Neurogenic Tumors and Paragangliomas




Keywords

Paraganglioma, schwannoma, neurogenic tumors, parapharyngeal tumors, carotid body tumors

 







Neurogenic tumors and paragangliomas form a very small percentage of all neoplastic lesions of the head and neck region. Although these tumors are considered under the major heading of “soft tissue tumors,” the unique presentation and systematic workup and imaging studies necessary for accurate diagnosis to facilitate selection of management strategy warrant their consideration as a separate entity.


Most paragangliomas and neurogenic tumors arise from or in the vicinity of the lower cranial nerves, carotid artery, internal jugular vein, and sympathetic chain in the upper part of the neck. Characteristically, these tumors are located in the parapharyngeal space (PPS) ( Fig. 14.1 ). The PPS is a potential space in the shape of an inverted cone with its base at the base of the skull and its apex at the level of the tip of the hyoid bone. The lateral pharyngeal wall and tonsillar fossa form its medial wall, and the pterygoid muscles, parotid gland, and prevertebral muscles form its posterolateral boundary. For clinical purposes, the PPS is divided into two components separated by the styloid process and its attached muscles ( Fig. 14.2 ).




Figure 14.1


Anatomy of the parapharyngeal space. a, Artery; Int. br., internal branch; n, nerve; m, muscle; mm, muscles; sup., superior; v, vein.



Figure 14.2


A cross section of the upper part of the neck at the level of the tonsil showing cross-sectional anatomy and the relationship of neurovascular structures in the parapharyngeal space.


The space anterolateral to the styloid process is also called the true PPS or the masticator space ; it contains loose areolar tissue, the deep lobe of the parotid gland, the retropharyngeal lymph nodes, blood vessels, and fat. The most common neoplasm occurring in this space is of salivary origin, arising either from the deep lobe of the parotid gland, from minor salivary glands in the lateral pharyngeal wall, or from salivary rests in the parapharyngeal space. The parapharyngeal region posteromedial to the styloid process is called the carotid space, and it contains the carotid artery, internal jugular vein, lower cranial nerves (IX, X, XI, and XII), and the sympathetic chain. The most common neoplasms in this space are paragangliomas and neurogenic tumors arising from the lower cranial nerves.




Neurogenic Tumors


The head and neck region is by far the most common location for benign peripheral nerve tumors ( Fig. 14.3 ). Neurogenic tumors of the cervical region are divided into those arising in either the medial or lateral compartment of the neck. Neurogenic tumors of the medial compartment arise from the lower cranial nerves or the sympathetic chain. Neurogenic tumors of the lateral compartment of the neck arise from the cutaneous or muscular branches of the cervical plexus or the brachial plexus. Occasionally these tumors arise at the spinal foramina with an intraspinal and extraspinal component presenting as a “dumbbell tumor.” The various types of benign and malignant tumors of neural origin are listed in Table 14.1 .




Figure 14.3


The location of benign peripheral nerve tumors.


Table 14.1

Benign and Malignant Tumors of Neural Origin






























Benign Malignant
Reactive Malignant peripheral nerve sheath tumors (MPNST)
Traumatic neuroma (malignant schwannoma, neurofibrosarcoma)
– Epithelioid MPNST
– Pigmented (melanotic) MPNST
– Peripheral primitive neuroectodermal tumor
(Askin tumor)
Hamartoma: mucosal neuromas (MEN IIB, Gorlin’s syndrome) Autonomic nerve tumor (plexosarcoma)
Schwannoma (neurilemmoma) Malignant melanoma of soft tissues (clear cell sarcoma)
Neurofibroma: solitary, multiple, diffuse, plexiform (NF-1)
Perineurioma (storiform perineurial fibroma)
Dermal nerve sheath myxoma
Granular cell tumor

MEN, Multiple endocrine neoplasia; MPNST, malignant peripheral nerve sheath tumor; NF, neurofibromatosis.


Schwannomas originate from the neuroectodermal sheath surrounding peripheral nerves. They can arise in any part of the head and neck region, including the face, scalp, cranial cavity, orbit, middle ear, nasal cavity, oral cavity, larynx, and neck. Schwannomas also frequently arise from cranial nerves V, VII, VIII, and X and the sympathetic chain. On rare occasions schwannomas can be seen in the glossopharyngeal or hypoglossal nerves and even less commonly in other cranial nerves. Schwannomas are usually solitary neoplasms. Multifocal presentation raises the suspicion for neurofibromatosis type 2 (NF2), which results from inherited mutations in the NF2 suppressor gene. The formation of nonfamilial schwannomas also has been attributed to somatic alterations of the NF2 gene. Histologically, schwannomas show pallisading nuclei from Verocay bodies in the cellular Antoni A areas. They are strongly and diffusely immunoreactive to S-100 protein ( Figs. 14.4 and 14.5 ).




Figure 14.4


The histologic appearance of a schwannoma (hematoxylin and eosin stain). Palisading nuclei form Verocay bodies in the cellular Antoni A areas. The looser, myxoid areas are referred to as Antoni B areas. Prominent thick-walled blood vessels are another common histologic feature.



Figure 14.5


An immunohistochemical stain for S-100 protein. Like their normal counterparts, schwannomas are strongly and diffusely immunoreactive for S-100 protein.


Neurofibromas are benign, unencapsulated tumors that may be localized, diffuse, or plexiform and are either familial or sporadic. The presence of a plexiform neurofibroma is virtually pathognomonic of familial neurofibromatosis (NF1). Neurofibromas typically present as ill-defined lesions in the scalp and skin of the head and neck. They occasionally may be seen from terminal branches of the trigeminal nerve in the sinonasal tract or in the larynx. Cutaneous neurofibromas have a raised, plaquelike appearance and are slow-growing, painless lesions that may be located in the dermis or in the subcutaneous fibroadipose tissue. Their borders can be indistinct, contributing to the high rates of incomplete excision and subsequent recurrence. Histologically, neurofibromas show loosely arranged collagen fibrils with small uniform nuclei. They are also positive for S-100 protein, although not as strongly as schwannomas ( Fig. 14.6 ).




Figure 14.6


The histologic appearance of a neurofibroma (hematoxylin and eosin stain). Histologically, a neurofibroma will have a loosely arranged background of collagen fibrils, which have been likened to “shredded carrots,” with small, uniform nuclei. These tumors are positive for S-100 protein, although not as strongly and diffusely as are schwannomas.


Malignant peripheral nerve sheath tumors (MPNSTs) are of Schwann or perineurial cell origin and arise either de novo or from a preexisting neurofibroma (NF1). At least two-thirds of MPNSTs are derived from neurofibromas in patients with NF1, and approximately 10% are induced by radiation. De novo MPNSTs most commonly occur in the fourth decade of life. When seen in conjunction with NF1, MPNSTs occur in younger patients and have a male predominance. In the sinonasal tract and nasopharynx, MPNSTs commonly arise from the ophthalmic and maxillary branches of the trigeminal nerve, but these tumors can arise from any cranial nerve. Quite rarely these tumors occur in the larynx, where they may cause mucosal ulceration. Operative findings of a thick pseudocapsule and firm adherence to surrounding soft tissue are harbingers of malignancy, and inspection of the cut surface of an MPNST often reveals hemorrhage and necrosis. Histologically, MPNSTs may be spindled or epithelioid. MPNSTs demonstrate immunoreactivity for the S-100 protein, but not to the same extent or intensity as a schwannoma. The local recurrence rate is quite high, and distant metastases can occur to the lungs, bone, and liver.


Paragangliomas


Paraganglia are neural cell aggregates of the sympathetic or parasympathetic nervous system and they typically reside in the adventitia of blood vessels and nerves. Whereas sympathetic paragangliomas secrete catecholamine and most commonly occur in the adrenal medulla, those of parasympathetic origin typically do not secrete catecholamines and primarily occur in the head and neck region. The distribution of paragangliomas of the head and neck region is shown in Fig. 14.7 . Most paragangliomas in the head and neck region arise in the carotid body jugulotympanic region, vagal body, superior and inferior laryngeal paraganglionic tissue, nasal cavity, or the orbit, reflecting the distribution of parasympathetic ganglia.




Figure 14.7


Distribution of paragangliomas of the head and neck region. UADT, Upper aerodigestive tract.


Paragangliomas typically occur in older persons, are unifocal, and are histologically benign. However, approximately 10% of head and neck paragangliomas can be malignant, 10% are bilateral or multiple, and 10% occur in patients with a family history of paragangliomas. Rarely, paragangliomas are functioning, and in those instances, patients present with a history of episodic flushing of the face and hypertension. In such patients, appropriate systemic imaging studies to rule out other paragangliomas should be undertaken, and serum and urinary catecholamine levels should be measured to establish an accurate diagnosis.


Carotid body tumors (also known as chemodectomas or nonchromaffin paragangliomas) are by far the most common of all paragangliomas in the neck and are more common in persons residing at high altitudes. Carotid body tumors arise from the chemoreceptor cells in the carotid sheath, which most commonly are located at the bifurcation of the carotid artery. These tumors are slow growing, are highly vascular, and are histologically benign in most instances. The characteristic location is in the upper part of the neck, where it may present as an external mass, or it may appear as a parapharyngeal mass pushing the lateral pharyngeal wall medially in the oropharynx. In either location, the mass usually has palpable pulsations. If the clinical diagnosis of a carotid body tumor is suspected, appropriate radiographic studies must be performed before deciding on a management plan. Shamblin classified carotid body tumors into three categories, based on the relationship of the carotid arteries and the adjoining nerves to the tumor ( Fig. 14.8 ). In type I, the external and internal carotid arteries are simply displaced by the tumor, and the hypoglossal and superior laryngeal nerves lie on the surface of the tumor. In type II, the tumor is indented by the external and internal carotid arteries, making a deep groove within the tumor, and the hypoglossal and superior laryngeal nerves are on the tumor’s surface. In type III, the arteries are encased by the tumor.




Figure 14.8


Shamblin’s classification of carotid body tumors.


Although they are rare, malignant paragangliomas have a significant potential for local invasion, cranial nerve paralysis, and regional or distant metastases. Histologically, paragangliomas have a characteristic nested or “Zellballen” appearance. Immunohistochemical staining shows positivity for S-100 protein, and a chromogranin stain for the cytoplasm of chief cells shows neurosecretory granules ( Figs. 14.9 through 14.11 ). Benign paragangliomas and malignant paragangliomas have a similar histologic picture, and often it is difficult for pathologists to differentiate between the two. Therefore the diagnosis of a malignant paraganglioma is made on the basis of the following features: (1) local invasion, cranial nerve paralysis, invasion of the carotid artery, or infiltration of the soft tissues in the parapharyngeal space or bone destruction at the skull base; (2) the presence of regional lymph node metastasis; or (3) distant metastasis. Clinically, adherence of the tumor with reduced mobility or cranial nerve paralysis suggests malignancy. Upon radiologic imaging, the presence of regional lymph node metastasis and evidence of invasion and infiltration into adjacent structures would raise suspicion of the tumor being malignant.




Figure 14.9


A paraganglioma (hematoxylin and eosin stain). Paragangliomas have a characteristic nested, or Zellballen, appearance.



Figure 14.10


Immunohistochemistry for S-100 protein highlights peripheral sustentacular cells in a paraganglioma.



Figure 14.11


Chromogranin labels the cytoplasm of the chief cells, reflecting the presence of neurosecretory granules. Similarly, synaptophysin also will be positive. Cytokeratin, carcinoembryonic antigen (CEA), and calcitonin are negative.


Paragangliomas that appear in younger patients and/or present in multiple locations raise concern for a genetic predisposition. Linkage analysis has identified four possible loci, termed “paraganglioma loci 1 to 4” (PGL 1, PGL 2, PGL 3, and PGL 4). Although the gene in PGL 2 remains to be identified, PGL 1, PGL 3, and PGL 4 have been identified as succinate dehydrogenases (SDHs), including SDHD, SDHC, and SDHB, respectively. These genes encode for components of the four-subunit mitochondrial complex II (also known as the succinate ubiquinone oxidoreductase ) that is involved in electron transport and the Krebs tricarboxylic acid cycle. The mitochondrial complex II is one of five complexes in the mitochondrial electron transport chain; it catalyzes conversion of succinate to fulminate and is essential for normal development. Homozygous defects in the mitochondrial complex II result in Leigh syndrome (associated with severe neurologic impairment), whereas heterozygous defects result in paraganglioma and pheochromocytoma development. The wild-type allele often is inactivated in paragangliomas ( Table 14.2 ).



Table 14.2

Significance of Genetic Abnormalities in Head and Neck Paragangliomas

















































SDHB (PGL4) SDHC (PGL3) SDHD (PGL1)
Chromosomal locus 1p35-36 1q21 11q23
Inheritance Monogenic, autosomal dominant Monogenic, autosomal dominant Monogenic, autosomal dominant with paternal imprinting
Penetrance >75% >75% ?
Pheochromocytoma + +
Percent with head and neck tumors 15%-50% 50%-100% 50%-100%
Frequency 5%-10% of cases <5% 80%-90% of cases
Malignancy + (5%-35%)
Multicentricity 15%-50% ~10% 50%-90%

PGL, Paraganglioma locus; SDH, succinate dehydrogenase.


PGL 2, SDHB, and SDHC are inherited as autosomal dominant traits. The SDHD gene is imprinted from the paternal line, and thus the phenotype is only inherited from the father. Penetrance is variable but is relatively high overall. Patients usually present by the first decade of life; fewer than 5% of paragangliomas are familial in patients older than 50 years. Although paragangliomas are common to all subtypes, pheochromocytomas also can develop in patients with PGL 1 and PGL 4.


Genetic testing is advocated for patients presenting with multiple paragangliomas or a suggestive family history. In addition, testing should be considered in patients with extraadrenal sympathetic paragangliomas or in younger patients, because germline mutations can be detected in SDHB or SDHD in up to 20% of the cases. The management of familial paraganglioma is a matter of debate. Retrospective studies suggest that intervention may do little to affect the long-term outcome, and observation may be warranted in most cases. Surgery should be considered in patients with carotid body tumors and tumors with rapid growth or significant symptoms.




Clinical Features and Diagnosis


The majority of patients with neurogenic tumors and paragangliomas in the head and neck region are asymptomatic. Presentation with a mass that is accidentally discovered in the neck or is consequent to an incidental finding on an imaging study, such as a computed tomography (CT) or magnetic resonance imaging (MRI) scan performed for other reasons, is common. Tumors arising from the lower cranial nerves usually present in the retromandibular region of the upper part of the neck with ill-defined fullness, and they can be pulsatile. The pulsatile nature of the mass reflects increased vascularity or, more commonly, transmitted pulsations from the carotid vessels. On the other hand, schwannomas and neurofibromas arising in the lateral aspect of the neck present as firm, discrete lesions without pulsations. These tumors usually are mobile in an axis perpendicular to the long axis of the nerve.


In the great majority of cases, the nerve of origin of schwannomas or neurofibromas retains its function. Presentation with paralysis of the involved cranial nerve is rare and should raise concern for malignancy. Neurogenic tumors and paragangliomas in the PPS often present as a submucosal mass in the lateral pharyngeal wall, pushing the tonsil and soft palate medially. Neurofibromas arising from sensory nerves occasionally are painful to touch and pressure.


Diagnosis of these tumors is usually made through clinical assessment and radiologic imaging. Biopsy and tissue diagnosis is seldom required and indeed may be hazardous. Fine-needle aspiration biopsy may establish the diagnosis of neurogenic tumor but is not helpful for paragangliomas. An open biopsy of a paraganglioma causes significant hemorrhage and should be avoided. A transoral open biopsy of a parapharyngeal mass should not be performed.




Radiographic Evaluation


Modern radiologic imaging has revolutionized the diagnosis and management of neurovascular lesions in the head and neck region. In the past, direct angiography was the only confirmatory radiographic test for a carotid body tumor or paraganglioma. However, with the advent of CT and MRI scanning, direct angiography is seldom performed today unless preoperative embolization of the tumor is required. CT angiography and MRA also provide a noninvasive means of angiography and three-dimensional reconstruction. As such, these imaging studies play an essential role in aiding preoperative diagnosis, surgical planning, or monitoring growth if a decision is made to observe these tumors.


Most neurogenic and vascular tumors of the suprahyoid neck arise from within the carotid space (CS). The CS spans the entire neck from the skull base to the aortic arch. Its contents include the carotid artery, internal jugular vein, cranial nerves IX to XII, and the sympathetic chain. The X nerve lies posterior and lateral to the carotid artery, whereas the sympathetic chain lies posterior and medial to the artery. Although it is a continuous space, the CS is further subdivided into the suprahyoid and infrahyoid portions, with the suprahyoid portion anatomically related to the PPS and the most common site of origin of neurovascular tumors in the head and neck. The suprahyoid CS is located posterior to the PPS and extends superiorly into the carotid canal and jugular foramen at the skull base ( Fig. 14.12 ).




Figure 14.12


Schematic diagram of the normal anatomy of the parapharyngeal space ( PPS ) for correlation with radiographic imaging. The prestyloid space is separated from the poststyloid compartment or carotid space ( CS ) by the tensor-vascular-styloid fascia ( white line ) that extends medially from the styloid process ( S ) to the pharynx and overlies the tensor veli palatini muscle.

(Courtesy Memorial Sloan Kettering Cancer Center.)


When assessing the imaging, it is important to examine contiguous slices on CT or MRI to avoid confusing anatomic variations such as a dominant jugular vein or tortuous carotid artery. In general, the distinction between suprahyoid CS and PPS tumors can be made simply by assessing the direction of displacement of the fat in the PPS ( Fig. 14.13 ). Tumors originating in the CS characteristically displace the PPS fat and internal carotid artery anteriorly and the internal jugular vein laterally. In contrast, tumors of the PPS result in posterior displacement of these structures.




Figure 14.13


The pattern of displacement of parapharyngeal space (PPS) fat by tumors of the surrounding spaces allows identification of the origin of tumors in relation to the PPS. A , Pharyngeal mucosal space (PMS). B , Masticator space (MS). C , Parotid space (PS). D , Carotid space (CS).

(Courtesy Memorial Sloan Kettering Cancer Center.)


The two most common tumors in the suprahyoid CS, paragangliomas and nerve sheath tumors, can be distinguished radiographically, because paragangliomas are very vascular tumors. Paragangliomas enhance intensely on CT and MRI and have flow voids on MRI ( Fig. 14.14 ). Although flow voids are diagnostic of paragangliomas, they may not be readily apparent if the tumor is less than 2 cm in diameter. A contrast-enhanced CT scan can help make the diagnosis in these situations, because paragangliomas become intensely enhanced compared with nerve sheath tumors that may or may not become enhanced. Paragangliomas on the CT scan show enhancement and have a characteristic spindle-shaped appearance on the coronal or sagittal views ( Fig. 14.15 ). MRI, on the other hand, characteristically shows the flow voids and also demonstrates the spindle-shaped nature of the tumor giving a “rat tail” appearance on coronal and sagittal sections ( Fig. 14.16 ).




Figure 14.14


A , A contrast-enhanced axial CT scan shows a densely enhancing mass in the left carotid space that displaces the internal carotid artery ( arrow ) anteromedially. The internal jugular vein is not visible on this section, because it is effaced by the lesion. B , An axial postcontrast T1-weighted magnetic resonance imaging scan shows intense enhancement of the mass. The mass displaces the internal jugular vein posterolaterally ( black arrow ) and the internal carotid artery anteromedially ( white arrow ). C , Multiple low-signal flow voids ( white arrow ) on T1-weighted magnetic resonance imaging are a typical characteristic of a paraganglioma.

(From Stambuk HE, Patel SG. Imaging of the parapharyngeal space. Otolaryngol Clin North Am 41[1]:77–101, vi, 2008.)



Figure 14.15


Contrast-enhanced computed tomography scan of a patient with vagal paraganglioma in axial ( A ) and sagittal ( B ) views. Note the contrast enhancement and the location of the tumor posterior to the carotid artery and jugular vein on the axial view and a spindle-shaped tumor posterior to the carotid sheath in the sagittal view.



Figure 14.16


Magnetic resonance imaging scans in T2-weighted axial view ( A ), postcontrast T1-weighted coronal view ( B ), and postcontrast T1-weighted sagittal view ( C ) showing a vagal paraganglioma. Note contrast enhancement and flow voids, as well as “rat tail” appearance on coronal and sagittal views, characteristic of a paraganglioma of lower cranial nerves ( arrows ).


The classic carotid body tumor is located within the carotid bifurcation in the infrahyoid neck and therefore is not in immediate proximity to the PPS. It tends to splay the internal carotid artery and the external carotid artery at the carotid bifurcation ( Fig. 14.17 ). Carotid body tumors enhance intensely on a contrast-enhanced CT scan ( Fig. 14.18 ). The location of the external and internal carotid artery in relation to the tumor is crucial in surgical treatment planning. The carotid vessels may be superficial to the tumor, indenting into the tumor, or encased by the tumor. To assess these relationships, it is often necessary to obtain a contrast-enhanced CT scan with three-dimensional reconstructions, as well as a contrast-enhanced MRI for detailed assessment of the location and extent of the tumor and its relation to the carotid arteries ( Fig. 14.19 ). Three-dimensional reconstructions are also helpful in differentiating various types of carotid body tumors in relation to the carotid arteries ( Fig. 14.20 ). Complete evaluation of the imaging studies is necessary, since some patients may present with multiple paragangliomas on the same side of the neck or bilaterally ( Fig. 14.21 ). In contrast to a carotid body tumor, a glomus vagale tends to displace the carotid artery anteriorly ( Fig. 14.22 ). Unlike carotid body tumors, other paragangliomas often have demonstrable feeder vessels that most commonly arise from the ascending pharyngeal artery. It is important to point out that these feeder vessels are not readily apparent on noninvasive vascular imaging such as computed tomographic angiography (CTA) or magnetic resonance angiography (MRA) ( Fig. 14.23 ). Conventional angiography would be needed to demonstrate the feeder vessels and is recommended only if embolization is part of the treatment plan ( Fig. 14.24 ).




Figure 14.17


Sagittal precontrast T1-weighted magnetic resonance imaging (MRI) shows a mass (M) located in the carotid bifurcation splaying the internal carotid artery posteriorly and the external carotid artery anteriorly ( A ). A T2-weighted MRI scan of the same patient demonstrates bilateral carotid body tumors splaying the internal carotid artery ( arrowheads ) posteriorly and the external carotid artery ( arrows ) anteriorly ( B ).

(From Stambuk HE, Patel SG. Imaging of the parapharyngeal space. Otolaryngol Clin North Am 41[1]:77–101, vi, 2008.)



Figure 14.18


An axial view of a contrast-enhanced computed tomography scan of the neck showing a Shamblin type 1 carotid body tumor on the right-hand side.



Figure 14.19


Three-dimensional reconstructions of computed tomography angiograms showing a shambling type 1 carotid body tumor on the right-hand side in anterior, lateral, and posterior view showing the relationship of external and internal carotid arteries to the tumor ( arrows ).



Figure 14.20


An axial view of a contrast-enhanced computed tomography (CT) scan ( A ) showing a Shamblin type 2 carotid body tumor. CT angiography ( B ) clearly shows the location and relationship of the carotid arteries to the tumor.



Figure 14.21


An axial view of a contrast-enhanced computed tomography scan of the neck showing bilateral carotid body tumors.



Figure 14.22


A sagittal postcontrast T1-weighted magnetic resonance imaging scan shows a heterogeneously enhancing carotid space mass displacing both the internal carotid artery ( arrow ) and external carotid artery anteriorly and with cephalad extension into the jugular foramen ( arrow ) ( A ). An oblique computed tomography angiogram three-dimensional reconstruction nicely illustrates the relationship to the surrounding structures ( B ).

(From Stambuk HE, Patel SG. Imaging of the parapharyngeal space. Otolaryngol Clin North Am 41[1]:77–101, vi, 2008.)



Figure 14.23


Magnetic resonance angiogram of a patient with a carotid body tumor.



Figure 14.24


A direct angiogram through the right common carotid artery shows feeding blood vessels to a vagal paraganglioma.


Radiographic differentiation of a schwannoma from a neurofibroma is not straightforward. Heterogeneity within the lesion is more commonly seen in schwannomas because of a cystic change or hemorrhage. Schwannomas are well-encapsulated tumors that appear as round or ovoid masses. On MRI they are isointense to muscle on T1 and hyperintense on T2, and they become enhanced after administration of contrast ( Fig. 14.25 ). These imaging characteristics are by no means unique to schwannomas; paragangliomas can have similar imaging characteristics. However, as previously described, schwannomas do not have flow voids, even when they are large ( Fig. 14.26 and Fig. 14.27 ). The endoscopic view of a schwannoma of the retropharyngeal space projecting through the right posterolateral pharyngeal wall is shown in Fig. 14.28 . Typically, schwannomas do not show contrast enhancement on CT scan but are characteristically bright on T2-weighted MRI scan ( Fig. 14.29 ). In addition, schwannomas at the skull base generally cause regressive remodeling of bone, whereas permeative changes are seen more classically with paragangliomas.




Figure 14.25


An axial T2-weighted magnetic resonance imaging (MRI) scan shows a heterogeneous high-signal mass in the left carotid space without flow voids ( A ). The mass enhances heterogeneously on a postcontrast T1-weighted MRI scan, which is the typical appearance of a schwannoma ( B ).

(From Stambuk HE, Patel SG. Imaging of the parapharyngeal space. Otolaryngol Clin North Am 41[1]:77–101, vi, 2008.)



Figure 14.26


A postcontrast T1-weighted axial view of magnetic resonance imaging scan ( A ) showing a contrast enhancing schwannoma posterior to the carotid sheath in the lower part of the neck. On T2-weighted sequence, it is bright ( B ).



Figure 14.27


A , Coronal view of the magnetic resonance image of the tumor shown in Fig. 14.28 demonstrates a well-circumscribed “round” tumor in the lower part of the neck. B , Outline of the relationship of the tumor to great vessels in the lower part of the neck. BV, Brachial vein; CCA, common carotid artery; IJV, internal jugular vein; SCA, subclavian artery.



Figure 14.28


Endoscopic view of the hypopharynx showing a submucosal tumor mass of the prevertebral space projecting into the pharynx.



Figure 14.29


Imaging studies of the tumor shown in Fig. 14.28 . A contrast-enhanced computed tomography scan ( A ) showing a nonenhancing tumor in the prevertebral space. T2-weighted magnetic resonance imaging scans in axial ( B ), coronal ( C ), and sagittal ( D ) views show a well-demarcated “bright” tumor in the prevertebral space.


MRI also is of significant help in demonstrating neurogenic tumors with intraspinal and extraspinal extension (i.e., dumbbell tumors). A myelogram generally is not used unless MRI is contraindicated, because an MRI scan provides superior information with appropriate contrast enhancement ( Fig. 14.30 ). Noninvasive imaging generally does not provide functional information on the adequacy of cerebral circulation, and dedicated tests should be performed if carotid artery resection is a surgical possibility. These tests include balloon occlusion testing and/or radioactive xenon perfusion imaging.




Figure 14.30


An axial T2-weighted magnetic resonance imaging (MRI) scan shows a dumbbell tumor of neurogenic origin with intraspinal extension ( A ). A coronal view of a postcontrast T1-weighted MRI scan clearly shows the intraspinal extension ( B ).




Treatment


The management of neurogenic or neurovascular tumors in the head and neck has evolved considerably during the past three decades, along with a better understanding of the natural history of these tumors. Because surgery for carotid body tumors generally does not cause cranial nerve injury or deficit, most patients with carotid body tumors up to 6 to 7 cm without extension to the skull base are treated surgically. On the other hand, surgery for paragangliomas arising from the lower cranial nerves inflicts considerable morbidity. In the past, disability resulting from compromise of function of multiple cranial nerves as a result of a potential increase in the size of the tumor was considered an indication for early surgical intervention. Longitudinal population-based studies in the Netherlands have shown that these tumors grow very slowly (approximately 1 mm per year on average) and that surgical intervention often is associated with more detrimental effects than would be encountered with natural progression of the disease. These findings support the philosophy of observation as the definitive management in most patients. Accordingly, surgery is now used selectively, and the role of radiation in the management of these tumors under select circumstances is increasing.


Treatment selection is based on the size and location of the tumor, surgical risk, age and profession of the patient, and the potential risk of cranial nerve deficits resulting from surgery versus the potential benefit of nonsurgical treatment approaches. In general, younger patients with isolated tumors in whom the risk is limited to one cranial nerve are the best surgical candidates. Older patients who have larger tumors and a high risk for the injury of multiple cranial nerves should be treated nonsurgically. An algorithm for treatment selection for paragangliomas and schwannomas of the lower cranial nerves is shown in Fig. 14.31 .




Figure 14.31


An age-related algorithm for selection of therapy of paragangliomas and schwannomas of the lower cranial nerves. R.T., Radiation therapy.




Nonsurgical Treatment


Observation


Once the diagnosis is established, observation of paragangliomas or schwannomas of the lower cranial nerves should be considered for most patients. A thorough and informed discussion with the patient and the family should take place. The pros and cons of surgery, observation, and radiotherapy should be discussed in detail. The possibility of future intervention should be discussed. Most importantly, the need for continued clinical and imaging surveillance should be emphasized. Close observation with serial radiographic imaging either with a CT or MRI is recommended. An annual MRI with contrast enhancement is adequate for surveillance for the first few years. If the tumor is relatively stable, the imaging may be extended to every 2 years. Development of symptoms or rapid tumor growth warrants consideration for intervention.


Radiotherapy


Accumulating evidence suggests that radiation therapy is effective in the treatment of schwannomas and paragangliomas. Radiation therapy does not eradicate the tumor, but it can arrest further growth, and thus on subsequent posttreatment imaging studies the tumor remains stable. Radiation delivery techniques, including conventional fractionated external beam radiotherapy, stereotactic radiosurgery, and gamma knife radiosurgery, have been shown to be safe. More recently, use of intensity-modulated radiation therapy has been increasing. The 10-year local progression-free rates range from 92% to 100% with radiation doses of 45 to 54 Gy. Although transient cranial nerve palsies have been observed, particularly with stereotactic radiosurgery, no permanent neuropathy has been reported. In selecting patients for treatment, the risk for a radiation-induced second malignancy needs to be balanced against the immediate and permanent risk of cranial neuropathies caused by surgical intervention. Based on this assessment, radiation therapy is generally not recommended for younger patients.


Medical Management


Patients with functioning paragangliomas present with a history of flushing and episodic hypertension. Appropriate medical management requires control of hypertension with alpha blockade. For young patients with large paragangliomas located high in the parapharyngeal space, surgical intervention poses the risk of multiple cranial nerve injuries. If the tumor in a young patient shows progressive growth, then intervention is required for tumor control. Because radiotherapy in young patients poses the danger of radiation-induced tumors at a later age, experimental treatment approaches are considered in these patients. In such patients, a metaiodobenzylguanidine scan is performed, and if the scan is positive at the site of the tumor, such patients are candidates for consideration of treatment with somatostatin analog inhibitors. Response with shrinkage of tumor is observed in approximately 15% of patients who undergo this treatment.




Surgical Treatment


Indications for surgery are related to tumor and patient factors. Tumor factors include malignancy, rapid growth, or local pressure effects. Patient factors are related to the severity of symptoms and level of apprehension. Because most patients have unifocal lesions, surgical excision may be considered in younger patients if the risk of loss of function of only a single cranial nerve is anticipated. Small paragangliomas usually involve only one cranial nerve, but as the tumor enlarges, involvement of multiple cranial nerves becomes a cause for concern.


On the other hand, when a patient has a relatively stable tumor that is under observation and the cranial nerves are functioning, justification of surgical intervention is difficult. Rapid growth, cervical lymph node metastasis, or radiologic features of local invasion indicate a malignant tumor, warranting consideration for surgery.


Schwannomas and Neurofibromas


Management of neurogenic tumors of lateral and central compartments of the neck require different considerations. Schwannomas and neurofibromas of the lateral compartment (i.e., the cervical plexus and brachial plexus) can be treated with early surgical intervention, because the resultant neurological deficit generally is not significant. The potential risk of a cervical root neurofibroma extending into the spinal canal as a dumbbell tumor warrants the need for surgical intervention. Similarly, a schwannoma of the brachial plexus should be treated surgically to avoid invasion of additional adjacent nerves and thus produce additional neurologic deficit. However, schwannomas of the medial compartment (i.e., cranial nerves VII, IX, X, XII, and the sympathetic chain) require significant consideration of the tumor and the patient before making a decision regarding surgical intervention. The involved nerve rarely retains function after surgical excision, even if the tumor is enucleated with preservation of the surrounding fibers of the nerve. Therefore, if the affected cranial nerve is functioning and the tumor is not observed to be growing in size, simple clinical surveillance with periodic imaging studies to monitor the growth of the tumor is advisable. If significant growth in the lesion is observed, then surgical intervention is warranted. In general, a neurologic deficit occurs only in the nerve of origin of the tumor.


Paragangliomas


Management of paragangliomas is more difficult and requires consideration of the patient’s age and occupation and the tumor size, location, and site of origin. In general, carotid body tumors are treated by early surgical intervention if the patient is a safe surgical candidate. Permanent neurologic deficit of lower cranial nerves is rare, although temporary paralysis may occur in one or more lower cranial nerves, due to manipulation during dissection and removal of the tumor. Paragangliomas arising in the vagus, hypoglossal, and glossopharyngeal nerves or the sympathetic chain are more complicated. Excision of small paragangliomas generally will result in paralysis of the affected nerve alone, whereas surgery for larger paragangliomas located high in the neck at the skull base may result in multiple cranial nerve deficits, often permanently, leaving the patient with a significantly morbid postoperative course. Therefore the indications for surgical intervention are (1) malignant paraganglioma as diagnosed by radiologic features, or with the presence of cervical lymph node metastasis or distant metastasis; and (2) significant growth in the lesion over a short period or a small (<4 cm) paraganglioma in a young patient in the cervical region not approaching the skull base. All other patients with larger paragangliomas or those located at the base of the skull are candidates for nonsurgical management with continued surveillance.


Preoperative Preparation


All patients undergoing surgical resection for neurogenic tumors and paragangliomas must have an understanding of the nature of the surgery, the intraoperative risks involved, and proper preoperative counseling regarding the potential nerve deficits that may result after surgery. If the lesion is large and highly vascular, then preoperative angiographic studies should be performed to demonstrate the feeding vessels, and consideration should be given to preoperative embolization, which ideally should be performed within 24 hours of the planned surgical procedure. Although blood transfusions are seldom required, blood should be available on demand in the event of unexpected hemorrhage.


For larger lesions where integrity of the internal carotid artery is at risk, appropriate balloon occlusion studies of the carotid arteries should be performed to demonstrate satisfactory intracranial crossover circulation. Thus a balloon occlusion test of the ipsilateral carotid artery and cross-perfusion from the contralateral carotid artery to the ipsilateral cerebral hemisphere should be demonstrated. Anatomic demonstration of cross perfusion and a patent circle of Willis does not guarantee preservation of neurologic function. However, absence of cross perfusion significantly raises the potential for a stroke and should enter into the decision regarding surgical intervention. Thus the preoperative risk of a neurologic deficit must be discussed and the patient informed of such a risk if ligation of the carotid artery becomes necessary during the course of the operation. Similarly, a vascular surgeon should be available in the event of the need for resection of a segment of the internal carotid artery and its reconstruction.


Although it occurs rarely, patients with functioning paragangliomas and episodic facial flushing and hypertension may require preoperative management of hypertension with alpha blockade. Thus careful intraoperative monitoring of blood pressure during mobilization of the tumor is necessary.


Excision of a Carotid Body Tumor (Shamblin Type II)


The patient described in this procedure has a 6-cm pulsatile mass in the upper part of the neck on the right-hand side ( Fig. 14.32 ). An axial view of the MRI scan shown in Fig. 14.33 demonstrates a tumor mass separating the internal and external carotid arteries, which indent the substance of the tumor. This tumor is a Shamblin type II tumor. An MR angiogram demonstrates splaying of the external and internal carotid arteries by the tumor on the right-hand side ( Fig. 14.34 ).


Sep 29, 2019 | Posted by in HEAD AND NECK SURGERY | Comments Off on Neurogenic Tumors and Paragangliomas
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