Adventitial cystic disease

INTRODUCTION — Adventitial cystic disease (ACD) is a condition in which cysts within the vessel wall containing gelatinous mucoid material result in nonatherosclerotic luminal stenosis or occlusion of arteries or veins.

The pathogenesis, clinical features, diagnosis, and treatment of ACD are reviewed. Other nonatheromatous vascular diseases are reviewed separately. (See "Nonatheromatous popliteal artery diseases causing claudication or limb-threatening ischemia".)

PATHOGENESIS — The etiology of ACD is largely unknown. The cysts that develop contain gelatinous mucoid material located between the adventitial and medial layers of the artery, causing luminal stenosis or occlusion as they enlarge [1]. The cysts are usually unilocular, lack a cellular lining, contain hyaluronic acid, protein, and proteoglycans, and are biochemically and histologically similar to ganglia [2,3].

Given the rarity of ACD, the pathogenesis has not been fully elucidated and is still debated. There are four main hypotheses to explain the origin of ACD:

●Cyst formation is in response to a synovial fluid that has leaked from the joint space into neighboring arterial (or venous) adventitia [4]. While trauma may cause the joint capsule defect, it is presumed that it is the exudation of synovial fluid that results in the pathology. A connection has purportedly been identified by various imaging modalities in patients with ACD, including computed tomography (CT), magnetic resonance (MR) imaging, and arthrogram of involved joints [5-7]. However, the cysts of ACD contain hyaluronic acid and protein as well as proteoglycans without lubricating ability, suggesting a ganglionic origin as opposed to synovial origin [2,3].

●Cysts form from primary adventitial degeneration following repetitive trauma. Given the common location of these lesions near joints, the presumed flexion/extension results in pathologic changes due to recurring stretching of the adventitia.

●A developmental abnormality results in mucin-secreting mesenchymal cells placed within the adventitia during embryogenesis [8]. Due to an unknown trigger later in life, these cells begin secreting mucin, resulting in pathologic changes.

●Adventitial cysts form in response to a systemic connective tissue disorder [9]. However, this has not been clinically demonstrated, as most patients with ACD do not consistently show signs of systemic illness or coexisting connective tissue disorder.

Anatomic locations

Arterial — ACD was first identified in 1946 in the external iliac artery of a 40-year-old man presenting with claudication [10]. Subsequently, it was described in other locations, most commonly within the popliteal artery, but also in the superficial femoral artery, and nearly all other arteries of the thigh. It has also been described in arteries of the upper extremity, most commonly in the distal upper extremity arteries. In most patients, a single vessel is affected, although multiple artery ACD has also been described [11]. Bilateral popliteal artery ACD has been described [12].

Venous — ACD has also been described in several lower extremity venous locations (eg, common femoral vein, great saphenous vein, popliteal vein, external iliac vein) [13].

INCIDENCE AND RISK FACTORS — The overall incidence is unknown; however, among patients presenting with symptoms of claudication, it is estimated to be present in 1 of 1200 patients [9]. Overall, ACD presents more commonly in males compared with females (4:1 ratio) [14], although in a review limited to venous ACD, males and females appeared to be equally affected [13]. The age of patients ranges anywhere from 5 to 75 years, with the mean age being 47 years, and while it can occur in older patients and pediatric populations, ACD is typically diagnosed in the fourth or fifth decade of life [13,14].

CLINICAL PRESENTATIONS — The clinical presentation of ACD varies with the location of the disease and the severity of obstruction.

Claudication — Patients with lower extremity ACD most commonly present with unilateral intermittent claudication [15]. Because the most common location for the lesion is the popliteal artery, the calf is the most commonly affected muscle group; the right and left lower extremity are affected with similar frequency [14]. As compared with peripheral artery disease (PAD), patients with ACD and claudication frequently have prolonged postexercise recovery time before pain resolution and may report a waxing and waning of symptoms due to fluctuating amounts of cyst content at any given time. Patients with ACD may also frequently lack the usual atherosclerotic risk factors found in those with PAD such as smoking.

Acute limb ischemia — Patients with ACD may also present with acute limb ischemia resulting from thrombosis of the stenotic vessel [15]. Symptoms of acute limb ischemia include pain, pallor, paresthesias, paralysis, and poikilothermia. (See "Clinical features and diagnosis of acute lower extremity ischemia".)

Limb swelling — Venous ACD most commonly presents with limb swelling resulting from venous compression from the cystic mass. The cystic structures may be mistaken for venous thrombus, although venous compression can also result in DVT due to low flow through the stenotic region [13,16]. (See "Clinical presentation and diagnosis of the nonpregnant adult with suspected deep vein thrombosis of the lower extremity".)

DIAGNOSTIC EVALUATION — ACD is a rare cause of unilateral lower extremity arterial symptoms, but it should be considered in any patient lacking typical cardiovascular risk factors and presenting with acute or chronic ischemic symptoms (eg, claudication), particularly in younger patients.

The pulse examination is variable depending on the severity of the compression by the cystic lesions; the patient can have normal, diminished, or absent distal pulses. With popliteal ACD, the "Ishikawa sign" may be present, which is a palpable pedal pulse that is lost with passive flexion of the knee or exercise [17]. This sign may be also noted during ABI determination.

Vascular imaging — Vascular imaging can demonstrate the cystic lesion(s) of the affected artery and the severity of any associated stenosis or complete occlusion [15].

●Ultrasound – In the hands of experienced sonographers, ACD lesions are noted as anechoic or hypoechoic masses (black) arising from the arterial wall with smooth contours and compressing the lumen of the vessel to varying degrees [18]. This compression is concentric, resulting in an "hourglass" appearance. Duplex ultrasound may demonstrate elevated peak systolic velocities at the point of maximal compression.

●CT angiography – CT angiography typically demonstrates hypodense lesions within the artery wall, and MR angiography shows homogenous low signal intensity on T1-weighted images and high signal intensity on T2-weighted images, and both modalities may reveal connections with adjacent joint capsules.

●Digital subtraction angiography – Digital subtraction angiography alone may demonstrate a stenotic lesion but cannot provide a specific diagnosis of ACD [19]. However, if performed, the classic "scimitar sign" (contrast filling the narrowed vessel in a curvilinear manner due to the eccentric luminal compression by the lesion) may raise suspicion for the diagnosis, which requires ultrasound or cross-sectional imaging to confirm.

●Intravascular ultrasound – Intravascular ultrasound at the time of angiography has been demonstrated to be useful. It may more clearly demonstrate the extravascular structure of the cyst in addition to confirming stenosis [20].

DIFFERENTIAL DIAGNOSIS — Other nonatheromatous diseases that can occur in those without significant risk factors for atherosclerosis and can cause extremity symptoms include popliteal entrapment, fibromuscular dysplasia, and vasculitis. (See "Nonatheromatous popliteal artery diseases causing claudication or limb-threatening ischemia".)

TREATMENT — Given its rarity, the natural history of untreated ACD has not been fully elucidated. However, treatment of symptomatic patients is warranted to prevent progression to a fixed lesion or to prevent limb-threatening ischemia due to thrombosis of the stenotic segment of the artery. Treatment is best described for managing popliteal ACD; there is insufficient clinical experience to guide treatment of ACD that occurs at other locations.

Several treatments have been described for popliteal ACD, including endovascular intervention, aspiration of the cyst contents, or cyst resection with or without vascular reconstruction (eg, interposition graft, bypass). Patients undergoing cyst resection are less likely to have recurrence compared with cyst aspiration. Vascular reconstruction has excellent long-term patency.

Endovascular angioplasty with or without stenting has been described in some case reports with success [21]. However, there are numerous other reports that highlight the short patency [22], or ultimate failure of endovascular intervention necessitating an eventual bypass [23-25]. One reason for the high failure rate may be because most ACD lesions are located at flexion points such as the knee that reduce the long-term durability of stents. Endovascular intervention has been described successfully for some anatomic locations such as ACD involving the external iliac arteries [26]. Given the poor long-term data and high risk of short-term recurrence, endovascular treatment is not typically performed.

The goal of cyst aspiration is to reduce the severity of compression and it can be performed via an open surgical approach or percutaneously using image guidance (ultrasound or CT). Technically, the procedure can be challenging given the location of the cyst within the popliteal space. In addition, given the multilocular nature of the cysts and the thickness of the contents, evacuation is often incomplete, leading to high rates of recurrence (up to 40 percent) or inadequate relief of symptoms [15].

Surgical management of ACD involves cyst resection with or without vascular reconstruction, either using an interposition graft or saphenous vein bypass graft. The surgical approach depends upon the extent of the cystic changes and location.

A short interposition saphenous vein graft is typically all that is required after excision of the cyst [27]. When compared with cyst resection alone, cyst excision with arterial reconstruction or bypass alone provides the best long-term symptomatic relief in patients [19].

SUMMARY AND RECOMMENDATIONS

●Adventitial cystic disease – Adventitial cystic disease (ACD) is a relatively rare cause of nonatherosclerotic arterial or venous occlusion that is due to luminal compression by cysts within the vessel wall. The cysts contain a gelatinous mucoid material, the etiology of which is largely unknown. (See 'Pathogenesis' above.)

●Locations – ACD has mostly been described in the lower extremity arteries including the popliteal artery, iliac artery, and the superficial femoral artery, but upper extremities arteries can also be affected. Venous ACD has also been described. (See 'Anatomic locations' above.)

●Clinical presentations – The clinical presentation of ACD varies with the location of the disease and the severity of obstruction. Patients with lower extremity ACD commonly present with symptoms of lower extremity claudication or acute limb ischemia. Venous ACD can present with chronic venous symptoms or acute venous thrombosis. (See 'Clinical presentations' above.)

●Diagnosis – A diagnosis of ACD should be considered in any patient lacking the typical cardiovascular risk factors associated with atherosclerotic peripheral artery disease (PAD) and presenting with lower ischemic symptoms (eg, claudication). ACD has characteristic features that suggest it as the cause of obstruction on ultrasound, CT, and MR angiography. (See 'Diagnostic evaluation' above.)

●Treatment – Treatment is indicated for symptomatic patients to prevent progression or thrombosis which may lead to limb-threatening ischemia. Treatment options for ACD includes cyst aspiration or cyst resection with or without vascular reconstruction or bypass.

•Surgical treatment is generally preferred. Cyst aspiration is an alternative for patients who are not surgical candidates or for ACD in difficult anatomic locations. However, cyst aspiration is often incomplete and recurrence rates are high.

•Treatment is indicated for symptomatic patients to prevent progression or thrombosis which may lead to limb-threatening ischemia. Treatment options includes cyst aspiration or cyst resection, with or without vascular reconstruction, or bypass. Surgical treatment is best described for managing popliteal ACD, for which we suggest cyst resection rather than cyst aspiration (Grade 2C). Popliteal cyst excision with arterial reconstruction or bypass provides long-term symptomatic relief. (See 'Treatment' above.)