13 Evaluation and Treatment of Vascular Neoplasms
13.1 Introduction
Vascular tumors of the head and neck consist of a diverse group of both benign and malignant neoplasms, many of which may arise in close association with blood vessels or nerves. Head and neck vascular tumors are exceedingly rare, with each type accounting for no more than 0.5% of head and neck neoplasms. Although they vary greatly in biologic behavior, with exceptions of a few, most of these tumors are similar in their indolent growth and tendency for local recurrence.
Vascular neoplasms of the head and neck present with a wide spectrum of signs and symptoms. Patients often complain of nonspecific symptoms, which often have been present for a prolonged period. Diagnosis, therefore, requires a high index of suspicion and is usually made after these tumors are large enough to be visually apparent or cause symptoms. This chapter discusses a variety of benign and malignant vascular tumors, with an emphasis on their evaluation and treatment.
13.2 Paraganglioma
13.2.1 Natural History and Physical Findings
Paragangliomas are vascular neoplasms that arise from the extra-adrenal paraganglia derived from the neural crest and most commonly occur in the head and neck region. These tumors are closely associated with either blood vessels (carotid artery, jugular bulb) or nerves (vagus, tympanic plexus). They are well-delineated tumors with a firm consistency and consist of cell nests (“zellballen”) of “chief” cells surrounded by sustentacular cells and separated by a highly vascular, fibrous stroma. Paragangliomas are usually slow-growing tumors with an average growth rate of 1 mm per year and a median doubling time of 4.2 years. Their growth pattern may be described as biphasic, as very small and very large paragangliomas have a lower growth rate compared with that of intermediate-sized tumors. 1
Although all paragangliomas have the potential of releasing vasoactive substances such as catecholamines and dopamine, 2 , 3 only 1 to 3% of paragangliomas produce the associated clinical findings. 2 , 4 Secreting paragangliomas release norepinephrine, and a fourfold to fivefold elevation of serum norepinephrine is necessary to produce symptoms 5 associated with increased catecholamine levels, such as excessive sweating, hypertension, tachycardia, nervousness, and weight loss. 2 Urinary laboratory screening tests, including 24-hour urinary metanephrine (normal < 1.3 mg) and vanillylmandelic acid levels (normal range, 1.8 to 7.0 mg), are frequently elevated 10 to 15 times that of normal in patients with actively secreting tumors. 2 Serum catecholamine levels, including serum norepinephrine and epinephrine, are also of value in evaluating the patient.
Because head and neck paragangliomas usually do not have the ability to secrete epinephrine, an elevated serum epinephrine level is suggestive of a concurrent pheochromocytoma. 2 Several reports have described an association between pheochromocytoma and both familial and nonfamilial paragangliomas. 6 , 7 , 8 Paragangliomas may occur in patients with familial multiple endocrine neoplasia (MEN), both type IIA (pheochromocytoma, medullary thyroid carcinoma, and parathyroid hyperplasia), and type IIB (also includes mucosal neuromas). 9 , 10
13.2.2 Multicentric and Hereditary Paragangliomas
A familial history of paragangliomas may be present, and there is a significant incidence of multicentric tumors, both in familial and sporadic cases. Familial or hereditary paragangliomas have been previously reported to account for 5 to 10% 11 , 12 of all cases of head and neck paragangliomas, but it appears that these estimates were low as a result of the complex mode of inheritance and variable phenotypic expression. 13 It may in fact account for up to 25 to 50% of cases. 14 , 15 Most (90%) cases of hereditary paragangliomas involve the carotid body. 16 If a family history is present, there is a 78 to 87% possibility of multiple paragangliomas. 12 , 17 Patients with hereditary paragangliomas develop their tumors at a younger age than do those with sporadic cases. Bilateral carotid body paragangliomas occur more frequently with familial cases (31.8%) than nonfamilial cases (4.4%). 11
Multiple paragangliomas may be present in up to 22% of patients diagnosed with paragangliomas. 11 , 17 , 18 Approximately 10% of sporadic paragangliomas are multicentric. 19 Because patients with inherited paragangliomas have a high rate of multiple tumors, all patients with this clinical finding should undergo genetic testing. The most common multicentric combination is two carotid body tumors ( Fig. 13.1 ), 11 and this occurs in approximately 20% of patients with carotid body tumors. 19 The potential to develop multicentric tumors has important clinical implications. The presence of bilateral carotid paragangliomas poses a difficult challenge in management because excision of these bilateral tumors results in loss of baroreceptive function and subsequent refractory hypertension. Multiple tumors, including vagal or jugular paragangliomas, present problems concerning significant morbidity of multiple lower cranial nerve dysfunction, perhaps bilaterally, resulting from direct tumor involvement or surgical resection. Because multicentric tumors may be metachronous, routine follow-up magnetic resonance imaging (MRI), 20 indium pentetreotide (OctreoScan), or 18F-dihydrophenylalamine (18F-DOPA) positron emission tomography (PET) imaging is indicated.
Genetics
The molecular genetic basis of hereditary paragangliomas has been identified in all four hereditary paraganglioma syndromes (PGL1–4), most recently in 2009. 21 Germline mutations in the succinate dehydrogenase (SDH) usbunit D gene (SDHD) were first discovered to be the underlying cause of PGL1 in familial head and neck paragangliomas in 2000. 22 It was thereafter recognized that the other subunits of this mitochondrial enzyme, SDHC and SDHB, were associated with PGL3 and PGL4, respectively. 23 , 24 In 2009, the gene responsible for PGL2 was identified. Mutations in SDHAF2, or succinate dehydrogenase complex assembly factor 2, formerly known as SDH5, were discovered to be the cause of this syndrome. 25 , 26 SDH is an enzyme complex composed by subunits or cofactors that function as the mitochondrial complex that plays an important role in the mitochondrial respiratory chain as well as the tricarboxylic acid cycle. 22 , 23 , 24 Important characteristics of the paraganglioma syndromes include the following:
Genetic transmission of PGL1, PGL2, and PGL3 is autosomal dominant with variable penetrance. In PGL1, paternal transmission results in tumor development and maternal transmission results in a carrier state.
PGL1 and PGL4 demonstrate multicentric tumors and pheochromocytomas.
PGL4 is associated with a higher incidence of malignant paragangliomas.
PGL3 is associated with exclusively benign, unifocal paragangliomas and has no association with pheochromocytomas.
Patients with neurofibromatosis type I, MEN-22, and Von Hippel-Lindau disease have a predisposition to develop paragagliomas.
Malignant Variant
Malignant paragangliomas are uncommon, and their diagnosis can be confirmed only by metastatic disease, usually within regional lymph nodes, because histologic examination of the primary tumor is unreliable for establishing a malignant diagnosis. The prevalence of malignancy depends on the site of the primary tumor, and there has been considerable variability in the reported frequency. Although malignant carotid body tumor has been reported in up to 20% of patients, most reports indicate a rate of 3 to 6% of cases. 27 , 28 The metastatic rate to regional lymph nodes is unknown. 29 The most common sites of distant carotid body tumor metastases are the bones, lungs, and liver. 30 Malignancy is generally less common in familial paragangliomas compared with sporadic cases. Grufferman et al, in a literature review of carotid body tumors, found a malignancy rate of 12% in nonfamilial tumor compared to a 2% rate in familial tumors. 11 Pacheco-Ojeda, 29 in a review of 43 cases of malignant carotid body tumors, found that there may be a long interval between treatment of a carotid body tumor and the appearance of a metastatic lesion, ranging from 20 months to 20 years. The growth rate of metastases is slow, with a doubling time of 2,000 days.
The jugulotympanic paraganglioma malignancy rate ranges widely, from less than 1 to 25%, but it is most often reported to be approximately 5%. 28 , 31 The most common sites of metastases for jugulotympanic paragangliomas, in decreasing incidence, are the lungs, lymph nodes, liver, vertebrae, ribs, and spleen. 32 Although the reported rate of malignancy of vagal paragangliomas is as high as 19%, 33 a 10% frequency is most frequently accepted; the regional lymph nodes and lungs are the most common sites of metastases. 3 Vagal paragangliomas probably represent the highest rate of malignancy (16–19%) of the more common types of head and neck paragangliomas. 28 Primary orbital and laryngeal tumors demonstrate the highest malignant rate (20–25%) of all head and neck paragangliomas. 19
Carotid Body Tumor
The carotid body is located in the adventitia of the posterior medial aspect of the carotid artery bifurcation. As the tumor grows, it tends to splay the carotid bifurcation and progressively involves the carotid adventitia. Classically, the internal carotid artery (ICA) is displaced posteriorly and laterally ( Fig. 13.2 ). 34 With continued growth, the tumor extends superiorly along the ICA to the skull base and may affect adjacent cranial nerves, most commonly the vagal and hypoglossal nerves. Occasionally, the sympathetic chain is involved. The intense vascularity of the tumor affects adjacent structures with a suffusion of dilated blood vessels, including the epineurium of nerves. Medial extension into the parapharyngeal space is reported in 20% of cases. 35 , 36 In some large carotid body tumors, continued growth results in extension to the skull base with bony erosion.
The median age of presentation for carotid body tumors is 45 to 54 years (range, 12 to 78 years). 36 , 37 , 38 Most series report a female predominance of approximately 2:1. 36 , 37 , 38 The most common presenting symptom of a carotid body tumor is a neck mass located at or superior to the carotid bifurcation and deep to the sternocleidomastoid muscle. 34 , 37 Carotid body tumors are slow growing and often have been present for months to years before the patient seeks medical attention. On palpation, they are vertically fixed and laterally mobile owing to fixation to the carotid artery 34 , 38 , 39 and may be pulsatile. 34 Bruits have been reported in 10 to 16% of cases. 36 , 38 , 40 Pain is present in approximately a quarter of the cases. 36 , 37 On gross examination, carotid body tumors are dark tan to purple and usually well circumscribed. Medial extension into the parapharyngeal space is reported in 20% of cases and may cause submucosal bulging of the lateral oropharynx and medial displacement of the tonsils. 35 , 36 Cranial neuropathies are present in approximately 10 to 30% of cases at diagnosis. 36 , 41 , 42
Patients occasionally have a history of having undergone an open incisional biopsy after an unsuspecting surgeon presumes that he or she is operating on an enlarged cervical lymph node. Open biopsy should be avoided because of the risk of hemorrhage 43 and subsequent fibrosis at the operative site. If the diagnosis of carotid body tumor is suspected, an incisional biopsy is contraindicated; however, a fine needle aspiration biopsy can be safely performed with minimal risk of bleeding.
Jugular and Tympanic Paragangliomas
Tympanic paragangliomas arise from the paraganglia associated with the Jacobson or Arnold nerves. They may fill the middle ear cavity and extend posteriorly into the mastoid air cells or inferiorly to the jugular bulb. Jugular paragangliomas tend to spread along the “paths of least resistance” in multiple directions and gain access to various portions of the temporal bone and base of skull neurovascular foramina. With progressive temporal involvement, additional growth leads to posterior cranial fossa involvement. Intracranial extension can occur via several pathways: posterior extension directly through the petrous bone, extension into and through the internal auditory canal, or infralabyrinthine extension. 44 , 45 There is early intraluminal jugular extension into the sigmoid sinus and internal jugular vein with possible growth into the inferior petrosal sinus. Tumor can invade into the middle ear cleft, the petrous apex, or the mastoid and retrofacial air cells. Inferiorly, jugular paragangliomas may extend into the infratemporal fossa and poststyloid parapharyngeal space into the neck ( Fig. 13.3 ). As with other paragangliomas of the head and neck, jugular and tympanic paragangliomas are slow growing; patients typically have symptoms for 2 to 3 years 46 before they are diagnosed. The progression of symptoms depends on the location and size of the paraganglioma and the direction of spread.
Tympanic paragangliomas occur most commonly during the sixth decade of life, have a marked female preponderance, and usually manifest with a conductive hearing loss, pulsatile tinnitus, and a mass behind the tympanic membrane. 46 On otoscopic examination, a red–blue middle ear mass that blanches on positive pneumotoscopic pressure (Brown sign) may be present. Perforation of the tumor through the tympanic membrane may occur, producing a vascular “polyp” that may bleed spontaneously. Within the middle ear, continued growth results in ossicular involvement and a subsequent conductive hearing loss. Continued growth with vestibular involvement produces a sensorineural hearing loss, vertigo, and occasionally pain from the associated inflammatory response. Jugular paragangliomas that invade the middle ear will result in signs and symptoms similar to those of a tympanic paraganglioma, but a computed tomography (CT) scan evaluation usually can distinguish the two by the presence or absence of erosion of the bony plate at the lateral aspect of the jugular fossa.
Jugular paragangliomas most commonly occur in the fifth and sixth decades of life 47 and demonstrate a female-to-male ratio of 4:1 to 6:1. 5 , 46 , 48 They often demonstrate early skull-base involvement with extension into the middle ear and internal jugular vein. Superior extension into the middle ear results in symptoms similar to tympanic paragangliomas and may result in a conductive or sensorineural hearing loss, depending on the extent of vestibular involvement. 49 , 50 Hearing loss (55–77%) and tinnitus (56–72%) are the most common initial symptoms. 46 , 51 , 52 , 53 Symptoms related to lower cranial nerve deficits (VII–XII) are also common. We previously reported a series in which all patients with jugular or vagal paragangliomas had dysfunction of at least one cranial nerve. 50 Ogura et al reported that 27 of 72 (38%) patients with jugular paragangliomas had at least one cranial nerve palsy at presentation. 52 Gardner et al, in their series of 36 patients, reported that 58% of patients with jugular paragangliomas exhibited at least one cranial nerve dysfunction preoperatively, with 28% having cranial nerve VIII dysfunction alone. 53 Tumors can invade into the middle ear cleft, the petrous apex, or the mastoid and retrofacial air cells with a resulting facial-nerve paralysis. Tumors of the skull base without extensive middle ear extension may involve isolated tongue weakness, hoarseness, dysphagia, or shoulder drop or with symptoms of multiple cranial nerve dysfunction. The jugular foramen syndrome (cranial nerves IX, X, XI palsy or Vernet syndrome) is occasionally encountered, and cranial nerve IX–XII palsy (Collet-Sicard syndrome) occurs in approximately 10% of jugular paragangliomas.
Vagal Paragangliomas
Vagal paragangliomas are uncommon and account for up to 5% of all head and neck paragangliomas. 16 , 17 Although they most commonly arise from the nodose (inferior) ganglion, vagal paragangliomas may also originate from the middle and superior ganglia and less frequently anywhere along the course of the vagus nerve. Compared with the discrete carotid body, vagal paraganglia are distributed more diffusely within the nerve or perineurium. Vagus nerve fibers “fan out” or “splay over” the surface of the vagal paraganglioma or, early in their development, enter the substance of the tumor; therefore, preservation of the vagus nerve is usually not possible with complete tumor resection. 17 , 54 , 55 , 56
Vagal paragangliomas have three basic patterns of spread. 17 Because most vagal parangliomas originate at the inferior (nodose) ganglion, they tend to spread inferiorly into the poststyloid parapharyngeal area. Extension superiorly toward the skull base in the area of the jugular foramen results in early involvement of the internal jugular vein (IJV) and adjacent cranial nerves (IX, XI, XII). The tumor causes early anterior displacement of the ICA ( Fig. 13.4 ). Paragangliomas presumably arise from the middle ganglion, previously termed paraganglioma juxtavagale, and typically extend into the jugular foramen. Vagal paragangliomas originating from the superior ganglion have a greater chance of assuming a “dumbbell” form with posterior cranial fossa tumor, in addition to extending into the parapharyngeal space inferiorly.
Vagal paragangliomas are ovoid or spindle-shaped tumors and most commonly appear as an asymptomatic mass of the upper neck, typically more cephalad than carotid body tumors. Vagal paragangliomas are slow growing with a female-to-female male preponderance of 2:1 to 3:1 and a mean duration of symptoms of 2 to 3 years before presentation. 16 , 17 , 46 , 57 As the tumor enlarges, it encroaches upon the lower cranial nerves and the adjacent sympathetic chain. Various authors report that 33 to 50% of patients have cranial neuropathy at presentation, 46 , 50 , 55 , 56 involving, in decreasing frequency, the vagal (20 to 47%), hypoglossal, spinal accessory, and sympathetic plexus nerves. Signs and symptoms include unilateral vocal cord paralysis, hoarseness, dysphagia, nasal regurgitation, atrophy of the hemitongue, shoulder weakness, and Horner syndrome. Hearing loss and pulsatile tinnitus are usually indicative of temporal bone extension. The progression of symptoms is often helpful in differentiating vagal paragangliomas from other head and neck paragangliomas. Leonetti et al 35 reported on five cases of vagal paragangliomas with vocal cord paralysis and hearing loss or tinnitus. In all cases, vocal cord symptoms preceded otologic symptoms by 2 to 2½ years. The initial presence of vocal cord paralysis with or without hoarseness helps differentiate vagal paragangliomas from carotid body tumors. 56
13.2.3 Diagnostic Evaluation
Both CT and MRI can usually establish the diagnosis of paraganglioma. 111Indium pentetreotide (OctreoScan) imaging can also be used to evaluate paragangliomas, define multiple tumors, and detect the possible presence of metastatic disease. 58 Angiography defines the vascular supply and may visualize vessel involvement (invasion) and pave the way for preoperative embolization, which is important if surgery is contemplated.
13.2.4 Treatment
Paragangliomas are highly vascular and characteristically have early blood vessel and neural involvement, in addition to skull base and potential intracranial extension. These factors contribute to the challenging nature of effectively treating these tumors. Traditionally, surgery has been the preferred treatment, especially with the evolution of more sophisticated skull-base approaches, safer embolization protocols, and advanced vascular bypass procedures. 49 , 51 However, postoperative cranial nerve dysfunction is anticipated in patients with paragangliomas characterized by early neural involvement and skull-base involvement, in which surgery would require extensive rehabilitation efforts.
Surgical resection has been the mainstay of treatment for paraganglioma; however, the outcome is dependent on many factors that might influence the ideal result of complete tumor removal. For example, vagal paragangliomas require vagus nerve sacrifice for adequate resection, which may result in significant vocal and deglutition dysfunction, 59 especially in older patients who do not adapt well to acute neural deficits that may define their postoperative course. 54 Even with pre-existing cranial nerve dysfunction, patients might not easily tolerate postoperative total nerve paralysis with absolute loss of function, especially in the setting of multiple nerve deficits or advanced age. The role of surgery should therefore be re-evaluated as the primary treatment of choice for these slow-growing tumors. The discovery of an early stage paraganglioma poses a dilemma in management in light of their natural history of slow growth. Some paragangliomas, especially very small ones, may not be progressive, and therefore a “wait and scan” management may be advisable. 1 Relative contraindications to surgery include extensive skull base or intracranial involvement, advanced age of the patient, medical comorbidities, and bilateral or multiple paragangliomas for which surgery may result in the unacceptable postoperative morbidity of bilateral lower cranial nerve palsies.
If surgery is the chosen treatment course, preoperative embolization has usually been performed. Embolization of paragangliomas has been an extremely useful adjunct in our treatment protocol. More recently, however, experience has allowed us to perform successful surgical resections of selective paragangliomas without preoperative embolization.
Although not uniformly accepted, 35 , 42 , 55 , 60 , 61 especially in carotid body tumors, preoperative angiography and combined endovascular embolization and subsequent surgery have major advantages, assuming certain criteria are fulfilled before performing embolization. 10 , 52 , 62 , 63 , 64 , 65 An experienced vascular radiology team must be thoroughly familiar with the complexities and possible variations in head and neck vascular anatomy. Percutaneous angiography and magnetic resonance angiography allow evaluation of the circle of Willis and the adequacy of contralateral cerebral perfusion, which will be especially important if intraoperative internal carotid artery clamping or sacrifice is necessary. Ipsilateral balloon occlusion of the ICA will also determine whether or not ICA ligation will be tolerated. Certainly, the possibility of a stroke may exist even when these tests indicate adequate cross-cerebral circulation. Additionally, many anastomoses exist between the external and internal carotid systems; without this knowledge, disastrous neurologic consequences may result. 66 Safe performance of this procedure by interventional vascular radiology has to be established and documented with acceptable rates of morbidity and mortality. 64 , 67
Preoperative Embolization
The main objectives are (1) to direct the embolism material to selectively permeate only the vascularity of the paraganglioma without proximal occlusion of the feeding artery, and (2) to avoid distal migration of emboli into the general systemic circulation, which would result in possible neurologic and pulmonary complications. Postembolization angiography should document the absence of tumor “blush” with continued patency of the external carotid system ( Fig. 13.5 ). Avoiding proximal vessel occlusion with embolization maintains adequate blood flow to normal tissue, avoids recruitment of internal carotid blood supply to the tumor, and provides future endovascular access for possible tumor recurrence.
The potential invasiveness of embolization is justified by the advantages it provides during surgery, which result in improved tumor resection directly related to decreased tumor vascularity. 68 Postembolization paragangliomas often manifest a reduction in tumor size by as much as 25% as a result of diminished blood flow to the tumor. Embolization of tumor vasculature reduces blood loss during dissection of the neoplasm. 18 , 34 , 67 , 69 Reduced bleeding during surgery improves exposure, better defines the planes of dissection, and ultimately reduces the need for transfusion. 39 , 64 , 65 In the literature, one can find support for embolizing only larger tumors. 64 , 70 , 71 , 72 The decision to embolize preoperatively should depend on the location and extent of the tumor, as well as the experience of the surgeon and the interventional radiologist.
Although elective intraoperative ligation of the external carotid artery (ECA) for hemostasis has been reported, we believe this procedure should be avoided. 52 , 55 , 69 Paragangliomas have multiple major arterial feeding vessels, and proximal ECA ligation does not prevent retrograde flow through the external carotid vessels providing tumor circulation. Proximal ligation, therefore, has little effect on tumor blood flow and complicates the possibility of future endovascular access to this area. ECA ligation also results in recruitment of the ICA blood supply, especially with recurrent skull-base tumors. Embolization of these tumors then becomes extremely hazardous, if not impossible.
Surgery
If embolization is elected, surgery is performed within 2 days of angiography and embolization to avoid recruitment of the collateral tumor blood supply and before onset of significant postinflammatory effect. 50 Short-term steroids are administered if there is concern about tumor edema that could compromise tumor dissection. The anesthesiologist must be prepared to counteract the α- and β-adrenergic catecholamine cardiovascular effect when dealing with “secreting” tumors.
Carotid Body Tumors
Carotid body tumors are exposed through a transverse or oblique incision along the anterior sternocleidomastoid muscle. Adequate tumor removal requires a subadventitial dissection of the carotid artery; therefore, it is important to obtain proximal and distal control of the common carotid artery, ICA, and ECA. Mobilization of the ICA is the initial step of tumor dissection. Occasionally, the tumor must be dissected through and “split” to remove the ICA from its encasement. Once the ICA is free, any tumor that extends inferior to the bifurcation should be dissected off the common carotid artery. The ECA and its branches can then be dissected, although difficulty with this part of the procedure may warrant sacrifice of the ECA, if necessary, for adequate tumor excision. The last step is freeing the tumor from the carotid bifurcation, where there is most intimate involvement of the artery because the tumor originates in the carotid body ( Fig. 13.6 ).
Nerves adherent to, but not infiltrated by, carotid body tumors can usually be mobilized in an intact fashion, including the vagus, hypoglossal, and occasionally the glossopharyngeal nerves. These nerves are at risk for postoperative dysfunction, especially with larger tumors. 16 , 50 The sympathetic chain and the superior laryngeal nerve are often adherent to the tumor, especially those with medial extension into the parapharyngeal space.
Jugulotympanic Paragangliomas
Tympanic paragangliomas confined to the middle ear (Glasscock-Jackson type I, Fisch class A) can be approached through a transcanal approach. 73 These small tumors do not require preoperative embolization. If the margins of the tumor are not easily discernable, but the bone over the jugular bulb and the carotid canal is intact (Glasscock-Jackson type II–III, Fisch class B), a postauricular, transmastoid extended facial recess approach provides excellent exposure for tumor resection. 5 , 73 A tympanoplasty can be performed at that time if necessary.
Involvement of the jugular bulb requires a combined transmastoid and transcervical approach. 74 If there is limited involvement of the jugular bulb without carotid artery involvement, a complete mastoidectomy and extended facial recess approach are performed. The sigmoid sinus is exposed and traced to the jugular bulb. Isolation and control of the IJV and ICA are performed, and cranial nerves IX through XII are dissected to the skull base. The IJV is ligated. Mobilization of the distal facial nerve at the second genu with the stylomastoid periosteum provides excellent exposure of the jugular bulb area. The superior sigmoid sinus is occluded, and the inferior sigmoid sinus is opened with mobilization of the tumor. Bleeding from the inferior petrosal sinus is controlled. Inadvertent trauma in this area risks damage to cranial nerves IX through XII in their courses through the jugular canal.
More extensive involvement of the jugular bulb or involvement of the intrapetrous ICA requires an infratemporal fossa approach as developed by Fisch and Mattox. 75 A wide mastoidectomy approach is performed. The facial nerve is mobilized from the geniculate ganglion to the stylomastoid foramen with anterior translocation of the nerve. The ICA, IJV, and cranial nerves IX through XII are dissected to the skull base with ligation of the IJV and control of the ICA. The mandibular condyle is retracted anteriorly. The ICA is followed through its intrapetrous course with transection of the eustachian tube. The sigmoid sinus, jugular bulb, and IJV are resected with the tumor. The tumor is meticulously dissected off the ICA. Additional exposure into the infratemporal fossa can be accomplished with resection of the mandibular condyle and zygomatic arch. Through this approach, access to the posterior, middle, and anterior cranial fossae is gained, and, if necessary, continued tumor resection is accomplished through a neurosurgical, intracranial approach. A pedicled temporalis, temporoparietal, or sternomastoid flap is used for reconstruction and obliteration of the defect.
Vagal Paragangliomas
Vagal paragangliomas vary in the extent of skull-base or intracranial involvement. A combined cervical and mastoid approach to the skull base is best for safe and wide exposure, and anterior displacement of the mandible will facilitate exposure of the parapharyngeal space. 54 A wide curving postauricular incision is carried into the neck. The carotid sheath structures and cranial nerves IX through XII are dissected up to the skull base with careful dissection of the ICA off the vagal paraganglioma. The posterior belly of the digastric muscle is resected, and the styloid process is transected at its attachment to the inferior petrous bone. Control of the ICA is obtained. Paragangliomas without skull-base involvement can be safely resected using this approach. If the tumor extends into the jugular canal, then a mastoidectomy with facial nerve mobilization and transposition will allow exposure of the jugular bulb. The sigmoid sinus can be packed off or ligated with subsequent removal of the sigmoid, jugular bulb, and IJV complex. The carotid canal is dissected superiorly, and the ICA is carefully separated off the tumor. The tumor can then be excised, and this almost always involves sacrifice of the vagus nerve and additional cranial nerves according to tumor size and local involvement. 17 Closure is achieved by obliterating the mastoid cavity with a fat graft. More extensive defects require a temporoparietal fascia flap 76 or a sternocleidomastoid muscle flap.
Radiation Therapy
Radiotherapy has traditionally been the treatment of choice for unresectable paragangliomas or tumors in medically infirm and elderly patients. Some authorities have advocated surgery as the only curative option based on the assumption that paragangliomas are radioresistant. For the past several decades, however, radiotherapy has proven to be an effective therapeutic option and therefore should be considered as a form of primary treatment, especially in the setting of significant potential morbidity that accompanies surgery for some tumors.
Radiotherapy has been used primarily to treat jugular paragangliomas of the temporal bone and significantly less frequently for treatment of carotid body or vagal paragangliomas. Both conventionally fractionated radiotherapy (45 Gy over 5 weeks) and stereotactic radiosurgery have been used. Radiotherapy is the preferred treatment option for advanced tumors. Moreover, a combined approach (surgery and radiation) does not appear to improve local control compared with radiotherapy alone. Kim et al 77 also emphasized that there is no obvious benefit of a debulking subtotal resection in conjunction with definitive radiotherapy.
Stereotactic radiosurgery (SRS) offers the possibility of a single, highly focused small-field treatment with a steep dose gradient to maximally spare the surrounding normal tissue. Multiple series have reported success using this approach to treat primarily jugular paragangliomas with good local control. 78 , 79 , 80 , 81 , 82 Limitations of SRS include eligibility restrictions, such as lesion size and location, as well as a greater risk for geographic miss owing to the sharp dose gradient. 82
13.3 Juvenile Nasopharyngeal Angiofibroma
13.3.1 Natural History and Physical Findings
Juvenile nasopharyngeal angiofibroma (JNA) is a highly vascular, histologically benign but locally aggressive and destructive tumor that exclusively affects boys of adolescent age. It accounts for approximately 0.5% of all head and neck neoplasms. 83 , 84 The cause and pathogenesis of the disease remain to be elucidated. The tumor appears to originate in the posterior nasal cavity instead of the nasopharynx, specifically in the posterolateral wall of the superior aspect of the nasal cavity, at the junction of the sphenoid process of the palatine bone, the horizontal ala of the vomer, and the root of the pterygoid process of the sphenoid bone, near the superior margin of the sphenopalatine foramen. 85 These tumors are unencapsulated and consist of proliferating, irregular vascular spaces lined by a single endothelial layer. These channels lack a complete muscular layer between the endothelial cells and stromal cells and are therefore subject to severe bleeding. 83
At diagnosis, most angiofibromas have extended beyond the nasal cavity and nasopharynx. Extension into the nasal cavity is followed by anterolateral erosion of the posterior wall of the maxillary sinus and lateral growth into the pterygomaxillary fossa. Extension into the pterygomaxillary fossa can erode the pterygoid process of the sphenoid bone. Further lateral extension via the pterygomaxillary fissure can fill the infratemporal fossa and produce the classic bulging cheek. Tumor can extend under the zygomatic arch and cause swelling above the arch. From the pterygomaxillary fossa, the angiofibroma can erode the greater wing of the sphenoid bone and into the middle cranial fossa and invade both inferior and superior orbital fissures. Posterior extension into the sphenoid sinus through the floor or ostium fills the sinus, pushes upward and back to displace the pituitary, and then can fill the sella turcica. Tumor in the sella or orbit can cause loss of vision. 85 These tumors typically grow by centrifugal expansion and not by invasion; therefore, they may be intracranial but usually are extradural. The cavernous sinus may be compressed but is not invaded. Cranial nerve palsies are rare even with large tumors. Particularly aggressive angiofibromas may invade the cavernous sinus, however, and threaten multiple cranial nerves, the ICA, hypophysis, and optic chiasm. 85 , 86
Several classification systems were established to describe JNA based on tumor extent. The commonly used systems are those of Fisch, Chandler, and Radowski, who adapted Sessions’ classification. 87 Despite its tendency to be invasive, the rate of growth of JNA, although not known, is thought to be slow. Because the tumor is rarely seen in young adults, it is believed to spontaneously regress. However, because regression cannot be assumed, these tumors should be treated. 85 The prognosis for patients with JNA is good with early diagnosis 88 ; unfortunately, diagnosis most often occurs during later stages of the disease as a result of the nonspecific and innocuous initial symptoms of JNA. 89 , 90 JNA is characterized by high recurrence rates, reportedly as high as 30 to 50%. 91 It is a benign disease that is not multifocal; therefore, recurrence usually reflects persistent disease. 92
Typically, JNA is found in adolescent boys ranging from 7 to 29 years of age (median age at diagnosis, 15 years). 93 Patients classically have the triad of unilateral nasal obstruction, recurrent severe epistaxis, and nasopharyngeal mass 92 ; other common but nonspecific symptoms are purulent nasal discharge from infection secondary to obstruction, hyponasal speech, and anosmia. Nasal obstruction and epistaxis occur in more than 80% of patients. Symptoms may be present for months to years before the diagnosis is made. Delay in presentation or diagnosis can be attributed to the tendency to associate the indolent symptoms of JNA with the more common entities, such as rhinitis, sinusitis, and nasal polyposis. 94
Examination often shows a red–gray and smooth, lobulated mass in the nasopharynx or in the posterior aspect of the nose. The overlying mucosa is rarely ulcerated unless the patient has had previous biopsy or therapy. Other signs include facial deformity, proptosis, palate extension, serous otitis media, and visual or auditory impairment. 95 , 96 Neurologic deficits may be seen in patients with angiofibromas with significant intracranial extension. 86
13.3.2 Diagnostic Evaluation
The radiographic findings of angiofibroma are characteristic. On CT scan, there is anterior bowing of the posterior wall of the maxillary sinus by a markedly enhancing mass, known as the Holman-Miller sign, and enlargement of the superior orbital fissure, which are considered diagnostic for JNA ( Fig. 13.7 ). 93 CT scan is also ideal for tumor localization and useful in the delineation of the extent of the tumor. MRI is indicated in patients with intracranial extension. Biopsy of these highly vascular lesions is contraindicated because of the resulting significant bleeding. Angiography is not necessary in most patients but is useful in patients whose diagnosis remains in question, usually patients for whom previous treatment has failed. It also is necessary for embolization, especially when surgery is anticipated.
13.3.3 Treatment
The mainstay treatment for JNA is surgery, especially for the early stage disease process. The various surgical approaches are transpalatal, transnasal (including endoscopic), transantral, transmandibular, transzygomatic, combined craniotomy and rhinotomy, lateral rhinotomy, and midface degloving. The approach chosen is determined by tumor location, extent of the tumor, and surgeon’s expertise. More recent advances in endoscopic surgical techniques have made this the procedure of choice depending on the extent of skull-base or intracranial extension. Recurrence does not necessarily indicate the need for further treatment unless associated symptoms of bleeding, nasal obstruction, ocular findings, or progressive growth as defined by radiographic studies are present. 85
The main blood supply of a JNA is from the internal maxillary artery; however, the thyrocervical trunk and the dural, sphenoidal, and ophthalmic branches from the internal carotid system can also contribute. Because of this extensive arterial supply, ligation of the external carotid artery before surgical excision does not help decrease bleeding but instead may have the opposite effect by encouraging arterial collateralization from vessels that are less accessible or inaccessible. 85 Techniques that have been used to decrease bleeding include embolization, ligation of the internal maxillary artery, electrocoagulation, and irradiation, as well as anesthetic adjuncts, such as hypotensive techniques and hypothermia. 85
Preoperative Embolization
Preoperative embolization of JNA may greatly reduce intraoperative blood loss, a major source of morbidity. Most commonly, the ipsilateral internal maxillary artery is the major arterial supply to these neoplasms. However, some tumors receive their blood supply from the contralateral external carotid system, and some receive branches from both the ipsilateral and the contralateral internal carotid systems, especially from the inferolateral branches off the cavernous carotid artery. The potential but small risk of embolization is outweighed by the overall surgical safety as the result of the ability to decrease ipsilateral as well as the contralateral blood supply. Several investigators 97 , 98 reported a 60 to 68% reduction in intraoperative blood loss in patients who received preoperative embolization compared with those who did not. Preoperative embolization has a questionable impact on recurrence rates, as some report recurrence rates to be lower in patients receiving preoperative embolization as a result of improved visualization and exposure; 99 however, others have reported an increased recurrence, which they attribute to poor demarcation of tumor margins and recession of the devascularized tumor into the cancellous spaces of the sphenoid bone. 98 Considerations for embolization should take into account the existence of an experienced interventional vascular radiology team who is able to perform such a procedure safely and with acceptable rates of morbidity and mortality.
Surgery
Selection of a surgical approach is based on extent of the tumor and the surgeon’s expertise and experience.
Endoscopic Endonasal
The endoscopic approach was previously reserved for tumors limited to the nasal cavity; however, as endoscopic instrumentation and skills of endoscopic surgeons improved, these techniques were adopted to expand the boundaries of minimally invasive skull-base surgery. Endoscopic excision is promoted as the preferred approach for JNA for several reasons. The tumor can often be pulled into the nasal cavity with minimal dissection. Additionally, endoscopic techniques provide excellent access to feeding vessels and enhance the surgeon’s ability to explore sites that are prone to residual tumor and, thus, recurrence. 98
Besides being minimally invasive, the endoscopic approach has several other potential advantages, including decreased intraoperative blood loss, complication rates, hospital stay, and recurrence rates. 98 Pryor et al reported an average blood loss of 225 ml in patients who underwent an endoscopic procedure compared with 1,250 ml of blood loss in patients undergoing excision via the lateral rhinotomy approach. They attributed this decreased loss to the careful attention to hemostasis, which is crucial to the outcome of endoscopic procedures, and claim that much of the blood loss in open approaches results from the incisions and osteotomies performed to provide tumor access. 98 Endoscopic surgery is rapidly becoming the method of choice and eventually may be replaced with robotic surgery. 100
Reported recurrence rates range from 6 to 39.5% in JNA surgery. Pryor et al reported a recurrence rate of 24% in patients treated by a standard surgical approach and 0% in endoscopic excisions. 98 This decreased recurrence, however, is perhaps more a result of patient selection than an advantage of the technique. In the series reported by Pryor et al, none of the patients chosen to undergo the endoscopic approach had intracranial extension, whereas 36% of the patients who underwent an open procedure had intracranial extension. 98 This is consistent with findings published by other investigators who have reported a 10 to 20% incidence of intracranial extension, with a rate of 50% recurrence. 98 , 101 , 102 , 103 The rates of complications such as intraoperative hemorrhage, cheek numbness, nasolacrimal duct obstruction, diplopia, serous otitis media, and wound infection were significant in patients who underwent an open procedure but were negligible in patients who had endoscopic excisions. 98
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