Aneurysmal Bone Cyst – Causes, Symptoms, Treatment

An aneurysmal bone cyst (ABC), maybe non-malignant, non-cancerous bone tumor-like, explosive, expansile nature like vascular lesions that can grow aggressively, be locally destructive, and weaken bones to the point of pathologic fracture, and it is composed of multiple varying sizes of spaces during a bone that is crammed with blood. The term may be a misnomer because the lesion is neither an aneurysm nor a cyst. It generally presents with pain edema and associated tissue swelling within the affected bone. Pressure on neighboring tissues may cause compression effects like neurological symptoms.

Histologically, they are classified in two variants.

• The classic (or standard) form (95%) has blood-filled clefts among bony trabeculae. Osteoid tissue is found in the stromal matrix.
• The solid form (5%) shows fibroblastic proliferation, osteoid production and degenerated calcifying fibromyxoid elements.

According to Buraczewski and Dabska, the development of the aneurysmal bone cyst follows three stages.

Stage	Description
Initial phase (I)	Osteolysis without peculiar findings
Growth phase (II)	Rapid increase in size of osseous erosion Enlargement of involved bone Formation of shell around central part of lesion
Stabilization phase (III)	Fully developed radiological pattern

They can also be associated with a TRE17/USP6 translocation.

Aneurysmal bone cysts may be intraosseous, staying inside of the bone marrow. Or they may be extraosseous, developing on the surface of the bone, and extending into the marrow. A radiograph will reveal a soap bubble appearance.

Sites

Commonly affected sites are metaphyses of the vertebra, flat bones, femur, and tibia. Approximate percentages by sites are as shown:

• Skull and mandible (4%)
• Spine (16%)
• Clavicle and ribs (5%)
• Upper extremity (21%)
• Pelvis and sacrum (12%)
• Femur (13%)
• Lower leg (24%)
• Foot (3%)

Causes of Aneurysmal Bone Cyst

The etiology of aneurysmal bone cysts is currently unknown, although they seem to flow from to vascular malformations within the bone.

There are three main theories for his or her etiology

Aneurysmal bone cysts occur as a result of a separate primary bone tumor; this might flow from to the relatively high rate (1 in 3) of an accompanying bone lesion. These lesions are frequently chondromyxoid, fibromas, chondrosarcomas, fibrous dysplasia, giant cell tumors of the bone, osteoblastoma, osteosarcomas, among others. They form because of the primary tumor. They form at the site of previous trauma.
A portion of aneurysmal bone cysts now appears to be neoplastic. Genetic studies of the tumor have revealed that up to 69% of primary aneurysmal bone cysts contain a clonal t(16,17) translocation. The t(16,17) fusion causes an upregulation of the TRE17/USP6 oncogene, which activates NF-kB and matrix metalloproteinases (MMPs). The MMPs break down the extracellular matrix, allowing the swift growth of the lesions. Secondary aneurysmal bone cysts haven’t been found to contain this translocation.

Symptoms of Aneurysmal Bone Cyst

Diagnosis of Aneurysmal Bone Cyst

The evaluation of aneurysmal bone cysts primarily consists of imaging studies, which may typically provide critical clues to the diagnosis.

• X-ray – Radiographs illustrate cystic or osteolytic lesions with thin “eggshell” sclerotic borders. The enclosed cavity contains many dividing septa the encompassing bone could also be pushed outwards from its normal anatomy, demonstrating the aggressive, expansile nature of the lesion.
• CT Scan – Computed tomography reveals similar characteristics as plain radiographs, although it’s going to define the cystic septa to a greater degree, highlighting the “eggshell” rim. Fluid-fluid levels could also be present within the cavities thanks to the separation of the cellular debris from the serum.
• MRI – Magnetic resonance imaging again demonstrates similar findings as CT. T1 contrast-enhanced and T2 weighted images can emphasize the septa within the lesion, revealing rims of low T1 and T2 signals. Variably aged blood contained within the cystic cavities are visible on MR as focal areas of hyperintense signal on both T1 and T2 weighted sequences, and double density fluid levels can also be visible. A pathologic fracture could also be evident, as demonstrated by osseous and soft tissue edema.
• EOS imaging – an imaging technology that makes 3-dimensional models from two flat images. Unlike a CT scan, EOS images are taken while the kid is in an upright or standing position, enabling improved diagnosis thanks to weight-bearing positioning.
• Angiography – a radiograph-type X-ray test that reveals the within of blood vessels and organs.
• Needle biopsy – which may be a procedure where a doctor places a little needle through the skin and into the lesion to withdraw a little sample of the abnormal tissue. The tissue is analyzed to verify any findings.

Laboratory studies hold a minimal benefit within the workup and diagnosis of aneurysmal bone cysts, although bears mentioning that alkaline phosphatase levels may present as increased thanks to the elevated activity of osteoblasts.

Treatment

Once diagnosed with an aneurysmal bone cyst, the patient should obtain a referral to an orthopedic oncologist. Surgical intervention is usually the treatment of options to prevent pathological fracture. supported the lesion size and therefore the region of bone involved, either intralesional curettage, intralesional excision, or en masse (complete) excision could also be an option.

Intralesional curettage involves evacuating the cavity of its contents and filling the remaining space with bone graft or cement to strengthen the bone.

• Intralesional excision – is the preferred treatment of choice, which is analogous to curettage: the surgeon makes a broad opening through the osseous wall of the lesion and removes the contents. This process allows a greater amount of the bone to stay intact to scale back patient morbidity in comparison to en masse excision. After the removal of the cystic contents, the surgeon can fill the lesion via bone grafting or other material to provide strength and promote healing of the bone. Differing from curettage, this sort of treatment allows the utilization of varied sorts of adjuvant therapy to scale back the rates of recurrence, thanks to the broad opening made to realize access to the cavity. Adjuvant therapies include high-speed burr, argon beam coagulation, phenol, and cryotherapy. this sort of excision is additionally beneficial in aneurysmal bone cysts that occur near joints and other structures where the will to take care of normal anatomy is crucial for functionality.
• En bloc excision – consists of removing the whole cavitary lesion from the bone that contains it. When considering en masse excision, the surgeon must weigh the risks and benefits of the procedure, considering the possible loss of functionality of the world, especially when operating near a joint. thanks to the results of significant patient morbidity, en masse resection is usually reserved for patients with recurrent lesions that weren’t adequately controlled by less invasive means.
• Selective arterial embolization (SAE) –  could also be considered before surgery as an adjuvant, or as a primary treatment if the clinician suspects a severe loss of function or destabilization as a result of local or wide excision of the lesion. In up to 40% of patients being treated primarily with SAE, a second or third embolization attempt is important.
• Radiotherapy – has also found utility as adjuvant therapy in recurrent aneurysmal bone cysts cases. However, clinicians must consider the many risks related to radiotherapy. there’s a minimum of one documented instance of radiation-induced sarcoma of a patient receiving treatment with external beam radiation for a vertebral aneurysmal bone cyst.[8]
  Medical therapies –  with monoclonal antibodies for non-surgical candidates is a neighborhood currently being explored
• Curettage and bone grafting – The most common treatment for an aneurysmal bone cyst, this is often an operation during which the cyst is scraped out of the bone with a special instrument called a curette that features a scoop, loop, or ring at its tip. The procedure itself is named curettage. The remaining cavity is then full of donor bone tissue (called an allograft), bone chips taken from another bone (autograft), or other materials.
• Extended curettage – In some cases, Children’s orthopedic surgeons perform an “extended” curettage employing a special instrument (a curette) to get rid of additional layers of cells around the bone cyst. this is often simply a more aggressive sort of procedure described above. it’s done to scale back the danger that the cyst will grow back.
• Marginal or wide excision – This operation removes the part of the bone involving the cysts at its margins or beyond its margins (known as a good excision). a good excision is suggested when the cyst is found in bones considered expendable, like the ribs or fibula. it’s avoided whenever possible when the cyst occurs during a location that would compromise the bone’s function.
• Sclerotherapy – This is a promising non-surgical technique for healing aneurysmal bone cysts. rather than surgery to get rid of the cyst, doctors inject special chemicals into the cyst so as to market the creation of connective tissue. This connective tissue eventually heals and hardens into bone, healing the cyst without the necessity for open surgery.
• Cryotherapy – Because it’s possible that the cyst will grow back, this procedure, which surgically freezes the cyst, is usually utilized in addition to curetting and bone grafting. However, it’s related to complications like fracture of the bone, nerve injury, et al.

Historical management of ABCs

The original description by Jaffe and Lichtenstein of ABCs included treatment by curettage and reconstructing the defect with bone graft, which remains the mainstay of recent treatment [1]. because the understanding of ABCs evolved and clinical series were published showing high recurrence rates, treatment strategies expanded. Below describes several approaches to the treatment of ABCs that are used historically but currently are used only in atypical cases.

En bloc excision

En bloc excision, or complete resection, is related to rock bottom rates of recurrence but at the value of high morbidity to the patient. Studies concerning en masse excision of ABCs report 95–100 % localized control. Front et al. retrospectively reviewed 26 patients undergoing en masse excision and reported no recurrences; however, morbidity (postoperative pain, limb length discrepancies, muscle weakness, and decreased ranges of motion) was increased with en masse procedures compared to intralesional procedures. Given the many morbidity of en masse excision, this procedure is now considered in cases of recurrent lesions refractory to less invasive treatment and people lesions in locations during which function isn’t compromised with such a resection.

Radiotherapy

Radiotherapy consists of external beam radiation to induce cellular death. Although radiation is most notably utilized within the treatment of malignancies, radiotherapy has historically been wont to treat ABCs primarily, as adjuvant therapy in cases of recurrence, and in inoperable ABC lesions. However, radiotherapy isn’t without risk. Marco et al. reported one case of radiation-induced sarcoma. Papagelopoulos et al. also observed one case of radiation-induced sarcoma during a review of 52 patients with spinal ABCs treated with radiation. Furthermore, radiotherapy has been implicated as an iatrogenic explanation for spinal deformity.

Although the adverse effects of radiotherapy should be taken into consideration, it’s possible that modern advances in radiotherapy have rendered this treatment safer than previously considered. during a 2015 case series of 12 patients treated with radiotherapy for ABC, Zhu et al. reported no recurrence and no complications at final follow-up. Feigenberg et al. reported that radiotherapy administered with 26–30 Gy with techniques to attenuate scatter was effective and minimally toxic within the treatment of inoperable or recurrent ABC lesions.

Radionuclide ablation involves the intralesional injection of radioisotopes, which emit radiation that ablates adjacent tissue. To our knowledge, there exists one report by Bush et al. who reported successful control of 5 skeletal structure ABCs with intralesional injection of chromic phosphate P32. They reported one complication of leakage of a little amount of the radiopharmaceutical, which was cleared by the patient with none negative effects.

Current management of ABCs

The standard of look after ABCs is curettage with or without bone-graft counting on the resultant void. Despite best efforts at curettage, clinical series have shown highly variable recurrence rates, with some series showing rates as high as 59 %. As a result, various adjuvants have evolved to scale back recurrence including the utilization of cement, high-speed burr, argon beam, phenol, and cryotherapy. Currently, there exist no high-level controlled, comparative studies regarding adjuvant efficacy, and therefore the specific adjuvant strategy utilized is essentially institution dependent. As such, the literature on adjuvant efficacy consists largely of case-series from single institutions.

High speed burr

After intralesional resection of an ABC lesion, a high-speed burr are often wont to augment curettage by mechanical disruption of the lesion to the extent of the circumscribing bone. during a case series of 40 patients, Gibbs et al. reported local control rates of nearly 90 to take care of a median 7.2-year follow-up by curettage and high-speed burr without the utilization of nitrogen , phenol, or other adjuvants. Dormans et al. reported that their surgical technique, including the utilization of a high-speed burr resulted in an 82 faith healing rate.

Argon beam coagulation

By utilizing a beam of inert argon gas, the argon beam coagulator produces a unipolar electrical current through tissue to induce desiccation and coagulation. Directing argon beam therapy at an ABC lesion following curettage has been shown to scale back recurrence rates. Cummings et al. reported that using the argon beam on the sides of the remaining lesion after curettage yielded a recurrence. Steffner et al. reported that curettage, high-speed burr, and therefore the use of argon beam coagulation produced a recurrence rate of seven .5 in comparison to twenty .6 % after curettage and high-speed burr alone.

Phenol

Phenol, also referred to as phenol, is produced in mass quantities from petroleum, and it’s a precursor to varied materials including plastics, pharmaceuticals, and analgesics. within the treatment of ABCs, phenols are wont to “sterilize” or wash the lesion, removing remaining neoplastic cells following curettage. during a retrospective case series, Capanna et al. reported a 7 rhythm rate following curettage and phenol versus 41 you bored with curettage alone. Bitzan et al. reported that curettage and phenol therapy employed in nine patients resulted in no recurrences. during a retrospective comparative study of 85 patients, Kececi et al. found no statistically significant difference between curettage alone, curettage with high-speed burr, and curettage, high-speed burr, and phenol/alcohol together.

Cryosurgery

Cryosurgery entails the utilization of liquid or aerosolized nitrogen to get freezing temperatures that have a cytotoxic effect on the ABC lesion following curettage. Despite low rates of recurrence, cryosurgery has not been widely adopted likely due its unfamiliarity and complication profile which incorporates postoperative fracture and skin necrosis/wound infection as high as 14 and eight %, respectively. Marco et al. reported a recurrence rate of 17.6 % with curettage and therefore the pouring of nitrogen , which reduced to 4 to take care of the second cryosurgery. With reference to aerosolized nitrogen, studies suggest that low rates of recurrence are achievable. Schreuder et al. reported a 3.7 rhythm rate with nitrogen spray, and during a series of 80 patients treated with curettage and nitrogen spray, Peeters et al. reported a 5 the speed of recurrence, which was all treated successfully after another treatment of cryosurgery.

Cement

Following curettage, bone graft reconstruction is usually employed to market osseous healing of the resultant cavity. Similarly, polymethylmethacrylate (PMMA) cement in pediatric benign bone lesions can provide immediate stabilization for the resultant cavity, and it can act as a recurrence reducing adjuvant through its exothermic effect because the cement hardens. With reference to the reduction of recurrence, the evidence is mixed on the efficacy of cement. Ozaki et al. reported lower recurrence with curettage and cementing compared to curettage and grafting alone, 17 and 37 %, respectively. during a retrospective comparative study examining the effect of cement versus bone grafting in benign pediatric bone lesions, Wallace et al. reported similar complication and recurrence rates, and Mankin et al. also reported similar rates of recurrence when using bone graft or cement. the appliance of PMMA to the predominantly pediatric population that’s afflicted with ABC warrants consideration with reference to its long-term effects: PMMA is biologically inert without the potential for osseous incorporation, has no growth potential, can cause stress shielding, thereby increasing the danger of future pathologic fracture, and as a far off body, may act as a nidus for infection.

Alternative strategies

In addition to curettage with local adjuvant therapies, some have proposed alternative treatment modalities. These strategies are proposed mostly by those outside the orthopedic community and are rarely employed by orthopedic oncologist but should be considered within the medical community’s armamentarium.

Adjuvant radiotherapy

Adjuvant radiotherapy is related to excellent control of ABCs, starting from 83 to 100% local control. However, complications from radiotherapy include chronic effects which will impair function and secondary malignancies, which have prevented its adoption into widespread practice. Feigenberg and Marks et al. argue that instances of radiation-induced complications reported within the literature were partially the results of outdated techniques and technology. To our knowledge, there exists no evidence with long-term follow-up regarding modern adjuvant radiotherapy within the treatment of ABCs.

Arterial embolization

Selective arterial embolization (SAE) are often used as an adjunct to surgery, but it’s also been employed as a primary treatment in ABC lesions that are difficult to access (i.e., pelvis, sacrum, etc.) or are at considerable risk for hemorrhage. consistent with Rossi et al., SAE provided local control in 94 you look after patients, although second or third embolization attempts were needed for 39 you look after patients to realize control [46]. Complications occurred in 5 you look after patients, including skin necrosis and transient paresis. High rates of local control have also been reported in treating spine ABCs. Despite these results, SAE remains a limited treatment option, as lesions may lack identifiable feeding vessels or could also be perfused by vessels that also feed nearby vital tissues and organs. Especially concerning are spinal ABCs perfused by the artery of Adamkiewicz, the embolization of which may cause irreversible neurologic deficits. Inadvertent arterial embolization can potentially impart devastating effects, and its indications should be scrutinized accordingly.

Sclerotherapy

Sclerotherapy acts by damaging the endothelium of vessels, triggering the coagulation cascade, and leading to thrombosis. By inducing sclerosis of the ABC’s vascular network, local control of the lesion are often achieved. Ethibloc may be a radiopaque alcoholic solution that causes local fibrogenic and thrombogenic effects upon contact with ABCs. Ethibloc has been related to healing rates as high as 92 %, with nearly 25 you look after patients requiring multiple treatments. Unfortunately, sclerotherapy with Ethibloc has been related to various complications like local inflammatory reactions in up to 94 you look after patients, aseptic bone necrosis, embolism , deep phlebothrombosis , and cerebellar infarct resulting in death which have led some institutions to scale back its utilization of Ethibloc.

Polidocanol (hydroxypolyaethoxydodecan) is another sclerosant commonly employed by dermatologists for the treatment of varicose veins. during a review of 72 patients with a mean follow-up of 34 months, Rastogi et al. found a clinical response of 84.5 you bored with a mean of three injections per patient [54]. during a randomized trial, Varshney et al. compared polidocanol sclerotherapy with curettage, high-speed burr, and bone graft: polidocanol had a healing rate of 93.3 in comparison with 84.8 % for curettage, although this difference didn’t reach statistical significance. There was no statistical difference in healing rates; however, it should be noted that sclerotherapy with polidocanol provided faster pain relief, better functional outcomes, and avoided the morbidity and costs related to surgery.

Emerging techniques within the management of ABCs

Given concerns that our community has historically been overly aggressive in treating these benign bone lesions, some groups have investigated less aggressive surgical techniques and medical management within the hopes of achieving equivalent results with fewer complications.

Curopsy

Curopsy” may be a recently described percutaneous technique that has gained interest thanks to its limited invasiveness and favorable rates of local control. consistent with Reddy et al., the technique evolved after it had been observed that some ABCs healed following biopsy alone [55•]. Under general anaesthesia within the OR , a percutaneous or “small open biopsy” utilizing a 5–10-mm incision is performed to get diagnostic material with a core biopsy and pituitary rongeur or curette. The rongeur or curette was wont to obtain lining membrane from various parts of the lesion. it’s hypothesized that the autopsy destroys a sufficient amount of internal cyst architecture to induce healing of the lesion.

Percutaneous doxycycline

Doxycycline is an antibiotic with known anti-neoplastic properties including the inhibition of matrix metalloproteinase and angiogenesis, both of which play a task in ABC expansion within bone [56, 57]. thanks to these anti-neoplastic properties, doxycycline has recently been proposed as a treatment for ABCs. during a preliminary study of ABCs treated with percutaneous placement of intralesional doxycycline, Shiels et al. reported evidence of healing and cortical thickening altogether 20 cases reviewed with a recurrence rate of 5 to try a mean follow-up of 20 months. In 2016, Shiels et al. reported healing altogether 16 cases of metaphyseal ABCs treated with percutaneous doxycycline with a 6 June 1944 recurrence rate at a mean follow-up of 18 months. Currently, this experimental treatment has not been widely adopted thanks to concern over repetitive treatments also because the incontrovertible fact that it’s yet to be replicated in other institutions.

Bisphosphonate medical therapy

Bisphosphonates are pyrophosphate analogs that inhibit osteoclast-mediated bone resorption. Additionally, bisphosphonates exhibit anti-neoplastic characteristics possibly by inducing apoptosis, inhibiting tumor cell adhesion and invasion, and thru indirect means like inhibition of angiogenesis. Cornelis et al. reported varying degrees of lesion ossification and near-universal pain relief following bisphosphonate treatment for symptomatic, inoperable benign bone tumors including ABCs.

RANKL inhibition and therefore the role of denosumab

The receptor activator of the nuclear kappa B ligand (RANKL) signaling pathway is a crucial mediator in bone homeostasis by promoting osteoclast activation, and hence bone resorption and remodeling. RANKL expression is seen during a sort of benign and malignant bone neoplasms, and there’s growing evidence that ABCs have above normal levels of RANKL expression. Denosumab may be a human antibody that directly inhibits RANKL signaling approved under several indications: to treat osteoporosis; to scale back the untoward effects of bone metastases from solid tumors, and to treat skeletally mature adolescents and adults with giant cell tumors of bone. Dubey et al. propose that denosumab may be a potentially effective neoadjuvant therapy for osteolytic bone lesions including ABCs. By reducing tumor size, denosumab has been found to scale back potential morbidity of surgical interventions. Similarly, Skubitz et al. and Pelle et al. observed pain relief, good drug tolerance, and radiographic evidence healing in patients with sacral ABCs. Tumor regression, pain reduction, and determination of neurologic symptoms were also reported during a separate case series of two spinal ABCs following denosumab treatment

Complications

The following complications may accompany these lesions:

1. Pathological fracture: The main complication of SBC is a fracture. Pain, younger age of presentation, proximal humeral lesion, change in the size of a cavity with age, distance from growth plate, multiple septations, and early recurrence are signs of an active cyst and increased fracture risk
2. Pain
3. Malignant transformation is rare in UBC. Rare cases of malignancies have been reported several years after the treatment of ABC
4. Arthritis
5. Pressure symptoms
6. Growth disorder: Limb length discrepancy or axial deviation may be induced in children if cysts transgress the physis or involve the epiphysis
7. Recurrence: No treatment guarantees complete cure except for complete surgical resection – the post-treatment recurrence rate in case of UBC is about 10 to 30%; hence, the least aggressive treatment is the initial option
8. Aggressive surgical treatment for femoral neck lesions has generally been advocated given the dreaded complications associated with pathological femur neck fractures (like avascular necrosis, residual coxa vara, etc.).
9. General risks related to the management of cysts: Unanticipated residual structural deformity and functional disability,  and injury to adjacent vital structures (e.g., neurovascular) can occ

References

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