Nasopharyngeal Giant Carcinoma Mimicking Intracranial Lesions: A Case Report and Literature Review

Introduction

Nasopharyngeal carcinoma (NPC) is a rare but aggressive malignancy that is the most common carcinoma among head and neck cancers. Approximately 68% of patients with NPC have locally advanced stage III and stage IV disease when they are first diagnosed [1]. Some patients present with intracranial invasion at the time of their first visit or present with cranial nerve symptoms as the main concern, which need to be differentiated from intracranial space-occupying lesions. In addition, due to the proximity of the nasopharynx to the pituitary gland, some patients with nasopharyngeal carcinoma may also be difficult to diagnose or are misdiagnosed with pituitary tumors. This report describes a 37-year-old woman with bilateral nasal congestion, diplopia, hearing loss, and headache diagnosed with a large nasopharyngeal carcinoma invading the cerebellum, pons, medulla oblongata, and cervical spinal cord, which was repeatedly diagnosed with difficulty as having meningioma or pituitary tumor in many large hospitals.

Case Report

A 37-year-old woman was admitted to our hospital presenting with bilateral nasal congestion, diplopia, auditory blurring for over 3 years, and a headache accompanied by left facial numbness for nearly 1 year.

Since 2020, the patient had blurred vision in the left eye but had not sought immediate medical evaluation. In early 2022, she developed gait instability and dysphagia, with progressive symptom exacerbation. In February 2022, physical examination revealed left-sided visual impairment, abducens nerve palsy, bilateral sensorineural hearing loss, and gait ataxia. Brain MRI identified a space-occupying lesion extending from the pterygopalatine fossa to the prepontine cistern and nasopharynx. Based on brain MRI and physical findings, intracranial neoplasms (meningioma or pituitary adenoma) were suspected. Craniotomy for tumor resection was advised, but the patient and spouse declined due to concerns regarding surgical morbidity and quality of life.

The patient sought evaluation at 2 tertiary care hospitals, including a specialized neurosurgical center. However, the diagnosis remained inconclusive due to reliance on previous inaccurate assessments, resulting in delayed definitive management. She subsequently received supportive herbal therapy, with progressive clinical deterioration.

In May 2022, she visited to our hospital, exhibiting dysarthria, bilateral sensorineural hearing loss, tenacious sputum, headache, facial hypoesthesia, diplopia, bilateral nasal obstruction, intermittent epistaxis, aspiration of liquids, and using a wheelchair. Physical examination revealed left conjunctival injection, left ocular fixation in adduction, left mydriasis with a nonreactive pupil, and a normal right pupillary light reflex. Leftward tongue deviation with ipsilateral hemiatrophy was observed, but trismus was absent.

Contrast-enhanced MRI revealed an extensive nasopharyngeal mass extending into the middle and posterior cranial fossae, involving the clivus, C1 vertebra, cavernous sinus, left thalamus, brainstem (midbrain, pons, medulla), and cerebellum (Figure 1). Routine pathology diagnostic investigation suggested the lesion (in the left nasal cavity) was a squamous cell carcinoma, non-keratinizing type (Figure 2).

According to the 8th edition of AJCC/UICC staging, the patient was classified as T4N0M0 IVA stage. She subsequently received 6 cycles of cisplatin/docetaxel (TP) chemotherapy with anti-PD-1 immunotherapy (tirelizumab). Post-treatment response assessment demonstrated partial response (PR).

In August 2022, she underwent intensity-modulated radiotherapy (IMRT) via tomotherapy with concurrent nivolumab, 70.4 Gy divided into 35 cycles to GTVnx, 64 Gy to CTV1, and 50 Gy to CTV2. Follow-up assessment after radiotherapy demonstrated a complete response (CR) (Figure 3). Throughout therapy, symptoms, including headache, dysarthria, and facial hypoesthesia, demonstrated significant improvement.

Discussion

Nasopharyngeal carcinoma (NPC) is classified as a prevalent malignant neoplasm of the head and neck. The etiology of NPC is understood to be multifactorial, involving Epstein-Barr virus (EBV) infection and environmental influences. Characteristic clinical manifestations encompass epistaxis, auditory impairment, cervical lymphadenopathy, and cranial nerve deficits.

The TNM staging system remains the criterion standard for treatment planning and prognostic assessment in nasopharyngeal carcinoma (NPC) [2–4]. Nevertheless, patients with super-T4 tumors present unique diagnostic challenges that merit particular attention [5].

NPC commonly extends to involve cranial nerves through direct invasion of the pterygopalatine fossa, skull base, and cavernous sinus, resulting in characteristic neurological deficits [6,7]. Cranial nerve involvement is observed in approximately 20% of patients at initial diagnosis [8], manifesting as headache, diplopia, or facial hypoesthesia. Consequently, NPC should be included in the differential diagnosis when patients present with both cranial nerve symptoms and intracranial space-occupying lesions.

The current case demonstrates an unusual pattern of tumor extension, with involvement not only of the cavernous sinus but also significant compression of the midbrain, pons, medulla oblongata, and cervical spinal cord. While cavernous sinus invasion occurs in 17.4% of NPC cases (classified as medium-risk), cervical vertebrae (3.3%) and meninges (1.4%) are low-risk sites [7]. Brainstem involvement, as observed in this patient, is exceptionally rare.

Diagnostic difficulties at tertiary referral centers may stem from several factors. First, the initial neurosurgical workup emphasized brain MRI over nasopharyngeal imaging. The uniformly enhancing intracranial lesions with skull base origin and external compression characteristics closely resembled meningioma. Second, the combination of pituitary stalk thickening and bilateral cavernous sinus invasion created diagnostic confusion with pituitary adenoma. These radiographic features, coupled with the omission of nasopharyngeal evaluation, likely resulted in the delayed diagnosis.

For patients presenting with cranial nerve symptoms, a thorough diagnostic workup must incorporate both brain MRI and nasopharyngeal examination. Distinctive radiographic features of NPC include skull base osteolysis and parapharyngeal space infiltration, contrasting with the dural tail sign and calcifications typical of meningioma. While pituitary adenomas are generally confined to the sella turcica [9–11], NPC extension into this region typically exhibits clival bone destruction [12,13]. In diagnostically complex cases, comprehensive MRI evaluation of bone integrity and enhancement patterns in the cavernous sinus and meninges is imperative. Multidisciplinary team (MDT) consultation incorporating neurosurgical, head and neck oncologic, and neuroradiologic expertise is crucial for accurate diagnosis [14–16].

Although uncommon, extensive NPC with skull base invasion may be erroneously diagnosed as primary intracranial neoplasms. Thus, the presence of cranial nerve symptoms should raise clinical suspicion for both skull base tumors and extracranial malignancies.

Conclusions

Skull base invasion is a frequent complication of nasopharyngeal carcinoma (NPC); however, widespread intracranial extension involving multiple neuroanatomical structures (cerebellum, brainstem, thalamus, medulla oblongata, and cervical spinal cord) is an extraordinary clinical manifestation. Herein, we describe a diagnostically complex case of advanced NPC with extensive tumor infiltration that was repeatedly challenging diagnosed as a pituitary adenoma. This report emphasizes 3 critical clinical considerations: (1) The imperative of maintaining heightened suspicion for skull base infiltration in advanced NPC, (2) The essential diagnostic role of nasopharyngeal MRI coupled with endoscopic evaluation in patients exhibiting cranial nerve symptoms, and (3) The vital importance of multidisciplinary team (MDT) coordination to minimize diagnostic delays in NPC with substantial skull base involvement.