T. F. Wang, S. C. Chu, M. H.

Wu, et al
Tzu Chi Med J 2006 18 No. 5 PTU
Recurrent Syncope as Initial Presenting Symptom of Non-Small
Cell Lung Cancer A Case Report
Tso-Fu Wang, Sung-Chao Chu, Meng-Hsiu Wu
1
, Raymond Yen-Yu Lo
2
, Chi-Cheng Li
Department of Hematology/Oncology, Cardiology
1
, Neurology
2
, Buddhist Tzu Chi General Hospital, Hualien, Taiwan
ABSTRACT
Syncope is a common problem that many clinicians encounter in daily practice. The causes range from common benign disorders to
severe life-threatening diseases. Although rare, syncope may result from malignancy. Most patients with this symptom have docu-
mented head and neck cancer. We report on a 70 year-old man with recurrent syncope that preceded the diagnosis of squamous cell
carcinoma of the lung with neck and mediastinal lymph node metastasis. Syncope resulted from direct involvement of the left vagus
nerve was clinically impressed. After treating with chemotherapy, the tumor shrunk and he did not suffer from syncope thereafter.
These findings suggest that malignancy should be considered in the differential diagnosis when an elderly patient with recurrent
syncope is examined. All the possibilities that caused neck metastases should be considered. (Tzu Chi Med J 2006; 18:378-381)
Key words: syncope, neck lymph nodes, lung cancer, non-small cell carcinoma
Received: December 12, 2005, Revised: December 28, 2005, Accepted: February 9, 2006
Address reprint requests and correspondence to: Dr. Chi-Cheng Li, Department of Hematology/Oncology, Buddhist Tzu Chi
General Hospital, 707, Section 3, Chung Yang Road, Hualien, Taiwan
CASE REPORT
INTRODUCTION
Syncope accounts for 3% of visits to emergency
departments and 6% of all admissions to the hospital
[1]. It occurs in all age groups, ranging from 15% in
children under 18 years to 23% in patients over 70 years.
Syncope is caused by a wide variety of problems that
range from common benign disorders to severe life-
threatening diseases. Even when an extensive evalua-
tion of syncope is undertaken, identifying its cause is
difficult. Syncope resulting from a neck tumor is very
rare. We present a case of non-small cell lung cancer
which initially presented with recurrent syncope.
CASE REPORT
The patient was a 70 year-old man with a 50 pack-
year smoking history. He had had a chronic cough with
scanty sputum for more than 10 years and had never
previously visited a medical clinic. He was brought to
the emergency department (ED) due to syncope. He re-
covered consciousness spontaneously 2 minutes before
arrival in the ED. He reported that he had an aggravat-
ing dry cough and multiple episodes of syncope for 2
months. The syncopal episodes seemed to occur when
he felt neck soreness. Findings on physical examination
of the heart, lungs, abdomen, and neurological system
were unremarkable except for a small ill-defined mass
over the left lower neck. There were no abnormalities in
blood glucose, electrolytes, or other blood chemistry
results. A chest radiograph showed an old left clavicu-
lar fracture but no active lung lesions (Fig. 1). The heart
size was normal and the aorta was tortuous with
atherosclerosis. An echocardiogram, electrocardiogram
(ECG), electroencephalogram and brain magnetic reso-
nance imaging showed nothing abnormal. One episode
of syncope was witnessed during hospitalization. The
patient lost consciousness for 1 minute with a weak pulse
Syncope as initial symptom of NSCLC
Tzu Chi Med J 2006 18 No. 5 PTV
of 60 bpm, blood pressure of 86/58 mmHg, and normal
regular heart sounds. A carotid sinus hypersensitivity
test assessed by carotid massage did not produce any
substantial slowing of heart rate or sinus pause. Ortho-
static hypotension and structural heart disease were also
ruled out as possible causes of syncope.
Neck and chest computed tomography showed
masses in the left lower neck and mediastinum, which
encased the left common carotid artery, left subclavian
artery and brachiocephalic artery without compromise
of blood flow (Fig. 2). A lesion with retraction of the
adjacent pleura in the left upper lung with mediastinal
lymphadenopathy and a left adrenal tumor were also
noted. Excisional biopsy of the left neck masses revealed
metastatic squamous cell carcinoma. Head and neck
examination revealed unremarkable findings. Non-small
cell lung cancer with multiple metastases was impressed.
He received systemic chemotherapy thereafter and tu-
mor shrinkage was noted on follow-up chest CT scan.
He had no more episodes of syncope. The patient died
of pneumonia 4 months later.
DISCUSSION
In older individuals, syncope is often caused by
underlying heart disease or other illnesses and carries a
serious prognosis. In addition to brain metastasis and
cardiac disease, there are many unusual etiologies of
syncope in cancer patients. Syncope as a result of ma-
lignancy is rare and most patients with this symptom
have documented head and neck cancer. MacDonald et
al [2] estimated that the incidence of syncope caused by
head and neck cancers was less than 0.4% in a review of
approximately 4,500 cases.
Fig. 1. Chest radiograph shows an old left clavicular frac-
ture but no active lung lesions.
Fig. 2. Chest computed tomography with contrast enhancement shows masses in the left lower neck and mediastinum next to the
trachea, which encase the left common carotid artery, left subclavian artery and brachiocephalic artery without compro-
mise of blood flow (A) A lesion with retraction of the adjacent pleura in the left upper lung is noted in the lung window
setting (B).
T. F. Wang, S. C. Chu, M. H. Wu, et al
Tzu Chi Med J 2006 18 No. 5 PUM
Many different mechanisms of malignancy-associ-
ated syncope have been reported. Weiss and Baker first
described carotid sinus syncope syndrome (CSS) asso-
ciated head and neck malignancy in 1933. Stimuli from
the carotid sinus pass afferently through the nerve of
Hering, a branch of the glossopharyngeal nerve, to the
nucleus of the vagus. Then, it generates an impulse to
the heart via the parasympathetic trunk of the vagus nerve
and/or to the vasodepressor center and blood vessels via
the cervical sympathetic trunk. In addition there is trans-
mission between the vasodepressor center and the
hypothalamus, where vasopressin is released for main-
tenance of normotension. Normally, reflex bradycardia
and hypotension occur during carotid sinus massage.
Although the mechanism of vasodilatation during syn-
cope is not clear, it may be due to (1) excessive vagal
activity, or (2) subnormal norepinephrine and elevated
epinephrine concentration in the plasma. The former is
the cardioinhibitory type, the latter is the vasodepressor
type. In cancer-induced CSS, the mixed cardioinhibi-
tory and vasodepressor type is the most common [3].
Glossopharyngeal neuralgia (GPN) and parapha-
ryngeal space lesion syncope syndrome (PSL) have also
been reported as etiologies of syncope in patients with
malignancy [4-6]. The clinical pictures of GPN and PSL
are different from that of CSS, however, the mechanisms
for developing syncope are similar. Tumor-induced
stimuli to the hypopharyngeal nerve and/or its inervated
area cause an afferent impulse to the dorsal vagal nucleus
which results in activation of the vagus nerve and tran-
sient cardioinhibition and vasodepression. In rare
situations, the tumor may directly stimulate the vagus
nerve and induce syncope [7]. All these mechanisms are
neurocardiogenic syncope involving the same pathway
despite different names (Fig. 3). The stimuli can be ei-
ther mechanical or chemical [8,9].
In our patient, probable etiologies such as epilepsy,
organic brain lesions, orthostatic hypotension, structural
heart disease, and metabolic problems were ruled out
after extended examination. A 24 hr Holter ECG was
not done, but sequential resting ECGs during hospital-
ization all showed normal sinus rhythm. The tumor en-
cased the left common carotid artery at the level of
branching from the aorta where the cardiac branch of
the vagus nerve went by. We propose that syncope in
this patient might be related to direct stimulation of the
vagus nerve by the tumor. Treatment of the underlying
disease with chemotherapy or radiotherapy should be
the main therapy for malignancy-related syncope. After
effective treatment with systemic chemotherapy, our
patient had no more episodes of syncope.
Other modalities of treatment could be considered
for malignancy-induced syncope. Immediate treatment
includes anticholinergic medications and cardiac pacing.
During episodes of syncope, anticholinergic agents such
as atropine give immediate relief of symptoms. Longer-
acting anticholinergics such as hyoscine and belladonna
have also been used. This can usually prevent syncope
but most patients continue to experience recurrent
dizziness. Carbamazepine can be useful in controlling
the pain of glossopharyngeal neuralgia and, by its in-
hibitory effect on brain stem reflex activity, can also
prevent bradycardia and hypotension. Pacemakers are
effective in the treatment of idiopathic carotid syndrome.
However, when it is induced by malignancy, where a
vasodepressor component is usually present, pacing has
often been ineffective [10]. Surgery is usually reserved
for those who do not respond to medical therapy and
dual chamber rate responsive cardiac pacing.
The point of interest in the present clinical case is
that the patient initially presented with a medical his-
tory typical of neurocardiogenic syncope. An oncologic
workup is not usually performed in patients with this
presentation, yet it proved to be fundamental for suc-
cessful diagnosis in this patient. In view of this
experience, we believe that an atypical medical history
in an elderly patient with newly developed neurocar- Fig. 3. Neurocardiogenic syncope in malignancy.
Carotid sinus
Glossopharyngeal nerve
Tumor-induced stimuli
(Mechanical or chemical)
Stimulation of dorsal vagal uncleus
Vagus nerve and/or cervical sympathetic trunk
Increase in vagal tone and decrease in sympathetic tone
Bradycardia and vasodilation
Cerebral hypoperfusion
Syncope
Syncope as initial symptom of NSCLC
Tzu Chi Med J 2006 18 No. 5 PUN
diogenic syncope should alert physicians to the possi-
bility of malignancy. The patient should not only be
examined for head and neck malignancies but also for
possible causes of neck metastasis.
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