The nasopharynx is a somewhat cuboidal space inferior to the skull base and posterior to the nasal cavities, with which it communicates via the posterior choanae (Fig. 1) 2349. The roof is formed by the sphenoid sinus, the basiocciput, and the atlas. In children it is covered by lymphoid tissue known as the adenoid or pharyngeal tonsil. The posterior wall, consisting of mucosa, aponeurosis, superior constrictor muscle, and buccopharyngeal fascia, abuts the first two cervical vertebrae. The floor is formed by the soft palate, communicating with the oropharynx via the pharyngeal isthmus. Laterally lie the eustachian tube orifices, each surrounded by the cartilaginous prominence of the torus tubarius. Posterolaterally lie the fossae of Rosenmüller which are adjacent to the posterior parapharyngeal space, including the internal carotid artery, internal jugular vein, cranial nerves IX, X, XI, and XII, and the cervical sympathetic ganglia. Adjacent to the nasopharyngeal wall are several foramina, which provide potential inflammatory and neoplastic pathways to the cranium; the most important of these are the foramen lacerum and foramen ovale. These pathways can allow spread of tumours to cranial nerves III, IV, V, and VI. Lymphatic drainage of the nasopharynx is primarily to the lateral pharyngeal nodes (including the retropharyngeal node of Rouviére), the jugulodigastric nodes, and the spinal accessory nodes. Absence of a midline lymphatic barrier accounts for the frequency of contralateral cervical metastases in nasopharyngeal carcinoma.

Nasopharyngeal carcinoma is most common in southern Chinese people from the province of Kwantung, and less so in south-east Asians of southern Chinese origin. The incidence is intermediate in American-born people of southern Chinese ancestry. It is rare among Caucasians, Japanese, and northern Chinese. The peak incidence occurs in the fourth to fifth decades, and males are affected more commonly than females.

Levels of antibodies to Epstein-Barr virus are elevated in patients with nasopharyngeal carcinoma, and the genome of this virus has been isolated from the malignant epithelium. The frequency of histocompatibility antigens HLA-A2 and HLA-B-SIN2 are elevated in Chinese patients with nasopharyngeal carcinoma, suggesting an additional genetic influence. Various environmental exposures have been thought to predispose to nasopharyngeal carcinoma, including inhalants such as polycyclic hydrocarbons and nitrosamines in salted fish. Chronic infection and trauma may also predispose to the disease. Despite careful scrutiny none of these factors plays a clear aetiological role.

The presentation of nasopharyngeal carcinoma is different to that of most other head and neck cancers. Initial discovery of the tumour itself by nasopharyngeal examination is unusual. More than half of all patients present with a mass in the neck. Unilateral serous effusion with hearing loss is also common. Facial pain, headache, nasal obstruction, epistaxis, hyponasal speech, cranial neuropathy, proptosis, and trismus are less common and are related to local tissue destruction in advanced disease.

The most common findings on physical examination include cervical adenopathy, unilateral serous otitis media, and a nasopharyngeal mass. Serous otitis which is refractory to antibiotics and decongestants is a strong indication for a careful examination of the nasopharynx.

Adenopathy is most common in the upper jugular nodal chain. However, nasopharyngeal carcinoma has the highest rate of metastasis to the posterior cervical triangle of all head and neck tumours. Supraclavicular adenopathy is also common. Metastasis is often bilateral or contralateral, in keeping with the relative lack of compartmentation of the primary tumour. The nasopharyngeal mass is often small and its size bears no relation to the degree of cervical adenopathy. The mass is most often noted as an ulceration or exophytic mass emanating from Rosenmüller's fossa or from the central posterosuperior wall. Local obstruction leads to eustachian tube dysfunction and consequent serous otitis media. The breath may have a foul odour secondary to tumour breakdown and slough.

Advanced disease affecting the skull base may be detected either by radiographic evidence of bone destruction or by the presence of various cranial neuropathies. Invasion of the foramen lacerum may spread to cranial nerve VI, followed by nerves III and IV, with resultant diplopia and ptosis. Tumour invasion of the jugular foramen and the more posterior skull base results in cranial neuropathies of nerves IX, X, XI, and XII.

Investigation of suspected nasopharyngeal carcinoma should include a complete head and neck examination with a careful indirect mirror examination of the nasopharynx. Fibreoptic examination of the nasopharynx may be necessary or useful to visualize the tumour fully. Nasopharyngoscopy and biopsy, usually under general anaesthesia, should be performed to confirm the diagnosis histopathologically.

CT scanning of the skull base and sinuses with contrast is useful in assessing the extent of primary disease and in planning radiotherapy (Fig. 2) 2350. The most important consideration is whether the tumour has invaded the skull base, with involvement of the foramen lacerum. Erosion of bone at the skull base or extension into the anterior fossa indicate a poor prognosis. Magnetic resonance imaging (MRI) shows soft tissue changes superbly, but lacks accuracy in depicting bony changes.

Detection of antibodies to Epstein-Barr virus capsid antigen and diffuse early antigen are useful in the early detection of nasopharyngeal carcinoma in high-risk groups. Titres of these antibodies are elevated primarily in patients with WHO types II and III disease (non-keratinizing and undifferentiated carcinoma). Antibody titres to the Epstein-Barr virus-induced membrane antigen complex appear to predict the clinical course following diagnosis. Clinical progression of the tumour at 3 years is strongly correlated with low titres to membrane antigen complex in WHO stage II and III disease.

All patients with nasopharyngeal carcinoma should undergo careful examination of the nasopharynx under anaesthesia to determine the exact extent of disease as well as for histological confirmation and typing. Early metastases to bones, lung, and liver are not uncommon, being present in over half of all patients with advanced cervical metastasis. Routine evaluation should include complete blood count, liver function testing, and chest radiography, as well as complete history and physical examination.

The TNM staging of nasopharyngeal carcinoma according to the American Joint Committee for Cancer Staging is useful prognostically and in treatment planning (Table 1) 609.

Cervical adenopathy is staged according to the American Joint Committee criteria for other head and neck squamous cancers. Staging does not show good correlation with prognosis: insufficient significance is given to the level of nodal disease and fixation. Other staging systems do take these factors into account. Nodal fixation and inferior location are associated with reduced survival, whereas bilateral nodal disease is not prognostically worse than unilateral disease. Neel has shown that the most important variables affecting survival are presence of extensive tumour in the nasopharynx, regional extension of tumour, cranial nerve disease, and the presence of supraclavicular adenopathy. T stage does not predict survival well, other than in far advanced disease.

According to the World Health Organization (WHO) nasopharyngeal carcinoma falls into three histological types, with considerable overlap between these categories. Differentiated squamous cell carcinoma (WHO type 1) accounts for about 25 per cent of the lesions; these contain features typical of squamous cell carcinoma found elsewhere in the head and neck. Non-keratinizing or transitional cell carcinomas form WHO type 2 nasopharyngeal carcinomas. Lymphoepitheliomas and anaplastic carcinomas form WHO type 3 carcinomas. Types 2 and 3 carcinomas appear to represent a continuum with features distinct from those of differentiated squamous cell carcinomas. They appear to be more highly associated with Epstein-Barr virus, more radiosensitive, associated with longer disease-free intervals after therapy, are found in a younger age group, and are associated with earlier and more extensive cervical adenopathy compared with differentiated nasopharyngeal carcinoma.

Other nasopharyngeal malignancies such as lymphomas, adenocarcinomas, plasmacytomas, sarcomas, and melanomas are found infrequently.

The mainstay of therapy is external beam radiotherapy to the primary site and both cervical areas. The primary tumour and cervical metastases are highly radiosensitive. En-bloc surgical resection of the primary site is impossible, and neck dissection is usually unnecessary unless disease is persistent or recurrent. Treatment considerations must include protection of the cervical spine and brain as part of the radiotherapy planning.

For T1 and T2 lesions treatment volumes should include the nasopharynx as well as overlapping adjacent regions along with the cervical nodes at risk. T3 and T4 lesions require inclusion of the entire nasal cavity, oropharynx, and relevant intracranial structures, respectively. Megavoltage and/or cobalt-60 &ggr;-rays are used for both primary site and cervical areas. Lateral opposed fields are used for the primary tumour and upper cervical areas with an anterior field for the lower neck. Conservative fraction doses of 170 to 180 Gy given five times per week are used to minimize severe mucositis. A minimum total dose of 6500 Gy to primary site and cervical areas is given with higher doses for T3, T4, and keratinizing squamous cell carcinomas. Qin recently noted improved survival in patients with residual disease after therapy who were boosted to over 90 Gy using a cone-down technique. Spinal cord and retinal doses should not exceed 4500 Gy. Intracavitary radium or caesium can be used to increase local tumour dose after completion of external beam irradiation or to treat recurrent tumour. The consequences of the requisite high-dose radiotherapy include xerostomia, dental caries, chronic otitis media, trismus, cranial neuropathy of nerves IX to XII, cervical fibrosis, transverse radiation myelitis, dysfunction of the hypothalamic–pituitary axis, hypothyroidism, retinopathy, and optic nerve injury. These effects can be minimized by proper planning and shielding.

Control rates for the primary tumour range from 66 to 80 per cent and for cervical metastasis from 82 to 91 per cent. Overall 5-year survival ranges from 25 to 57 per cent. Some series reveal a better prognosis in WHO 2 and 3 carcinomas compared with WHO 1. Continued elevated levels of antibody to Epstein-Barr virus capsid antigen and to the diffuse component of early antigen following therapy are predictive of recurrence. Patients with recurrences within the first 2 years have a poorer prognosis than those whose disease recurs later. Other favourable prognostic factors may include age below 40, female sex, and adequate cell-mediated immunity.

Induction and adjuvant chemotherapy, including cis-platinum, 5-fluorouracil, leucovorin, cytoxan, bleomycin, methotrexate, and vincristine, have been used along with radiotherapy to improve local control in some medical centres but not in others. Chemotherapy is useful in palliation of recurrences. Immunotherapy may offer adjunctive benefit in the future: nasopharyngeal carcinoma patients have depressed T-cell immunity.

Because en-bloc resection of the nasopharynx is not possible, surgery has no role in the primary treatment of nasopharyngeal cancer. In recent years there has been a revival in the use of surgical palliation after failure of radiation and chemotherapy. Such treatment uses the infratemporal fossa and the transparotid temporal bone approaches to the skull base. The procedures require limitation of the tumour to one wall, and no invasion of the cavernous sinus or mediastinum.

Angiography is first performed to assess the presence of collateral cerebral circulation if carotid resection is required. Assessment of the arterial supply to the tumour can also assist the surgeon in estimating and controlling blood loss. Subtemporal craniectomy is performed to assess pericarotid extension and resectability, as well as to perform a retrogasserian rhizotomy for pain control if needed. Carotid ligation is then performed under electroencephalographic monitoring in order to assess tolerance of carotid resection and the possible need for revascularization. The tumour resection is undertaken as a second procedure, involving removal of the temporal bone, upper ramus of mandible, the glenoid fossa, and the pterygoid plates.

Malignant lymphoma seldom involves the nasopharynx initially and exclusively. A full examination should be undertaken following histological confirmation. Histologically, these tumours can be difficult to distinguish from undifferentiated carcinomas; electron microscopy and stains for lymphocytic cell markers may be required. Lymphomas in the nasopharynx are primarily of B-cell, large cell, type with a diffuse growth pattern. Radiotherapy is the mainstay of treatment; adjuvant chemotherapy potentially improves survival. Total radiation dose to the nasopharynx ranges from 4000 to 6000 Gy and 5-year survival is generally better than that in nasopharyngeal carcinoma.

Angiofibroma is a histologically benign but locally aggressive tumour primarily affecting adolescent males. It is highly vascular, with a blood supply primarily from the internal maxillary branch of the external carotid artery, but occasionally also from the internal carotid and vertebral arteries. Angiofibroma usually presents with nasal obstruction and epistaxis, but often causes other localizing symptoms related to local destruction of the sinuses, orbits, nasal cavities, and cranium.

Diagnosis is usually confirmed by CT scan and angiography rather than by biopsy, because of the potential for massive haemorrhage. Smaller, localized tumours are treated by surgical removal, often following selective arterial embolization using absorbable gelatin. The surgical approach is determined by the location and extent of the tumour. Removal usually requires a combination of transpalatal, transantral–retromolar trigone, and frontoethmoid approaches. For more advanced lesions with intracranial spread, radiotherapy using 30 to 55 Gy is the treatment of choice. A combined intracranial–extracranial surgical approach with or without adjunctive radiotherapy is also possible.

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