NONCHROMAFFIN PARAGANGLIOMA OF THE CERVICAL
PORTION OF THE VAGUS NERVE
AN UNUSUAL CASE
PAUL JERNSTROM, M.D., AND KENNETH FRY, M.D.
Departments of Pathology, Clinical Laboratories, and Surgery, Jefferson Medical
College Hospital, Philadelphia 7, Pennsylvania
Tumors of the carotid body and structurally similar lesions arising elsewhere
in the body have been attracting increased attention, especially those of intravagal paraganglioma tissue." These neurogenic neoplasms are classified as nonchromaffin paragangliomas. They arise from cells found in close association with
certain parasympathetic nerves and large blood vessels in a variety of locations
above and below the diaphragm. 1 They have been described most frequently in
connection with the carotid body and glomus jugulare in a ratio of approximately
3 to I.4 Those of the aortic (pulmonary or mediastinal) bodies, ganglion nodosum
(glomus intravagale), the orbit (paraganglion ciliare), and the infradiaphragmatic retroperitoneal regions are more unique. Instances of multiple or bilateral
nonchromaffin paragangliomas, or both, are quite unusual and the occurrence of
such tumors has been described only in the region of the head and neck. 4 '"
Recently, Conley4 cited what seems to be the thirteenth example of multiple
lesions of this type. Marcuse and Chamberlin11 described a patient with bilateral
tumors of the carotid body and 2 additional masses of similar tissue. One island
of paraganglionic tissue was observed within the substance of the vagus nerve
adjacent to the tumor of the left carotid body, and the other was attached to the
vagus nerve 5 cm. inferior to the bifurcation of the left common carotid artery.
Except for this instance, a perusal of the literature (papers published up to May
1.957) discloses that true intravagal paraganglionic tumors inferior to the ganglion nodosum (paraganglion intravagale or vagal body) have not been described.
As far as the authors could ascertain, the tumor described in this paper represents the second recorded instance of a nonchromaffin paraganglioma of the
cervical portion of the vagus nerve.
R E P O R T OF CASE
Clinical data. A 28-year-old white woman complained of gradual enlargement
of a nodule in the upper left side of her neck during the preceding 8 months.
It had increased from less than Y2 cm. to more than 2 cm. in diameter. A concomitant cough that had been present approximately 14 yr. increased in intensity during her recent pregnancy, and the coughing became almost continReceived, May 13, 1057; accepted for publication June 14.
Dr. Jernstrom is Assistant Professor of Pathology, and Dr. Fry is Clinical Professor
of Pathology.
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nous. Furthermore, the dry, hacking cough persisted although her confinement
terminated 5 months previously. The patient accidentally noticed that the
cough could be induced merely by pressing upon the nodule in her neck. There
was no recollection of such increased coughing during or following her previous
LEFT
FIG
1.
Diagrammatic
representation of the anatomic relation between the
tumor of the cervical portion of the vagus nerve and
the usual sites of nonchromaffin paragangliomas: A —
ganglion nodosum
(paraganglioma in t r a v a g a l e ) ;
B—nonchromaffin
paraganglioma of the cervical portion of the vagus nerve, as
observed in the patient described in this paper; C—
left vagus nerve; D—glossopharyngeal nerve; E—parag a n g l i o n t y m p a n i c u m;
F—glomus
jugulare; G—
carotid body (glomus caroticum).
2 pregnancies. Physical examination revealed a firm, ovoid mass beneath the
superior third of the left sternocleidomastoid muscle. The slight pulsation of the
mass was barely transmitted and there was no bruit. Digital pressure applied
to the cervical tumor elicited a bout of protracted coughing. The pulse and blood
Oct. 1957
PARAGANGLIOMA OF VAGUS NERVE
395
pressure remained normal. Observation of the larynx with a mirror disclosed
fixation of the left side of the larynx, the left arytenoid region was tilted forward,
and the tension of the left vocal cord seemed to be normal. A neurologic examination revealed no abnormality. Since there were no definite symptoms or signs of
a tumor of the carotid body, the preoperative diagnosis was "neurofibroma,
possibly of the left recurrent laryngeal nerve." At operation, a vascular, fusiform
tumor, 2 cm. in the longer axis, was encountered, and it seemed to bean integral
part of the cervical portion of the left vagus nerve. The mass was situated approximately 2 cm. inferior to the ganglion nodosum (paraganglion intravagale)
and superior to the bifurcation of the common carotid artery (Fig. 1). The
tumor was freed from surrounding structures and the normal vagus nerve was
explored upward to the jugular foramen, where the slight bulbous enlargement
of the ganglion nodosum was identified. Similarly, the vagus nerve was traced
downward from the site of the tumor to a point beyond the bifurcation of the
common carotid artery. No other abnormality of the vagus nerve or contiguous
tissues was found. The tumor was excised with margins of normal nerve. During
the operation, there was a slight diminution in the pulse rate from 100 to 90
per min. in association with manipulation of the lesion, but the blood pressure
remained stable at 100/60. Paralysis of the left vocal cord was noted postoperatively, and this condition remained fixed. Hoarseness was moderate, but decreased with the passage of time, and the woman no longer had the cough.
Three years have elapsed and the patient's condition remains unchanged.
Pathologic Studies
Gross examination. The tumor was elliptical, 1.5 by 1.2 cm., red-gray, and
firm. Its poles were cylindrical, 0.3 cm. in diameter, and simulated the severed
ends of a nerve. Hemisectioned surfaces were pink-yellow to tan, moist, rubbery,
and homogeneous (Fig. 2).
Microscopic examination. Study of the histologic sections disclosed a lesion
confined by neural tissue that included occasional ganglion cells (Fig. 3). The
tumor consisted of packed nests of uniform cells ("zellballen") with rather
small, dark, vesicular, central nuclei and abundant, pale, acidophilic cytoplasm
with indistinct borders (Figs. 4 and 5). The vascular stroma was accentuated by
the typical pattern of the reticulum stain. Thus, the lesion was classical of a
carotid body-like tumor and it was diagnosed as a nonchromaffin paraganglioma
of the cervical portion of the left vagus nerve.
DISCUSSION
The histogenesis of clusters of paraganglioma cells is controversial. In the
past, chromaffin and nonchromaffin paragangliomas were thought to originate
from tissue of common embryonic anlage. 1, u Kohn, 8 in 1900, regarded them as
analogues of the adrenal medulla and they were subsequently classified as
chromaffin paraganglia. DeCastro 5 demonstrated and Hollinshead7 emphasized
that the cells of nonchromaffin paragangliomas do not produce a true chromaffin
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JERNSTBOM AND FRY
Vol. 28
reaction, that their innervation is chiefly sensory or afferent, and that they do not
secrete epinephrine or a similar hormone. In a study of tumors of the carotid
and aortic bodies, Comroe3 demonstrated a chemoreceptive sensitivity that
reflexly affected respiration and the vascular bed, as a result of chemical changes
in the blood (i.e., carbon dioxide). In 1950, Mulligan13 chose the term chemodectoma for such lesions. A functional uniformity of these tumors in other locations,
however, has not been established. Thus, we prefer the designation, nonchromaffin
paraganglioma, which is universally accepted.
Since the first description of a normal carotid body, by von Haller in 1743,l5
and the first recorded instance of a tumor of the carotid body, by Marchand in
1891,10 there have been more than 350 reports of tumors of the carotid body
and 102 of the glomus jugulare. 4 Although MacDonald 9 reported in 1956 what
was recorded as the third example of a tumor of the human aortic body, McDonald and his associates (1954)12 listed the fifth instance of a chemodectoma (nonchromaffin paraganglioma) of the mediastinum, and this tumor presumably
originated in an aortic body. Up to May 1957, Fisher and Hazard 6 published
the only case of a nonchromaffin paraganglioma of the orbit (paraganglion
ciliare) in man. Block and co-authors1 discuss the need for clarification of features
of neoplasms that occur below the diaphragm and seem to be nonchromaffin
paragangliomas; they describe an example of such a growth in the pelvic retroperitoneal region. According to Coldwater and Dirks,2 tumors of the ganglion
nodosum (paraganglion intravagale or vagal body) total 9 in the literature.
The distribution of parasympathetic paraganglia along the course of the vagus
nerve, as demonstrated by Watzka 16 and by Seto and his associates,14 leads one
to expect the occurrence of paragangliomas attached to this nerve at various
locations. These expectations are fulfilled (1) in the case cited by Marcuse and
Chamberlin11 in 1956, and (2) for the second time, in the example described in
this paper, where a nonchromaffin paraganglioma formed an integral part of the
vagus nerve in the upper cervical region more than 2 cm. inferior to the ganglion
nodosum (paraganglion intravagale).
I t is generally understood that the vast majority of nonchromaffin paragangliomas are benign in spite of variation in their histologic pattern from one
that is relatively regular to one that is rather bizarre. A few of the descriptions
deal with tumors that were locally invasive and some were known to metastasize
to lymph nodes, viscera, and bones. Coldwater and Dirks 2 further commented
that neoplasms of the ganglion nodosum (as a group) are more aggressive than
those of the carotid body, with 3 of their 9 examples having manifested malignant
characteristics.
FIG. 2 (upper). Photograph of the longitudinally hemisectioned tumor of the cervical
portion of the left vagus nerve.
FIG. 3 (middle). Semimicroscopic view of a paraffin section of the intravagal tumor
surrounded by neural tissue of the vagus nerve. X 5.
FIG. 4. (lower left). Photomicrograph of a portion of the intravagal tumor. Note the
classical arrangement of well-defined nests of cells simulating the histologic structure of
the usual tumor of the carotid body. Hematoxylin and eosin. X 200.
FIG. 5. (lower right). Photomicrograph of a specially stained section of the tumor of
the cervical portion of the vagus nerve, illustrating the typical "zellballen" and stromal
features. Reticulum stain. X 200.
Oct. 1967
•»•
397
PARAGANGLIOMA OF VAGUS N E R V E
ft
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^>TJ'^fArLJ
FIGS.
2-5
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J E R N S T R O M AND F R Y
Vol. 28
There does not seem to be any significant social, sexual, or racial incidence
with regard to nonchromaffin paragangliomas, but they do occur most frequently
in adults in the third and fourth decades. The tumors are usually asymptomatic
in their early stages of development, but, as they increase in size, they may cause
pain, pressure, syncope, or affect a special organ. In lesions of the glomus jugulare, vertigo, deafness, involvement of cranial nerves, and discharges from the
ear have been described. Those involving the cervical portion of the vagus nerve
may stimulate protracted coughing, as observed in the patient described in this
paper.
There is unanimous agreement that surgical extirpation is the proper treatment for nonchromaffin paragangliomas when such a procedure is feasible
without jeopardizing the patient's life. In the past, however, especially with
reference to tumors of the carotid body, the operative mortality and morbidity
was significantly high. The postoperative course of the patient described in this
paper has been uneventful.
SUMMARY
This paper deals with the clinical and pathologic findings in a 28-year-old
white woman who had a tumor interpreted as a nonchromaffin paraganglioma
that involved the cervical portion of the vagus nerve, approximately 2 cm. inferior to the ganglion nodosum (paraganglion intravagale) and superior to the
region of the carotid bulb on the left side of her neck. It seems to be the second
instance in which such a tumor was observed in a location that was remote from
previously recorded sites of paragangliomas.
SUMMARIO I N I N T E R L I N G U A
Iste articulo presenta le constatationes clinic e pathologic facite in le caso de
un femina blanc de 28 annos de etate qui habeva un tumor interpretate como
paraganglioma non-chromaffin, afficiente le portion cervical del nervo vage circa
2 cm infra le ganglion nodose (paraganglion intravagal) e supra le region del bulbo
carotic al latere sinistre del collo. Isto es apparentemente le secunde caso in que
un tal tumor esseva observate in un loco distante ab le previemente documentate
sitos de paragangliomas.
Acknowledgment. T h e authors wish t o t h a n k Margaret Engel for t h e illustrations and
Regina Nekludov for t h e histologic preparations.
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