Cystic adventitial disease of the popliteal artery in female: case report and literature review of a rare differential diagnose of artery stenosis

Abstract

Background

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Cystic adventitial disease (CAD) is a rare vascular condition that causes arterial stenosis due to the presence of a cyst in the adventitia (outer layer) of the artery. It is most commonly seen in young and middle-aged men, with an occurrence rate of around 0.1% among vascular diseases. Symptoms may include intermittent claudication, rest pain, and, in severe cases, ulcers or limb ischemia. CAD is often underdiagnosed due to its rarity and the broad range of differential diagnoses for arterial obstruction.

Case presentation

This case describes a 36-year-old female who presented with sudden left lower limb soreness that worsened with activity over five days, but without symptoms such as intermittent claudication or rest pain, which are typically associated with other vascular diseases. The patient had no significant history of smoking or other risk factors for peripheral arterial disease. Imaging studies, including angiography, revealed a focal filling defect and luminal narrowing in the popliteal artery (PA), which suggested the presence of an abnormality in the vessel wall. Given the findings and the patient’s symptoms, surgical intervention was planned. The procedure involved the resection of the affected portion of the artery and replacement with an autologous vein graft. Pathological examination of the resected arterial segment confirmed the diagnosis of CAD, revealing a cyst in the adventitia filled with a gelatinous substance.

Conclusion

CAD is a rare but important cause of arterial obstruction and the etiology of CAD is still unclear. It should be considered in younger patients with symptoms of limb ischemia, especially without smoking history or traditional risk factors. Imaging techniques, such as ultrasound and CT/MRI angiography, are crucial for diagnosis. Surgical management, typically involving resection and autologous grafting, is often required to alleviate symptoms and prevent further vascular complications. However, it is worth mentioning that conservative treatments, such as avoiding triggering movements, are sometimes sufficient. Since CAD is rarely suspected, awareness of this condition can help in making an early diagnosis, potentially avoiding misdiagnosis and improving patient outcomes.

Introduction

Lower extremity peripheral artery disease (PAD) is a specific form of cardiovascular disease characterized by reduced blood flow due to obstructive atherosclerosis. PAD may result in lower extremity ischemia, potentially precipitating serious complications such as tissue necrosis, critical limb ischemia, and in severe cases, mortality [1]. Globally, PAD is estimated to affect over 230 million individuals [1], with cases involving the popliteal artery (PA). Stenosis of the PA, resulting from various etiologies, manifests with symptoms and signs indicative of lower limb ischemia, which often overlap across different causes. These include atherosclerosis, PA aneurysms, PA embolism, trauma, and Cystic Adventitial Disease (CAD). CAD, a rare non-atherosclerotic vascular condition, accounts for only 0.1% of vascular diseases [2].

Typically, CAD affects young to middle-aged men who present without signs of atherosclerotic disease or cardiovascular and cerebrovascular risk factors. The popliteal artery is the most common site for CAD, involved in approximately 80–90% of cases [3, 4, 12]. Symptoms of CAD can include decreased skin temperature, intermittent claudication, reduced ankle-brachial index (ABI), and rest pain.

This paper details the case of a 36-year-old woman diagnosed with popliteal cystic artery disease, emphasizing the importance of early diagnosis and intervention. The rarity of this condition in females makes the case particularly noteworthy. Additionally, the paper reviews the relevant literature to further enhance the understanding of CAD.

Case presentations

A 36-year-old Chinese woman was admitted to the Union Hospital, Tongji Medical College, Huazhong University of Science and Technology on March 10, 2024. The patient presented with an acute, unexplained soreness in her left lower limb for the past five days, which worsened with physical activity. There were no associated symptoms such as pain, edema, or other discomfort. The dorsalis pedis artery was palpable, and there was no history of trauma, prior surgeries, smoking, or other cardiovascular risk factors. Apart from this, no relevant family history of genetic diseases was reported.

An ultrasound examination conducted at a local hospital revealed “left PA dissection with true cavity stenosis (75%-99%)”, though no special treatment was administered. Further diagnostic imaging via computed tomography (CT) revealed a low-density lesion within the left PA, showing severe narrowing of the lumen [Fig. 1a]. A computed tomography angiography (CTA) was then performed, which demonstrated filling defects within the left PA, with a cumulative range of about 2.2 cm and severe stenosis of the local lumen [Fig. 1b]. However, the diagnosis provided by the radiologist is: Dissection? Thrombus?

To further clarify the diagnosis, a magnetic resonance imaging (MRI) was conducted, revealing a cystic structure in the left PA with well-defined boundaries. The lesion appeared hypointense on T1-weighted imaging (T1WI) and hyperintense on T2-weighted imaging (T2WI), suggesting that it may represent thrombus or dissection [Fig. 1c and Fig. 1d]. The MRI findings were consistent with those from magnetic resonance angiography (MRA), which showed results similar to the CTA findings [Fig. 1e]. Despite these imaging results, the radiologist’s diagnosis remained inconclusive, similar to the earlier assessment.

Fig. 1

comprehensive preoperative examinations were conducted. (a) Red arrow indicates a low-density lesion obstructing the PA. (b) Filling defects observed in PA CTA. (c, d) Arrow points to PA lesion, hypointense on T1WI and hyperintense on T2WI. (e) MRA shows a filling defect with smooth margins in the PA

The patient was initially diagnosed with popliteal artery stenosis. To both confirm the diagnosis and restore the proper blood flow to the affected limb, she underwent a lower extremity artery exploration under general anesthesia. A carefully performed S-shaped incision in the popliteal fossa allowed for a layer-by-layer dissection of the tissue. As shown in Fig. 2a, localized arterial dilation was noted and after removing the diseased segment of the artery, a translucent cystic cavity was discovered within the vessel wall. The cyst had a smooth surface and distinct boundaries, consistent with prior imaging results, and it obstructed most of the vascular lumen [Fig. 2].

Fig. 2

(a) Local dilation of the PA. (b, c) Translucent cystic cavity in the arterial wall with smooth surface and clear boundaries

To restore blood flow, the affected segment of the artery was reconstructed using an autologous great saphenous vein. [Fig. 3a]. The pathological examination after surgery confirmed the presence of an adventitial cyst containing gelatinous substance, aligning with the imaging findings. [Fig. 3b and Fig. 3c]. The patient’s symptoms improved significantly following the procedure, with a strong pulse observed in both the dorsalis pedis artery and posterior tibial artery.

Fig. 3

Operation was successful. (a) Popliteal artery reconstruction using autologous vein. (b, c) Pathology reveals CAD, with the red arrow pointing to the cystic cavity and the black arrow indicating the cyst wall. (d) Three-month follow-up CTA shows patent blood flow in the popliteal artery

Postoperative management included anticoagulant, antiplatelet, and vasodilatory therapies to prevent thrombosis, which included Dabigatran Etexilate Capsules (110 mg/day), Aspirin (100 mg/day), and Beraprost Sodium Tablets (1 tablet, three times daily). A three-month follow-up, including a CTA scan, showed “uninterrupted blood flow post-reconstruction of the left PA, without significant narrowing,” confirming the success of the procedure and restoration of arterial function. [Fig. 3d].

Literature review and discussion

The popliteal artery (PA), as a direct continuation of the femoral artery, plays a crucial physiological role in maintaining the blood supply to the distal lower extremities, thus ensuring the normal function of the lower limbs. While common causes of PA stenosis or occlusion include atherosclerosis, popliteal aneurysms, and arterial embolism, the significance of Cystic Adventitial Disease (CAD)-a rare vascular disease-should not be underestimated. The case described above demonstrates classic features of arterial CAD, which warranting reporting.

CAD primarily affects the vascular adventitia, resulting in the secretion of mucinous material and the formation of cystic expansions. These expansions compromise both structure and function of affected blood vessels, leading to symptoms and signs that correspond to the specific site of involvement. This condition is notably more prevalent among younger to middle-aged individuals, with a marked male predominance (approximately 15:1) [5], possibly linked to the antiproliferative and vasodilatory effects of estrogen [6]. Furthermore, CAD shows a strong preference for arterial involvement over venous, with arterial cases being approximately 15 times more common than venous cases [7]. Typically, CAD patients do not exhibit atherosclerosis or other peripheral vascular disease risk factors, such as history of smoking, surgery or trauma. Historically, the first CAD case was documented in 1947 by Atkins and Key in the external iliac artery [8]. Since then, numerous case reports have been published. Literature indicates that the popliteal artery is the most commonly affected, accounting for 80–90% of cases, followed by the femoral artery [7]. When the cyst exerts pressure on the PA, leading to stenosis or even occlusion, patients may experience a variety of symptoms associated with lower limb ischemia. The most characteristic symptom is sudden intermittent claudication, especially noticeable after intense physical activity, which may rapidly worsen. Furthermore, around 30% of patients may experience rest pain or other acute ischemic symptoms due to complete arterial occlusion [9], correlating with the volume of the cyst and the degree of artery compression. The popliteal and pedal pulse may be palpable in a neutral position but diminish or disappear during knee flexion. This classic clinical finding is known as Ichikawa sign [9,10,11]. Given the increasing symptom burden of CAD [11], early diagnosis and timely intervention are crucial to prevent irreversible arterial occlusion and associated complications.

The exact etiology of CAD remains unclear, although four primary hypotheses have been proposed: developmental, ganglionic, microtraumatic, and degenerative. Among these, the developmental and the ganglionic theory are more widely recognized. The microtaumatic theory suggests that repeated trauma can lead to destruction and cystic degeneration of adventitial, but only 4% of CAD patients report a clear history of trauma [12]. The degenerative theory posits that the adventitial degeneration may be linked to systemic processes. The developmental hypothesis assumes that remnants of undifferentiated mesenchymal cells are improperly expressed in the adventitia during vessel development, resulting in the secretion of mucoid substances [2, 13]. The ganglionic theory suggests that adventitial cysts may be directly connected to the adjacent joint cavity, having migrated along vascular branches from a joint capsule or tendon sheath [13, 14]. The gelatinous substance within the cysts closely resembles that found in the joint capsule, supporting this theory [15]. The evidence that 17% of CAD cases have a direct joint connection further supports this point [12].

In addition to evaluating typical clinical symptoms, the clinical diagnosis of CAD requires several imaging techniques, including vascular Doppler ultrasound, CTA, and MRA. Doppler ultrasonography is commonly used for routine screening of vascular diseases due to its simplicity, cost-effectiveness, non-invasive nature and lack of radiation exposure. Gray-scale ultrasound imaging typically reveals a hypoechoic or anechoic mass surrounding the vessels, while Color Doppler ultrasound can identify vascular stenosis characterized by turbulence or occlusion. However, the ultrasound sensitivity in the aortoiliac region is limited [2]. In contrast, CTA and MRA offer more accurate depictions of the anatomical relationships among cysts, vessels and muscle tissue, as well as a better evaluation of cysts size and arterial stenosis. These imaging modalities are vital for disease diagnosis and subsequent surgical planning. On CT images, cysts often appear as hypoattenuating masses within the arterial wall, compressing the artery and causes stenosis. After contrast agent injection, the cyst wall typically enhances, while the internal mucus remains unaffected [11]. On MR images, the cysts show hyperintensity on T2-weighted images (T2WI), with signal intensity on T1-weighted images (T1WI) varying depending on the type of mucoid material present within the cyst [11, 16]. Notably, angiography may reveal normal or non-specific complete occlusion in about 30% of cases [17], increasing the risk of missed or incorrect diagnoses. Therefore, angiography is considered diagnostic primarily when typical scimitar or hourglass signs are observed.

At our center, we emphasize the importance of the differential diagnosis between dissection, thrombus, and CAD. In this case, some radiologists initially suspected CAD might be a dissection or thrombus based on the CT findings, due to their limited experience with CAD. The symptoms of these conditions often overlap significantly, making imaging crucial for accurate differentiation. Imaging findings of dissection may include vascular wall discontinuity and the presence of a double lumen. Thrombus imaging may show variable signals based on its composition, and its shape may differ. CAD typically appears hypointense on T1WI and hyperintense on T2WI, often displaying a regular shape and well-defined cystic structures.

CAD is frequently confused with other peripheral arterial diseases, highlighting the need for precise differential diagnosis. In the discussed case, the patient is young and presents with signs of lower limb artery stenosis, raising the possibility of Popliteal Artery Entrapment Syndrome (PAES) or Thromboangiitis Obliterans (TAO). Patients with PAES are typically young individuals with muscle hypertrophy but normal anatomy [18]. PAES develops after running or strenuous exercise, and leads to progressive intermittent claudication. Functional ultrasound enables PAES diagnosis [18]. CTA and MRI can clearly visualize the relationship between the popliteal vessels and surrounding muscle tissue, aiding in a definitive diagnosis. TAO typically presents with symptoms such as intermittent claudication, rest pain, ulcers, or gangrene, along with weakened arterial pulses and imaging findings of multiple stenoses and occlusions in small to medium-sized arteries, helping distinguishing it from CAD [19, 20]. In contrast, Arteriosclerosis obliterans (ASO) predominantly affects the elderly, often with a long history of smoking, diabetes, hyperlipidemia, hypertension, and relevant family medical history. Physical examination findings are similar to those seen in TAO, and imaging can reveal diffusely distributed atherosclerotic plaques and vascular stenosis, assisting in diagnosis. Moreover, popliteal artery aneurysm (PAA) can lead to thrombotic complications and lower limb ischemia, but imaging typically shows local or saccular dilatation of the vascular lumen, which generally does not impede blood flow [18].

The primary goal of CAD treatment is to restore normal distal flow promptly. Timely intervention before arterial occlusion is associated with a more favorable prognosis [11]. Common treatment modalities include nonsurgical management, needle aspiration of cyst, angioplasty or surgical treatment. Among these, open surgery is considered the preferred approach in symptomatic patients. This preference persists because endovascular treatment continues to be associated with suboptimal clinical outcomes, including high recurrence rates observed particularly in the early postoperative period (between 24 h and 8 weeks) [4, 21]. The principle of cyst aspiration is to extract the mucus in the cyst under ultrasound or CT guidance to reduce the compression on blood vessels. However, due to the high viscosity of the cyst contents and frequent recurrence of cyst formation [16, 17, 22], aspiration is generally not considered a definitive treatment. It is usually reserved for patients who decline surgical option. Moreover, balloon angioplasty has proven insufficient, often failing to fully relieve vascular compression caused by cysts [16, 18].

Surgical intervention involves cyst resection and vascular reconstruction. The primary goal is to completely excise the cyst wall while preserving the medial and intimal layers of the artery to maintain its continuity and integrity [9]. This approach involves removing both the diseased vessels and cyst tissues, followed by reconstruction using autologous veins or synthetic materials. Autologous vein grafts generally yield better outcomes compared to synthetic materials [23]. The success rate of autologous vein graft reconstruction is approximately 95% [3, 24]. Since graft thrombosis is the leading cause of failure [3, 24], long-term anticoagulant therapy is crucial for patients undergoing this procedure.

Conclusion

We have summarized several reported cases of cystic adventitial diseases (Table 1). The case presented underscores the critical importance of accurate imaging for differential diagnosis as it is essential to avoid unnecessary or inappropriate interventions. When surgical excision is indicated and performed in a timely manner, it can lead to favorable outcomes. This highlights that, although diagnosing CAD can be challenging, adopting a passive approach can lead to serious complications, such as limb ischemia. Nevertheless, with prompt and appropriate management, a positive outcome remains achievable.

Table 1 Reported cases of CAD