Nasopharyngeal carcinoma is relatively rare in most countries of the world, with an age-adjusted incidence rate of less than 1 per 100000. The incidence, however, varies from country to country, showing that geographic and ethnic features are among the aetiological factors. The reported incidence in southern China is 10 to 20 per 100000 in males and 5 to 10 per 100000 in females, with the highest incidence among the residents of Guangdong Province. The incidence of nasopharyngeal carcinoma among Chinese born in North America is, however, consistently lower than that in those born in China. This finding suggests that environmental factors probably contribute to the aetiology of the disease. Factors implicated as causes of nasopharyngeal carcinoma include Epstein-Barr virus, nitrosamines, dry salted fish, chronic infection, polycyclic hydrocarbons, and poor hygiene.

The lateral walls of the nasopharynx, including the fossa of Rosenmüller are the most common site of the primary tumour, followed by the roof and posterior wall. Less than 10 per cent of carcinomas originate from the anterior wall. Microscopically, nasopharyngeal carcinoma can be classified into three types, depending on the predominant histological finding in biopsy specimens examined under light microscopy. The three histological types are: squamous cell carcinoma (WHO type 1), non-keratinizing carcinoma (WHO type 2), and undifferentiated or poorly differentiated carcinoma, including lymphoepithelioma and anaplastic varieties (WHO type 3). In contrast to WHO type 1, WHO types 2 and 3 tumours are associated with a characteristic pattern of antibodies against Epstein-Barr virus. Tumours of WHO type 2 and 3 have a better prognosis.

As the nasopharynx is richly endowed with lymphatic channels which drain into the cervical nodes, it is not surprising that the most common presenting symptom is an enlarged cervical lymph node. This occurs in 60 to 75 per cent of patients, and the upper cervical group of lymph nodes is usually involved. The primary tumour in the nasopharynx is usually small and the trivial symptoms related to it sometimes escape notice.

As nasopharyngeal carcinoma most frequently arises from the fossa of Rosenmüller and the lateral wall, eustachian tube function may be impaired: about 40 per cent of patients present with otological symptoms such as deafness and tinnitus. If the primary tumour is bulky nasal airway obstruction may occur; when the tumour surface ulcerates the patient also complains of epistaxis.

Nasopharyngeal carcinoma sometimes extends superiorly into the skull base via the foramen lacerum or the foramen ovale. Cranial nerve palsies are present in 13 to 25 per cent of patients on presentation. Facial pain or paraesthesia suggests that cranial nerve V is affected, while ophthalmoplegia reflects involvement of cranial nerve III, IV, or VI. More extensive disease at the skull base results in lower cranial nerve (IX, X, XI, XII) deficits. Occasionally the cervical sympathetic chain is affected, leading to Horner's syndrome.

The incidence of distant metastasis at diagnosis is less than 5 per cent and the most frequently involved sites are the bones, lungs, and liver.

A complete history and physical examination are essential. Exophytic or polypoid tumours are easily visualized by indirect mirror examination in a co-operative patient. A thorough examination of the nasopharynx can be achieved through a direct rigid or flexible fibreoptic endoscope. The rigid instrument provides a better optical image (Fig. 1) 2710, but the flexible endoscope has the advantages of allowing a full examination of the nasopharynx and allowing biopsy specimens to be obtained from exact sites.

Macroscopically, nasopharyngeal carcinoma may present as friable exophytic lesions, or as submucosal bulges. Multiple biopsies of the nasopharynx are therefore indicated, even when endoscopic examination shows no abnormality, particularly in patients from high-risk regions who have high levels of antibody to Epstein-Barr virus. Subclinical carcinoma can be detected in this way. Examination and biopsy of the nasopharynx should be carried out under general anaesthesia when indicated.

Plain radiographs of the skull base may reveal bony erosions or abnormal widening of the foramina. A contrast-enhanced high resolution CT scan of the head, nasopharynx, and neck helps to define the extent of the disease (Fig. 2) 2711. This imaging technique, besides helping with staging of the disease and planning of treatment, also provides a baseline for objective assessment of treatment results. Magnetic resonance imaging may define the extent of soft tissue involvement more accurately.

There is a strong relationship between nasopharyngeal carcinoma and Epstein-Barr virus infection. The Epstein-Barr virus nuclear antigen has been found within malignant cells from biopsies of nasopharyngeal carcinoma. Serological tests for antibodies to the virus may help in confirming the diagnosis, especially in patients who present with cervical metastasis from an inconspicuous primary tumour. Of clinical significance are the two antibodies (IgA) that are induced by the viral capsid antigen and the early antigen of the Epstein-Barr virus. The early antigen produces two different patterns of immunofluorescence, a diffuse staining of both the nucleus and cytoplasm, and a restricted staining of cytoplasm only. Antibodies against the diffusely distributed antigen show a stronger correlation with nasopharyngeal carcinoma.

Indirect immunofluorescence assays performed on sera are positive (titre > 1:10) for antibodies to viral capsid antigen in 65 per cent of patients (85 per cent of those whose tumour is of WHO type 2 or 3; 15 per cent when the histological type is WHO type 1). IgA against the diffuse pattern of early antigen is more specific but less sensitive: it is present in 47 per cent of patients with nasopharyngeal carcinoma and in less than 2 per cent of patients suffering from other head and neck malignancies.

The antibody-dependent cellular cytotoxicity assay is used to measure levels of antibody against the Epstein-Barr virus-induced membrane antigen complex. High titres have been associated with a better prognosis in patients with WHO types 2 and 3 nasopharyngeal carcinoma.

Several staging systems for nasopharyngeal carcinoma are in use throughout the world. These include the system of the International Union Against Cancer (UICC), the American Joint Committee on Cancer Staging and End-Results Reporting (AJCC), and the Ho System, each of which has its merits and deficiencies. As submucosal spread of nasopharyngeal carcinoma is not uncommon, the exact extent of disease is often difficult to determine. The anatomical boundaries of the lateral wall and the roof are also imprecise. Attempts to stage according to the extent of tumour in the nasopharynx as T1 and T2 by the AJCC and UICC staging systems are not meaningful; this is recognized by the Ho system. The nasopharynx is an anatomical region in the midline, with lymphatic drainage to both sides of the neck. The AJCC and UICC systems, dealing with cervical lymph node classification as homolateral versus contralateral neck nodes, are not appropriate. The Ho system recognizes the importance of the level of node involvement rather than unilateral or bilateral nodal involvement (Table 1) 653: patients with lower neck node involvement has a poor prognosis. In view of the deficiencies of the various staging systems, a prognostic scoring system has been suggested. This takes into account the presenting symptoms, extent of tumour, histological type, serology, and age. It predicts the prognosis more precisely than the traditional systems.

The mainstay of treatment for nasopharyngeal carcinoma is external radiotherapy. Although the techniques vary among centres, most would include the primary tumour and the first echelon of nodes in large lateral opposed faciocervical portals. Coverage of the primary tumour includes the adjacent structures that are the potential sites of extension. A radiation dose between 65 and 70 Gy is required. The size of portals is decreased to avoid the spinal cord before the tolerance dose is reached, usually around 40 Gy. The upper neck nodes are then treated by electrons or through anteroposterior neck portals. If the lower neck is unaffected, prophylactic irradiation of 50 to 55 Gy is administered, usually by anteroposterior neck portals. The primary tumour and the neck are often considered as a single treatment volume, since the primary tumour is in close proximity to the first echelon nodes located at the parapharyngeal space. These nodes may sometimes be continuous with the primary tumour, and their omission from the field of irradiation results in a high incidence of neck node relapse.

The 5-year survival for patients with tumours of stages I, II, III, and IV after radiotherapy is about 80 per cent, 70 per cent, 40 per cent and 15 per cent respectively. Xerostomia is inevitable; other problems such as dental caries, trismus, serous otitis media, and neuroendocrine damage occur occasionally.

Nasopharyngeal carcinoma is chemosensitive, and sequential chemotherapy and radiation have been used for the treatment of patients with advanced locoregional disease. Despite the high rate of tumour response to chemotherapy, long-term benefit in terms of disease-free and actuarial survival is not encouraging. Chemotherapy may, however, provide symptomatic relief and sometimes prolongs survival in patients with recurrent or metastatic disease.

Surgery is indicated when, despite control of the primary tumour with radiotherapy, persistent or recurrent disease occurs in cervical lymph nodes. This is seen in about 18 per cent of patients. Further doses of radiation produce a reported cure rate of 14 to 28 per cent. Radical dissection is mandatory for cure, as pathological study of the resected specimens has shown that the lymph node involvement is more extensive than clinically evident. The 5-year survival rate has been reported to be 49 per cent. We have employed radical neck dissection in the management of 51 patients with persistent or recurrent neck disease from nasopharyngeal carcinoma after radiotherapy. There was one in-hospital death, and the overall morbidity was minimal. The follow-up period ranged from 1 to 9 years (median 2 years). The actuarial survival of this group of patients at 5 years was 38 per cent and the probability of control of neck disease was 66 per cent. Radical neck dissection is therefore effective in controlling post-irradiation cervical metastasis from nasopharyngeal carcinoma.

Although nasopharyngeal carcinoma is radiosensitive, local failure in the form of persistent or recurrent tumour is not uncommon. Administration of further external radiation is limited by the tolerance of structures such as the inner ear and brain-stem. Brachytherapy has been successfully employed in the management of local disease. This requires adequate exposure of the nasopharynx to allow accurate insertion of radioactive implants. Under general anaesthesia, the hard and soft palates can be split in the midline to expose the tumour in the nasopharynx; radioactive gold grains can then be inserted into the tumour under direct vision. The operative procedure is simple and the complication rate is minimal. Small recurrent or persistent tumours in the nasopharynx can be managed successfully in this way.

Because of its midline location at the base of the skull, the nasopharynx is difficult to approach surgically and is traditionally considered to be an unresectable structure. However, a number of surgical approaches have been designed to provide access to the nasopharynx. Most of these have been developed to allow removal of tumours in the maxilloethmoidal region, but they have also been employed for resection of malignant tumours in the nasopharynx. In most of the described approaches, the nasopharynx and paranasopharyngeal space are not exposed sufficiently to allow an oncological procedure to be carried out. Recent advances in the surgery of the skull base have led to the development of aggressive approaches to the nasopharynx.

Surgical resection is indicated when local recurrent or persistent tumour in the nasopharynx after external radiotherapy is too large for brachytherapy, and when no regional or distant metastases are present. Successful transpalatal excision of localized tumour in the nasopharynx has been reported. A lateral approach through the infratemporal fossa has also been reported: both palliation and salvage procedures can be carried out using this method. A multistage transparotid temporal bone approach has also been described, and some degree of palliation can be achieved in selected patients.

We have employed the maxillary swing approach for resection of recurrent or persistent tumour in the nasopharynx after radiotherapy. The operation is performed under general anaesthesia. A maxillectomy skin incision is employed, but the incision only exposes a narrow strip of bone over the anterior wall of the maxilla for osteotomy. The cheek flap remains attached to the anterior wall of the maxilla during the whole procedure (Fig. 3) 2712. Using an oscillating saw, osteotomies are made on the zygoma and continued on to the anterior wall of the maxilla. The hard palate and the medial wall of the maxilla are also divided with a saw. The maxillary tuberosity is separated from the pterygoid plates using a curved osteotome (Fig. 4) 2713. The maxilla can be swung laterally while remaining attached to the masseter muscle and cheek flap (Fig. 5) 2714. The whole mucosal surface of the nasopharynx with the orifices of the eustachian tubes are thus exposed and en-bloc resection of the tumour is possible. After resection, the maxilla and attached cheek flap are returned to position and fixed to the zygoma and opposite maxilla with miniplates and screws (Fig. 6) 2715. Local tumour control is possible with a low complication rate.

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