Carotid body tumors typically present as a slowly enlarging asymptomatic deep neck mass at the level of the carotid bifurcation. In a small minority of patients, pain is present around the tumor. Because of the association with the carotid artery they are laterally mobile, but rostrocaudally fixed on examination. As the tumor enlarges, a bruit may be auscultated and in addition to a neck mass, a parapharyngeal extension results in the lateral displacement of the soft palate medially and anteriorly. Cranial nerve paralysis symptoms are unusual and present in very large tumors with superior extension toward the jugular foramen. Shamblin classification is commonly used to stage carotid body tumors, and though this is based on intraoperative findings, it can be applied to radiologic findings prior to treatment (Table 127.2, Fig. 127.5).

Jugular and tympanic paragangliomas occur predominantly in the fifth and sixth decades of life with an overwhelming female predominance. They are slow growing,
and their pattern of growth follows the pathways of least resistance in the temporal bone and surrounding skull base structures. In their later stages, both types produce similar symptoms including cranial nerve deficits, while in the early stages tympanic and jugular paragangliomas differ in presentation.

Tympanic paragangliomas present early with pulsatile tinnitus and conductive hearing loss. On otomicroscopic examination, a red-blue middle ear mass that blanches with positive pressure on pneumatic otoscopy is appreciated (Brown sign). With subsequent growth, there is ossicular erosion and filling of the middle ear cleft. Extension through the tympanic membrane will produce an ear canal polypoid mass that may spontaneously cause bloody otorrhea. Extension to the mastoid can occur through a number of pathways. Involvement of the facial nerve, usually in the mastoid, can produce facial paralysis as a presenting symptom. Anterior growth toward the pericarotid air cells can involve the petrous carotid artery and occupy the eustachian tube. Medial growth into the infralabyrinthine air cells can reach the petrous apex and petroclival area as well as cavernous sinus. Intracranial extension is possible through extension through the jugular foramen and/or petrous apex. More infrequently, there is involvement of the otic capsule and the inner ear with attendant sensorineural hearing loss and vertigo at presentation.

Jugular paragangliomas, due to their origin location within the jugular bulb, have the capacity for early and extensive skull base invasion with involvement of cranial nerves 9 through 12. Growth through Jacobson nerve canal and the hypotympanic air cells leads to involvement of the middle ear and mastoid bone leading to conductive hearing loss, tinnitus, and facial paralysis. Intracranial involvement through the jugular foramen is frequent. Erosion of the jugulocarotid spine leads to involvement of the vertical petrous carotid artery, and further anterior extension leads to involvement of the horizontal portion of the petrous carotid artery. More medial extension to the infralabyrinthine air cells lead to involvement of the petrous apex. Further medial extension along this pathway leads to involvement of the clivus and cavernous sinus. Occasionally, jugular paragangliomas will escape the confines of the temporal bone and involve the infratemporal fossa and parapharyngeal space. Lower cranial nerve involvement is frequent and ranges from 38% to 58% (28,29). Multiple cranial nerves are frequently involved with Vernet syndrome (paralysis of cranial nerves 9, 10, and 11) or Collet-Sicard syndrome (paralysis of cranial nerves 9, 10, 11, and 12) in at least 10% of those with jugular paragangliomas (Fig. 127.6). The attendant symptomatology is hoarseness, swallowing difficulty, hemipalatal dysfunction with nasal air escape, shoulder motion restriction, and dysarthria due to tongue hemiparalysis. Two surgical classification systems are in wide use today and can be used preoperatively based on radiographic findings: the Fisch classification system, which makes no distinction between tympanic and jugular paragangliomas and is predicated
on detailed patterns of progressive disease extension, and the Glasscock-Jackson classification system, which treats tympanic and jugular paragangliomas differently (15,28) (Tables 127.3 and 127.4).

Vagal paragangliomas account for 5% of all head and neck paragangliomas and originate in the vagus nerve where the paraganglia are diffusely distributed in the superior, middle, and inferior vagal ganglia. There is a female preponderance of 3:1. Tumors originating superiorly will often present with a dumbbell appearance with an intracranial component in the posterior cranial fossa. Tumors originating inferiorly will extend into the poststyloid compartment of the parapharyngeal space. Vagal paragangliomas are frequently associated with multiple cranial neuropathies at presentation in up to 50% of patients. The vagus nerve is affected most commonly, followed by the hypoglossal and spinal accessory (30) (Fig. 127.7).

Computed tomography (CT) with contrast is an excellent imaging choice for the diagnosis and delineation of paragangliomas. Since these tumors are highly vascular, early and intense contrast enhancement is seen. The relation of the tumor to the external and internal carotid arteries, as well as the jugular vein, makes this modality essentially diagnostic (31). The delineation of the pattern of invasion of the temporal bone and skull base is indispensable in treatment and especially preoperative planning for paragangliomas. Carotid body tumors display the characteristic splaying of the internal and external carotid arteries by a well-circumscribed mass occupying the carotid bifurcation. Carotid body tumors displace the internal carotid artery posterolaterally. Vagal paraganliomas typically will displace the internal carotid artery anteriorly and occupy the high parapharyngeal space, with or without involvement of the skull base. Jugulotympanic paragangliomas can be distinguished in their early phases, especially when a tympanic paraganglioma is confined to the tympanic
cavity. Characteristic patterns of bone destruction occur with jugulotympanic paragangliomas. These include erosion of the jugulotympanic spine, enlargement of the jugular foramen with bone destruction, and involvement of the middle ear and mastoid (31,32). Multiplanar reconstruction of high-resolution CT scans in the axial, sagittal, and coronal planes is of great assistance in the planning of operative management of these tumors. Middle ear and/or eustachian tube involvement will create postobstructive fluid accumulation in the aerated spaces of the temporal bone, including the mastoid (Fig. 127.8).

Magnetic resonance imaging (MRI) is a complementary and equally important imaging modality in the evaluation and treatment of head and neck paragangliomas. MRI with gadolinium contrast serves three purposes: delineation of the tumor in question, surveillance and detection of concurrent paragangliomas of the head and neck, and confirmation of the diagnosis of paraganglioma. The classic, “salt and pepper” appearance of paragangliomas on T2-weighted images is due to the high-flow vascular voids that are essentially pathognomonic. Paragangliomas show intense signal enhancement with gadolinium contrast (33). Fat-suppressed sequences are exceptionally useful in delineating the extent of the tumor. Patterns of carotid artery displacement can be accurately determined distinguishing carotid body tumors from vagal paragangliomas (33). More importantly, in tumors with intracranial extension, intradural versus extradural involvement can be appreciated, and the relationship of the tumor to important intracranial structures can be delineated. Specialized techniques such as MR angiography and contrast time-of-flight three-dimensional angiography increase the sensitivity of the diagnosis of concurrent tumors but do not supplant selective angiography in the preoperative planning setting (34,35) (Figs. 127.9 and 127.10).

With the evolution of detailed MRI and CT techniques, angiography plays a much more limited role in the
diagnosis of head and neck paragangliomas but is of paramount importance in preoperative planning for resection of these tumors. Angiography is essential in providing a detailed map of tumor blood supply and venous drainage, demonstrating the tumor flow dynamics and detailing the general vascular anatomy of the head and neck and intracranial space. Four-vessel cerebral angiography allows for qualitative and quantitative blood flow studies of the cerebral circulation. Preoperative preparation through superselective embolization of the feeding arterial supply to the tumor decreases the risk of intraoperative blood loss.

Arterial supply of carotid body tumors takes place directly from the feeding vessels to the carotid body that hypertrophies when a tumor is present (15,28,36). Arterial supply of jugulotympanic tumors is well defined when these tumors are early in their development and involve the ascending pharyngeal artery. As these tumors grow, they recruit additional blood supply that comes from the internal carotid circulation via the caroticotympanic arteries. With invasion of the posterior fossa and medial extension of the tumor toward the cavernous sinus, additional vascular recruitment is possible through the posterior circulation via the vertebral arteries through the clival anastomoses as well as the cavernous sinus microcirculation. This is significant in the preoperative angiographic and embolization management of these tumors. Assessing tolerance to interruption of the internal carotid artery is of paramount importance for extensive paragangliomas that involve the internal carotid artery that can be injured during surgery
or where a planned internal carotid resection is contemplated. An angiographic balloon occlusion test involves the threading of a transfemoral catheter to the internal carotid and involves temporarily occluding the internal carotid artery, usually at the carotid siphon within the cavernous sinus to determine whether there will be neurologic deficit (9,11). Several modalities for neurologic monitoring during balloon occlusion testing of the internal carotid artery are available. In order of decreasing sensitivity, they are clinical neurologic examination, electroencephalography (EEG), and quantitative blood flow examination through xenon CT concurrent examination. Xenon CT angiography is a precise quantitative study with the best sensitivity but is cumbersome and rarely available (37,38) (Fig. 127.11).

Radionuclide imaging of paragangliomas targets the biochemical pathways of catecholamine synthesis, storage, and secretion by chromaffin tumor cells. A variety of different imaging techniques exist:

¹²³I-metaiodobenzylguanidine (MIBG), ¹⁸F-3,4 dihydroxyphenylalanine-positron emission tomography (¹⁸F-DOPA-PET), ¹⁸F-fluorodopamine (¹⁸F-FDA-PET), ¹⁸F-fluoro-2-deoxyglucose (¹⁸F-FDG-PET) and Indium octreotide scanning (¹¹¹In-octreoscan) (39,40).

Different functional imaging agents target paraganglioma tumor cells through different mechanisms. ¹²³I- and ¹³¹I-labeled MIBG and ¹⁸F-FDA are actively transported into neurosecretory granules of catecholamine-producing cells via the vesicular monoamine transporters after uptake into cells by the norepinephrine transporter. In contrast, ¹⁸F-DOPA enters the cell via the amino acid transporter based on the capability of PGL and other neuroendocrine tumors to take up, decarboxylate, and store amino acids and their biogenic amines. Instead of targeting catecholamine pathways, ¹⁸F-FDG enters the cell via the glucose transporter, and its accumulation is an index of increased glucose metabolism whereas ¹¹¹In-octreoscan images indicate somatostatin type 2 receptors that are expressed in paragangliomas (9,10).

¹¹¹In-octreoscan specificity and sensitivity is approximately 90% in head and neck paragangliomas, which makes it a very effective way to screen for secondary tumors and postoperatively screen for recurrent disease when structural studies like CT and MRI may be compromised postoperatively. ¹²³I-MIBG shows similar sensitivities and specificities. Malignant and metastatic paragangliomas are best imaged with ¹⁸F-FDG-PET, which shows sensitivities of 74% to 88% (9,10).

It is increasingly understood that there is a link between genotype-specific tumor biology and imaging. For example, ¹⁸F-FDG-PET has an excellent sensitivity for paragangliomas due to SDHB-associated mutation. The SDHB gene encodes for subunit B of the mitochondrial SDH complex II that catalyzes the oxidation of succinate to fumarate in the Krebs cycle and feeds electrons to the respiratory chain, which ultimately leads to the generation of ATP (oxidative phosphorylation). SDHB mutations can lead to complete loss of SDH enzymatic activity in malignant paragangliomas, with up-regulation of hypoxic-angiogenetic responsive genes (23). Impairment of mitochondrial function due to loss of SDHB function may cause tumor cells to shift from oxidative phosphorylation to aerobic glycolysis, a phenomenon known as the Warburg effect. Higher glucose requirements for anaerobic metabolism explain the increased ¹⁸F-FDG uptake by malignant SDHB-related paragangliomas (40).