Peer Reviewed


Nasopharyngeal Carcinoma Presenting as Third Nerve Palsy

Catherine Anderson-Quiñones, BM1 • Kinza Khan, BA1 • Sonal Khedkar, BS2 • Jay Patel, MD2 • Andrew Wilner, MD2

1University of Tennessee Health Science Center, College of Medicine, Memphis, TN
2Department of Neurology, University of Tennessee Health Science Center, Memphis, TN

Anderson-Quiñones C, Khan K, Khedkar S, Patel J, Wilner A. Nasopharyngeal carcinoma presenting as third nerve palsy. Consultant. Published online January 30, 2023. doi:10.25270/con.2023.01.000008

Received May 23, 2022. Accepted November 16, 2022.

The authors report no relevant financial relationships.


Catherine Anderson-Quiñones, BM, University of Tennessee Health Science Center, College of Medicine, 920 Madison Avenue, Memphis, TN 38163 (

Case presentation. Our patient was a 48-year-old man who presented with headache, left eye ptosis, a dilated pupil, and tooth pain for 10 days duration.

Patient history. Our patient had a history of hypertension and poorly controlled type 2 diabetes.

Physical examination. Physical examination was only remarkable for cachexia and elevated blood pressure of 181/104 mm Hg. Best corrected visual acuity was 20/30 in both eyes with Snellen chart. Intra-ocular pressure was within normal limits. Cranial nerve examination revealed left eye ptosis and anisocoria. The right pupil was 2 mm and reactive, while the left pupil was 3 mm and minimally reactive. There was no relative afferent pupillary defect. The left eye had medial and inferior gaze restrictions.

Diagnostic testing. Consultation with ophthalmology specialists confirmed the left third nerve palsy and raised the possibility of a concomitant fourth nerve palsy. The neurologic examination was otherwise within normal limits, including speech and swallowing. Notable abnormal laboratory values were platelets 86,000 mcL, glucose 358 mg/dL, and HbA1C 13.4%.

The possibility that the fourth cranial nerve was involved complicated medical decision making as the differential diagnosis of an isolated cranial nerve palsy differs significantly from multiple cranial nerve palsies. Initial brain computed tomography (CT), brain CT angiogram, brain CT venogram, non-contrast magnetic resonance imaging (MRI), and magnetic resonance venography were interpreted as within normal limits. CT angiography of the neck demonstrated 50% narrowing of the petrous portion of the left internal carotid. This stenosis was initially attributed to atherosclerosis, which was plausible given the patient’s atherosclerotic risk factors of hypertension and poorly controlled diabetes. Isolated third cranial neuropathies are the most common presentation of diabetic cranial neuropathy.1

A lumbar puncture was performed to look for evidence of carcinomatosis, infection, or subarachnoid hemorrhage. The patient’s cerebrospinal fluid was clear and colorless with one white cell, one red cell, glucose 127 mg/dL, protein 50 mg/dL, and negative bacterial culture.

Initial neuroimaging studies were reported as negative. However, later review of CT imaging revealed erosion of the left carotid canal, consistent with an invasive tumor (Figure 1).

Figure 1

Figure 1. The patient’s initial head CT scan demonstrates an enlarged left carotid canal (arrow), but was initially interpreted by radiology to be within normal limits.

Identification of this infiltrative malignancy required both CT and MRI scans, including the use of contrast. Contrast brain MRI ultimately demonstrated a mass lesion in the cavernous sinus (Figure 2).

Figure 2

Figure 2. This axial T1 MRI post-contrast demonstrates a clearer view of a suspicious soft tissue mass in the left cavernous sinus (arrow).

Consultation with otolaryngology specialists led to a fine needle aspiration biopsy of an enlarged left cervical lymph node. Histopathological diagnosis was metastatic non-keratinizing squamous cell Epstein–Barr virus positive carcinoma.

Treatment and management. The patient received treatment with induction chemotherapy followed by concurrent chemoradiotherapy at an outside hospital.

Patient outcome and follow-up. The patient’s symptoms and cranial nerve palsies resolved after treatment. Follow-up brain MRI and positron emission tomography scans were without evidence of disease. If a neoplasm had not been considered as a cause for this third nerve palsy, the lack of definitive treatment would likely have resulted in a poor prognosis for this patient rather than complete recovery.

Differential diagnosis. The differential diagnosis for acute third nerve palsy is extensive and includes aneurysm, diabetes (microvascular), migraine, Miller-Fisher syndrome, stroke, surgery, trauma, tumor, and many others.2 The differential diagnosis of a third nerve palsy hinges upon whether it is isolated or not. A practical diagnostic algorithm is presented by Bruce and colleagues.3

Careful evaluation of symptoms can suggest localization of the lesion. For example, an oculomotor nerve palsy with isolated muscular involvement is most likely due to ischemic microvascular pathologies. In contrast, one with pupillary involvement suggests a compressive lesion such as an aneurysm.4 Aneurysms that cause third nerve palsies seldom spare the pupil. For example, in a series of 143 third nerve palsies due to aneurysm, only 2% spared the pupil.2 The presence or absence of other cranial nerve dysfunction also guides the investigation.3

An ischemic microvascular etiology is the most common cause of oculomotor nerve palsy.3 This etiology would not be surprising in this patient with known hypertension and poorly controlled diabetes.5 Although the patient complained of headache and tooth pain, he did not complain of eye pain. While the MRI may show thickening and enhancement of the nerve in diabetic oculomotor palsy, this occurs in only approximately two-thirds of cases.6 It was unclear whether a second cranial neuropathy was present in the trochlear nerve. If so, an ischemic microvascular etiology was less probable because multiple simultaneous acute diabetic cranial neuropathies are uncommon. In the largest review article to date, the most common etiology of multiple cranial nerve palsies was tumor, which was responsible in approximately 30% of cases.7 Thus a timely work-up to confirm or rule out a diagnosis of tumor should be considered in patients with multiple cranial nerve palsies.

Nasopharyngeal carcinomas are relatively common tumors of the head and neck. They are more likely to cause cranial nerve palsies than other tumors in this region, presenting with cranial nerve palsies up to 29% of the time.8,9 When cranial nerves are involved, cranial nerves V (38%), VI (26%), and XII (11%) are the most commonly affected. Presentation with a third nerve palsy has been reported but is unusual.9 In fact, Leung and colleagues8 report that cranial nerve III lesions never appear alone. Consequently, nasopharyngeal carcinoma was not high on our initial differential diagnosis.

Discussion. The oculomotor nerve controls lens accommodation, pupillary constriction, and most simple eye movements.4 An oculomotor nerve lesion may affect some or all of these functions depending upon its severity and location. Due to the location of our patient’s tumor and subtle appearance on CT imaging, it was initially overlooked. Features on physical examination including left eye ptosis, anisocoria, and cachexia were essential to localizing the site of cranial nerve involvement and the etiology.

An acute third nerve palsy raises the possibility of a neurological emergency. One must accurately diagnose third nerve palsies because they may signal intracranial aneurysm, pituitary apoplexy, or temporal arteritis.3 Third nerve palsies presenting with headache and pupillary defect raise the possibility of a cerebral aneurysm because an aneurysm may compress the superficial pupillomotor fibers of the ipsilateral third nerve and their blood supply.3 While aneurysms cause only a minority of third nerve palsies (6-10%), such an aneurysm is life-threatening and prone to rupture, requiring immediate diagnosis and treatment.2,5 In our case, neuroimaging including digital angiography, the gold standard for diagnosis,10  did not reveal any sign of aneurysm.

This patient’s presentation is unusual as there was isolated third cranial nerve involvement in the cavernous sinus without invasion into the orbit. To our knowledge, there is only one other case reported in the literature with similar presentation of a unilateral isolated cranial nerve III palsy and anatomic involvement.11

Conclusion. Physicians must consider a wide range of diagnoses when faced with a patient presenting with headache and an acute third nerve palsy. Our case is an unusual example of an oculomotor nerve palsy secondary to a locally infiltrating non-keratinizing nasopharyngeal carcinoma. In our patient, an acute third nerve palsy was caused by an infiltrating nasopharyngeal carcinoma, a rare presentation of this tumor. Despite appropriate brain CT scans, MRI, digital angiography, and venography, the diagnosis was nearly missed. Reporting this case emphasizes how locally invasive carcinoma should be kept in the differential diagnosis in patients presenting with an isolated third nerve palsy. When the diagnosis is not apparent, it may be beneficial to re-examine radiological studies for subtle abnormalities that may have been overlooked or misinterpreted. In this case, narrowing of the left carotid artery was misattributed to atherosclerosis rather than tumor compression. A diagnosis of microvascular third nerve palsy suggested by normal neuroimaging should not be made until less common and potentially life-threatening etiologies, such as infiltrating tumors, have been considered.


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