Abstract
Two cases of cystic adventitial disease treated at our institution over the last year are presented. They were middle-aged and apparently healthy patients, and the symptoms begin with a sudden onset of unilateral claudication. After performing a magnetic resonance angiography, a cystic formation attached to the adventitia of the popliteal artery was identified. Both patients were treated in the same manner, with resection of the affected arterial segment and vein bypass interposition. Both remain asymptomatic after one year of follow-up in one case and six months in the other. Cystic adventitial disease is a rare entity, which presents in patients without cardiovascular risk factors, so sometimes it takes long to reach a definitive diagnosis. Concerning the different treatment options, cyst excision together with the affected arterial segment seems to offer better mid- and long-term results when compared with other treatment options such as cyst aspiration or endovascular techniques, although there are no multicenter trials evidencing the superiority of one against the others.
Introduction
Cystic adventitial disease (CAD) is a rare vascular disease of unknown etiology which results in unilateral intermittent claudication in young patients without classic cardiovascular risk factors. 1
Diagnosis is made from imaging tests such as ultrasound, computed tomography (CT) angiography (CTA), or magnetic resonance angiography (MRA), the latter being the diagnostic modality that offers more information. 2
Regarding the treatment, multiple techniques are described, the open surgical management being the one which count on the greatest acceptance.
Case report 1
A 54-year-old man, with paroxysmal atrial fibrillation as sole cardiovascular risk factor, presents to our consultations, with a sudden onset of left calf claudication at 100 m of six-week duration. Left lower limb (LLL) presents normal femoral and popliteal pulses, with absence of distal pulse and an ankle-brachial index (ABI) of 0.76; in the contralateral limb, all pulses are present with an ABI of 1.25.
With all these data, we suspect an embolic event already compensated, the reason why we start anticoagulant therapy with low-molecular-weight heparins prior to oral anticoagulation.
One month later, the patient returns with clinical worsening. The patient maintains femoral pulse but has lost popliteal pulse (which was present during the first consultation); in the same way, ABI has fallen to 0.30.
Suspecting a new embolic event, we decided to perform a percutaneous arteriography, in which we note that all arteries (iliac, femoral, popliteal, and distal vessels) are patent and without lesions (Figure 1). After arteriography, the patient recovers popliteal and distal pulses spontaneously, without clinical claudication, so hospital discharge is authorized.
First arteriography performed which shows that all the arteries are patent and without lesions.
Four days after hospital discharge, the patient presents with rest pain in LLL. Physical examinations have changed once again, with a femoropopliteal obstruction and an ABI of 0.40. We decided patient admission and initiated treatment with intravenous E1 prostaglandins, waiting for CTA performing. This CTA is performed two days later and shows an occlusion in the mid portion of the popliteal artery, without lesions at the other arterial territories. In view of the CTA findings, we perform an embolectomy. Fogarty catheter progresses till the foot, providing resistance to the passage of the catheter through the mid portion of the popliteal artery, but no thrombus could be extracted. During the same procedure, we perform a control arteriography which shows a 2-cm length occlusion at the popliteal artery (Figure 2). As the surgical procedure is being carried out under local anesthesia, we decide to conclude the surgical intervention, and then perform an MRA in the next few days which can provide more information about the case, to try to reach a definitive diagnosis. It is in this MRA where we note the presence of the cystic formation at the popliteal artery, which explains the occlusion that the patient presents at this level (Figure 3).
Arteriography showing an occlusion at the popliteal artery. MRA where the presence of the cystic formation at the popliteal artery is noted first.
Once diagnosed, and although the patient recovers popliteal and distal pulses again, we offer him to perform a surgical intervention for a complete resolution of the problem. The patient accepts, and the surgical intervention is carried out through a posterior approach, with a cyst excision together with the affected arterial segment (Figure 4), for later to perform an end-to-end bypass using the ipsilateral lesser saphenous vein.
Affected popliteal artery segment in which we observe the arterial lumen collapsed by de cystic formation at the tunica adventitia.
Both the procedure and the immediate postoperative period elapse without complications; the patient recovers popliteal and distal pulses and continues asymptomatic after one-year follow-up.
Case report 2
A 49-year-old woman presents to the consultation with left calf claudication at 300 m of one-year duration; she presents hypercholesterolemia as the only cardiovascular risk factor. LLL presents normal femoral and popliteal pulses, with absence of distal pulses, and the contralateral limb has normal pulses at all levels, with an ABI of 0.70 and 1.10, respectively.
We add acetylsalicylic acid (ASA) at dose of 100 mg/day to her previous treatment, and we make an appointment within three months.
When the patient is reevaluated, she complains about clinical worsening; there are no changes in physical examination, although the ABI is now of 0.60. An MRA is performed on an outpatient, which shows as in the previous case a cystic formation at the adventitia tunica in the mid portion of the popliteal artery.
Because the patient is unable to very basic activities of daily living, we offer her the same surgical intervention that was done with the previous patient. She accepts surgical management and as in the first case, both the procedure and the immediate postoperative period elapse without complications, recovering popliteal and distal pulses. After six-month follow-up, she continues asymptomatic.
Discussion
CAD is a rare disease, with an estimated incidence of <0.1% among patients with intermittent claudication. 3
This cystic formation can be localized in both arterial and venous territory, although the percentage of settlement on the arteries is 20 times more common than the venous involvement. 4 There is also difference in gender involvement, being much more common in men, with a male–female ratio of 15:1 5 ; this ratio corresponds to cases of arterial involvement, because in case of vein involvement, ratio equals to 1:1. 1 The age of peak incidence is 40–50 years. 6
In the cases described on arterial territory, popliteal artery is the most frequently affected (over 85% of cases), as in the case of patients presented here. 6 The cyst can also involve other arterial territories as the external iliac, common femoral, axillary, brachial, ulnar, and radial arteries. 6 Interestingly, the first case described in 1947 by Atkins and Key, 7 affected the external iliac artery.
In the case of vein involvement, the common femoral vein is the most affected one. 8 These cysts will be clearly separated from the medial muscular layer, thus differing from degenerative changes in the medial layer of the aorta and other elastic or muscular arteries (Gsell–Erdheim syndrome). 9
Regarding histopathology, they will also show a characteristic composition, with different combinations of proteoglycans: mucopolysaccharides and mucoproteins as well as a high content of hyaluronic acid.
10
In both cases described here, the histopathology study showed the same result, describing the received samples as cystic formations with rich content in mucoproteins and mucopolysaccharides. Several theories have attempted to explain the etiology of adventitial cysts, although none of them are globally accepted:
Microtraumatic theory: distortion of an arterial segment adjacent to a joint that result into a destruction and degradation of the most external layer. This theory was proposed because sometimes cysts develop in sportsmen; however, later it was shown that the degree of exercise was not related to the onset of symptoms.
11
Synovial herniation of the joint into the arterial wall.
12
Ganglionic theory: sinovial ganglions that migrate to the adventitia layer.
11
Degenerative theory: associated with connective tissue diseases.
13
Developmental theory: is the most widely accepted and proposes that during embryonic development there is an ectopic migration of mesenchymal cells that land on the adventitia layer. Subsequently, these ectopic cells will develop, leading to cysts formation.
11
There are differences between these patients and patients with intermittent claudication of atherosclerotic origin, as the first one will not present the classic cardiovascular risk factors, being common that we are faced with a patient between the fourth and fifth decade, usually male as previously described, and apparently healthy, with no medical history. 5
In the cases described, both patients are in this age range, the first patient presented a single episode of paroxysmal atrial fibrillation, and hypercholesterolemia in the second one, with no other cardiovascular risk factor or toxic habits.
Clinical presentation is usually of sudden onset, starting as a unilateral gemellary claudication at short distances, sometimes after intense exercise. 6 Symptoms may subside spontaneously as in the first patient described here, alternating periods of short distance claudication and even rest pain, with asymptomatic periods where distal pulses were present; however, this is not the most common presentation form. Symptoms usually progress quickly, 6 in this way in the second case, the patient presented a clear worsening of her claudication in a short period of three months, and unlike claudication of atherosclerotic origin, these patients will need a long recovery period after the onset of pain before starting off again (more than 15–20 min) 14 ; this is explained by an increase in pressure inside the cyst during exercise and the subsequent slow resorption of mucous material towards the knee joint, resorption which can also be difficulted by valve mechanisms that would prevent this backflow of fluid into the joint. 15
Cyst size will influence in the degree of involvement of the vessel, and therefore also in clinical symptoms; the higher the cyst, the higher intensity symptoms. 1 There are a wide range of symptoms which can be the disease onset, as the previously described claudication (sudden onset with quickly progress), rest pain, burning sensation, paresthesias, or cyst rupture.16,17 In cases of venous involvement, vein thrombosis is also described. 18
At physical examination is not uncommon the presence of distal pulses that disappear with knee hyperflexion, is the so-called Ishikawa sign. 19 ABI may also vary with knee hyperflexion. 19
With everything described above, and given that the patient we are going to find is an apparently healthy middle-aged person and without cardiovascular risk factors, it is necessary to rule out other possible causes that could be responsible for the clinical chart, as popliteal entrapment, fibromuscular dysplasia, endofibrosis, Baker cyst, or particularly a popliteal aneurysm. 16
For the diagnosis, different imaging tests can be performed, from the least invasive as Doppler ultrasound to other more aggressive as arteriography.
Doppler ultrasound, may be quite informative, although not enough to determine a surgery if it was the only evidence on. Given its high availability and low cost, Doppler ultrasound serves as a first approach to the case. The image offered by Doppler ultrasound, should be carefully analyzed, since it is not uncommon that the cyst be mistaken for a popliteal aneurysm. 6 This is because any dilatation at the popliteal artery is immediately considered a priori as a popliteal aneurysm, and the absence of flow in the alleged “widened part of the artery” can be interpreted as mural thrombus. 6 Following Doppler ultrasound, other imaging tests as arteriography, CTA, or MRA should be performed.
Among all of them, arteriography is probably the less useful one, because arteries will usually look healthy and without injuries or signs of atherosclerosis, while it is true that if cyst is causing a compression of the popliteal artery itself, we can note a characteristic “hourglass image” in cases where the cyst grows concentrically, or the “scimitar sign” in cases of eccentric growth or near to occlusion. 2 These compressions may not be proven with the limb extended but does when the test is performed with knee hyperflexion. 6 Another feature of this disease is the absence of post-stenotic dilatation. 20 The limited usefulness of arteriography as a diagnostic method for these cases is demonstrated in the first case; with a normal first arteriography and a second one showing an obstruction of the popliteal artery but unable to identify the cause. This obstruction can only be noted if the arteriography is performed when the cyst is full of mucous material, resulting in an arterial compression (Figure 2), but not when the mucous material has been reabsorbed into the knee joint (Figure 1).
The cyst may also be overlooked with the CTA, observing only the arterial stenosis or obstruction.
MRA is the image test that offers more information and most useful to us in assessing about possible treatment options (as seen on both cases), since it clearly identifies the presence of the cystic formation, length of the arterial segment affected, and degree of compression, all of them factors to keep in mind in case of a future surgery. 1
Regarding the treatment, multiple techniques are described; they can be divided into resectional techniques or non-resectional techniques, each of them with their respective advantages and disadvantages. 6
Non-resectional techniques include open cyst excision with preservation of the arterial wall, intraoperative cyst aspiration, percutaneous ultrasound-guided or CT-guided aspiration, and endovascular techniques such as percutaneous transluminal angioplasty (PTA) or stent placement. 6
The resectional ones include all those in which a complete resection of the affected arterial segment is performed, for later perform a reconstruction by interposition of a vein graft, a prosthetic graft, an homograft, or an end-to-end anastomosis. 6
Among the non-resectional, open cyst excision with preservation of the arterial wall is the one that offers better results, with an initial success rate of 94%. 6 There is a modification of this technique that reaches similar initial success rates but with fewer recurrences, and it consists in performing an extended adventitial resection all around the circumference of the affected artery segment. 21
Both CT-guided aspiration and intraoperative cyst aspiration have the disadvantage of presenting a high rate of early recurrence, around 10%. 22 Furthermore, aspiration is often difficult due to the high density of the mucinous material. 23
Endovascular techniques have also been used for treatment of CAD, although with poor results. PTA did not seem to solve the problem, since the stenosis that occurs at the artery is from extrinsic etiology to the artery itself. 24 These poor results were thought at first that could be solved with a stent placement; however, cases published to date have not provided satisfactory results; 25 in fact, there are communications of stent fracture and thrombosis within a week after stent placement. 25 Moreover, stent is placed in a flexion area, which together with the median age of these patients do stenting a non-recommended technique.
Resectional techniques seem to offer a more permanent solution, both with vein graft interposition or with prosthetic graft interposition, although they may also present complications such as intimal hyperplasia with subsequent stenosis at the anastomosis, bypass thrombosis, or aneurysmal degeneration. The initial success rate for venous bypass interposition is estimated at 95%, being slightly lower in case of prosthetic grafts.
6
One of the possible causes of recurrence is an incomplete cyst resection.
20
It is important to identify all communications between the affected artery and joint, which should be sectioned to prevent further recurrences; in the case of the female patient, at least two or three tubular communications between the cyst wall and the joint were identified during surgery, so we proceed to its section (Figure 5).
Surgery instant in which we identified one of the communications between the cyst and the joint.
There are reported cases of spontaneous resolution, sometimes due to cyst rupture or also to drainage of its contents into the joint.14,26
Conclusions
Published cases between 1979 and 2014 in PubMed database (English and Spanish language).
Extended adventitial resection is the other treatment option that also offers better results, with a 100% of success in the 12 reported cases.
Some authors think that the first one (arterial segment resection + bypass interposition) should be used in cases of complete arterial occlusion or degeneration of the medial layer of the arterial wall6,27 and that the extended adventitial resection can be used in cases of arterial stenosis, offering the same or better results.6,27
In both cases we report, popliteal artery was completely occluded, so we decided to perform a complete resection of the affected arterial segment; moreover, we think that resecting the entire segment can prevent future recurrences.
Cyst aspiration can be an option for those patients who refuse performing a bypass, or for those with high surgical risk (as this technique can be performed on an outpatient as many times as necessary, avoiding anesthetic risk; although this is an unusual condition in these patients because they are usually healthy patients without cardiovascular risk factors); however, high recurrence rates (3/15) and some failed cases (2/15) make this treatment option a less attractive one. Stenting presents the problem that the device is placed at a flexion area and in an active person, with consequent complications such as fracture or migration of the device due to continuous microtrauma from repeated flexion and extension of the knee and because the cause of compression is not solved; the cause of compression also remains unresolved with PTA. Endovascular techniques, both PTA and stenting offer poor results in the majority of the reported cases and that is the reason why we think they are not an appropriate treatment for this disease.
Ethical approval
Both patients described in this manuscript gave their consent by signing the informed consent form, for performing the surgical intervention as for the possible publication of images, however there is no data or image in this manuscript where they can be identified.
Footnotes
Conflict of interest
None declared.
Funding
This research received no specific grant from any funding agency in the public, commercial, or not-for-profit sectors.