage
• Malignant transformation (very rare)
• Secondary ABC in malignant tumour

Advantages:

• Near-zero recurrence rate
• Definitive treatment

Disadvantages:

• Loss of bone stock
• May require reconstruction
• Functional impairment possible

Reconstruction Options:

• Fibula autograft
• Allograft
• Endoprosthesis (rare)

Reserve en bloc resection for expendable bones or recurrent/aggressive lesions.

Selective Arterial Embolisation (SAE)

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Indications:

• Surgically inaccessible locations (spine, pelvis)
• Pre-operative to reduce bleeding
• Primary treatment in selected cases
• Recurrent ABC

Technique:

• Angiographic identification of feeding vessels
• Embolisation with particles, coils, or glue
• May require multiple sessions

Outcomes:

• Complete response in 25-50%
• Partial response allowing subsequent surgery
• Recurrence rate 20-40%

Denosumab (Emerging Treatment)

Mechanism:

• RANK-ligand inhibitor
• Reduces osteoclast activity
• Targets giant cells in ABC

Evidence:

• Several case series showing good response
• Resolution of lesions in many cases
• May avoid surgery in some patients

Role:

• Surgically challenging locations
• Patients unfit for surgery
• Recurrent disease
• As bridge to surgery (reduce vascularity)

Dosing:

• Similar to GCT protocol
• 120mg SC monthly

Denosumab is an emerging option for ABC but long-term data are limited.

Special Situations

Spinal ABC:

• May present with neurological deficit
• Posterior elements most commonly affected
• Treatment options include:
  • Embolisation + surgery
  • Curettage with stabilisation
  • Radiation (controversial, reserved for inaccessible)
• Denosumab showing promise

Pathological Fracture:

• Initial immobilisation/splinting
• Allow fracture to heal before definitive treatment if possible
• May proceed with curettage and internal fixation
• Higher recurrence rate

Extended Curettage Technique

Complications

Local Recurrence:

• Most important complication
• Rate: 20-30% after curettage
• Usually within first 2 years
• Risk factors:
  • Open physes (growth-related)
  • Inadequate surgical margins
  • No adjuvant use
  • Pathological fracture at presentation

Treatment-Related:

• Pathological fracture (intra- or post-operative)
• Infection
• Joint stiffness (periarticular lesions)
• Growth disturbance (paediatric patients)
• Neurological injury (spinal ABC)

Malignant Transformation:

• Extremely rare
• Usually to secondary osteosarcoma
• Often after radiation therapy

Prognosis

Excellent Overall Prognosis:

• Benign lesion with zero metastatic potential
• Local control achievable in most cases
• 10-year disease-free survival over 90%

Recurrence Management:

• Re-curettage usually effective
• May consider resection after multiple recurrences
• Embolisation or denosumab for difficult locations

Long-term Follow-up:

• Clinical and radiographic at 3-6 monthly intervals for 2 years
• Then annually for 5 years
• Longer follow-up for spinal or pelvic lesions

Post-operative Protocol

ABC Treatment Outcomes

• Optimal first-line modality: extended curettage remains standard, but the only randomised trial (Varshney 2010) 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 role and risks: effective for inaccessible/recurrent ABC but evidence is case-series level. Concerns include rebound lytic activity and hypercalcaemia after cessation (especially in children), uncertain treatment duration, and effect on the open physis. 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: must be distinguished from giant cell reparative granuloma and low-grade malignancy; 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)

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