CASE REPORT

James I. Cohen, MD, PhD, Section Editor

SYMPATHETIC PARAGANGLIOMA AS AN UNUSUALCAUSE OF HORNER’S SYNDROME

Jeffrey S. Moyer, MD, Carol R. Bradford, MD

Department of Otolaryngology, Head and Neck Surgery, University of Michigan Medical Center, 1500 E MedicalCenter Drive, 1904 Taubman Center, Ann Arbor, MI 48109-0312

Accepted 11 July 2000

Abstract: Background. Paragangliomas are rare tumors aris-ing from paraganglionic tissue of neural crest origin. They arepresent in any location where autonomic ganglia are found. Themost common location in the head and neck is the carotid body,followed by the jugular bulb and vagus nerve.

Methods. A 30-year-old woman with a slowly growing leftneck mass, aniscoria, and left eyelid ptosis was found to have avascular tumor consistent with a paraganglioma arising near theleft carotid bifurcation. After preoperative embolization, the pa-tient underwent resection of the tumor.

Results. The tumor was found to be arising from the left sym-pathetic trunk and did not involve any other surrounding struc-tures. Histopathologic analysis revealed the typical findings of aparaganglioma.

Conclusions. Sympathetic paragangliomas are exceedinglyrare tumors in the head and neck and should be considered in thedifferential diagnosis when clinical and radiographic evidencesuggest a paraganglioma. The presentation is typically a slow-growing neck mass with the presence of an ipsilateral Horner’ssyndrome. © 2001 John Wiley & Sons, Inc. Head Neck 23: 338–342, 2001.

Keywords: paraganglioma; sympathetic nerve; Horner’s syn-drome; neck mass; Zellballen

A 30-year-old woman was seen with a 1-year his-tory of a slowly enlarging left neck mass and aseveral month history of aniscoria and left eyelidptosis. The patient denied problems with hoarse-ness, dysphagia, hypertension, palpitations, tin-nitus, or hearing loss. The medical history wasremarkable for hypothyroidism, and 2 years be-fore presentation the patient underwent an openneck biopsy for a benign enlarged left cervicallymph node.

On physical examination, there was a diffuse,ill-defined mass in the left level II neck that wasnontender and nonpulsatile. There was no detect-able bruit. There was obvious aniscoria and ptosisof the left eyelid with a constricted left pupil. Theremainder of the physical examination was unre-markable, including intact cranial nerves II-XIIand a normal laryngeal and otoscopic examina-tion.

A contrast CT scan revealed a hypervascularmass posteromedial to the carotid vessels mea-suring 6 × 4 cm, 1 to 2 cm superior to the carotidbifurcation displacing the internal and externalcarotid arteries anterolaterally (Fig. 1). A four-vessel angiogram was performed to further char-acterize the lesion and for preoperative embolization(Fig. 2). Angiography demonstrated a hypervas-

Correspondence to: C. R. Bradford

© 2001 John Wiley & Sons, Inc.

338 Sympathetic Paraganglioma as a Cause of Horner’s Syndrome HEAD & NECK April 2001

cular mass at the C2–C4 level fed by a left as-cending cervical branch of the inferior thyroid ar-tery; left vertebral artery branches; and branchesoff the left external carotid, occipital, and ascend-ing pharyngeal arteries. Embolization of approxi-mately 90% of the feeders was achieved by acombination of particles, coils, and Gelfoam.Postembolization angiography revealed only re-sidual filling of the tumor directly from the leftexternal carotid artery.

One day after embolization, the patient wastaken to the operating room for surgical resectionof the left neck mass. Wide exposure of the leftside of the neck was performed and proximal anddistal control of the common carotid artery wasobtained. Several enlarged lymph nodes wereidentified and removed for pathologic evaluation.The mass was identified deep to the carotid arteryand was not in continuity with the vagus nerve.The sympathetic trunk, however, was noted torun directly into the inferior portion of the massat the level of the midthyroid cartilage, and themass was noted to extend superiorly to the levelof the midstyloid process. To remove the mass,

the sympathetic trunk was divided inferiorly andthe mass was dissected off the deep cervical fasciaand surrounding structures in an inferior to su-perior direction. All cranial nerves and major ves-sels were spared.

Histologic examination of the mass revealedthe characteristic clusters of epithelioid cells(Zellballen configuration) and extensively branch-ing vascular sinusoids that are typical of para-gangliomas (Fig. 3). All lymph nodes were nega-tive for metastatic paraganglioma. Of incidentalnote, embolic material was found in the largeblood vessels of the specimen.

Postoperatively, the patient did well with noneurologic sequelae other then the left Horner’ssyndrome that was present preoperatively. Twomonths after surgery, the patient continues tocomplain of slowly improving left jaw discomfortwith eating.

DISCUSSION

Paragangliomas are rare causes of tumors in thehead and neck arising from paraganglionic tissue

FIGURE 1. CT scan of an enhancing mass measuring 6 × 4 cmnear the left carotid bifurcation.

FIGURE 2. Four-vessel angiogram revealing a hypervascularmass at the C2-C4 level in the left neck. The mass is noted to besuperior to the carotid bifurcation.

Sympathetic Paraganglioma as a Cause of Horner’s Syndrome HEAD & NECK April 2001 339

of neural crest origin that surrounds blood vesselsand nerves. The incidence of head and neck para-gangliomas in a review of more than 600,000 tu-mors at Memorial Sloan-Ketttering Cancer Cen-ter was 0.012%, and there was only one incidentalparaganglioma identified in more than 13,400 au-topsies.1 The most common anatomic location forparagangliomas in the head and neck is the ca-rotid body (61.7%), followed by the jugular bulb/tympanic plexus (26.7%), and the vagus nerve(9.3%).2 Paragangliomas have also been describedin the larynx, orbit, nasal cavity, thyroid, and in-volving the hypoglossal nerve.1,3

The tumors are generally slow growing andaffect surrounding structures by mass effect.Symptoms rarely occur until the tumor is largeenough to affect surrounding cranial nerves orother vital structures. On average, the time spanfrom the presence of symptoms to diagnosis is 3.3to 6 years.4 The most common presenting symp-toms are a painless neck mass in patients withcarotid and vagal tumors and hearing loss andtinnitus in patients with jugular bulb/tympanicplexus paragangliomas. As the tumors increase insize, associated local cranial nerve deficits de-velop.

Both regional and distant metastases are un-common in paragangliomas of the head and neck,occurring in approximately 4% to 10% of cases.Carotid body and vagal paragangliomas seem tohave a greater risk of metastasis than paragan-gliomas of the temporal bone.5 Metastases mostcommonly involve the lymph nodes, followed bythe lung, bone, and brain.

Synchronous paragangliomas may also occurin the head and neck. Multicentricity has been

reported in as many as 10% of nonfamilial casesof head and neck paragangliomas.6,7 In addition,approximately 10% of patients with a paragan-glioma have an inherited form of this tumor, andof these, 25% to 33% have multiple paraganglio-mas.8–10

In addition to a complete history and physicalexamination, diagnostic evaluation includes a CTscan to identify the anatomic location and vascu-larity of the tumor and osseous changes of theskull base and middle temporal bone. MR imag-ing has advantages over CT in that is better ableto characterize the tumor’s relationship to sur-rounding structures (soft tissue resolution) andits overall vascularity. In addition, tumor inva-sion into the posterior fossa is better demon-strated on MR imaging. The finding of flow voidsin the poststyloid compartment on T1-weightedimages is thought by some surgeons to be virtu-ally diagnostic of a paraganglioma. However,other hypervascular tumors of the parapharyn-geal space (such as metastatic hypernephromaand metastatic thyroid carcinoma) may havesimilar appearances but can be usually differen-tiated on the basis of location, shape, and contoursmoothness.11 The differential diagnosis of theparaganglioma is aided by the direction of dis-placement of the internal and external carotid ar-tery and internal jugular vein relative to the vas-cular mass. Splaying of the common carotidbifurcation is suggestive of a carotid body tumor,whereas vagal paragangliomas push the externaland internal carotid artery anteromedially, sepa-rating the internal jugular vein from these ves-sels. Sympathetic paragangliomas, because of thelocation of the sympathetic trunk posteromedialto the carotid system, would be expected to dis-place the internal and external carotid artery an-terolaterally.

MR imaging is also useful in detecting lesionsthat are smaller than 5 mm12 and is used by somephysicians to screen for synchronous paraganglio-mas.13 The addition of MR angiography does notincrease the diagnostic value of MR imaging butdoes add information on the vascularity of thetumor.14 However, the sensitivity of MRA in de-tecting important vascularization is lower thandigital subtraction angiography.15 In addition, fortumors larger than 2.5 cm, four vessel angiogra-phy and preoperative embolization is useful inminimizing bleeding and injury to surroundingneurovascular structures.16 Digital subtractionangiography also allows the determination of ca-rotid artery invasion and the performance of bal-

FIGURE 3. H & E stain of the left neck sympathetic paragan-glioma. Note the characteristic clusters of epithelioid cells (Zell-ballen configuration) and branching vascular sinusoids.

340 Sympathetic Paraganglioma as a Cause of Horner’s Syndrome HEAD & NECK April 2001

loon occlusion studies to assess collateral cerebralcirculation.

Head and neck paragangliomas secrete cate-cholamines in approximately 2% of cases, in con-trast to pheochromocytomas (a histologicallysimilar tumor), which are frequently vasoactive.Headaches, flushing, hypertension, palpitations,or other symptoms of catecholamine overproduc-tion are suggestive of a vasoactive paragangliomaand should illicit examination of the urine formetanephrines or catecholamines. If present, ap-propriate adrenergic blockade during surgerycould prevent a hypertensive crisis. Because ofthe rarity of secreting tumors in the head andneck, however, lack of symptoms likely obviatesthe need for these tests.

The current treatment for paragangliomas ofthe head and neck includes surgical excision forthose lesions where resection would not result insignificant morbidity or mortality. The risk of sig-nificant postoperative cranial nerve deficits afterexcision of tumors greater than 5 cm has beenreported to be between 20% and 50%.17,18 How-ever, rehabilitation and compensation for acutecranial nerve loss in young patients is more com-plete than that found in elderly patients.19 Thus,surgery may not be appropriate for some lesionsin the elderly. Alternatively, radiation therapyhas been reported to have local control rates ashigh as 100% in some series.20 However, the ab-sence of cure and the lack of long-term follow-upof late onset complications (osteoradionecrosis,radiation-induced malignancies, CNS injury) inmost radiation series makes its use in youngerpatients less favorable than surgery.

Although the overall incidence of head andneck paragangliomas is low, the incidence of sym-pathetic paraganglioma is exceedingly rare. Inseven studies of more than 500 cervical paragan-gliomas,2 there were no reported cases of a cervi-cal sympathetic paraganglioma. Studies havefound paragangliomas associated with the sym-pathetic trunk in the thorax and retroperitoneumbut not in the cervical region.

There are only two case reports that we areaware of describing cervical sympathetic para-gangliomas. One case was a solitary tumor2 andthe other was in a patient with the inherited formof the disease with multiple cervical paraganglio-mas.21 The solitary sympathetic paragangliomawas found in a 24-year-old man with a long-standing history of Horner’s syndrome and aslowly growing left neck mass. The tumor mea-sured 5 × 4.5 × 3 cm on CT scan. The other sym-

pathetic paraganglioma was described in a 28-year-old woman found to have a paraganglioma ofthe right sympathetic chain and the left carotidbody. This sympathetic paraganglioma did notmanifest with a Horner’s syndrome. This patienthad three siblings who also had multiple cervicalparagangliomas, but none of them were sympa-thetic in origin.

Our patient had an approximately 6-monthhistory of a Horner’s syndrome preceded by 6months of a slowly enlarging left neck mass. OnCT scan, the tumor measured 6 × 4 cm and dis-placed the internal and external carotid arteriesanterolaterally. The patient was otherwiseasymptomatic and had no cranial nerve findingson physical examination. This is in contrast tovagal paragangliomas where on CT scan the in-ternal and external carotid arteries are displacedanteromedially, and nearly 50% of cases are seenwith ipsilateral vocal cord paralysis.22 Postopera-tively, the patient had no neurologic deficits otherthan the left Horner’s syndrome that was presentpreoperatively. The patient, however, does com-plain of left jaw discomfort while eating, which isthought to be either temporal mandibular joint inorigin or secondary to “first bite syndrome.” Thecause of “first bite” is thought to be sympatheticdenervation of the parotid gland leading to myo-epithelial cell spasm.

CONCLUSION

Sympathetic paragangliomas are a rare cause ofHorner’s syndrome in patients with a slowlygrowing neck mass. Their presence should be con-sidered in the overall differential when the diag-nosis of paraganglioma is considered. The treat-ment is complete surgical resection with themeticulous dissection of surrounding tissues andpreservation of neurovascular structures.

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