Pathology of the carotid space

The carotid body is the largest collection of paraganglia in the head and neck and is found on the medial aspect of the carotid bifurcation bilaterally. Carotid body tumors are usually found in the fourth or fifth decade of life and are the most common head and neck paraganglioma. These tumors tend to grow slowly and painlessly and present as a lateral neck mass at the level of the carotid bifurcation. Given the lesion’s close proximity to cranial nerves 10–12, patients may also present with dysphagia, odynophagia, hoarseness of voice, or other cranial nerve deficits [11]. Due to their location, and when large enough, they tend to splay the internal and external carotid arteries apart from each other [4] (Fig. 2).

Paragangliomas at the jugular foramen may arise from the tympanic branch of the glossopharyngeal nerve (Jacobson’s nerve), or the auricular branch of the vagus nerve (Arnold’s nerve), and are referred to as glomus jugulare (Fig. 3). These tumors have a 3:1 predilection for females over males and typically present in the fifth or sixth decades of life. Patients clinically present with pulsatile tinnitus, hearing loss or vertigo, and other symptoms related to the cranial nerves within the jugular foramen (glossopharyngeal, vagus, and accessory) [4]. Demineralization of the bony cortex surrounding the jugular foramen causes an enlargement of the foramen due to permeative, “moth-eaten” appearance of erosion on CT [6]. These tumors can extend into the tympanic cavity (glomus jugulotympanicum) and may also involve the internal carotid artery or internal jugular vein.

The vagus nerve is the longest cranial nerve, and although paragangliomas may arise anywhere along its tract, they are most commonly found at the ganglion nodosum (inferior ganglion) at the level of the C1 lateral mass [12]. These tumors have a heavy predilection for females in the fifth or sixth decades of life, however they are less common than the carotid body tumor or glomus jugulare [13]. Clinically, these present as asymptomatic masses posterior to the angle of the mandible; however, symptoms of vagal nerve dysfunction such as dysphagia, hoarseness, and vocal cord paralysis may develop late in the course. Although usually confined to the carotid space, these tumors can grow superiorly into the posterior fossa, entering via the jugular foramen, or inferiorly to the carotid bifurcation. As mentioned previously, the vagus nerve lies within the posterior aspect of the carotid space, and therefore, a large glomus vagale will anteriorly displace the carotid artery (Figs. 4 and 5).

Neurofibromas are most frequently solitary lesions in young patients between 20 and 30 years of age. Ten percent of these neurofibromas are associated with neurofibromatosis and can be categorized as localized, plexiform, or diffuse. Diffuse neurofibromas are a subcutaneous lesion that do not present within the carotid space. Localized neurofibroma appear similar to solitary lesions but tend to be larger, multiple, and deeper in location. Due to a neurofibroma’s intimate association with the affected nerve, these tumors grow in a longitudinal and fusiform manner (Fig. 6). Tapered ends of the tumor, with an appearance of the parent nerve “entering and exiting,” the tumor can also be seen. A characteristic target sign or fish-eye appearance of the lesion referring to a central hypointense region has also been described [15]. Plexiform neurofibromas are pathognomic for neurofibromatosis type I (Fig. 7); these tumors are extensive and grow along a nerve and plexus and carry an increased risk of malignant transformation.

Schwannomas represent up to 5% of benign soft tissue neoplasms and typically present in patients 20–40 years of age. Most schwannomas are solitary; however, they are associated with neurofibromatosis, in which case they can be multifocal and plexiform as well. Schwannomas are also typically asymptomatic until late in the disease course, where neurologic symptoms associated with compression of the associated nerve may present. As mentioned previously, enhancement pattern of schwannoma can be similar to neurofibroma, and therefore, a salient differentiating imaging finding between the two is the eccentric position relative to the parent nerve in schwannoma (Figs. 6 and 8). Schwannomas are also more likely to be heterogeneous in appearance with areas of degeneration and cystic cavitation when large [15]. “Ancient” schwannoma, presenting with very advanced degeneration, calcification, and hyalinization, have also been described in the literature [14]. It is important to remember that in addition to schwannomas involving the cranial nerves, they may also be found within the sympathetic chain. These lesions will be located anteriorly or medially within the carotid space, displacing the carotid vessels laterally (Fig. 9).

Arterial dissection occurs when the innermost and least elastic layer of an arterial wall, the tunica intima, tears and allows the blood to enter, and form hematoma, in the tunica media (Figs. 11 and 12). An intimal tear can occur spontaneously, or may be related to trauma or iatrogenic causes. Regardless of the cause, it usually results in narrowing of the true vessel lumen. Carotid arterial dissection accounts for roughly 20% of causes of stroke in patients under 45 years of age. Typical symptoms include pain, ipsilateral Horner syndrome, and sequelae of brain ischemia [18]. It is important to remember the sympathetic fibers that carry innervation for a facial sweating run along the external carotid artery; thus, a dissection that involves only the internal carotid artery will only result in ptosis and meiosis, or a partial Horner’s syndrome [19]. A conventional angiogram is considered the gold standard for diagnosis but is invasive and only assesses luminal diameter and not arterial wall thickness or configuration. Color duplex ultrasound detects mural hematoma/thrombus as a thickened hypoechoic wall and can demonstrate the effects of luminal compromise dynamically. CT angiography offers a higher spatial resolution for evaluation of the intimal flap and vessel expansion than MRI, but is less sensitive for intracranial sequelae of ischemia and can be limited by artifact when in close proximity to the bone. MRI with T1 fat-suppressed sequences are highly sensitive for intramural blood, and post-contrast imaging can reliably characterize luminal narrowing [20].

Pseudoaneurysm occurs when there is an injury of the tunica intima and media, resulting in a hematoma that is contained only by the thin outer adventitial layer of the vessel (Fig. 13). A pseudoaneurysm can form as a result of trauma (Fig. 14), dissection, vasculitis, infection, or be iatrogenic (Fig. 15). This entity can often be asymptomatic, and discovered incidentally; however, it carries a significant risk of rupture with high mortality rates. On ultrasound, a hypoechoic cystic structure can be demonstrated adjacent to the true vessel. Color duplex imaging can demonstrate a “to and fro” color flow and bidirectional Doppler waveform in the pseudoaneurysm neck. Within the sac itself, swirling blood can create the so-called “yin-yang” sign. CT imaging can demonstrate irregularity of a vessel wall and irregular outpouching. Hematoma with contrast extravasation seen on angiographic studies is compatible with rupture and active bleeding. When a pseudoaneurysm is large enough, it is important to note that the entire sac may not enhance, as the pseudoaneurysm can partially thrombose. MRI with T1-weighted fat-suppressed sequences allows for evaluation of intraluminal thrombus and of pseudoaneurysm sac size. Digital subtraction angiography remains the gold standard for evaluation of pseudoaneurysm and simultaneously offers a therapeutic potential [21].

Carotid thrombus can occur as a result of direct trauma or in relation to severe carotid artery stenosis with atherosclerotic plaque. Patients with internal carotid artery thrombosis carry a 5 times higher rate of recurrent stroke than patients without thrombosis. Duplex sonography is capable of demonstrating intraluminal thrombus; however, CT angiography is more sensitive [22]. Magnetic resonance (MR) angiography can also demonstrate intraluminal filling defects, and concurrent MRI is important when looking for downstream sequelae of thrombus, such as infarct. In patients with occlusive thrombus, inflammatory changes about the carotid arteries including surrounding tissue edema, free fluid, and vessel expansion may also be visualized.

Fibromuscular dysplasia of the carotid vessels is an uncommon and often asymptomatic pathology and therefore often an incidental finding. However, symptomatic patients can present with cerebral infarction, transient ischemia, or subarachnoid hemorrhage. Although fibromuscular dysplasia can occur in any of the three arterial wall layers, the involvement of the tunica media is most common, representing over 90% of cases. The arterial wall becomes dysplastic due to fibrous thickening and destruction of the elastic lamina, often leading to multifocal stenosis and areas of luminal expansion (Fig. 16). It is important to note that the mural dilation is often greater than the normal vessel diameter, thus helping distinguish fibromuscular dysplasia from atherosclerotic disease. This yields the characteristic “string-of-beads” appearance of the dysplastic vessel, a sign that is seen in over 80–90% of cases. In severe cases, fibrous dysplasia can be complicated by arterial dissection, saccular aneurysm formation, or arteriovenous fistula formation. CT angiography and MRI angiography are both utilized regularly; however, CTA is preferred due to being readily available, fast scan time, higher spatial resolution, and decreased potential for artifact [23].

Also known as Fay syndrome, carotidynia is a rare entity characterized by unilateral pain in the region of the carotid bifurcation. Pain tends to be pulsating and continuous in sensation, but is a self-limiting process, and often spontaneously resolves in 1–2 weeks. Laboratory workup is negative for immunological markers, and patients are often treated with NSAIDs. Although controversial, the etiology of carotidynia is stipulated to be related to an idiopathic inflammatory process of the carotid bifurcation and, therefore, has recently been termed transient perivascular inflammation of the carotid artery syndrome (TIPIC). Ultrasound, CT, and MRI of the carotid arteries demonstrate fusiform transmural thickening without luminal compromise. Doppler ultrasound demonstrates normal flow velocities without evidence of turbulent flow, as opposed to other pathologies that may cause narrowing of the lumen (such as severe atherosclerotic disease). CT and MRI fail to demonstrate signs of vascular inflammation outside of the carotid vessels. MRI demonstrates hypointensity of the vessel wall on fat-saturated T1-weighted imaging, precluding the possibility of a mural hematoma. Post-contrast MR images demonstrate intense enhancement of the carotid bifurcation, supporting the proposed inflammatory etiology (Fig. 17). Follow-up imaging after resolution of symptoms usually demonstrates a normal appearance of the carotid bifurcation [24].

The paired internal jugular veins drain the majority of blood from the cranium, serving as cervical extensions of the dural venous sinuses. Thrombosis of the internal jugular veins can occur for many reasons, including extrinsic compression, chronic indwelling catheter, recent surgery, head and neck infections (Lemierre syndrome), malignancy, hypercoagulability syndromes, an extension of dural sinus thrombosis, and spontaneous thrombosis. Venous duplex ultrasonography is the diagnostic test of choice and demonstrates a dilated and incompressible vein; the intraluminal thrombus is often visualized as low-level echogenicity (Fig. 18). There is a limited evaluation of the vessels behind the clavicle and sternum, but Doppler ultrasound can demonstrate abnormal, monophasic waveforms due to a more proximal occlusive thrombus, and no significant flow change with Valsalva maneuver. CT findings of IJ thrombus include vessel expansion, surrounding inflammatory change and fluid/edema within the retropharyngeal space (Fig. 18) [25]. Contrast-enhanced CT can also help delineate the intraluminal thrombus, and enhancement of the vessel wall can be seen due to contrast uptake by the vasa vasorum. MRI is not used routinely for primary diagnosis of vein thrombosis due to expense and inconvenience in the acute setting; however, similar findings of vessel expansion, surrounding inflammatory change and T1 hyperintense intraluminal filling defect can be visualized.

Hodgkin lymphoma (HL) and non-Hodgkin lymphoma (NHL) commonly involve the head and neck. HL and NHL cannot be reliably distinguished via imaging, however should be considered in patients with B symptoms (fever, unintentional weight loss, or night sweats). Lymphoma typically presents as painless or growing lymphadenopathy [27]. On CT imaging, lymphomatous involvement can have varying degrees of enhancement, and involvement can be extensive. A conglomeration of lymph nodes may insinuate within the deep spaces of the neck, encasing important structures. It is important to remember that lymphoma does not typically cause luminal narrowing of arterial vasculature, a feature which may help distinguish the disease from others (Fig. 20). Although CT is the gold standard for the initial evaluation and staging of lymphoma, it only provides structural information. Positron emission tomography (PET) has an increasing role in lymphoma evaluation as it adds functional information. PET is the key to assessing disease response to therapy, as well as finding residual or recurrent disease after treatment.

Metastatic disease is also a common cause of adenopathy in the deep cervical chain. Although squamous cell carcinoma is the most common (representing 90% of head and neck cancers) [28], many other malignancies including EBV-related nasopharyngeal carcinoma, thyroid carcinoma, breast carcinoma, melanoma, and even lung carcinoma are also seen to metastasize to the neck lymph nodes [29]. Squamous cell carcinoma and papillary thyroid carcinoma are well known to demonstrate cystic nodal metastasis (Fig. 21) [30].

It is important to remember that primary malignancy of the head and neck has the potential to directly invade the carotid space, which ultimately has staging and treatment implications. For example, in the setting of oropharyngeal non-HPV associated squamous cell carcinoma, encasement of the carotid artery upstages the lesion to T4b disease using the American Joint Committee on Cancer (AJCC) 8th edition criteria (Fig. 22) [31].

Incomplete obliteration of a branchial tract during development can result in a branchial cleft cyst (BCC). The second branchial cleft yields 95% of all branchial lesions. It is important not to confuse a developmental anomaly such as a BCC for a cystic lymph node, as the former is a completely benign entity. These lesions are usually well-defined, thin-walled cystic structures. A second BCC typically occurs lateral to the carotid space, along with the anterior margin of the sternocleidomastoid muscle, and can extend deep to the muscle (Fig. 23). Occasionally, these cysts may demonstrate a “beaked” appearance, when they invaginate between the internal and external carotid arteries. They can occasionally be complex and demonstrate low-level echoes on ultrasound, as well as internal septa. These lesions do not typically appear hyperemic on ultrasound or enhance on CT and MR; however, if they are infected or inflamed, thickening of the wall with intense enhancement and surrounding fat stranding can also be seen [32].