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From the Archives of the AFIP¹

Paragangliomas of the Head and Neck: Radiologic-Pathologic Correlation

¹ From the Departments of Radiologic Pathology (A.B.R., K.K.K.) and Otolaryngic and Endocrine Pathology (C.F.A.), Armed Forces Institute of Pathology, 14th St at Alaska Ave, Bldg 54, Rm M-121 Washington, DC 20306-6000 and the Departments of Radiology and Nuclear Medicine (K.K.K.) and Pathology (C.F.A.), Uniformed Services University of the Health Sciences, Bethesda, Md. Received May 5, 1999; revision requested May 20 and received June 21; accepted June 21. Address reprint requests to K.K.K.

	Abstract

Top Abstract INTRODUCTION HISTORICAL PERSPECTIVE ORIGIN, LOCATION, AND SPREAD CLINICAL MANIFESTATIONS FAMILIAL PARAGANGLIOMAS FUNCTIONING PARAGANGLIOMAS PATHOLOGIC CHARACTERISTICS IMAGING OF PARAGANGLIOMAS DIFFERENTIAL DIAGNOSIS THERAPY SUMMARY References

 
Paragangliomas of the head and neck are ubiquitous in their distribution, originating from the paraganglia or glomus cells within the carotid body, vagal nerve, middle ear, jugular foramen, and numerous other locations. The typical patient is middle-aged and presents late in the course of the disease, with a painless slow-growing mass. Clinical manifestations include hoarseness of voice, lower cranial nerve palsies, pulsatile tinnitus, and other neuro-otologic symptoms. The overall prognosis of patients with a cervical paraganglioma is favorable, whereas its temporal bone counterpart often results in recurrence, residual tumor, and neurovascular compromise when in the advanced stage. Pathologic examination reveals a characteristic biphenotypic cell line, composed of chief cells and sustentacular cells with a peripheral fibrovascular stromal layer that are organized into a whorled pattern ("zellballen"). Imaging hallmarks of paragangliomas of the head and neck include an enhancing soft-tissue mass in the carotid space, jugular foramen, or tympanic cavity at computed tomography; a salt-and-pepper appearance at standard spin-echo magnetic resonance imaging; and an intense blush at angiography. Imaging studies depict the location and extent of tumor involvement, help determine the surgical approach, and help predict operative morbidity and mortality. Surgical treatment is definitive. Radiation treatment is included as a palliative adjunct for the exceptional paraganglioma not amenable to surgery.

Index Terms: Head and neck neoplasms, 127.3642, 21.369, 276.369 • Paraganglioma, 127.3642, 21.369, 276.369

	INTRODUCTION

Top Abstract INTRODUCTION HISTORICAL PERSPECTIVE ORIGIN, LOCATION, AND SPREAD CLINICAL MANIFESTATIONS FAMILIAL PARAGANGLIOMAS FUNCTIONING PARAGANGLIOMAS PATHOLOGIC CHARACTERISTICS IMAGING OF PARAGANGLIOMAS DIFFERENTIAL DIAGNOSIS THERAPY SUMMARY References

 
The extraadrenal neuroendocrine system comprises an integrated and complex system of dispersed tissue throughout the body that possesses unique regulatory functions. A single collection of this tissue is called a paraganglion (coined by Kohn in 1903), and the entire chain of tissue constitutes the paraganglia (1). Paraganglia are frequently located near nerves and vessels, belying their special chemoreceptor function (2). They arise from neural crest progenitor cells and are therefore of neuroectodermal origin. Paraganglia in the head and neck migrate along a branchiomeric (of the branchial mesoderm) distribution, whereas those in the chest, abdomen, and pelvis follow the path of parasympathetic nerve fibers along the perivertebral-periaortic axis.

Paragangliomas, the tumors of the paraganglia, arise from this specialized tissue at any site along these specific locations within the body. Accordingly, the distribution of these lesions is widespread. Within the head and neck, the four most common sites are the carotid body at the common carotid artery (CCA) bifurcation, the jugular foramen, along the vagus nerve, and within the middle ear. These masses produce characteristic findings on radiologic images, particularly computed tomographic (CT), magnetic resonance (MR) imaging, and angiographic studies. In this article, using approximately 90 cases from the Thompson Archives of the Department of Radiologic Pathology at the Armed Forces Institute of Pathology, we correlate the imaging features of paragangliomas with the underlying pathologic findings and highlight the distinctive features that allow the radiologist to suggest the diagnosis.

	HISTORICAL PERSPECTIVE

Top Abstract INTRODUCTION HISTORICAL PERSPECTIVE ORIGIN, LOCATION, AND SPREAD CLINICAL MANIFESTATIONS FAMILIAL PARAGANGLIOMAS FUNCTIONING PARAGANGLIOMAS PATHOLOGIC CHARACTERISTICS IMAGING OF PARAGANGLIOMAS DIFFERENTIAL DIAGNOSIS THERAPY SUMMARY References

 
Often confused for other head and neck tumors by the clinician and pathologist for nearly three-quarters of a century, the paraganglioma has defied categorization and logic. Marchand reported the first paraganglioma (of the carotid body) in 1891 (3). Numerous terms have been used since then to describe these tumors. The term glomus tumor was used to describe the rich arborization of blood vessels and nerves seen in these masses (4). Mulligan (5) proposed the term chemodectoma to reflect the chemoreceptor tissue of origin. Other names have included endothelioma, perithelioma, sympathoblastoma, fibroangioma, and sympathetic nevi (6). Based on the work of Glenner and Grimley (1), the term paraganglioma is currently accepted and widely used in the modern medical lexicon to describe these lesions. Paragangliomas are classified based on their location, innervation, and microscopic appearance (1) (Table 1).

	ORIGIN, LOCATION, AND SPREAD

Top Abstract INTRODUCTION HISTORICAL PERSPECTIVE ORIGIN, LOCATION, AND SPREAD CLINICAL MANIFESTATIONS FAMILIAL PARAGANGLIOMAS FUNCTIONING PARAGANGLIOMAS PATHOLOGIC CHARACTERISTICS IMAGING OF PARAGANGLIOMAS DIFFERENTIAL DIAGNOSIS THERAPY SUMMARY References

View larger version (144K): [in this window] [in a new window] [Download PPT slide]   Figure 1.   Drawing illustrates the most common locations of paraganglia of the head and neck. The carotid body paraganglion is a discrete mass found at the CCA bifurcation. Other locations include along the path of the vagus nerve, the jugular foramen, and the middle ear. The paraganglia tend to occur along the path of either vessels or nerves. (Reprinted from reference 3.)

A carotid body paraganglioma arises within the carotid body and characteristically splays the bifurcation of the CCA. As the tumor enlarges, it encases but does not narrow the caliber of the ECA and ICA. With disease progression, the lesion may involve the lower cranial nerves and adjacent pharynx. Superior extension to the skull base and invasion into the intracranial cavity have also been reported (9,10). The rate of growth of a carotid body paraganglioma is slow (ie, at about 5 mm/year) (11).

Unlike the carotid body, the paraganglia of the vagus nerve are not organized into a compact mass. On cross-section of the nerve, intravagal paraganglia are dispersed within the perineurium, below the nerve sheath, or between the nerve fiber fascicles. Along the long axis of the nerve, paraganglia typically occur within or below the inferior ganglion (nodose ganglion) or within the superior ganglion (jugular ganglion) (1).

In 1935, Stout (12) identified the first paraganglioma of the vagus nerve, and Birrell (13) proposed the term vagal body tumor in 1953. However, this term is technically inaccurate, because there is no discrete "vagal body." (3). The vagal paraganglioma most commonly arises from glomus tissue rests within the inferior (nodose) ganglion. Other locations include the superior ganglion or elsewhere along the course of the vagus nerve (Fig 2) (1). When a paraganglioma originates from the inferior ganglion, it appears spindle shaped, compresses the internal jugular vein (IJV), displaces the carotid vessels anteromedially, and typically pushes the lateral pharyngeal wall medially (14,15). There is typically minimal destruction of the skull base. When a paraganglioma originates from the superior ganglion, the tumor appears "dumbbell shaped," extending superiorly into the posterior fossa and inferiorly into the infratemporal space (15). With progressive growth of the tumor, a vagal paraganglioma can grow medially to involve the arch of the atlas (16), encase and displace the ICA (17), extend superiorly into the posterior fossa with compression of the brain stem (18), or extend laterally to involve the middle ear structures (19).

View larger version (149K): [in this window] [in a new window] [Download PPT slide]   Figure 2.   Drawing illustrates the sites of paraganglia of the skull base. Jugulotympanic paraganglia are located near the jugular bulb. The vagal paraganglia may arise at the jugular ganglion, at the nodose ganglion, or along the path of the vagus nerve (within the perineurium, between the nerve fascicles, or within the nerve itself). (Reprinted from reference 3.)

View larger version (125K): [in this window] [in a new window] [Download PPT slide]   Figure 3.   Diagram shows the major nerves and vessels of the jugular fossa. The inferior tympanic branch, or Jacobson nerve (J), of the glossopharyngeal nerve (IX) arises from and travels anterior to the IJV (JV) toward the middle ear, where it lies against the cochlear promontory. The auricular branch, or Arnold nerve (A), of the vagus nerve (X) follows a path posterior to the IJV on its way to the facial canal. Paraganglia are distributed along the course of these two nerves. Both nerves may give rise to paragangliomas. With current terminology, those residing in the middle ear and mastoid are called glomus tympanicum tumors, whereas those arising from the jugular foramen and adjacent skull base are called glomus jugulare tumors. XI = spinal accessory nerve, VII = facial nerve. (Reprinted, with permission, from reference 20.)

	CLINICAL MANIFESTATIONS

Top Abstract INTRODUCTION HISTORICAL PERSPECTIVE ORIGIN, LOCATION, AND SPREAD CLINICAL MANIFESTATIONS FAMILIAL PARAGANGLIOMAS FUNCTIONING PARAGANGLIOMAS PATHOLOGIC CHARACTERISTICS IMAGING OF PARAGANGLIOMAS DIFFERENTIAL DIAGNOSIS THERAPY SUMMARY References

 
Paragangliomas account for 0.6% of all neoplasms in the head and neck region and 0.03% of all neoplasms (17). About 80% of all paragangliomas are either carotid body tumors or glomus jugulare tumors (29). However, there are conflicting reports regarding the prevalence of these two paraganglioma subtypes. Some investigators describe the glomus jugulare tumor as the most common paraganglioma followed closely by those of carotid body origin (17,30), whereas others believe that the carotid body tumor is most common, slightly ahead of the glomus jugulotympanic tumors (15,31,32). There is general consensus that the vagal paraganglioma (5% of paragangliomas) is a distant third in terms of prevalence. In addition, the paraganglioma is the second most common neoplasm of the temporal bone, second only to acoustic schwannomas (25,33), and the glomus tympanicum tumor is the most common neoplasm of the middle ear (33).

A higher prevalence of carotid body tumors has been noted in some patients with chronic obstructive pulmonary disease (34) and in certain populations living at high altitudes (eg, Peruvian Andes, Colorado, and Mexico City); this is believed to be secondary to chronic hypoxia in combination with genetic factors (35). The carotid body tumor can occur at any age, with a peak prevalence in the 45–50 year-old age group (3). It is uncommon in the pediatric population (3,36,37). No gender predilection is noted. The peak age of occurrence of both the vagal paraganglioma and glomus jugulotympanicum tumors is the 5th and 6th decades of life (9), with a female-male ratio of 2.7:1 for vagal body tumors (30) and 4–6:1 for glomus jugulotympanicum tumors (16,38).

The classic clinical manifestation of a carotid body tumor is a nontender, insidiously enlarging lateral neck mass in an otherwise asymptomatic patient. The mass can be moved from side to side, transmits pulsations, and is often associated with a bruit (39). Other symptoms include hoarseness, stridor, tongue paresis, vertigo, and mild dysphagia (9).

The vagal paraganglioma manifests as a slowly growing, painless lateral neck mass, most commonly located behind the angle of the mandible (83% of cases). Intraoral and neck masses may be discovered simultaneously (46% of cases). Least commonly, it may manifest as a solitary intraoral mass with medial displacement of the pretonsillar structures (16% of cases) (17). Vagal nerve deficits are seen late in the clinical course of these lesions, as the fibers of the vagus nerve are usually splayed over the surface of the tumor (18). Other lower cranial nerve palsies from hypoglossal, accessory (33,40,41), or glossopharyngeal involvement (15) also commonly occur as late manifestations, typically 2 years after initial presentation with an overall prevalence of 20%–50%. Horner syndrome (ptosis, miosis, anhidrosis, and enophthalmos) with infiltration into the cervical sympathetic chain occurs in 25% of patients (17,42,43). Rare manifestations include isolated hoarseness or vocal cord paralysis (17,44).

In a review of 107 patients, Remley et al (45) found that the glomus jugulare-tympanicum tumor was the most common cause of pulsatile tinnitus in association with a retrotympanic vascular mass (vascular tympanic membrane). Other possible clinical manifestations of these lesions include conduction deafness, vertigo, hoarseness, and aural pain or discharge. Cranial nerve palsies occur late in the course of the disease resulting in Vernet (jugular foramen) syndrome (motor paralysis of cranial nerves IX, X, and XI) (33), Collet-Sicard syndrome (Vernet syndrome with additional involvement of cranial nerve XII) (46), and Horner syndrome (33).

Paragangliomas may be multicentric and may manifest as unilateral or bilateral lesions (47). These multicentric lesions may occur either synchronously or metachronously. Bilateral carotid body tumors occur in 5% of sporadic and 33%–38% of familial paragangliomas (Fig 4) (48,49). Hereditary deficiencies of clotting factors are associated with familial carotid body tumors (3). Known combinations of head and neck paragangliomas include vagal–carotid body paragangliomas, carotid body–glomus jugulare tumors (50), and carotid body–glomus jugulotympanicum tumors (Fig 5) (51). Simultaneous occurrence of pheochromocytoma, papillary thyroid carcinoma, Carney triad (gastric leiomyosarcoma or leiomyoblastoma, pulmonary chondroma, and functioning extraadrenal paraganglioma) (52), and other endocrine disorders along with the carotid body tumor have also been reported, suggesting the possibility of a rare form of multiple endocrine neoplasia (3).

View larger version (161K): [in this window] [in a new window] [Download PPT slide]   Figure 4a.   Bilateral carotid body tumors in a 40-year-old man with progressive bilateral neck swelling, dysphagia, and dyspnea. (a) Sagittal T1-weighted MR image shows a left-sided neck mass (m) that is isointense relative to muscle at the level of the common carotid bifurcation. The ECA (short arrow) is splayed from the ICA (long arrow). An additional component of the mass (*) extended inferiorly. (b) Different sagittal T1-weighted MR image reveals numerous flow voids (arrowheads) throughout the right-sided neck mass (m). (c) Axial T1-weighted MR image demonstrates bilateral carotid space masses (m). c = right CCA, i = left ICA, v = IJV, arrow = ECA.

View larger version (161K): [in this window] [in a new window] [Download PPT slide]   Figure 4b.   Bilateral carotid body tumors in a 40-year-old man with progressive bilateral neck swelling, dysphagia, and dyspnea. (a) Sagittal T1-weighted MR image shows a left-sided neck mass (m) that is isointense relative to muscle at the level of the common carotid bifurcation. The ECA (short arrow) is splayed from the ICA (long arrow). An additional component of the mass (*) extended inferiorly. (b) Different sagittal T1-weighted MR image reveals numerous flow voids (arrowheads) throughout the right-sided neck mass (m). (c) Axial T1-weighted MR image demonstrates bilateral carotid space masses (m). c = right CCA, i = left ICA, v = IJV, arrow = ECA.

View larger version (151K): [in this window] [in a new window] [Download PPT slide]   Figure 4c.   Bilateral carotid body tumors in a 40-year-old man with progressive bilateral neck swelling, dysphagia, and dyspnea. (a) Sagittal T1-weighted MR image shows a left-sided neck mass (m) that is isointense relative to muscle at the level of the common carotid bifurcation. The ECA (short arrow) is splayed from the ICA (long arrow). An additional component of the mass (*) extended inferiorly. (b) Different sagittal T1-weighted MR image reveals numerous flow voids (arrowheads) throughout the right-sided neck mass (m). (c) Axial T1-weighted MR image demonstrates bilateral carotid space masses (m). c = right CCA, i = left ICA, v = IJV, arrow = ECA.

View larger version (121K): [in this window] [in a new window] [Download PPT slide]   Figure 5.   Bilateral vagal paragangliomas in a 58-year-old man with asymptomatic suprahyoid neck masses. Contrast material-enhanced axial CT scan shows heterogeneous bilateral carotid space masses (m) with displacement of the parapharyngeal fat (arrows) anteriorly. The styloid processes are indicated by arrowheads. Preoperative embolization could not be performed secondary to vasospasm. At surgery, only the left vagal paraganglioma was removed following uneventful ligation of the left ICA.

The mortality rates for patients with jugulotympanic tumors and carotid body tumors are estimated at 15% and 9%, respectively (29,56). The prevalence of local recurrence and local invasion is estimated at 40%–50% for glomus jugulare tumors (1), 17% for vagal paragangliomas, and about 10% for carotid body tumors (56). Intracranial extension from skull base paragangliomas is estimated at 14.6%–20% (33, 57). Although Gardner et al (58) have claimed that most cases of intracranial extension of paragangliomas are confined to the extradural compartment, approximately half of the skull base paragangliomas in a series of 24 lesions reported by Anand et al (59) had intradural extension.

	FAMILIAL PARAGANGLIOMAS

Top Abstract INTRODUCTION HISTORICAL PERSPECTIVE ORIGIN, LOCATION, AND SPREAD CLINICAL MANIFESTATIONS FAMILIAL PARAGANGLIOMAS FUNCTIONING PARAGANGLIOMAS PATHOLOGIC CHARACTERISTICS IMAGING OF PARAGANGLIOMAS DIFFERENTIAL DIAGNOSIS THERAPY SUMMARY References

 
Chase (60) first described the familial occurrence of paragangliomas in 1933. Familial paragangliomas have an overall prevalence of 7%–9% (55, 61–63), with approximately 90% of cases arising from the carotid body (30), and a higher prevalence in younger patients with an average age of 38.8 years (61,64). The mode of transmission is described as autosomal dominant with incomplete penetrance. An alteration in the genetic code (on the long arm of chromosome 11) causes deactivation of tumor suppressor proteins and results in the familial phenotype (65,66). According to the theory of genomic imprinting, there may be "deactivation of genes during oogenesis and reactivation of the same during spermatogenesis." (31). The disease therefore manifests exclusively through the paternal line (ie, only the gene transmitted through the father of a pedigree will manifest as a familial paraganglioma) (31,64). Some authors postulate that sporadic paragangliomas might represent a forme fruste of familial paragangliomas that have been clinically occult for generations because of transmission through the female members of an afflicted family (64).

	FUNCTIONING PARAGANGLIOMAS

Top Abstract INTRODUCTION HISTORICAL PERSPECTIVE ORIGIN, LOCATION, AND SPREAD CLINICAL MANIFESTATIONS FAMILIAL PARAGANGLIOMAS FUNCTIONING PARAGANGLIOMAS PATHOLOGIC CHARACTERISTICS IMAGING OF PARAGANGLIOMAS DIFFERENTIAL DIAGNOSIS THERAPY SUMMARY References

 
Extraadrenal paragangliomas that are hormonally active are called functioning paragangliomas (1). These tumors secrete catecholamines, often causing increased morbidity and mortality. However, functioning carotid body tumors and glomus jugulotympanicum tumors produce clinical manifestations (such as hypertension, headaches, palpitations, and tachycardia) less commonly than expected (2). Researchers speculate that this discrepancy reflects a requirement of at least a four- to fivefold increase in circulating catecholamines to produce clinical symptoms (17). Accordingly, the true prevalence of functioning paragangliomas is not known, but some authors estimate that they occur in 1%–3% of cases (17). Contributory laboratory data include urinary (elevated 24-hour metanephrine and vanillylmandelic acid levels) and serum (catecholamine and glucose levels) screening tests (67).

	PATHOLOGIC CHARACTERISTICS

Top Abstract INTRODUCTION HISTORICAL PERSPECTIVE ORIGIN, LOCATION, AND SPREAD CLINICAL MANIFESTATIONS FAMILIAL PARAGANGLIOMAS FUNCTIONING PARAGANGLIOMAS PATHOLOGIC CHARACTERISTICS IMAGING OF PARAGANGLIOMAS DIFFERENTIAL DIAGNOSIS THERAPY SUMMARY References

 
The carotid body tumor manifests as a well-defined, lobulated solid mass with a fibrous pseudocapsule. The size varies between 1.0 and 8.5 cm, with an average of 3.8 cm (56). The external surface is usually tan-gray to reddish-purple, whereas the cut surface has multiple blood vessels. Although a homogeneous appearance is characteristic, foci of necrosis, sclerosis, and cystic change are described in rare cases (3). The vagal paraganglioma is fusiform or globular in shape, with many of its gross characteristics resembling those of the carotid body tumor. Useful discriminating features include larger areas of sclerosis and the identifiable stump of the excised vagus nerve. The jugulotympanic paraganglioma is usually excised in multiple fragments, with much of its in situ appearance otherwise resembling that of the carotid body tumor (3).

Both light and electron microscopy of paragangliomas reveal a biphasic or biphenotypic pattern identical to that seen in pheochromocytoma (adrenal paraganglioma) and composed of chief (type 1) cells and sustentacular cells (type 2) surrounded by a fibrovascular stroma (2,3). The chief cells are arranged into compact cell nests or balls of cells (termed zellballen by Kohn) and classically exhibit a whorled architecture (Fig 6) (68). The chief cells are more numerous and are centrally distributed within the cell clusters. These cells are polygonal, round, or oval (2), with large rounded nuclei and prominent nucleoli (69). The sustentacular cell is peripherally situated, is spindle-shaped, and has long cytoplasmic processes that may mimic vascular pericytes. These characteristic, long cytoplasmic processes typically confer a whorled configuration. Less commonly, trabecular, pseudorosette, or pseudoglandular patterns of cellular arrangements may be seen. The stroma surrounding these two cell lines is an admixture of nerve fibers, endothelial cells, and vascular pericytes (2).

View larger version (221K): [in this window] [in a new window] [Download PPT slide]   Figure 6a.   Paraganglioma with typical histologic features. (a) High-power photomicrograph (original magnification, x200; reticulin stain) shows the characteristic zellballen (cell ball) growth pattern. The reticulin stain accentuates the delicate fibrovascular network (primarily collagen and capillaries) that surrounds each "ball" (arrows) of chief cells. (b) High-power photomicrograph (original magnification, x300; hematoxylin-eosin stain) reveals a sea of chief cells with abundant granular cytoplasm. Some degree of nuclear pleomorphism is often present. Two nuclei with different morphology are indicated (arrow and arrowhead). The zellballen pattern is very inconspicuous in a routine hematoxylin-eosin stained section and better demonstrated by immunohistochemical techniques.

View larger version (229K): [in this window] [in a new window] [Download PPT slide]   Figure 6b.   Paraganglioma with typical histologic features. (a) High-power photomicrograph (original magnification, x200; reticulin stain) shows the characteristic zellballen (cell ball) growth pattern. The reticulin stain accentuates the delicate fibrovascular network (primarily collagen and capillaries) that surrounds each "ball" (arrows) of chief cells. (b) High-power photomicrograph (original magnification, x300; hematoxylin-eosin stain) reveals a sea of chief cells with abundant granular cytoplasm. Some degree of nuclear pleomorphism is often present. Two nuclei with different morphology are indicated (arrow and arrowhead). The zellballen pattern is very inconspicuous in a routine hematoxylin-eosin stained section and better demonstrated by immunohistochemical techniques.

Various electron microscopic features of paragangliomas have been described in the literature, but they have limited usefulness in making the diagnosis and predicting the prognosis of paragangliomas (2). Identification of osmiophilic neurosecretory granules in the chief cells (1,16) is considered a hallmark feature, essential for the electron microscopic diagnosis of paragangliomas (2).

Immunohistochemical techniques, besides being easier to perform, have greater utility in the diagnosis and in predicting the behavior of paragangliomas (2). Chromogranins, the structural proteins within the neurosecretory granules of chief cells, are specific for neuroendocrine tumors (2). S-100 protein, a sustentacular cell marker (2,29), is commonly used in combination with chromogranin to demonstrate the biphasic cellular makeup of paragangliomas (Fig 7). S-100 staining is diminished in malignant paragangliomas, a finding indicating a loss of sustentacular cells (2,29). Sy 38 is a marker for synaptophysin, an integral membrane glycoprotein, and is a sensitive but not entirely specific marker for neuroendocrine tumors (2).

View larger version (213K): [in this window] [in a new window] [Download PPT slide]   Figure 7a.   Two cell types seen in a paraganglioma. (a) High-power photomicrograph (original magnification, x400; S-100 protein stain) shows sustentacular cells with prominent brownish stain found at the periphery of the cell balls of chief cells. Two such cells are indicated by the arrows. (b) High-power photomicrograph (original magnification, x400; chromogranin stain) reveals brownish stain (arrows) of chromogranin in the cytoplasm of chief cells. The nuclei of the chief cells remain bluish.

View larger version (217K): [in this window] [in a new window] [Download PPT slide]   Figure 7b.   Two cell types seen in a paraganglioma. (a) High-power photomicrograph (original magnification, x400; S-100 protein stain) shows sustentacular cells with prominent brownish stain found at the periphery of the cell balls of chief cells. Two such cells are indicated by the arrows. (b) High-power photomicrograph (original magnification, x400; chromogranin stain) reveals brownish stain (arrows) of chromogranin in the cytoplasm of chief cells. The nuclei of the chief cells remain bluish.

	IMAGING OF PARAGANGLIOMAS

Top Abstract INTRODUCTION HISTORICAL PERSPECTIVE ORIGIN, LOCATION, AND SPREAD CLINICAL MANIFESTATIONS FAMILIAL PARAGANGLIOMAS FUNCTIONING PARAGANGLIOMAS PATHOLOGIC CHARACTERISTICS IMAGING OF PARAGANGLIOMAS DIFFERENTIAL DIAGNOSIS THERAPY SUMMARY References

 
Virtually all patients with a paraganglioma of the head and neck region undergo some type of cross-sectional imaging, usually CT or MR imaging. Both CT and MR depict these highly vascular, soft-tissue masses equally well on contrast-enhanced images. Which study is performed first or whether a second imaging study is required before embarking on more invasive procedures will depend on the availability of the specific imaging modality at a particular institution and the preferences of the referring physician and the radiologist.

CT Appearance
The typical CT appearance of a carotid body tumor is a well-defined soft-tissue mass within the carotid space of the infrahyoid neck (Figs 8, 9). The underlying hypervascularity of the tumor results in homogeneous and intense enhancement following intravenous administration of contrast material. Splaying of the common carotid bifurcation is very suggestive of a carotid body tumor. Rare manifestations include a heterogeneous pattern of enhancement due to focal thrombi or hemorrhage in larger lesions (79) and superior extension into the suprahyoid neck, seen in 8% of carotid body tumors (80).

View larger version (147K): [in this window] [in a new window] [Download PPT slide]   Figure 8a.   Carotid body tumor in a 67-year-old woman with a slowly growing, left-sided neck mass for several years and recent onset of left ear tinnitus. (a) Contrast-enhanced axial CT image demonstrates an intensely enhancing left carotid space mass (m) that splays the ECA (short arrow) from the ICA (long arrow). (b) Lateral angiographic view obtained after a left CCA injection reveals splaying of the ECA from the ICA by a hypervascular mass (arrows) that extends to the bifurcation. (c) Lateral angiographic view obtained after a selective left ascending pharyngeal artery injection reveals the hypervascular mass (arrows) with primary vascular supply from this artery.

View larger version (149K): [in this window] [in a new window] [Download PPT slide]   Figure 8b.   Carotid body tumor in a 67-year-old woman with a slowly growing, left-sided neck mass for several years and recent onset of left ear tinnitus. (a) Contrast-enhanced axial CT image demonstrates an intensely enhancing left carotid space mass (m) that splays the ECA (short arrow) from the ICA (long arrow). (b) Lateral angiographic view obtained after a left CCA injection reveals splaying of the ECA from the ICA by a hypervascular mass (arrows) that extends to the bifurcation. (c) Lateral angiographic view obtained after a selective left ascending pharyngeal artery injection reveals the hypervascular mass (arrows) with primary vascular supply from this artery.

View larger version (131K): [in this window] [in a new window] [Download PPT slide]   Figure 8c.   Carotid body tumor in a 67-year-old woman with a slowly growing, left-sided neck mass for several years and recent onset of left ear tinnitus. (a) Contrast-enhanced axial CT image demonstrates an intensely enhancing left carotid space mass (m) that splays the ECA (short arrow) from the ICA (long arrow). (b) Lateral angiographic view obtained after a left CCA injection reveals splaying of the ECA from the ICA by a hypervascular mass (arrows) that extends to the bifurcation. (c) Lateral angiographic view obtained after a selective left ascending pharyngeal artery injection reveals the hypervascular mass (arrows) with primary vascular supply from this artery.

View larger version (149K): [in this window] [in a new window] [Download PPT slide]   Figure 9a.   Carotid body tumor in a 63-year-old woman with a slowly enlarging, left-sided neck mass over a 2-year period. (a) Contrast-enhanced axial CT image obtained at the level of the hyoid bone (partially seen secondary to asymmetry of the patient in the scanner) reveals a heterogeneously enhancing mass (m) within the left carotid space. (b) Contrast-enhanced axial CT image of the suprahyoid neck shows the mass (m) extending superiorly within the left carotid space. (c) Photograph of the gross specimen shows the smooth surface and thin capsule of the carotid body tumor. Numerous vessels feed the tumor along the capsular surface.

View larger version (146K): [in this window] [in a new window] [Download PPT slide]   Figure 9b.   Carotid body tumor in a 63-year-old woman with a slowly enlarging, left-sided neck mass over a 2-year period. (a) Contrast-enhanced axial CT image obtained at the level of the hyoid bone (partially seen secondary to asymmetry of the patient in the scanner) reveals a heterogeneously enhancing mass (m) within the left carotid space. (b) Contrast-enhanced axial CT image of the suprahyoid neck shows the mass (m) extending superiorly within the left carotid space. (c) Photograph of the gross specimen shows the smooth surface and thin capsule of the carotid body tumor. Numerous vessels feed the tumor along the capsular surface.

View larger version (111K): [in this window] [in a new window] [Download PPT slide]   Figure 9c.   Carotid body tumor in a 63-year-old woman with a slowly enlarging, left-sided neck mass over a 2-year period. (a) Contrast-enhanced axial CT image obtained at the level of the hyoid bone (partially seen secondary to asymmetry of the patient in the scanner) reveals a heterogeneously enhancing mass (m) within the left carotid space. (b) Contrast-enhanced axial CT image of the suprahyoid neck shows the mass (m) extending superiorly within the left carotid space. (c) Photograph of the gross specimen shows the smooth surface and thin capsule of the carotid body tumor. Numerous vessels feed the tumor along the capsular surface.

View larger version (150K): [in this window] [in a new window] [Download PPT slide]   Figure 10a.   Vagal paraganglioma in a 29-year-old woman with an asymptomatic, painless neck mass for several years that recently enlarged. (a) Contrast-enhanced axial CT image reveals intense enhancement of a left carotid space mass (m). (b) Lateral angiographic view obtained with a left CCA injection demonstrates the hypervascular mass (arrow) displacing both the ECA and ICA anteriorly.

View larger version (133K): [in this window] [in a new window] [Download PPT slide]   Figure 10b.   Vagal paraganglioma in a 29-year-old woman with an asymptomatic, painless neck mass for several years that recently enlarged. (a) Contrast-enhanced axial CT image reveals intense enhancement of a left carotid space mass (m). (b) Lateral angiographic view obtained with a left CCA injection demonstrates the hypervascular mass (arrow) displacing both the ECA and ICA anteriorly.

View larger version (151K): [in this window] [in a new window] [Download PPT slide]   Figure 11a.   Vagal paraganglioma in a 30-year-old woman with left-sided neck swelling and a pulsatile mass at physical examination. (a) Contrast-enhanced CT image shows mild heterogeneous enhancement of a large left carotid space mass (m). (b) Contrast-enhanced CT image shows inferior extension of the mass (m) to the level of the hyoid bone.

View larger version (147K): [in this window] [in a new window] [Download PPT slide]   Figure 11b.   Vagal paraganglioma in a 30-year-old woman with left-sided neck swelling and a pulsatile mass at physical examination. (a) Contrast-enhanced CT image shows mild heterogeneous enhancement of a large left carotid space mass (m). (b) Contrast-enhanced CT image shows inferior extension of the mass (m) to the level of the hyoid bone.

View larger version (147K): [in this window] [in a new window] [Download PPT slide]   Figure 12a.   Vagal paraganglioma in a 46-year-old man with a nontender, slowly enlarging, right-sided neck mass. (a) Contrast-enhanced axial CT image shows a well-defined right carotid space mass (m) with smooth margins and enhancement. (b) Lateral angiographic view obtained after an ECA injection reveals an enlarged ascending pharyngeal artery as the primary supply to the hypervascular mass (arrow). (c) Another lateral angiographic view from the same injection in the later arterial phase shows an intense blush more prominent in the superior half of the mass (arrow).

View larger version (140K): [in this window] [in a new window] [Download PPT slide]   Figure 12b.   Vagal paraganglioma in a 46-year-old man with a nontender, slowly enlarging, right-sided neck mass. (a) Contrast-enhanced axial CT image shows a well-defined right carotid space mass (m) with smooth margins and enhancement. (b) Lateral angiographic view obtained after an ECA injection reveals an enlarged ascending pharyngeal artery as the primary supply to the hypervascular mass (arrow). (c) Another lateral angiographic view from the same injection in the later arterial phase shows an intense blush more prominent in the superior half of the mass (arrow).

View larger version (142K): [in this window] [in a new window] [Download PPT slide]   Figure 12c.   Vagal paraganglioma in a 46-year-old man with a nontender, slowly enlarging, right-sided neck mass. (a) Contrast-enhanced axial CT image shows a well-defined right carotid space mass (m) with smooth margins and enhancement. (b) Lateral angiographic view obtained after an ECA injection reveals an enlarged ascending pharyngeal artery as the primary supply to the hypervascular mass (arrow). (c) Another lateral angiographic view from the same injection in the later arterial phase shows an intense blush more prominent in the superior half of the mass (arrow).

View larger version (154K): [in this window] [in a new window] [Download PPT slide]   Figure 13a.   Glomus jugulare tumor in a 56-year-old man with positional vertigo, left sensorineural hearing loss, and paresis of the left facial and hypoglossal nerves. (a) Axial CT image (bone window) shows a left jugular foramen mass (m) with mildly irregular margins. (b) Coronal CT image (bone window) reveals the mass (m) with irregularity along the superior rim. (c) Coronal CT image (bone window) shows soft tissue extending into the left middle ear (arrow). (d) Contrast-enhanced axial T1-weighted MR image shows the enhancing mass (arrow) of the left jugular foramen.

View larger version (123K): [in this window] [in a new window] [Download PPT slide]   Figure 13b.   Glomus jugulare tumor in a 56-year-old man with positional vertigo, left sensorineural hearing loss, and paresis of the left facial and hypoglossal nerves. (a) Axial CT image (bone window) shows a left jugular foramen mass (m) with mildly irregular margins. (b) Coronal CT image (bone window) reveals the mass (m) with irregularity along the superior rim. (c) Coronal CT image (bone window) shows soft tissue extending into the left middle ear (arrow). (d) Contrast-enhanced axial T1-weighted MR image shows the enhancing mass (arrow) of the left jugular foramen.

View larger version (113K): [in this window] [in a new window] [Download PPT slide]   Figure 13c.   Glomus jugulare tumor in a 56-year-old man with positional vertigo, left sensorineural hearing loss, and paresis of the left facial and hypoglossal nerves. (a) Axial CT image (bone window) shows a left jugular foramen mass (m) with mildly irregular margins. (b) Coronal CT image (bone window) reveals the mass (m) with irregularity along the superior rim. (c) Coronal CT image (bone window) shows soft tissue extending into the left middle ear (arrow). (d) Contrast-enhanced axial T1-weighted MR image shows the enhancing mass (arrow) of the left jugular foramen.

View larger version (152K): [in this window] [in a new window] [Download PPT slide]   Figure 13d.   Glomus jugulare tumor in a 56-year-old man with positional vertigo, left sensorineural hearing loss, and paresis of the left facial and hypoglossal nerves. (a) Axial CT image (bone window) shows a left jugular foramen mass (m) with mildly irregular margins. (b) Coronal CT image (bone window) reveals the mass (m) with irregularity along the superior rim. (c) Coronal CT image (bone window) shows soft tissue extending into the left middle ear (arrow). (d) Contrast-enhanced axial T1-weighted MR image shows the enhancing mass (arrow) of the left jugular foramen.

View larger version (124K): [in this window] [in a new window] [Download PPT slide]   Figure 14a.   Glomus jugulare tumor in a 44-year-old woman with headaches, visual loss in the right eye, diplopia, and periorbital pain. (a) Contrast-enhanced coronal CT image shows a large infratemporal fossa mass (m) with soft tissue extending into the right middle ear (arrow). (b) Contrast-enhanced coronal CT image (bone window) demonstrates extensive skull base destruction and extension of the mass into the middle cranial fossa. Numerous calcifications are scattered throughout the mass.

View larger version (141K): [in this window] [in a new window] [Download PPT slide]   Figure 14b.   Glomus jugulare tumor in a 44-year-old woman with headaches, visual loss in the right eye, diplopia, and periorbital pain. (a) Contrast-enhanced coronal CT image shows a large infratemporal fossa mass (m) with soft tissue extending into the right middle ear (arrow). (b) Contrast-enhanced coronal CT image (bone window) demonstrates extensive skull base destruction and extension of the mass into the middle cranial fossa. Numerous calcifications are scattered throughout the mass.

View larger version (136K): [in this window] [in a new window] [Download PPT slide]   Figure 15a.   Glomus jugulare tumor in a 75-year-old woman with progressive right hearing loss, tinnitus, and right ear pruritus. Deficits involving cranial nerves VII-XII of the right side were documented at physical examination. (a) Axial CT image (bone window) reveals an expanding mass (m) and lytic changes of the right temporal bone (arrows). Soft tissue extends into the middle ear and external auditory canal (arrowheads). (b) Axial CT image (bone window) shows extensive destruction of the right temporal bone centered in the jugular fossa (arrows). Soft-tissue attenuation is present within the mastoid air cells and middle ear secondary to inflammatory change.

View larger version (136K): [in this window] [in a new window] [Download PPT slide]   Figure 15b.   Glomus jugulare tumor in a 75-year-old woman with progressive right hearing loss, tinnitus, and right ear pruritus. Deficits involving cranial nerves VII-XII of the right side were documented at physical examination. (a) Axial CT image (bone window) reveals an expanding mass (m) and lytic changes of the right temporal bone (arrows). Soft tissue extends into the middle ear and external auditory canal (arrowheads). (b) Axial CT image (bone window) shows extensive destruction of the right temporal bone centered in the jugular fossa (arrows). Soft-tissue attenuation is present within the mastoid air cells and middle ear secondary to inflammatory change.

View larger version (130K): [in this window] [in a new window] [Download PPT slide]   Figure 16a.   Glomus jugulotympanicum tumor in a 67-year-old woman with pulsatile tinnitus, episodic dizziness, and left hearing loss. At otoscopic examination, a reddish purple mass was seen filling the left middle ear; conductive hearing loss was also documented. (a) Axial CT image (bone window) shows a soft-tissue mass (arrowheads) filling the hypotympanum of the left middle ear. There is erosion (arrow) of the anterolateral segment of the jugular fossa wall. Soft-tissue attenuation fills the left mastoid air cells secondary to inflammatory change. (b) Axial T1-weighted MR image reveals soft-tissue signal intensity within the middle ear (arrow) and inflammatory change within the left mastoid air spaces. (c) Axial T2-weighted MR image shows hyperintensity of the lesion (arrow) and masto