Disclaimer: The information contained within the Grand Rounds Archive is intended for use by doctors and other health care professionals. These documents were prepared by resident physicians for presentation and discussion at a conference held at Baylor College of Medicine in Houston, Texas. No guarantees are made with respect to accuracy or timeliness of this material. This material should not be used as a basis for treatment decisions, and is not a substitute for professional consultation and/or peer-reviewed medical literature.

Nasopharyngeal carcinoma (NPC) is relatively rare in the U.S., representing only 0.2% of all malignancies. However, in a number of endemic areas it is the most common tumor found, comprising 18% to 25% of all cancers These endemic areas include southern China, Hong King, Taiwan, Kenya, the Philippines, Singapore, Tunisia, Sudan and Uganda. In contrast to this, the prevalence of NPC in neighboring oriental countries, including northern China and Japan is quite low. Emigrants from endemic countries to non-endemic areas such as the U.S., continue to carry this high risk, while first and second generation descendants carry progressively lower risks.

The most frequently suspected etiologic factors are viral, genetic and environmental. The link between NPC and the Epstein-Barr virus (EBV) was discovered in 1966. Multiple series have demonstrated the presence of EBV positive serology in approximately 90% of patients with NPC, compared to less than 10% in normal patients. A genetic predisposition is suggested by the increased prevalence of NPC in certain HLA subclasses. Finally, the relationship between environmental conditions and development of NPC has generated a great deal of interest. Worldwide, the most likely environmental factors are smoky surroundings and foods such as salted fish, smoked meat, sausage or duck. High levels of N-nitrosamines, a group of chemicals which are mutagenic in vitro, may be the carcinogenic agent in these foods. In the U.D., cigarette smoke has been shown to be a significant risk factor, while heavy alcohol use is associated with a slightly increased risk. At this time, it is believed that the cause of NPC is probably multifactorial, requiring the interaction of more tan one of these risk factors.

A variety of terms have been used to describe the histologic appearance of NPC, and this has led to a great deal of confusion. The World Health Organization classification system simplifies this. Under this scheme, there are three main histologic types, WHO types 1, 2, and 3. Type 1 carcinoma is the most differentiated and is also known as keratinizing squamous cell carcinoma. These account for 25% of all NPC. Type 2 NPC is also referred to as non-keratinizing. It is the least common, representing only 12% of NPC. WHO type 3 is also called undifferentiated carcinoma and accounts for 63% of NPC. Despite their histologic appearance, all of these tumors have been demonstrated by electron microscopy to be varieties of squamous cell carcinoma.

A number of descriptive terms are in common usage, including the term lymphoepithelioma. This term actually describes one type of undifferentiated NPC which is characterized by malignant epithelial cells within a background of lymphoid cells. The lymphoid cells are reactive in nature and are not in themselves malignant.

NPC is notoriously difficult to diagnose. This is due to a number of factors, including the inaccessibility of the nasopharynx, nonspecificity of symptoms when the disease is in its early stages and the tendency of the tumor to spread submucosally, and thus to remain clinically inapparent even to direct inspection. The mean delay form the onset of the first symptom to diagnosis was reported by Skinner et al to be six months. A neck mass is consistently one of the most common presentations, and, unfortunately, is a sign of advanced disease. Hearing loss is a common symptom and is usually attributable to a serous effusion. Cranial nerve deficits are also common.

Following appropriate history, evaluation of NPC requires a combination of visualization, biopsy, radiologic studies and in some cases the use of serologic studies. Visualization by way of fiberoptic endoscopy is essential, and use of mirror examination should not be considered adequate. Despite the major advance sin optics, tumors may still evade the examiner secondary to submucosal spread of tumor, tumor hidden in the fossa of Rosenmuller, or a very small primary. As a result, a normal appearing nasopharynx does not rule out NPC. Biopsy of the nasopharynx may prove challenging for many of the reasons. Mucosa covering a tumor which has spread submucosally my be histologically normal. Repeated or more aggressive biopsies may be required. Radiologic studies consisting of thin cut CT scans with intravenous contrast are essential in defining the extent of tumor, both as an aid in staging and in determining the radiotherapeutic plan. CT scans may help in detecting very early and hard to locate tumors, although subtle asymmetries in the nasopharynx are common and tumor may be difficult to distinguish from normal variation. Finally, serologic markers for EBV may play a role in detection of the disease. Positive serology for EBV in a patient with a cervical metastasis of unknown primary may direct attention toward the nasopharynx.

The mainstay of treatment of NPC is radiation. This is due both to the inaccessibility of the tumor to surgery, and also to the surprising radiosensitivity of the lesion. NPC is also one of the most challenging tumors for the radiotherapist to treat. This is due to the close proximity of the tumor to many vital structures. Although a wide variety of protocols is used, a standard treatment regimen recommended by Ho is 6500 to 7000 cGy delivered to the tumor by a linear accelerator by one anterior and two laterally opposed fields. Shielding of the eyes, tongue, brainstem, and spinal cord is essential.

Chemotherapy may be used as an adjunct to radiation therapy. Although an impact on survival has not been demonstrated, chemotherapy theoretically may decrease the possibility of distant metastatic spread by eradicating micrometastases. Two clinical situations have been mentioned in which chemotherapy may play a specific role. The first of these is the patient with massive cervical lymphadenopathy, in which cytoreduction may improve the neck geometry so that radiation may be more effectively used. The second is the patient with distant metastases which could not be treated by local or regional therapy.

Surgery plays a supportive role in the treatment of NPC. Surgery on the primary lesion has been described but is limited by the inaccessibility of the lesion and the difficulty in achieving resection of the tumor with clear margins in the face of the convoluted nasopharyngeal anatomy. In refractory cases, reirradiation techniques such as arc radiation or intracavitary implants would generally be considered preferable to surgery. Surgery for cervical lymphadenopathy is usually reserved for salvage following radiation therapy. Unlike cervical metastases from most other head and neck primaries, even very large metastases from NPC usually respond well to XRT. The use place for neck dissection is in the case of persistent neck disease after XRT where the primary lesion appears to be cured. Finally, surgery may play a supportive role in treating symptoms or complications. The most common instance of this is in placement of pressure equalization tubes for a serous effusion.

Case Presentation

A 62-year-old black male presented with a 3 month history of decreased hearing in both ears and a two week history of right ear pain. In addition to this he complained of a one to two week history of numbness of the left cheek. On physical examination he was found to have bilateral serous effusions. Fiberoptic nasopharyngoscopy revealed a necrotic mass filling the posterior wall of the nasopharynx. A 0.5 by 0.5 cm right posterior triangle lymph node was palpated. The skin in the distribution of V2 on the left was noted to be anesthetic. Biopsy of the mass revealed poorly differentiated carcinoma consistent with lymphoepithelioma. CT scan revealed an extensive tumor with invasion of the left pterygomaxillary fissure. He was treated with 7040 cGy of external beam radiation and is currently clinically free of disease two months after treatment.

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