Aneurysmal Bone Cyst

Aneurysmal bone cyst is a benign, locally aggressive, expansile bone lesion composed of blood filled cystic spaces separated by fibrous septa that contain osteoclast type giant cells and reactive woven bone. It is a true neoplasm in its primary form, and arises secondary to another lesion in about 30%.

It accounts for 1 to 2% of primary bone tumours, and 75 to 90% occur under age 20, with a slight female predominance. Sites are the metaphysis of long bones (femur, tibia, humerus, fibula, 50 to 60%), the posterior elements of the spine (10 to 30%) and the pelvis and sacrum. Secondary lesions follow giant cell tumour, osteoblastoma, chondroblastoma, fibrous dysplasia, non-ossifying fibroma and, importantly, telangiectatic osteosarcoma.

Complications are pathological fracture, spinal cord or nerve root compression, deformity, growth disturbance, local recurrence (10 to 30% after curettage, mostly within 2 years), and loss of function. The lesion can grow quickly over weeks.

Pathophysiology.

Primary lesions carry a USP6 gene rearrangement (commonly CDH11-USP6) in about 70%, which drives overexpression of USP6 in the spindle cell component, and leads to osteoclast recruitment, matrix metalloproteinase production and bone resorption. The cystic spaces are lined by fibroblasts, not endothelium, and fill with blood that does not circulate quickly. Secondary lesions are due to haemodynamic changes in a pre-existing tumour.

Pain and swelling over weeks to months, sometimes sudden pain after a minor injury (fracture), a palpable mass in a superficial bone, restricted motion, and a limp. Spinal lesions cause neck or back pain, scoliosis, and neurological signs (radiculopathy, myelopathy, bladder and bowel dysfunction). Pelvic and sacral lesions can be large before diagnosis.

Examine the mass (warmth, tenderness, bruit), joint motion, spinal alignment and neurological function.

• Radiographs: an eccentric, expansile, lytic "blown out" lesion in the metaphysis with a thin, sometimes invisible, eggshell cortex, and a "soap bubble" appearance.
• MRI is the key investigation: a multiloculated expansile lesion with multiple fluid fluid levels (due to sedimentation of blood products), thin low signal septa, and enhancing septa. Fluid levels occupying over two thirds of the lesion suggest a primary aneurysmal bone cyst, and solid enhancing components suggest an underlying tumour or telangiectatic osteosarcoma.
• CT: shows the thin shell, extent and matrix, and is useful in the spine and pelvis.
• Biopsy is needed to confirm the diagnosis and exclude telangiectatic osteosarcoma and giant cell tumour. Biopsy through the planned surgical tract. USP6 fluorescence in situ hybridisation separates primary lesions from secondary ones.
• Blood tests: full blood count and clotting (to exclude coagulopathy before biopsy).

Differential diagnosis.

• Telangiectatic osteosarcoma and giant cell tumour.
• Unicameral bone cyst and osteoblastoma.
• Chondroblastoma and fibrous dysplasia.
• Brown tumour of hyperparathyroidism and infection.

Treatment aims to stop growth and restore bone while avoiding damage to the physis, nerves and the spinal cord. Choice depends on site, size and the patient's age.

Surgery.

• Extended intralesional curettage with a high speed burr and an adjuvant (phenol, cryotherapy, argon beam), followed by bone graft, bone substitute or cement. Recurrence is 10 to 30% (lower with adjuvants).
• En bloc excision for expendable bones (fibula, rib, clavicle, distal ulna, metatarsals), and for recurrence.
• Spine: staged embolisation and resection, with stabilisation. Preoperative arterial embolisation reduces blood loss in the spine, pelvis and sacrum.
• Pathological fracture: allow healing where possible, then treat the cyst.

Minimally invasive treatment (preferred for surgically difficult sites, and often for first line treatment).

• Image directed percutaneous sclerotherapy: polidocanol 3% injected into the cyst under imaging (about half of the estimated cyst volume, not exceeding 2 mg/kg in a session), repeated every 4 to 6 weeks for up to 4 to 6 sessions. Success is about 90 to 95% in series. Avoid with a communication to the spinal canal or major vessels, and with known allergy; watch for transient pain, allergic reaction, skin necrosis, embolisation, and neurological symptoms. Doxycycline foam is an alternative.
• Selective arterial embolisation (cyanoacrylate or particles) in spinal, pelvic and sacral lesions, alone or before surgery.
• Percutaneous curettage and bone graft or cement, or intralesional steroid injection in selected cases.

Denosumab (off label; for unresectable, recurrent or spinal and sacral disease). Denosumab 120 mg subcutaneously every 4 weeks, with additional doses on days 8 and 15 of the first month, for 3 to 6 months, until ossification. Give colecalciferol 800 to 2000 IU daily and calcium to a total of 1000 to 1200 mg daily; check calcium before each dose; avoid with uncorrected hypocalcaemia or pregnancy; perform a dental review beforehand.

In children with open physes, a rebound hypercalcaemia can follow stopping, so monitor calcium for 3 to 6 months. Osteonecrosis of the jaw and atypical femoral fractures are risks with prolonged use.

Radiotherapy. Avoided (risk of sarcoma and growth disturbance); reserved for life threatening, inoperable lesions.

Operative antibiotic prophylaxis. Cefazolin 2 g intravenously (3 g when weight is 120 kg or over; 30 mg/kg to a maximum of 2 g in children) within 60 minutes before incision as a single dose (repeat after 4 hours or blood loss over 1500 mL); with severe penicillin allergy, vancomycin 15 mg/kg intravenously starting 90 to 120 minutes before incision as a single dose, with levels and creatinine checked in prolonged cases.

Tranexamic acid (spinal, pelvic and sacral surgery). Tranexamic acid 15 mg/kg (maximum 1 g) intravenously over 10 minutes before incision, repeated once after 3 hours if bleeding continues (maximum 2 g); avoid with a history of thromboembolism, active intravascular clotting, or seizures; reduce the dose at creatinine clearance under 50 mL/min.

Analgesia.

• Paracetamol 1 g orally every 6 hours as needed for up to 5 to 7 days (maximum 4 g daily; 3 g daily when weight is under 50 kg, with chronic alcohol use or hepatic impairment).
• Ibuprofen 400 mg orally every 8 hours with food for up to 5 days (maximum 1200 mg daily); avoid with eGFR under 30 mL/min/1.73 m2, peptic ulcer, heart failure or anticoagulant use.
• Children: paracetamol 15 mg/kg orally every 4 to 6 hours (maximum 75 mg/kg daily and not exceeding 4 g daily) and ibuprofen 10 mg/kg orally every 6 to 8 hours with food (maximum 40 mg/kg daily and not exceeding 2400 mg daily), for up to 5 days.

Monitoring. Clinical review and imaging (radiograph, MRI) at 6 weeks, 3 months, 6 months and 12 months, then yearly for 3 years, since most recurrences occur within 2 years. Sclerosis and reossification show healing. Calcium during denosumab, and again 3 to 6 months after stopping. Neurological state and spinal alignment.

Referral and escalation. Refer every suspected aneurysmal bone cyst to a bone tumour service for biopsy before treatment. Emergency referral for a new neurological deficit, a rapidly expanding lesion, an unstable spine or a pathological fracture of a major bone.

Special groups.

• Children: protect the physis; prefer sclerotherapy or curettage, and avoid denosumab where possible because of rebound hypercalcaemia.
• Spine and sacrum: embolisation before surgery; multidisciplinary planning.
• Pregnancy: avoid denosumab, and NSAIDs in the third trimester.
• Kidney impairment: avoid NSAIDs; monitor calcium closely with denosumab.