Malignant Nasopharyngeal Tumors

Updated: Oct 07, 2016
  • Author: Ho-Sheng Lin, MD, FACS; Chief Editor: Arlen D Meyers, MD, MBA  more...
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Overview

Practice Essentials

External beam radiation therapy with or without chemotherapy is the primary mode of therapy for previously untreated nasopharyngeal carcinoma (NPC). Recurrent or persistent disease remains a challenge to clinicians. Typically, re-irradiation is advocated. In some institutions, salvage nasopharyngectomy is used for the treatment of recurrent disease. [1]

External beam radiation therapy is the primary mode of management of NPC, both at the primary site and in the neck. This is mainly because of this tumor's high degree of sensitivity to radiation, as well as the anatomical constraints for surgical access to the highly complex nasopharyngeal region.

Management of locally recurrent diseases can be accomplished with either re-irradiation or salvage nasopharyngectomy. Patients whose treatment failed regionally can be treated with either re-irradiation or salvage neck dissection. A high prevalence of distant metastases has been observed for patients with NPC.

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History of the Procedure

In 1988, Fee and Tu published results of salvage nasopharyngectomy in a series of patients with recurrent NPC that failed previous treatment with radiation. [2, 3] The results were encouraging [2] and inspired other investigators to start using surgery in the treatment of patients with recurrent NPC. Since then, various surgical approaches to the nasopharynx have been proposed. These include the transpalatal-maxillary-cervical, maxillary swing, transmandibular, transcervico-mandibulo-palatal, infratemporal fossa, lateral temporal, endoscopic, and robotic approaches.

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Problem

Despite recent advances in the management of NPC, locoregional failure is still significant, with reported rates of 15.6-58% (median, 34%). [4, 5, 6, 7] Salvage treatment for local failure continues to be challenging because of the proximity of tumors to vital structures.

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Epidemiology

Frequency

Nasopharyngeal carcinoma (NPC) is a prevalent malignancy in Southeast Asia. [8] In areas such as southern China, Hong Kong, Singapore, Malaysia, and Taiwan, the reported incidence rate ranges from 10-53 cases per 100,000 persons per year. The incidence is also high among Eskimos in Alaska and Greenland and in Tunisians, ranging from 15-20 cases per 100,000 persons per year. Although NPC is a relatively uncommon disease in Western countries (< 1 case per 100,000 persons), it poses a significant health problem in regions of the United States with large Asian populations. The prevalence rate for people of Asian descent in the United States is 3.0-4.2 cases per 100,000 persons.

A study by Tang et al found that between 1970 and 2007, the age-standardized incidence rate of NPC saw significant reductions in southern and eastern Asia, North America, and the Nordic nations, with the average annual percent declines being 0.9-5.4% in males and 1.1-4.1% in females. Age-standardized mortality rates between 1970 and 2013 also fell, showing average annual percent reductions of 0.9-3.7% in males and 0.8-6.5% in females. The investigators suggested that the incidence reductions were associated with tobacco control, dietary changes, and economic development, while the drop in mortality rates stemmed not only from the reduced incidence but also from diagnostic advancements and improved radiotherapy techniques. [9]

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Etiology

A clear etiology for nasopharyngeal carcinoma (NPC) is still lacking. In general, NPC is thought to be the result of both genetic susceptibility and environmental factors such as carcinogens and infection with Epstein-Barr virus (EBV). Evidence in support of genetic factors is the association of NPC with genotypes HLA-A2 and HLA-Bsin2, which are prevalent in individuals from southern China but rare in whites. Furthermore, abnormalities of multiple chromosomes, including 1, 2, 3, 4, 5, 6, 8, 9, 11, 13, 14, 15, 16, 17, 22, and X, have been identified.

Possible environmental or cultural factors that may be associated with NPC include the ingestion of Cantonese-style salted fish and preserved foods that contain carcinogenic nitrosamines, especially during childhood. Evidence of EBV-DNA in almost all NPC cells that were studied supports the association of NPC with EBV. Further, the detection of clonal EBV-DNA in NPC suggests that the malignancy is a clonal expansion of a single EBV-infected progenitor cell. This finding indicates that EBV is present within the cell at the time of malignant transformation and suggests a role for the virus in contributing to the early transformation event. The contribution of both genetic factors and environmental factors for this disease is reflected in the observation that the incidence of NPC for American-born, second-generation Chinese individuals is lower than that for Chinese-born individuals in China but remains higher than that for white individuals in the United States.

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Presentation

Although reported in all age groups, a bimodal peak incidence appears to occur in individuals aged 30-40 years and 50-60 years. Nasopharyngeal carcinoma (NPC) is observed predominantly in males, with a male-to-female ratio of 3:1. Clinically, NPC has few early warning signs, which often means late diagnosis. Early but nonspecific symptoms include nasal obstruction, blood-tinged sputum or nasal discharge, tinnitus, headache, ear fullness, and unilateral conductive hearing loss from serous otitis media or recurrent acute otitis media. In advanced cases, the tumor can invade the skull base and spread intracranially through one of the many nearby foramina. Evidence of cranial nerve involvement (III-VI), including diplopia and numbness of the face, suggests cavernous sinus invasion.

The abundant supply of regional lymphatic vessels in the nasopharynx contributes to the high prevalence of cervical metastasis. Approximately 44-57% of patients initially seek medical attention because of a metastatic lymph node that manifests as a neck mass. At the time of diagnosis, 60-85% of patients already have cervical metastasis.

Systemic dissemination also occurs more readily in NPC than in other head and neck cancers. The most frequently involved sites are bone, lung, and liver. Distant metastases are present in 5-10% of patients at the initial presentation.

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Indications

Salvage nasopharyngectomy and neck dissection may be indicated in patients with nasopharyngeal carcinoma (NPC) that persisted or recurred locoregionally following prior treatment with radiation with or without chemotherapy. The proper selection of patients and surgical approach are essential for a successful outcome.

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Relevant Anatomy

Nasopharynx

The nasopharynx is defined anteriorly by the posterior choanae, posteriorly by the clivus and the first 2 cervical vertebrae, superiorly by the floor of the sphenoid, and inferiorly by the level of the free border of the soft palate. The nasopharynx is divided into 3 subsites: the posterosuperior wall, the lateral walls, and the posterosuperior surface of the soft palate. The torus tubarius is the opening of the eustachian tube into the lateral nasopharyngeal wall. The fossa of Rosenmüller is the groove or recess posterior to the torus at the junction between the lateral and posterior walls. Nasopharyngeal carcinoma (NPC) most commonly occurs in this location.

The posterior and lateral nasopharyngeal walls are composed of 3 layers of tissue. The mucosal epithelium of the nasopharynx is complex, consisting mainly of pseudostratified columnar ciliated epithelium near the choanae and the adjacent part of the roof of the nasopharynx, a transitional epithelium in the roof and the lateral walls, and stratified squamous epithelium along the posterior and inferior portions of the nasopharynx. The superior constrictor muscle and the buccopharyngeal fascia surround the mucosa. Superiorly, the buccopharyngeal fascia unites with the pharyngobasilar fascia, which is attached to the skull base.

The buccopharyngeal fascia extends posterolaterally from the free edge of the medial pterygoid plate to the lateral border of the carotid artery. This fascia separates the nasopharynx from the parapharyngeal (paranasopharyngeal) space. A line joining the free edge of the medial pterygoid plate posterolaterally to the styloid process divides the paranasopharyngeal space into the prestyloid space anteriorly and the retrostyloid space (containing the carotid sheath and the cranial nerves) posteriorly.

The paranasopharyngeal space is bound anteriorly by the pterygomandibular raphe, which joins the lateral pterygoid plate to the mandible. The retropharyngeal space contains the retropharyngeal lymph nodes and the node of Rouviere. This space is located posterior to the buccopharyngeal fascia and anterior to the prevertebral fascia; therefore, lesions that extend beyond the buccopharyngeal fascia posteriorly involve the retropharyngeal space, while lesions extending laterally beyond this fascia reach the parapharyngeal space.

The nasopharynx is an anatomically difficult area to expose surgically. This area is in close proximity to several foramina and associated vital neurovascular structures. These include the foramen ovale, the foramen spinosum, the foramen lacerum, the carotid canal, and the jugular foramen.

Neck

Ho originally described the supraclavicular fossa as a triangular region defined by 3 points: the sternal end of the clavicle, the lateral end of the clavicle, and the point where the neck meets the shoulder. [10] This area is clinically significant in that any nodal involvement within this triangle is, by definition, an N3 lesion and, therefore, stage IV cancer.

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Contraindications

Salvage nasopharyngectomy is contraindicated in patients with locally unresectable recurrent nasopharyngeal cancer and patients with distant metastasis.

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