The nasopharynx is anatomically, functionally and histologically different from the other parts of the head and neck. It is the site of nasopharyngeal carcinoma, a unique malignancy that has wide geographic variation in incidence. There are three distinct types:
- Non-keratinising nasopharyngeal carcinoma (NPC), the more common form that usually occurs in endemic areas
- Keratinising NPC, much less common and more likely to occur in the low risk areas such as Australia
- Basaloid squamous cell carcinoma, which is described only in case reports
Epidemiology
Nasopharyngeal carcinoma has a highly varied incidence that is based on geographic location.
- In Australia, the US and the UK nasopharyngeal carcinoma is an uncommon disease (incidence <0.5/100,000)
- In South East Asia, China, North Africa and West Africa nasopharyngeal carcinoma is endemic (incidence 50/100,000)
By comparison, breast cancer in Australia has an incidence of 83/100,000. The highest risk area is Hong Kong, with 1/40 men developing nasopharyngeal carcinoma by the age of 75.
In the endemic areas, the peak age of diagnosis is 40-60. It is uncommon before age 30. NPC is more common in men (2-3 times). The rates of nasopharyngeal carcinoma are decreasing in all parts of the world.
Aetiology and Pathogenesis
Epstein Barr Virus is the single most commonly associated risk factor for endemic NPC. The evidence is significant:
- Higher levels of anti-EBV IgA molecules in patients with NPC
- Higher titres of anti-EBV IgA in patients with large volume NPC
- Presence of clonal EBV DNA/RNA in nearly all tumour cells (suggesting incorporation prior to transformation)
- Presence of EBV in precursor lesions but not normal nasopharyngeal mucosa
EBV infection is thought to occur later in carcinogenesis (ie. it acts like a promotor, not an initiator)
Diet is also an important factor. Highly salted and preserved foods, particularly when administered in childhood, are associated with an increased risk of NPC (RR 5 - 6). Other risk factors include smoking and radiation exposure.
Natural History
Most malignancies arise in the pharyngeal recess (fossa of Rosenmuller), which lies behind the torus and the salpingopharyngeal fold. The malignancy is renowned for highly aggressive behaviour:
- Local invasion is common and extensive, with destruction of the bones of the skull base and invasion and tracking of cranial nerves.
- Lymphatic spread occurs to all lymphatic levels (except IA) of the neck; the most commonly palpable node is the jugulodigastric node (II). The posterior cervical triangle is commonly involved. The extent of lymphatic involvement reflects the risk of haematogenous spread. Most clinicians believe that the cancer spreads by passing through the thoracic duct into the great vessels
- Haematogenous spread is common, and occurs to bone, lung and liver.
Clinical Presentation
Symptoms and Signs
About 10% of patients have no symptoms. Common symptoms are due to local invasion or lymphatic spread:
- Bloody post nasal drip
- Difficulty breathing through the nose
- Serous otitis media due to pharyngotympanic tube obstruction
- Painless cervical lymphadenopathy
- Cranial nerve neuropathy if involved
Symptoms related to distant disease are uncommon at presentation.
Imaging
MRI is the most helpful test to judge local invasion, including involvement of the skull base and cranial nerves.
CT-PET is used for staging of distant disease. Bone scan allows detection of bony metastases.
Tumour Features
All types of nasopharyngeal carcinoma have a variety of appearances on nasendoscopy, from barely visible abnormalities to ulcerated, exophytic masses.
Non-keratinising NPC
Non-keratinising NPC has a variety of appearances on microscopy. There is usually a distinction made between 'differentiated' and 'undifferentiated' types; this distinction has no effect on prognosis.
Undifferentiated NPC usually has large cells with indistinct borders, containing large and vesicular nuclei with a scanty amount of cytoplasm.
Differentiated NPC has smaller cells with a lower nucleus-cytoplasm ratio. The cells have distinct borders and the nucleus lacks vesicles.
Both types may have a variety of infiltration with lymphocytes; in some cases there may be lymphocytes infiltrating between individual cells. This is termed lymphoepithelial carcinoma.
Immunohistochemistry shows positive staining for cytokeratins (AE1/3) but not for CK7 or CK20. The lymphoid population is polyclonal. In-situ hybridisation techniques are used to detect EBV (which is present in 100% of non-keratinising NPC).
Electron microscopy is able to show evidence of squamous differentiation.
Keratinising NPC
The less common variant of NPC (even in non-endemic areas, only about 25% of cases match this type in the USA). This tumour histologically resembles squamous cell carcinoma seen in most other head and neck mucosal malignancies. There is evidence of intercellular bridging and keratin formation. There is usually a significant stromal component. The tumour is graded based on the degree of differentiation and pleomorphism.
Importantly, keratinising NPC is usually more locally aggressive but spreads later in the course of disease.
Basaloid squamous cell carcinoma
Only 6 case reports exist. It appears to be less aggressive than basaloid squamous cell carcinomas in other head and neck regions.
Staging
Staging is through the TNM system.
T Stage
| T Stage | Description |
|---|---|
| T1 | Confined to nasopharynx, or extension to oropharynx/nasal cavity without posterolateral spread |
| T2 | Extension into posterolateral pharyngeal soft tissues |
| T3 | Invasion of bony structures (skull base, sinuses) |
| T4 | Intracranial extension, cranial nerve involvement, spread to hypopharynx/orbit/infratemporal fossa |
N Stage
| N Stage | Description |
|---|---|
| N1 | Unilateral metastasis to cervical nodes, < 6 cm size, not level IV/Vb and/or Unilateral or bilateral involvement of retropharyngeal nodes, < 6 cm size |
| N2 | Bilateral metastasis to cervical nodes, < 6 cm size, not level IV/Vb |
| N3a | Nodes > 6 cm in size |
| N3b | Involvement of nodes in levels IV/Vb (supraclavicular fossa) |
M Stage
| M Stage | Description |
|---|---|
| M1 | Distant metastases |
Final Stage
| Stage | T | N | M |
|---|---|---|---|
| I | T1 | N0 | M0 |
| II | T2 T1-2 |
N0 N1 |
M0 |
| III | T3 T1-3 |
N0-1 N2 |
M0 |
| IVA | T4 | N0-2 | M0 |
| IVB | Tany | N3 | M0 |
| IVC | Tany | Nany | M1 |
