Approach

Nasopharyngeal cancer (NPC) arises from epithelial cells within the lymphocyte-rich nasopharyngeal mucosa.

Worldwide, NPC is a rare cancer with such a unique geographical distribution that patient ethnicity alone can point towards a diagnosis of NPC. NPC has an especially high incidence in southern China and southeast Asia (>70% of new cases) where the predominant form of NPC is the undifferentiated (non-keratinising) type and associated with Epstein-Barr virus infection.[1][7]​​​ NPC is most frequently diagnosed after patients present with a neck mass from lymph node metastases, including in the posterior triangle/level V of the neck, rather than with symptoms associated with the primary tumour. 

Compared with smoking-associated head and neck cancers, NPC tends to affect a younger population and is more responsive to systemic therapy and radiotherapy.​[18]​​

History

The patient may report epistaxis, nasal obstruction, unilateral otitis media with effusion (serous otitis media), tinnitus, or impaired hearing in one ear. Aural symptoms are common in people presenting with NPC (62%) and should raise suspicion of NPC, particularly in an Asian patient.[4] ​The presenting symptoms are common but are not specific to NPC. Headaches, facial numbness, or diplopia may suggest cranial nerve involvement. Fever, night sweats, and unintentional weight loss should raise suspicion of malignancy in general.

Ask about risk factors for NPC, such as a diet rich in preserved foods (salted fish in particular), smoking or other tobacco use, or a family history of NPC in a first-degree relative. In patients who smoke, document the pack years smoked.[19]​ 

Physical examination

Perform a comprehensive head and neck examination and, in particular, palpate the neck for masses that may indicate lymphadenopathy.[19]​ Perform a targeted physical examination, including visualising the mucosa of the larynx, base of tongue, and pharynx.[20]

How to examine the nasal cavity
How to examine the nasal cavity

Video outlining how to perform an examination of the nose and nasal cavity

​​ A neck mass in patients >40 years should increase suspicion of malignancy and is the most common presenting symptom for NPC.[4][21]​ Nodal metastases are usually present at diagnosis. 

Among people with NPC who present with neck masses, lymphadenopathy in level II is the most common location, which is similar to other head and neck mucosal squamous cell carcinomas.[5][6]​​ However, level V lymphadenopathy in the posterior cervical triangle is relatively common in NPC and this pattern of lymph node spread distinguishes NPC from many other head and neck cancers.

[Figure caption and citation for the preceding image starts]: Lymph node groups in the head and neck; the numbers refer to the anatomical levels of the lymph nodesCancer Research UK [Citation ends].com.bmj.content.model.Caption@2236f649

Examine the cranial nerves. Cranial nerves III, IV, V, and VI are most commonly affected due to disease invading the skull base/cavernous sinus.

Initial investigations

Perform nasopharyngoscopy.[19]​ Most NPC arises from the lateral pharyngeal recess (fossa of Rosenmüller).[2][22]​​ Establish the diagnosis with an endoscopic biopsy of the primary tumour and/or fine-needle aspiration/core biopsy of neck nodal metastasis.[2][19]​​[22]​​​

[Figure caption and citation for the preceding image starts]: Endoscopic image of left-sided nasopharyngeal tumourSakthivel P et al. BMJ Case Reports CP 2020;13:e237392; used with permission [Citation ends].com.bmj.content.model.Caption@1b8dbe17

Use magnetic resonance imaging (MRI) with or without contrast (preferred) or computed tomography (CT) with contrast for T and N staging.[2][19]​​​ MRI is superior to CT to evaluate skull base and cranial nerve involvement.[2]

Use 18F-fluorodeoxyglucose positron emission tomography and/or chest CT with contrast for M staging.[2][19]​​​​ Bone is the most common site for metastasis, followed by lung and liver. 

Other investigations

Consider the following pre-treatment laboratory studies:

  • Plasma EBV DNA level is prognostic.[2][19][23]​​ High plasma EBV (>4000 copies/mL) is associated with a higher chance of distant metastasis.

  • EBV-encoded RNA in situ hybridisation (EBER ISH) is not routinely performed on tumour tissues in endemic countries, but it is useful in establishing a diagnosis in cases of occult primary tumours, particularly in non-endemic countries.[2]

  • Full blood counts, serum biochemistry, and liver and thyroid function tests.

  • Hepatitis B (HBsAg, anti-HBc, and anti-HBs) and HCV (anti-HCV) screening.

  • Serum or urine pregnancy test and contraceptive counselling.[19]

Other investigations/assessments that are useful to perform as baseline evaluations prior to starting treatment include:[2][19]

  • Audiogram (not required, but highly recommended prior to platinum chemotherapy)

  • Speech and swallowing consultation and formal assessment by modified barium swallow/videofluoroscopy

  • Dental evaluation and counselling in preparation for radiotherapy

  • Nutrition evaluation

  • Screening for hepatitis B

  • Smoking cessation advice, where necessary

  • Consider ophthalmological and endocrine evaluation, especially baseline pituitary function tests.

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