*Introduction

Arteriovenous malformations (AVM) are congenital, complex vascular anomalies belonging to the isolated, fast-flow subgroup in the International Society for the Study of Vascular Anomalies (ISSVA) classification.1 These lesions are characterized by direct, high-flow communications between arteries and veins, bypassing the capillary bed, and are inherently complex and heterogeneous.2,3 While AVM may arise in any anatomical location, the brain, spine, and extremities are most commonly affected.3,4 Extremity AVM, though less frequent than intracranial lesions, pose significant clinical challenges, due to their potential for progressive growth and expansion, functional impairment, and life-threatening complications.4,5

The aim of this narrative review was to critically evaluate the contemporary role of major limb amputation in the management of extremity arteriovenous malformations (AVM). By synthesizing current evidence from peer-reviewed literature, this paper sought to clarify the clinical indications, timing, technical considerations, and outcomes associated with amputation in extremity AVM. Particular emphasis was placed on postoperative quality of life, functional recovery, and the multidisciplinary strategies that optimize patient-centered care.

Methods

A comprehensive narrative review of the literature was conducted to evaluate the management of extremity AVM, with particular focus on the role and outcomes of limb amputation. A extensive, electronic search of the PubMed, Scopus, and Web of Science databases was performed for studies published between January 2000 and September 2025. The search strategy used various combinations of the following keywords: “arteriovenous malformation”, “extremity”, “limb”, “amputation”, “embolization”, “surgical excision”, “outcome”, and “quality of life”. The last search was run on 09 October 2025. Only articles published in English and indexed in peer-reviewed journals were included. Eligible publications comprised clinical studies, case series, case reports, and review articles reporting on diagnosis, management, and outcomes of extremity AVM in adults or mixed-age populations. Studies focusing exclusively on cerebral, spinal, or visceral AVM were excluded. Reference lists of relevant papers were also screened to identify additional sources. Data were extracted and synthesized narratively, emphasizing the epidemiology, pathophysiology, treatment strategies, and long-term results of amputation, with cross-referencing to original reports whenever possible. The review adheres to the principles of transparency and reproducibility in narrative reviews, though no formal meta-analysis or quantitative synthesis was performed, due to the heterogeneity among the available studies.

Results – Discussion

Epidemiology

The prevalence of extremity AVM is difficult to ascertain precisely due to underdiagnosis, misclassification, overlapping terminology in older series, and variable detection methods, but estimates suggest that extremity AVM represent around 20-30% of all AVM, with an overall prevalence of approximately 1 in 100,000 individuals in the general population.6,7 Extremity AVM are usually located in the lower limbs, most commonly in the thigh and knee regions, followed by the lower leg and foot.2 Upper limb AVM are more commonly found in the hand than in the arm, accounting for around 10% of extremity cases.5

Pathophysiology

The formation of AVM is attributed to defective vascular morphogenesis during early embryogenesis, typically between the 4th and 10th week of gestation.2,7 In these lesions, failure of capillary network development results in persistent arteriovenous shunts, which are hemodynamically abnormal and prone to progressive enlargement.2,7 Histologically and angiographically, AVM consist of hypertrophic and tortuous feeding arteries, a central nidus composed of dysplastic vessels, and dilated, thin-walled draining veins.2 The low-resistance, high-flow shunting inherent to AVM leads to venous hypertension, tissue congestion, distal ischemia due to steal phenomena, and progressive local tissue destruction.7,8 Over time, these processes may manifest as pain, edema, ulceration, hemorrhage, and, in extensive lesions, high-output cardiac failure.7,8

Unlike many vascular tumors, AVM do not involute, and are distinguished by their capacity for continuous growth, which may be triggered by external or physiological factors, such as trauma, infection, thrombosis, surgery, or hormonal changes during puberty or pregnancy.7,9 Such stimuli can transform a previously quiescent lesion into a rapidly enlarging, symptomatic, or even life-threatening vascular anomaly.7,9 This characteristic growth behavior underpins the need for vigilant monitoring and timely intervention, and explain why therapeutic strategies typically aim at durable symptom control rather than guaranteed cure.3

Clinical presentation

Clinically, extremity AVM may remain quiescent for long periods or present with a clinical spectrum of extremity that ranges from subtle skin changes to severe deformity and functional impairment.2 Early-stage lesions may manifest as localized warmth, pink skin blush, or minimal swelling, often remaining asymptomatic for years.10,11 As lesions progress, patients may present with palpable thrills, pulsatile masses, audible bruits, and dilated superficial veins.10,11 Advanced disease is characterized by pain, ulceration, bleeding, tissue necrosis, and progressive deformity, whereas high-output cardiac failure can occur due to extensive arteriovenous shunting.10,11 The Schobinger staging system12 remains the most widely adopted clinical framework to communicate disease severity, guide follow-up, and determine timing of intervention:

• Stage I (quiescence): pink-blush skin, warm area
• Stage II (expansion): pulsatile mass, thrill, bruit, dilated veins
• Stage III (destruction): pain, ulceration, bleeding, tissue necrosis
• Stage IV (decompensation): high-output heart failure

Importantly, stage correlates with risk: many lesions remain in stages I-II for extended periods, but a substantial proportion progress to destructive (stage III) disease requiring active intervention.12 Functional impairment in extremity AVM may include reduced range of motion, weakness, and difficulty performing daily tasks, particularly when lesions involve the hand or wrist.10,11 Steal phenomena can exacerbate distal ischemia, and large AVM may cause limb hypertrophy or deformity.10,11 Chronic pain, recurrent bleeding, and repeated infections are common and significantly impact quality of life.10,11 Figure 1 depicts the ex vivo examination of a hand with an extensive, destructive, Schobinger stage III arteriovenous malformation, showing major digital deformity, extensive skin and soft tissue breakdown, multiple ulcerative lesions, dystrophic nails, and exposed phalanx bones. The patient had presented at our emergency department with spontaneous, major, life-threatening hemorrhage, and underwent an emergent mid-forearm amputation.

Diagnosis

Accurate diagnosis of extremity AVM relies on a combination of clinical assessment and imaging.2,12 Colored Duplex ultrasonography is often the first-line imaging modality, providing information on flow velocity, direction, resistance, and shunting, as well as serving as a tool for surveillance.12-14 Magnetic resonance imaging and magnetic resonance angiography are essential for delineating the lesion extent, soft tissue and bone involvement, and relationships to neurovascular structures.12-14 Computed tomography angiography is particularly useful when skeletal involvement must be assessed.14 Despite advances in noninvasive imaging, digital subtraction angiography remains the gold standard for detailed mapping of nidus architecture and feeding/draining vessels, particularly when endovascular intervention is being considered.12,15 Biopsy of suspected AVM is contraindicated due to the risk of significant hemorrhage.14

Differential diagnosis should consider low-flow vascular malformations, hemangiomas, pseudoaneurysms, angiosarcomas, or non-vascular soft tissue lesions such as abscesses or tumors.2 Correct classification using ISSVA criteria is critical to avoid mislabeling and to guide appropriate management.1

Treatment strategies

Various treatment modalities exist for extremity AVMs.16 Conservative management, including compression therapy, analgesia, and close observation, is reserved for small, quiescent, or asymptomatic lesions (Schobinger stage I).14,16 Interventional therapy is indicated in rapidly progressive lesions, those causing pain, bleeding, ulceration, functional impairment, or systemic complications such as high-output cardiac failure16,17. Given the tendency of AVM to grow and recur, early and aggressive treatment is generally recommended, once clinical progression is established, even in younger patients, before the point of no return is reached.8,16 However, the treatment itself is a major challenge, due to the high rate of failure and recurrence.8,16 Thus, the primary and rational goal of therapy is symptom amelioration, preservation of function, and prevention of irreversible tissue damage, rather than guaranteed angiographic cure.11 Multiple series emphasize that outcomes are best when interventional radiology, vascular surgery, orthopedics, plastic surgery and physical rehabilitation specialists collaborate within a vascular anomalies multidisciplinary team.17

Endovascular embolization

Endovascular embolization remains the cornerstone of AVM therapy.11,17 The target is the nidus, which may be approached transarterially, transvenously, or via direct percutaneous puncture.2,17 Embolic agents include absolute ethanol, cyanoacrylate adhesives (NBCA), non-adhesive liquid embolic such as Onyx, coils, newer polymer-based agents such as PHIL and Squid, and detachable balloons.2,17 The choice of agent is lesion-dependent and considers factors including nidus size, venous outflow anatomy, the need to preserve distal perfusion, and the vascular team’s experience.13,16,18 Ethanol achieves permanent endothelial destruction, but carries a risk of systemic toxicity, and requires careful dosing with anesthetic support.19 Non-adhesive copolymers allow controlled penetration of the nidus, and are preferred in lesions with complex flow patterns or difficult architecture.20

Success varies, and reported series indicate that recurrence remains a challenge.4,11,13,16 Even technically successful embolization often achieves temporary symptom control, particularly in diffuse lower extremity lesions.13,16 Recurrence rates are high within the first year, and up to 98% of diffuse AVM may re-expand within five years without subsequent intervention.11,21 While upper extremity AVMs often respond well, lower limb lesions frequently recur, sometimes requiring amputation, despite a technically successful embolization. This highlights the importance of careful angiographic evaluation, nidus-directed technique, and staged procedures.17

Surgical excision

Surgical resection is the most definitive approach when complete excision with negative margins is feasible.2,13 In practice, many extremity AVM are diffuse, infiltrating critical structures, or associated with bone involvement, which makes surgery technically challenging, and functionally risky.7,21 Even with maximum resection, recurrence rates of 8-9% are reported, particularly in diffuse lesions.16 Surgery alone carries high risks of blood loss, neurovascular injury, and postoperative morbidity.2 Multidisciplinary approach and a staged hybrid strategy, combining embolization followed by surgery within 72 hours optimize outcomes by reducing intraoperative bleeding and improving the likelihood of complete resection.11,17 Reconstruction using local flaps, skin grafts, or free tissue transfer is often necessary to restore both function and form.2

Sclerotherapy with sodium tetradecyl sulfate has also been used for low-flow AVM.22 Pharmacologic agents, particularly mTOR inhibitors, like sirolimus, have emerged as adjuncts for unresectable or recurrent AVM, offering symptom reduction and lesion stabilization in selected cases, although their efficacy remains under investigation.22

The role of limb amputation

Major limb amputation remains a legitime, last-resort option for advanced, multifocal, diffuse or functionally devastated extremity AVM (Schobinger stage III-IV).8 Indications include intractable pain, progressive tissue necrosis, non-healing ulcers, recurrent infections, hemorrhage, ischemia, severe deformity, and, rarely, refractory high-output cardiac failure.8,23,24 Moreover, it is the ultimate treatment option for cases refractory to multiple embolization/surgical attempts, or the only practical solution when the limb has become severely hypertrophic or deformed and can no longer be considered as functional.8,23 Finally, amputation is urgent and can be life-saving, when there is major hemorrhage or progressive high-output cardiac failure, unresponsive to other treatments.8,24 The level of amputation depends greatly on the extent of the AVM, distal tissue viability and functional assessment.2,8

It is estimated that up to 22% of AVM patients with advanced Stage III or ΙV disease may end up needing major amputation, and some studies have shown that even patients with technically successful embolization can undergo amputation within the following years, due to recurrence, particularly in lower extremity AVMs.21,24,25 According to a large retrospective review of 993 patients with extremity AVM, the median interval from first intervention to amputation was approximately 10 years.24 Contemporary series emphasize that amputation is reserved only for cases in which less-radical strategies cannot safely or reasonably control symptoms and complications.22 From an ethical perspective, the decision to amputate should be viewed not as therapeutic failure, but as a legitimate endpoint of disease management when limb salvage no longer serves the patient’s best interest.8,22 Prolonged attempts at salvage in the face of progressive pain, infection, or bleeding can lead to cumulative morbidity, delayed rehabilitation, and psychological exhaustion.8 Thus, a timely and well-executed amputation in appropriate cases may restore dignity, autonomy, and quality of life, and provide superior long-term outcomes compared to repeated unsuccessful limb salvage procedures.8

Amputation carries distinct perioperative and longer-term risks in the AVM population.2,8 Intraoperative hemorrhage is the principal technical hazard, because vascular malformations often have large, low-resistance channels and thin-walled dilated veins, that will not respond to standard vascular control measures.24-26 Preoperative planning, pre-amputation angiographic mapping, use of tourniquet, and selective embolization of feeding or outflow vessels can reduce bleeding risk, if time and resources allow; some teams perform pre-operative staged embolization (or proximal ligation) within 24-72 hours before surgery, specifically to lower intraoperative blood loss.17,18,22,27 In emergent scenarios, such as uncontrollable hemorrhage, tourniquet application, rapid proximal control, and decisive amputation are often required to save life.23

Post-amputation problems include delayed wound healing or stump breakdown (particularly where prior radiation or repeated interventions have compromised local tissues), persistent or recurrent AVM at the margin if nidus elements remain, and the usual long-term challenges of phantom limb pain and prosthetic rehabilitation.8,21,28 Thus, informed consent, preoperative psychological counselling and psychological support are essential components of care.17 Patients should be fully apprised of the risks, benefits, and alternatives to amputation, and a plan for early prosthetic fitting and rehabilitation should be in place whenever feasible to accelerate functional recovery and to improve quality of life.17,29,30 Therefore, a multidisciplinary, evidence-based, and patient-centered approach is ideal for sharing the burden of this difficult decision-making process.17

Postoperative amputation outcomes are described in small series and case reports, but are generally favorable when amputation is appropriately indicated, and when postoperative rehabilitation is well supported.24-28 Studies have shown that most patients experience relief from pain, resolution of recurrent bleeding or infection, and improved quality of life.24-28 Early prosthetic rehabilitation results in good ambulation, and is associated with better functional recovery and independence, and eventual return to daily activities.29 This is even more favorable in patients receiving timely prosthetic rehabilitation, especially after distal limb amputations (transtibial or transradial).29

Regarding quality of life, most studies report improved quality of life and functionality post-amputation, particularly when coupled with prosthetic rehabilitation and psychological support.29-31 In a multicenter series, patients undergoing amputation for advanced lower limb AVM reported mean pain scores reduced by more than 70%, with 85% achieving satisfactory prosthetic use and significant improvement in quality of life at one year.32 Similarly, another study found that most patients who underwent below-knee amputation achieved full mobility and independence, while those with more proximal amputations required adaptive aids but still expressed high satisfaction.33 Thus, multidisciplinary care with psychological support is essential for optimal long-term outcomes.17 Finally, systematic long-term follow-up is necessary both to monitor for stump complications, and to provide ongoing prosthetic adjustments, psychological evaluation, and pain management, including treatment for phantom limb pain when it arises.7,17

Future directions

Despite advances in imaging, embolic agents, hybrid procedures, and adjunctive pharmacologic therapy, substantial gaps in the literature remain. Most published data derive from retrospective single-center studies with heterogeneous outcome definitions. Prospective multi-institutional registries with standardized imaging, staging, outcome metrics, and long-term follow-up are needed to identify predictors of durable response, refine treatment algorithms, and better define the role of amputation in contemporary practice. Additionally, molecular and genetic research may clarify the pathophysiology of AVM and guide the development of targeted therapies.

Conclusion

Extremity AVM are rare, biologically active lesions with a potential for progressive local destruction and systemic complications. Management requires a nuanced, multidisciplinary approach. Endovascular nidus-directed embolization, staged or combined with surgical excision, remains central to treatment, with the primary goal of symptom control and functional preservation. Amputation retains a critical, last-resort role for lesions that are refractory to other modalities or life-threatening, providing substantial relief, functional recovery, and improved quality of life, when performed in a controlled, multidisciplinary setting. In all cases, candid patient counselling, comprehensive preoperative planning (including angiographic mapping and consideration of preoperative embolization), perioperative hemodynamic support, and structured postoperative rehabilitation and psychosocial support are essential to optimize outcomes. Future prospective multi-institutional research with standardized definitions and long follow-up is needed to refine indications and to improve prognostication so that the right therapy can be chosen at the right time.

References

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