eMedicine Specialties > Radiology > Head/Neck

Nasopharynx, Squamous Cell Carcinoma

Simon Lo, MBBS, Assistant Professor, Department of Radiation Oncology, Indiana University School of Medicine
Nancy Lee, MD, Consulting Staff, Department of Radiation Oncology, Memorial Sloan-Kettering Cancer Center; Sasan Karimi, MD, Assistant Professor of Radiology, Weill Medical College of Cornell University; Director of Neurospectroscopy, Director of Neuroradiology Fellowship Program, Director of Radiology at 55th Street Imaging Center, Memorial Sloan-Kettering Cancer Center; Assistant Attending Radiologist, Neuroradiology Section, Memorial Hospital for Cancer and Allied Diseases; Alan Tim-shing Choy, MBBS, FRCR(UK), FHKCR, FHKAM(Clinical Oncology), Staff Clinical Oncologist, Department of Clinical Oncology, Queen Elizabeth Hospital, Hong Kong; Sameer R Keole, MD, Staff Physician, Department of Radiation Oncology, Gershenson Radiation Oncology Center, Karmanos Cancer Institute, Harper Hospital, Wayne State University School of Medicine; J Jay Lu, MD, MBA, Consulting Staff, Director of Research, Department of Radiation Oncology, National University Hospital, The Cancer Institute, National Healthcare Group, Singapore; Kam-wang Siu, MBChB, FRCR (UK), FHKCR, Associate Consultant, Department of Diagnostic Radiology and Imaging, Queen Elizabeth Hospital, Hong Kong; Lawrence Chun-kuen Chow, MBChB, FRCSEd (ORL), FHKCORL, Associate Consultant in Otorhinolaryngology, Department of Surgery, Section of Otolaryngology, Queen Mary Hospital, Hong Kong; Vivek Sehgal, MD, Assistant Professor of Radiology, Wayne State University; Director of Magnetic Resonance Imaging, Department of Radiology, Harper University Hospital; Harold E Kim, MD, Assistant Professor, Department of Radiation Oncology, Wayne State University School of Medicine; Clinical Chief, DMC-Crittenton Radiation Oncology Center, Harper Hospital; Arthur J Frazier, MD, Assistant Professor of Radiation Oncology, Residency Program Director, Wayne State University School of Medicine; Radiation Oncologist, Barbara Ann Karmanos Cancer Institute, Gershenson Radiation Oncology Center, Harper Hospital/DMC

Updated: Feb 12, 2009

Introduction

Background

Nasopharyngeal carcinoma (NPC) is uncommon in the United States and in most countries of the world. Although NPC accounts for less than 1% of all cancers in Americans, it is common among Southeast Asians, especially in Chinese persons from the southern provinces of Kwantung, Kwangsi, and Fukien. Native populations in Canada, Alaska, Greenland, and Africa also have elevated rates compared with those of the rest of the world.

Nonenhanced T1-weighted MRI shows nasopharyngeal cancer invading the left side of the clivus. Signal intensity of the marrow fat is lost on the left side of the clivus compared with the right side.

Contrast-enhanced CT scan shows nasal involvement resulting from nasopharyngeal carcinoma.

Current epidemiologic and experimental data suggest at least 3 major etiologic factors, namely, viral, environmental, and genetic.

For excellent patient education resources, visit eMedicine's Cancer and Tumors Center. Also, see eMedicine's patient education articles Cancer of the Mouth and Throat and Skin Cancer.

Pathophysiology

Patients with locally advanced disease have poor treatment outcomes after definitive radiotherapy, especially patients with cervical lymph nodes that clinically test positive, those with cranial nerve (CN) involvement, and those with invasion of the skull base. These patients often develop distant metastases despite control of locoregional disease. Most recurrences occur within 5 years of diagnosis, but late relapses are possible. The incidence of second primary malignancy in patients with nasopharyngeal carcinoma (NPC) appears to be less than that of other head and neck cancers, which are usually related to smoking.

Tumor invasion into the skull base occurs in approximately 25% of cases and may lead to cranial nerve (CN) deficit. CN V and CN VI are most commonly involved, followed by CN III and CN IV. Patients with this involvement present with changes in ocular motion.

Unlike malignancies of the oral cavity and oropharynx, NPCs often metastasize to level V lymph nodes. Bilateral metastases are common (with rates as high as 50%) on presentation.

The Epstein-Barr virus (EBV) is associated with NPC. Titers of EBV antibodies can be elevated in patients with NPC, regardless of their ethnic and/or geographic origin. The EBV genome has been demonstrated by using nucleic acid hybridization in biopsy specimens from NPC lesions. Compared with other head and neck cancers, NPCs have high EBV antibody titers and an overexpression of the BCL2 product. Differences in the ability of the immune system to control EBV infection on the basis of the efficiency of human leukocyte antigen (HLA) haplotypes to present EBV-latent membrane protein antigen have been shown.

All NPCs are associated with EBV-latent gene products, unlike other head and neck carcinomas. About 80% of NPCs overexpress the BCL2 product. These findings are consistent and may contribute to the development of NPC by inhibiting apoptosis. Immunoglobulin A titers of EBV-replicative antigens precede the development of NPC, and they may be used as tumor markers of a response to treatment. As a result of the near-universal presence of EBV in humans, it cannot be the sole causative factor in the NPC because rates of NPC vary dramatically with geography.

Case control studies have shown an association between the consumption of salt-preserved fish at an early age and an increased risk for NPC among people from southern China. Tumor-promoting chemicals in traditional foods have been identified in areas with high rates of NPC, such as Tunisia, southern China, and Greenland. No obvious occupational exposures have been linked to NPC, though smoking increases the risk of NPC by 3 times. An inherited predisposition for NPC may exist, as evidenced in the almost 100-fold increase in incidence in a relatively homogeneous genetic group of southern Chinese individuals compared with the incidence in a comparable group of white persons.¹

Emigration does not reduce the increased risk, even into the second immigrant generation of southern Chinese in whom environmental exposures are comparable to those of other population groups. Certain HLA haplotypes occupying the short arm of chromosome 6 have been implicated. Overexpression of oncogenes has been noted, as has the overexpression of ras (76% of patients) and C -myc (90% of patients) proteins in NPC lesions. Overexpression of the C -myc protein is an adverse prognostic factor.

Despite the TP53 mutations that commonly occur in patients with other carcinomas, less than 10% of patients with NPC have mutations in the TP53 gene. Accumulation of p53 protein is often demonstrated and may be the result of a breakdown in the inactivation pathway of p53 or interference in inactivation due to the presence of viral protein or aberrant native protein. Functional inactivation may occur as a result of a homozygous deletion of the p16 (p19) gene because its product blocks normal functioning of the MDM2- induced TP53 gene function.²

Patterns of spread

NPC has common patterns of spread that are often related to the primary site. Midline tumors often spread bilaterally. As lateral tumors enlarge, they may cross the midline. Pathologic lymph nodes appear soon afterward. Tumors often grow into the lumen and extend to the orbits, maxillary sinus, nasal cavity, and soft palate. The most common route of spread is along the lymphatic pathways to the node of Rouviere. Direct extension into the retropharyngeal space, with destruction of the lateral aspect of the atlas, is possible.

Parapharyngeal invasion often results in CN impairment. Pain due to involvement of the sensory fibers of the trigeminal nerve usually precedes motor fiber involvement. When the levator veli palatini muscle is involved, the soft palate may be asymmetric at rest. Facial asymmetry result from involvement of the facial nerve is rare. Trismus occurs with direct invasion of the medial or lateral pterygoid muscles. When tumor infiltrates the pterygoid muscles, the infratemporal fossa is at risk. The maxillary sinus and orbits may be involved with invasion of the tumor from the pterygoid muscles.

Tumor may invade posteriorly to the base of the skull to involve CNs IX-XII. The sphenoid body, sphenoid sinus, greater wing of the sphenoid, foramina lacerum, ovale, and rotundum may be invaded superiorly. Downward extension of the tumor into the palate may lead to referred ear pain due to involvement of the trigeminal nerve. The parotid and submandibular glands may be invaded. The tumor may spread intracranially from the fossa of Rosenmüller and from erosion of the base of the skull.

The tumor may follow the internal carotid artery or invade through the foramen lacerum into the cavernous sinus. Symptoms from this invasion include ophthalmoplegia due to the involvement of CNs III, IV, and VI and facial numbness from involvement of the CN V. Invasion of major blood vessels may cause compressive symptoms with thrombosis or rupture. Involvement of the inner ear is uncommon but may occur with invasion of the petrous bone.

Staging

The Union Internationale Contre le Cancer (UICC) and the American Joint Committee on Cancer (AJCC) have maintained a primary tumor, regional lymph nodes, and distant metastasis (TNM) classification for NPC. However, the staging system that Ho developed is used far more frequently than the TNM system in Southeast Asia and appears to be superior.³

In 1993, the UICC and AJCC collaborated to form a task force at the international level to initiate a process of consultation with the objective of developing a relevant staging classification. The fifth edition of the TNM classification published by the UICC and AJCC in 1977 featured a complete revision of staging classification for NPC.³ The sixth edition, published in 2002, is the same as the fifth edition.

The AJCC/UICC classification system is as follows:

• Primary tumor (T)
  • TX - Primary tumor not assessable
  • T0 - No evidence of primary tumor
  • Tis - Carcinoma in situ
  • T1 - Tumor confined to the nasopharynx
  • T2 - Tumor extending to soft tissues of oropharynx and/or nasal fossa
    • T2a - Without parapharyngeal extension
    • T2b - With parapharyngeal extension
  • T3 - Tumor invading bone structures and/or paranasal sinuses
  • T4 - Tumor with intracranial extension and/or involvement of CNs, infratemporal fossa, hypopharynx, or orbit
• Regional lymph nodes (N)
  • NX - Regional lymph nodes not assessable
  • N0 - No regional lymph node metastasis
  • N1 - Unilateral metastasis in lymph node(s), 6 cm or less in greatest dimension, above the supraclavicular fossa
  • N2 - Bilateral metastasis in lymph node(s), 6 cm or less in greatest dimension, above the supraclavicular fossa
  • N3 - Metastasis in a lymph node(s)
    • N3a - Greater than 6 cm in dimension
    • N3b - Extension to the supraclavicular fossa
• Distant metastasis (M)
  • MX - Distant metastasis not assessable
  • M0 - No distant metastasis
  • M1 - Distant metastasis

AJCC/UICC stages are as follows:

• Stage 0 - Tis, N0, M0
• Stage I - T1, N0, M0
• Stage IIA - T2a, N0, M0
• Stage IIB
  • T1, N1, M0
  • T2, N1, M0
  • T2a, N1, M0
  • T2b, N0, M0
  • T2b, N1, M0
• Stage III
  • T1, N2, M0
  • T2a, N2, M0
  • T2b, N2, M0
  • T3, N0, M0
  • T3, N1, M0
  • T3, N2, M0
• Stage IVA
  • T4, N0, M0
  • T4, N1, M0
  • T4, N2, M0
• Stage IVB - Any T, N3, M0
• Stage IVC - Any T, any N, M1

Survival is consistently correlated with the stage of disease. Patients with disease in early stages fare markedly better than others, with overall survival rates of 80% for stage I and 65% for stage II. Survival rates for patients with more advanced disease are 45% in stage III and 30% in stage IV. The extension of the tumor behind the styloid process or into the masticator space is common and is associated with poor survival, with 5-year relapse-free survival rates of 46% and 43%, respectively.

Adverse prognostic features include CN palsies, involvement of the paranasopharyngeal space, advanced age, male sex, and involvement of the lymph nodes. The prognosis is worse with distal lymph node involvement proceeding from the upper cervical chain to the middle and lower cervical chain; patients with bilateral involvement have a 5-year overall survival rate of less than 10%.

Pathology

Approximately 80-99% of all malignant nasopharyngeal tumors arise from the epithelium and should be considered variants of squamous cell carcinoma. According to the World Health Organization (WHO), NPC is classified into 3 subtypes: (1) WHO type 1, or squamous cell carcinoma; (2) WHO type 2, or nonkeratinizing carcinoma; and (3) WHO type 3, or undifferentiated carcinoma.

The term lymphoepithelioma or lymphoepithelial carcinoma is used to describe nonkeratinizing and undifferentiated carcinoma with an abundant lymphoid stroma.

In North America, WHO types 1, 2, and 3, account for 20%, 10%, and 70% of all NPCs, respectively. In Hong Kong, the respective rates are 3%, 9%, and 88%.

Frequency

United States

In Hawaii, the incidence among whites is 0.7 case per 100,000 men and 0.9 case per 100,000 women. The incidence among people of Chinese descent in Hawaii is 8.9 cases per 100,000 men and 3.7 cases per 100,000 women. The incidence among people of Chinese descent in Los Angeles is 6.5 cases per 100,000 men and 3.7 cases per 100,000 women. These data were extracted from the International Agency for Research on Cancer, 1992.⁴

International

In Hong Kong, the incidence is 28.5 cases per 100,000 men and 11.2 cases per 100,000 women. In Singapore, among Chinese persons, the incidence is 18.1 cases per 100,000 men and 7.4 cases per 100,000 women. In Shanghai, the incidence is 4.0 cases per 100,000 men and 1.9 cases per 100,000 women. In Tianjin, China, the incidence is 1.8 cases per 100,000 men and 0.6 case per 100,000 women. In Miyagi, Japan, the incidence is 0.5 case per 100,000 men and 0.2 case per 100,000 women. In Manila, the Philippines, the incidence is 8.3 cases per 100,000 men and 3.4 cases per 100,000 women. In Setif, Algeria, the incidence is 5.0 cases per 100,000 men and 2.2 cases per 100,000 women. In Yorkshire, United Kingdom, the incidence is 0.2 case per 100,000 men and 0.1 case per 100,000 women. In the Northwest Territories and the Yukon, Canada, the incidence is 6.4 cases per 100,000 men and 2.3 cases per 100,000 women.⁴

Mortality/Morbidity

The 5-year survival rate after radiation therapy is 36-58%. For locally advanced disease, the 3-year overall survival rate is reported to be 78% for chemoirradiation versus 47% for radiotherapy alone.

As a result of the large treatment volume and high radiation dose required in most patients with nasopharyngeal carcinoma (NPC), various complications can occur. The overall complication rate is 31-66%. Severe complications occur in 6-15% of patients, and fatal complications occur in 1-3% of patients. Complication rates increase with concurrent chemoirradiation or coexisting medical conditions, such as hypertension or diabetes mellitus.

• Xerostomia is the most common sequela. Dental problems occur in 4-17% of patients. The use of dental topical fluorides and good dental hygiene before, during, and after radiation therapy can reduce the incidence of dental caries. Chronic otitis media occurs in 3-18% of patients after radiation therapy, and hearing loss occurs in 6-8%. The incidence of hearing impairment is related to the dose to the cochlea, and doses higher than 50 Gy significantly increase the incidence of hearing deficits.
• Trismus occurs in 5-10% of patients as a result of fibrosis and contraction of the pterygoid muscles or fibrosis of the temporomandibular joint. Patients should be advised to perform mandibular exercises to prevent the progression of trismus. Surgical intervention may be considered to relieve severe trismus. Soft tissue, bone necrosis, or both occur in 5-16% of patients.
• Brain necrosis occurs in 2-3% of patients. The incidence of cranial nerve (CN) entrapment (especially for the last 4 CNs) due to soft tissue fibrosis is approximately 1-6%. Transverse myelitis has been reported to occur in 1-4% of patients. Because a portion of the orbit, and sometimes the eye (especially in patients with advanced disease), is usually included in the clinical target volume, radiation-induced retinopathy and injury to the optic nerve can occur, causing blindness. Therefore, the daily fraction should be limited to 2 Gy or less, and the retina and optic apparatus should be shielded after 45-50 Gy to prevent this devastating complication.
• In patients who receive radiation therapy to the entire thyroid gland, the rate of hypothyroidism is increased by 30-40%. Thyroid-function testing should be done before therapy to provide a baseline and then repeated after treatment for monitoring. Hypothyroidism is highly treatable with medical approaches.

Race

The incidence of nasopharyngeal carcinoma (NPC) is highest among southern Chinese populations, particularly those originating from Kwantung province. Mixed Chinese populations of Southeast Asians and Eskimos have the next highest rates. The incidence is intermediate among people of North African or Filipino descent. NPC is rare in whites and in the Japanese population.

Sex

Nasopharyngeal carcinoma (NPC) occurs more frequently in men than in women, with a male-to-female ratio of 2-3:1. Some series have shown that the prognosis is better in women than in men, but other series have not demonstrated this difference.

Age

The mean age at presentation is 45-55 years. Younger patients appear to have survival rates better than those of older patients. In 1 series from Hong Kong, a statistically significant difference was found between the 5-year survival rates in patients younger than 40 years and patients aged 40 years or older. However, data from the Children's Cancer Study Group regarding patients younger than 30 years showed that the 5-year survival rate was 51%, which was not significantly different from those reported in other adult series.

Anatomy

The nasopharynx is a space. As the name implies, it contains 2 distinct parts: (1) the anterior upper division, which is histologically, embryologically, and morphologically related to the nasal cavity, and (2) the inferior posterior division, which is similarly related to the oral cavity, as both are foregut structures. The nasopharynx measures 2-3 cm in the anteroposterior dimension and as much as 3-4 cm in the vertical and transverse dimensions. It lies behind the nasal fossa, marked by the posterior choanae.

The base of the skull, specifically, the clivus and the first 2 vertebral bodies, form the posterior bone border. The lateral aspects of the space are flanked by the pharyngeal fascia and mucosa, which also overlies the posterior bone border. The oropharyngeal cavity is underneath it, and the soft palate demarcates the anterior inferior edge. The superior border blends with the posterior wall and houses abundant lymphoid tissue in children, which usually fades with age. If this lymph tissue (adenoid tonsils) persists into adulthood, it may be confused with tumor during examination. This space, without many natural barriers of spread or growth, has many critical structures in the immediate vicinity. The diffuse nature of this border contributes to the variety of routes of spread and multiple complaints at presentation.

Identifiable anatomic structures normally visible on examination include the eustachian tubes on the lateral walls. The cartilaginous ends of the tubes push the mucosa outward to form a ridge; the torus tubarius; and a recessed space, the fossa of Rosenmüller.

Depiction of the fossa of Rosenmüller is difficult but crucial because it is the most common site of origin in NPC. The borders of the fossa are the eustachian tube anteriorly, the levator veli palatini muscle anterolaterally, the retropharyngeal space posteriorly, the upper edge of the superior constrictor muscle inferiorly, and the tensor veli palatini muscle and pharyngeal space laterally. The superior border is the base of the skull with the foramen lacerum medially, the petrous apex and carotid canal posteriorly, and the foramina ovale and spinosum anterolaterally. These anatomic relationships provide explanations for the symptoms commonly found in patients and the pathways for direct extension.

Sensory innervation of the nasopharynx and the posterior soft palate is derived from CN IX, except for a variable area adjacent to the tubal orifices supplied by the maxillary division of CN V. Several separate small nerves of CN IX comprise the glossopharyngeal nerve, including a communicating fiber from the tympanic branch of CN IX that follows the same route as the greater petrosal nerve. The sensory pathway for the trigeminal component runs from the roof of the nasopharynx along the palatovaginal canal and past the pterygopalatine ganglion to the pterygopalatine fossa. The origin of the motor component for the pharyngeal musculature is the cranial root of the accessory nerve that courses with the vagus nerve. Further muscular innervation derives from the pharyngeal plexus, a commingling of the motor fibers of CNs IX and X.

Embryologic remnants may persist and be confused with cancer. A pharyngeal hypophysis, a vestige of the Rathke pouch (the origin of the anterior pituitary gland), may persist in the vomerosphenoidal articulation, appearing as a midline submucosal mass between the posterior border of the nasal septum and pharyngeal tonsil. Although usually small, the hypophysis may reach 10 mm. Capable of hormone production, it may hypertrophy in women undergoing menopause without hormone replacement.

Lymphatic drainage

Lymphoid tissue is abundant in the nasopharynx, as evidenced in the high rate of nodal metastases found at diagnosis. Three main groups of submucosal collecting pathways drain the pharynx, the superior, middle, and inferior pathways. The superior pathway provides the primary drainage of the nasopharynx along with a small contribution by the middle pathway. The superior pathway drains the oropharynx, soft palate, eustachian tube and fossa of Rosenmüller, tympanic cavity, and nasal fossae.

The superior pathway is divided into median and lateral groups. The median group drains the roof and posterior border of the nasopharynx into the lateral retropharyngeal node. This node may be bypassed, in which case, the first echelon node is the upper deep cervical lymph node chain located near the internal jugular vein. The lateral group drains the lateral nasopharynx, including the fossa of Rosenmüller, and flows into the lateral half of the upper internal jugular chain or into the lateral retropharyngeal node. The retropharyngeal nodes atrophy with age and usually are obliterated by adulthood. They lie in a potential space behind the posterior wall of the nasopharynx and anterior to the prevertebral fascia. The lateral group is often a single node or several confluent nodes, termed the node of Rouviere. Occasionally, the node is absent on 1 side and usually nonpalpable.

The node of Rouviere is the most commonly involved lymph node. It usually lies below the base of the skull near the level of the atlas and may overlay the internal carotid artery. The upper cervical lymph node chain encases the internal jugular vein and receives lymph from the node of Rouviere. Nodes exist at the angle of the mandible, the superior sternocleidomastoid muscle, and the apex of the posterior triangle. Nodes also course adjacent to the pathways of CNs XI and XII. The chain runs inferiorly to the anterior neck triangle where the jugulodigastric node is present, which is the most important and constant node. The efferent pathway descends along the internal jugular vein to the lower deep cervical nodes, terminating at the junction of the internal jugular vein and subclavian vein on the right and the thoracic duct on the left.

Presentation

In patients with nasopharyngeal carcinoma (NPC), the most common presentation is a neck mass representing a metastatic lymph node. Nonspecific, nonsensitive complaints include symptoms of allergic rhinosinusitis, such as nasal congestion, rhinorrhea, and epistaxis. When the eustachian tube is blocked, as often occurs with tumors in the fossa of Rosenmüller, serous otitis media, ear pain, and ipsilateral hearing loss may occur.

One function of the nasopharyngeal space is to increase the resonant quality of the voice, which may be attenuated by the mass effect of a tumor. Anterior invasion into the soft palate results in resting asymmetry of the posterior oral cavity. The Trotter triad consists of decreased hearing, mandibular pain, and impaired soft palate mobility. With invasion of the base of the skull, headaches may occur in the temporal and occipital regions. Superior invasion into the orbit may result in proptosis.

Routes into the orbit are from the posterior nasal fossa through the ethmoid air cells or tracking along the CNs into the eye from previous cavernous sinus invasion. Cavernous sinus invasion occurs because the tumor tracks through the foramen lacerum, which often leads to multiple CN deficits. The order of loss is CNs VI, III, V1, V2, and IV as the tumor invades the superior orbital fissure (CNs III, IV, V1, and VI), foramen rotundum (CN V2), and foramen ovale (CN V3.) The most common deficits are ophthalmoplegia (CN VI), ptosis (CN III), and pain and anesthesia of the supraorbital and superior maxillary regions (CN V1 followed by CN V2). Complete ophthalmoplegia occurs with CN III, IV, and VI involvement. Metastatic parapharyngeal nodes can compress the posterior CNs, namely, CNs IX, X, XI, and XII. A tumor in the fossa of Rosenmüller can directly invade these nerves because they exit the base of the skull in the parapharyngeal space.

A deficit indicating CN involvement is dysphagia from hemiparesis of the muscles innervating the superior constrictor muscles (CN IX) and soft palate (CN X). Sensory deficits in the mucous membranes of the soft palate, pharynx, and larynx result from CN X injury and dysgeusia from CN IX. CN XI injury results in atrophy and paralysis of the trapezius and sternocleidomastoid muscles, and CN XII injury results in deviation of the tongue to the side of injury, with atrophy of the muscle, causing difficulty with deglutition. Horner syndrome with ptosis, miosis, and anhydrosis occurs when the cervical sympathetic plexus coursing along the carotid is involved. NPC is more likely to extend into the cranium through the foramen lacerum or foramen ovale than invade the bone.

Preferred Examination

Preferred examinations include the following: clinical examination of the neck, fiberoptic examination, CT scanning of the nasopharynx and neck, and MRI of the nasopharynx and neck.^5,6

Pathologic diagnosis is achieved by examining biopsy specimens from the nasopharyngeal mass. Workup includes assessment of the tumor by means of flexible or rigid endoscopic examination; documentation of the extent of the tumor and the location of neck nodes; assessment of CN function, vision, and hearing; CT or MRI of the head and neck regions (see CT Scan, Findings and MRI, Findings); chest radiography; and blood work, including complete blood counts and serum chemistry panels, particularly renal function tests.

Creatinine clearance is determined by using 24-hour urine specimens. Any clinical or laboratory findings suggestive of distant metastasis warrant further investigation. Baseline endocrine function is established. Dental and oral hygiene evaluation is necessary before radiation therapy is started. MRI is often more helpful than CT in depicting abnormalities and in defining the extent of tumors.

Limitations of Techniques

Evaluation of mucosal lesions is best achieved endoscopically. Imaging findings often lead to incorrect estimates of the extent and frequency of mucosal involvement. Conversely, clinical evaluation is inadequate in tumors located entirely or almost entirely beneath the mucosa. Hence, the full staging process should include endoscopy, clinical examination of the neck, and imaging.

The role of CT is well established. CT remains the most common modality for tumor mapping and nodal staging, particularly in the regions of the globe in which nasopharyngeal carcinoma (NPC) occurs with high frequency, because access to MRI remains limited.

MRI is superior to CT in demonstrating the extent of soft tissue tumors. This is particularly relevant in tumors with extensive submucosal involvement. Generally, CT is accepted as being superior to MRI in the detection of skull base involvement; however, contrary to common belief, changes in the skull base are better identified on MRI than on CT. Although cortical erosion often is diagnosed more confidently by using CT, marrow infiltration is better determined with MRI. MRI is also more sensitive than CT in detecting perineural invasion; the obliteration of fat just external to the foramen rotundum or foramen ovale is as a good sign of early perineural infiltration.

Cervical lymphadenopathy is depicted better by using CT scans than MRIs, especially in terms of nodal necrosis and extracapsular spread. Although large amounts of data exist regarding the superiority of CT over MRI in the assessment of nodal metastasis, both modalities are adequate in routine clinical practice. Compared with MRI, CT rarely provides additional information that results in a change in treatment options.

MRI is recommended for use in staging tumor recurrences. Although MRI has limitations in separating postirradiation fibrosis from tumor recurrence, it is superior to CT in identifying submucosal infiltration, replacement of marrow in the skull base, and intracranial spread.

In many tumors that are staged with CT, their classification may be changed on MRI, especially in patients with involvement of the skull base or early CN infiltration and intracranial extension. This disparity of staging results between CT and MRI can potentially affect treatment recommendations, which may in turn pose problems in comparing treatment outcomes.

Differential Diagnoses

Other Problems to Be Considered

Malignant neoplasms

Malignant lymphoma
Plasmacytoma
Adenocarcinoma
Melanoma
Sarcoma

Benign neoplasms

Angiofibroma
Neuroma

Normal variants

Lymphoid tissue

Radiography

Findings

Before the era of CT, plain radiography was used to determine the extent of skull-base involvement by nasopharyngeal carcinoma (NPC). The classic 5 views of NPC that Ho described consist of lateral, submentovertical, occipitosubmental, 25° occipitomental, and occipitomaxillary views.⁷

Degree of Confidence

Currently, CT and MRI have replaced plain radiography for the purpose of staging. Plain skeletal radiography still has a role in the initial evaluation of suspected bone metastases.

Computed Tomography

Contrast-enhanced CT scan shows nasopharyngeal carcinoma with right parapharyngeal extension and retropharyngeal adenopathy.

Contrast-enhanced CT scan shows nasal involvement resulting from nasopharyngeal carcinoma.

Nonenhanced CT scan (coronal view) shows thickening of the right parapharyngeal wall (same patient as in the 2 Images above).

Findings

Primary tumor

Currently, imaging of nasopharyngeal carcinoma (NPC) tumors includes thin-section contrast-enhanced neck CT performed in the helical mode from the base of the skull to the thoracic inlet (see Images 6-8). This scanning helps in the easy reconstruction of 3-dimensional data and volumetric measurements.^{8,9,10,11,12,13}

For tumors confined to the nasopharynx (as in 13% of patients with NPC), the delineation of small-volume disease can be difficult by using imaging, and an evaluation of the extent of mucosal disease without knowledge of the endoscopic findings or positive biopsy findings may lead to errors in interpretation. Evaluation of the symmetry of the nasopharynx on CT scans is difficult because of inflammatory changes, secretions, and lymphoid tissue in this region. This is particularly true in the fossa of Rosenmüller, in which the presence of minor asymmetry should not be mistaken for disease. A modified Valsalva maneuver may open a collapsed lateral pharyngeal recess.

For tumors extending out of the nasopharynx, complex anatomic structures and spaces may be involved. The tumor may extend laterally to involve the extrapharyngeal portion of the levator palatini muscle, tensor palatini muscle, pterygoid plates, parapharyngeal fat space containing branches of CN V3, the medial pterygoid muscle, the lateral pterygoid muscle, temporalis and masseter muscles, mandible, and, posterolaterally, the parotid gland. Posterior extension of the tumor can involve the prevertebral muscles, clivus, anterior portion of the foramen magnum and the C1 and C2 vertebral bodies, and, posterolaterally, the carotid space containing the internal carotid artery, jugular vein, CNs IX-XII, the cervical sympathetic plexus, and retropharyngeal nodal metastasis.

Anterior extension of the tumor can involve the pterygoid process, nasal cavity, pterygomaxillary fissure, pterygopalatine fossa, maxillary sinus, and posterior ethmoid air cells. Superior extension of the tumor can involve the structures in the skull base including petrous temporal bone; sphenoid muscle; foramina lacerum, ovale, and rotundum; carotid canal; sphenoid sinus; cavernous sinus; cranium; and orbit. Inferior extension of the tumor can involve the oropharyngeal area.

The sinus of Morgagni is an opening in the pharyngobasilar fascia through which the levator palatini and eustachian tube pass to the fascia to reach the nasopharyngeal mucosal space. This defect is located close to the lateral pharyngeal recess, which is most common site for the development of NPC. Tumor extension to the parapharyngeal space frequently occurs at this point. On CT scans, the parapharyngeal space is the most common region in which lateral extension is revealed, with involvement occurring in 84% of the patients. Parapharyngeal extension is associated with serous otitis media due to the blockage of the eustachian tube. Opacification of the middle ear and mastoid air cells is seen frequently on CT scans.

Thin-section axial and coronal CT scans obtained with a bone window can reveal invasion of the skull base, which can occur in locally advanced NPC. Thin-section axial and coronal CT scans are sensitive for early cortical invasion; however, an increasing body of evidence suggests that MRI has several advantages over CT in the depiction of skull-based invasion in NPC (see MRI, Findings).

Intracranial disease may extend to involve the cavernous sinus, middle cranial fossa, and (less commonly) the posterior cranial fossa. MRI is more sensitive than CT in delineating the extent of disease.

Invasion of the paranasal sinus may occur, involving the sphenoid sinus and posterior ethmoid air cells in 26% and 18% of patients, respectively. Extension to the maxillary sinus occurs in 9% of patients and usually is associated with sphenoid infiltration and very advanced disease.

Nodal metastases

The retropharyngeal, submandibular, submental, and lateral cervical nodes are the clinically important lymph nodes in NPC. Approximately 75% of patients with NPC have palpable cervical lymphadenopathy. Neck node involvement in NPC occurs by means of downward stepwise spread. The lower the level of spread, the worse the prognosis. This finding was used in development of the most recent AJCC/UICC staging system for NPC (1997).³

Retropharyngeal lymph nodes and the most superior internal jugular nodes are not palpable on clinical examination, and clinical examination has false-positive and false-negative rates of 25% and 10-15%, respectively, in the detection of lymph nodes. In addition, differentiating a single large lymph node from multiple matted nodes is difficult. CT scans can provide information about the patient's nodal status.

Diagnostic criteria for a metastatic lymph nodes depicted on CT scans are as follows: size, shape, extracapsular invasion, nodal grouping, and central necrosis.

Regarding size, the upper limits of normal for maximal nodal diameter are 1.5 cm and 1.0 cm for jugulodigastric and submandibular nodes and for other lymph nodes, respectively. Nodes exceeding these limits have an 80% likelihood of being metastatic. The minimum axial diameter has been suggested as a more accurate criterion for evaluation. The accepted limits for digastric nodes and other cervical nodes (except retropharyngeal nodes) are 1.1 cm and 1.0 cm, respectively. For retropharyngeal nodes, 0.4 cm is the upper limit in the lateral group, and any visible node is regarded as abnormal in the medial group.

In terms of shape, metastatic nodes are usually more spherical than hyperplastic nodes.

Regarding extracapsular invasion, the nodal capsule is enhancing, and poorly defined margins are present around the node.

For the criterion of nodal grouping, 3 or more contiguous and confluent lymph nodes are present, each of which has a maximum diameter of 8-15 mm (or minimum axial diameter of 8-10 mm).

Central necrosis is the most accurate CT diagnostic criterion for a metastatic node. On nonenhanced CT scans, central necrosis appears as an area of low attenuation in the center of the node. On contrast-enhanced CT scans, the necrosis appears as a nonenhancing area in the center of the node surrounded by a thin rim of peripheral enhancement. Nodal lipid metaplasia sometimes appears like central nodal necrosis.

Degree of Confidence

In tumors confined to the nasopharynx (as in 13% of patients with NPC), the delineation of small-volume disease can be difficult by using imaging, and any evaluation of the extent of mucosal disease without knowledge of the endoscopic findings or positive findings in biopsy sites may lead to errors in interpretation.

Evaluation of symmetry of the nasopharynx by using CT scans is difficult because of inflammatory changes, secretions, and lymphoid tissue within the region. This limitation is particularly true in the fossa of Rosenmüller, where minor asymmetry should not be mistaken for disease. A modified Valsalva maneuver may open a collapsed lateral pharyngeal recess.

CT versus MRI

MRI has the advantage over other studies in this area because T2-weighted and contrast-enhanced T1-weighted images can be used to differentiate the high signal intensity of the mucosa from the lower signal intensity of the adjacent torus tubarius and intrapharyngeal portion of the levator palatini muscle. In the evaluation of parapharyngeal extension, CT is inferior to MRI in distinguishing compression as a large bulging tumor still confined within the mucosal space resulting from direct invasion. For the detection of skull-base invasion, thin-section axial and coronal CT scans with bone windows are inferior to MRIs. See the Findings section above.

The node of Rouviere (retropharyngeal node) is the first-echelon node for lymphatic drainage of the nasopharynx. The medial retropharyngeal nodes are usually not visible. Any CT or MRI finding of medial retropharyngeal node is abnormal.

Multidetector-row CT

With the advent of multidetector-row CT (MDCT) scanners, images with unprecedented resolution can readily be obtained. These scanners can substantially reducing scanning time and, therefore, artifact generated by patient motion. MDCTs have a row of detectors to collect the X-ray beam transmitted through the patient and thereby allow for the collection of rich volume data.

Simply, the volume data can be used to construct thin images with high spatial resolution. Thin axial images result in decreased artifact due to partial-volume averaging. Technical improvements of these scanners, such as high special resolution in longitudinal axis and voxels that are virtually isotropic, have led to improved quality of sagittal, coronal, and any other intermediate reformatted or 3-dimensional (3D) images.

One of the many advantages of MDCT scanners is the reduction, and essentially elimination, of misregistration artifact that was commonly seen on reformatted images obtained with older scanners. A high-quality CT scan can be accurate in delineating the extent of primary nasopharyngeal tumor, metastatic adenopathy, and destructive bony changes at the skull base. Fast scanning also allows for imaging when the bolus of contrast agent is mostly intra-arterial; therefore, it provides exquisite depiction of the vascular anatomy. This information can be helpful in assessment the vasculature when the primary tumor or the adenopathy is extensive and causes vascular encasement.

False Positives/Negatives

Evaluation of the symmetry of the nasopharynx by using CT scans is difficult because of the inflammatory changes, secretions, and lymphoid tissue in this region, particularly the fossa of Rosenmüller, in which the presence of minor asymmetry should not be mistaken for disease. A modified Valsalva maneuver may open a collapsed lateral pharyngeal recess. Occasionally, CT scans may fail to depict an early cortical erosion of the skull base that is depicted on MRIs.

Magnetic Resonance Imaging

Nonenhanced T1-weighted MRI shows nasopharyngeal cancer invading the left side of the clivus. Signal intensity of the marrow fat is lost on the left side of the clivus compared with the right side.

Gadolinium-enhanced axial T1-weighted MRI shows nasopharyngeal cancer with left parapharyngeal involvement.

Coronal gadolinium-enhanced T1-weighted MRI shows nasopharyngeal cancer with parapharyngeal extension (same patient as in Image above).

Axial T2-weighted image shows a left-sided cervical nodal metastasis resulting from nasopharyngeal cancer.

Coronal T2-weighted MRI shows a left-sided cervical nodal metastasis resulting from nasopharyngeal cancer (same patient as in Image above).

Findings

Primary tumor

MRI is extremely helpful because of its multiplanar capabilities and its superior depiction of soft tissue details (see Images 1-5). Evaluation of the symmetry of the nasopharynx can be difficult by using CT scans.^{14,15,16,17,18,19,20,21,22}

T2-weighted and contrast-enhanced T2-weighted MRIs can be used to differentiate the high signal intensity of the mucosa from the low signal intensity of the adjacent torus tubarius and intrapharyngeal portion of the levator palatini muscle. The tumor has a long relaxation time and is slightly hyperintense relative to muscle on T2-weighted images and isointense on T1-weighted images.

After gadolinium enhancement, the signal intensity of the tumor is greater than that of muscle but less than that of the mucosa on T1-weighted images. T2-weighted images demonstrate good contrast between the tumor and adjacent structures in the nasopharyngeal mucosal space. The pharyngobasilar fascia is usually well demonstrated on MRI but not on CT scans.

T1-weighted images are also ideal for the depiction of anatomic structures, and are less prone to artifact than other images. Generally, the primary tumor and area of metastatic adenopathy (pathology) are hyperintense and appear conspicuous on a background of predominately isointense-to-hypointense signal on short-tau inversion recovery (STIR) images. A similar effect can be achieved by suppressing fat signal intensity on the routine T2-weighted images.

For the evaluation of parapharyngeal extension, CT is inferior to MRI in distinguishing compression as a large bulging tumor still confined within the mucosal space resulting from direct invasion. Extension of disease to the nasal cavity is well demonstrated on multiplanar MRI, especially around the superior meatus and sphenoethmoidal recess. MRI can help in distinguishing direct tumoral extension from retropharyngeal nodes in the evaluation of oropharyngeal involvement.

Contrary to common belief, involvement of the skull base is better identified on MRI than on CT. Although cortical erosion is often diagnosed more confidently with CT than with MRI, MRI better depicts bone marrow infiltration, which appears as moderately low signal intensity against the high signal intensity of fatty bone marrow on T1-weighted images without gadolinium enhancement. However, after the administration of contrast agent, the enhancing tumor may have signal intensity similar to that of bone marrow, rendering interpretation more difficult. Contrast-enhanced and fat-saturated T1-weighted sequences have been used to overcome this problem. In the evaluation of intracranial extension of disease, MRI is superior to CT because MRI provides better contrast between the tumor and brain tissue and because MRI is multiplanar.

Nodal metastases

Fat surrounding the nodes decreases the conspicuity of the nodes on MRIs. Diagnostic criteria for nodal metastasis on CT also apply to MRI. The most accurate diagnostic criterion is central necrosis. Nodes with central necrosis usually have a heterogeneous appearance on both T1- and T2-weighted MRIs. Because blood products may have low, intermediate, or high signal intensity, hemorrhage into a metastatic lymph node may have a relatively homogeneous appearance. Contrast enhancement increases the sensitivity for central necrosis, but the surrounding hyperintensity of fat on T1-weighted MRI obscures the enhancing rim. Fat-suppressed contrast-enhanced sequences may be the optimal sequences for detecting nodal metastasis. The retropharyngeal nodes, which are usually affected first, are easily demonstrated on MRI.

The acquisition time for MRI is significantly longer than that of CT. Therefore, the patient must be instructed to minimize swallowing and not to move during imaging. As stated earlier, CT significantly reduces motion artifact because of its short acquisition time. It also allows for scans to be obtained during a breath hold. Dynamic maneuvers such as modified Valsalva maneuver can be done during CT scanning to expand the pharyngeal recess to evaluate lesions that are poorly demonstrated because of apposition of mucosal surfaces

Gadolinium-based contrast agents (gadopentetate dimeglumine [Magnevist], gadobenate dimeglumine [MultiHance], gadodiamide [Omniscan], gadoversetamide [OptiMARK], gadoteridol [ProHance]) have been linked to the development of nephrogenic systemic fibrosis (NSF) or nephrogenic fibrosing dermopathy (NFD). For more information, see the eMedicine topic Nephrogenic Fibrosing Dermopathy. The disease has occurred in patients with moderate to end-stage renal disease after being given a gadolinium-based contrast agent to enhance MRI or MRA scans. 

NSF/NFD is a debilitating and sometimes fatal disease. Characteristics include red or dark patches on the skin; burning, itching, swelling, hardening, and tightening of the skin; yellow spots on the whites of the eyes; joint stiffness with trouble moving or straightening the arms, hands, legs, or feet; pain deep in the hip bones or ribs; and muscle weakness. For more information, see the FDA Public Health Advisory or Medscape.

Degree of Confidence

Overlap exists between nonspecific adenopathy, nodes involved by granulomatous disease, and malignant nodes when the MRI relaxation time is used to characterize lymphadenopathy. By comparing signal intensities of the lymph nodes in nonenhanced and contrast-enhanced MRIs, benign nodes have a ratio of signal intensity significantly lower than that of metastatic nodes, as shown in a small series. Sensitivity and specificity are reportedly 95% and 84%, respectively. However, this method is impractical if performed routinely because nonenhanced and contrast-enhanced MRIs must be obtained 10-48 hours apart.

The node of Rouviere (retropharyngeal node) is the first-echelon node for lymphatic drainage of the nasopharynx. The medial retropharyngeal nodes are usually not visible. Any CT or MRI finding of medial retropharyngeal node is abnormal.

Ultrasonography

Findings

Because the size of lymph nodes is not a highly reliable criterion for malignancy compared with their structure, fine-needle aspiration cytology under ultrasonographic (US) guidance offers additional information about enlarged lymph nodes. Because US can show malignancy in small lymph nodes not detected with other methods, it can be recommended in most patients with head and neck cancer, irrespective of the use of CT or MRI. One group from Europe demonstrated a slightly lower sensitivity with US than with other studies, but they had superior specificity with US and US-guided fine-needle aspiration biopsy compared with CT in detecting regional metastases in clinically negative necks.^23,24

US diagnostic criteria for an abnormal node include size, shape, internal structure of the node, and nodal borders. Regarding size, lymph nodes smaller than 5 mm are rarely metastatic. Nodes larger than 9 and 7 mm in transverse diameter in the jugular and in the submandibular and submental areas, respectively, are considered metastatic. Overall, these dimensions are smaller than the diagnostic limits accepted for CT or MRI.

In terms of shape, a short axis–to–long axis ratio (SALAR) of greater than 0.5 indicates a spherical node, whereas a SALAR less than 0.5 signifies an oval node. Benign nodes tend to be oval, and metastatic nodes tend to be round. By using a combination of the shape and size criteria, lymph nodes larger than 10 mm in the long axis with a SALAR of greater than 0.5 have a high incidence of malignancy.

Regarding the internal architecture of the node, coagulation necrosis, echogenic hilus, and cystic necrosis have been depicted on sonograms; however, distinguishing a benign from a malignant node often is not possible on the basis of the internal architecture alone.

Lymph nodes with well-delineated borders are more likely to be malignant than lymph nodes with poorly delineated borders.

Data from Hong Kong have shown that metastatic neck nodes from NPCs are always hypoechoic relative to the surrounding tissues, and calcification is absent.²⁵ About 74% of the nodes are spherical, 91% have sharp borders, 84% show no echogenic hilus, 94% are homogeneous, 6% show central nodal necrosis, and 12% show distal enhancement. Most nodes are found in the upper cervical area (22%) and in the posterior triangle (64%).

Degree of Confidence

In the evaluation of cervical adenopathy, high-resolution US has a sensitivity greater than that of clinical examination (92% vs 70%) and a high specificity when combined with cytologic analysis of specimens from fine-needle aspiration cytology (92.7%). As such, it is a useful initial tool for distinguishing benign from malignant disease. US can also be use to monitor posttherapeutic changes and to confirm a lack of evidence of disease in the neck.

Nuclear Imaging

Findings

In some centers, bone scanning has been used to detect bone erosion; however, because of its low spatial resolution, bone scanning is limited in the modern management of nasopharyngeal carcinoma (NPC). The main role of such nuclear medicine studies is the detection of metastatic disease to the bone.²⁶

The use of positron emission tomography (PET) to detect distant metastases has been gaining popularity, but its role in the management of NPC is still not well defined. One study from Taiwan showed that [18]F-fluoro-2-deoxy-D-glucose (FDG) PET may be better than CT in detecting neck lymph node metastases of NPC and for assessing the stage of NPCs.

A group from Japan reported the use of imaging fusion between FDG PET MRI/CT to improve the delineation of target in planning irradiation of head-and-neck cancers in 9 patients with NPC. Gross tumor volume was determined on the basis of result of clinical examination and on FDG uptake on the fusion images. Clinical target volume was determined by following the usual pattern of lymph node spread for each disease entity and by evaluating the clinical presentation of each patient. The authors showed that fusion techniques improve delineation of the gross tumor volume and clinical target volume, as well as tissue sparing.

Angiography

Findings

Angiography has a limited role in diagnosing nasopharyngeal carcinoma (NPC). However, the use of angiography and embolization to control problematic severe or recurrent epistaxis after irradiation has been described in a small group of patients in Hong Kong; the procedure was safe and effective in this group.

Intervention

Primary disease

CT-guided needle biopsy is a safe and reliable, minimally invasive technique that is useful for the diagnosis of poorly accessible or deep-seated lesions of the head and neck. Diagnostic needle biopsy allows for the acquisition of adequate tissue for diagnosis of primary and recurrent disease. Potential pitfalls include false-positive diagnoses after radiation therapy and procedural or sampling limitations in cases of deep neck and paraspinal lesions. The use of MRI-guided fine-needle aspiration biopsy of the primary retropharyngeal tumors in the retropharynx is feasible, safe, and sensitive enough to obviate open biopsy in many patients. US-guided biopsy of cervical nodes is discussed above.^{27,28,29,30,31,32,33,34}

Unlike other head and neck cancers, nasopharyngeal carcinomas (NPCs) with no distant metastasis are typically treated with nonsurgical means. Radiation therapy has been the standard of care in patients with NPC for several decades. High-dose radiation therapy is the primary treatment, both for the primary tumor site and the neck. Surgery is usually reserved for nodes that fail to regress after irradiation or for nodes that reappear after an apparently complete clinical response. Doses and field margins used in radiation therapy are individually tailored to the location and size of the primary tumor and the lymph nodes. Although most tumors are exclusively treated with external-beam irradiation, in some tumors, radiation therapy may be boosted with radioactive intracavitary interstitial implants or with radiosurgery when clinical expertise is available and the anatomy is suitable.

The results of a phase III randomized controlled trial reported in 1998 established that concurrent chemoirradiation followed by adjuvant chemotherapy is the standard of care for NPC in the United States. This study included 185 patients with stage III or IV NPC who were treated with either radiation therapy alone or with cisplatin, fluorouracil, and radiation therapy. The 3-year progression-free survival rate was 69% in the group receiving concomitant therapies compared with 24% in the group receiving only irradiation (P <.001); respective 3-year overall survival rates were 78% and 47% (P = .005). Median follow-up was 31 months.

A randomized trial from Hong Kong showed significantly prolonged progression-free survival in patients with advanced tumor and nodes who received concurrent cisplatin-based chemotherapy and radiation therapy.

In regions in which the incidence of NPC is high and the ethnic population differs from those in these studies, the distribution of the tumor histologies must be considered. The sensitivity of undifferentiated carcinoma to radiation therapy without chemotherapy is high in Chinese patients in Southeast Asia and in Canadian cities, such as Toronto and Vancouver, in which the Chinese population is large. Currently, 2 phase III randomized trials have been performed in Canada (Toronto and Vancouver) and Hong Kong; the investigators attempted to confirm the best treatment modality for patients with advanced T-stage and N-stage disease.

Intensity-modulated radiation therapy (IMRT) is a 3D conformal technique and has gained popularity in the treatment of NPC. Compared with conventional 2- and 3D conformal techniques, IMRT techniques improve coverage of the tumor target, with significantly improved sparing of sensitive normal tissue structures in the treatment of locally advanced NPC (Xia, 2000). Data from the University of California at San Francisco showed an excellent locoregional progression-free rate of 98% with significant sparing of the salivary glands and other nearby critical normal tissues.{Ref27}

Recurrent disease

After recurrence, selected patients may be treated again by using moderate-dose external-beam radiation therapy with limited fields and a brachytherapy boost at the site of recurrence. 3D conformal radiation therapy has been used. Repeat radiation therapy also can be administered by means of stereotactic radiosurgery with a gamma knife or a linear accelerator (LINAC)–based radiosurgical unit. Fractionated stereotactic radiotherapy also has been used. IMRT is currently under evaluation in some centers. Data from multiple series showed a 5-year survival rate of 16-45% with a second series of irradiation. The complication rate in patients undergoing repeat irradiation is 6-34%.

Surgical resection may be considered in highly selected patients with small tumors. If a patient has distant metastasis or local recurrence that is amenable to surgical resection or radiation therapy, chemotherapy should be considered.

Medicolegal Pitfalls

• Because nasopharyngeal carcinoma (NPC) is a relatively rare condition in Western countries (except for those with cities with a large population of Chinese or Asian individuals), missing an early diagnosis is always a risk.
  • A high index of suspicion is important for a correct diagnosis.
  • The prognosis depends on the stage of the disease; therefore, missing an early disease could be detrimental.
  • Although CT or MRI demonstrates advanced disease well, early disease is frequently not evident on the images.
  • Endoscopic examination with biopsy (if necessary) should always supplement scanning if the patient has symptoms and signs suggestive of NPC.
• The accurate delineation of the extent of the disease is crucial, as NPC has a propensity to invade the fissures of the skull base.
  • Because the mainstay of treatment for NPC is radiotherapy, a geographic miss can result from inaccurate delineation of the target volume, especially in this modern era of radiation therapy in which 3D conformal and IMRT (image-guided irradiation) is frequently used to minimize toxicity.
  • If only CT is available, a bone window should always be used. A coronal view is also useful.
  • The skull base should be examined carefully for any invasion, especially in patients with headaches and CN deficits.
• Posttreatment follow-up with CT or MRI should always be supplemented with endoscopic examination and biopsy if necessary. CT or MRI may not be sensitive enough to detect a recurrence of small volume.

Multimedia

Media file 1: Nonenhanced T1-weighted MRI shows nasopharyngeal cancer invading the left side of the clivus. Signal intensity of the marrow fat is lost on the left side of the clivus compared with the right side.

Media file 2: Gadolinium-enhanced axial T1-weighted MRI shows nasopharyngeal cancer with left parapharyngeal involvement.

Media file 3: Coronal gadolinium-enhanced T1-weighted MRI shows nasopharyngeal cancer with parapharyngeal extension (same patient as in Image above).

Media file 4: Axial T2-weighted image shows a left-sided cervical nodal metastasis resulting from nasopharyngeal cancer.

Media file 5: Coronal T2-weighted MRI shows a left-sided cervical nodal metastasis resulting from nasopharyngeal cancer (same patient as in Image above).

Media file 6: Contrast-enhanced CT scan shows nasopharyngeal carcinoma with right parapharyngeal extension and retropharyngeal adenopathy.

Media file 7: Contrast-enhanced CT scan shows nasal involvement resulting from nasopharyngeal carcinoma.

Media file 8: Nonenhanced CT scan (coronal view) shows thickening of the right parapharyngeal wall (same patient as in the 2 Images above).

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Keywords

nasopharyngeal squamous cell carcinoma, squamous cell carcinoma of the nasopharynx, NPC, nasopharyngeal carcinoma, nasopharyngeal cancer, nasopharyngeal tumor, nonkeratinizing carcinoma, undifferentiated carcinoma, lymphoepithelioma, lymphoepithelial carcinoma

Contributor Information and Disclosures

Author

Simon Lo, MBBS, Assistant Professor, Department of Radiation Oncology, Indiana University School of Medicine
Simon Lo, MBBS is a member of the following medical societies: American College of Radiology, American Medical Association, American Society for Therapeutic Radiology and Oncology, and Radiological Society of North America
Disclosure: Nothing to disclose.

Coauthor(s)

Nancy Lee, MD, Consulting Staff, Department of Radiation Oncology, Memorial Sloan-Kettering Cancer Center
Disclosure: Nothing to disclose.

Sasan Karimi, MD, Assistant Professor of Radiology, Weill Medical College of Cornell University; Director of Neurospectroscopy, Director of Neuroradiology Fellowship Program, Director of Radiology at 55th Street Imaging Center, Memorial Sloan-Kettering Cancer Center; Assistant Attending Radiologist, Neuroradiology Section, Memorial Hospital for Cancer and Allied Diseases
Sasan Karimi, MD is a member of the following medical societies: American College of Radiology and American Society of Head and Neck Radiology
Disclosure: Nothing to disclose.

Alan Tim-shing Choy, MBBS, FRCR(UK), FHKCR, FHKAM(Clinical Oncology), Staff Clinical Oncologist, Department of Clinical Oncology, Queen Elizabeth Hospital, Hong Kong
Disclosure: Nothing to disclose.

Sameer R Keole, MD, Staff Physician, Department of Radiation Oncology, Gershenson Radiation Oncology Center, Karmanos Cancer Institute, Harper Hospital, Wayne State University School of Medicine
Sameer R Keole, MD is a member of the following medical societies: American Society for Therapeutic Radiology and Oncology
Disclosure: Nothing to disclose.

J Jay Lu, MD, MBA, Consulting Staff, Director of Research, Department of Radiation Oncology, National University Hospital, The Cancer Institute, National Healthcare Group, Singapore
J Jay Lu, MD, MBA is a member of the following medical societies: American College of Radiology, American Society for Therapeutic Radiology and Oncology, Radiological Society of North America, and Southern Association of Therapeutic Radiation Oncology
Disclosure: Nothing to disclose.

Kam-wang Siu, MBChB, FRCR (UK), FHKCR, Associate Consultant, Department of Diagnostic Radiology and Imaging, Queen Elizabeth Hospital, Hong Kong
Kam-wang Siu, MBChB, FRCR (UK), FHKCR is a member of the following medical societies: Royal College of Radiologists
Disclosure: Nothing to disclose.

Lawrence Chun-kuen Chow, MBChB, FRCSEd (ORL), FHKCORL, Associate Consultant in Otorhinolaryngology, Department of Surgery, Section of Otolaryngology, Queen Mary Hospital, Hong Kong
Lawrence Chun-kuen Chow, MBChB, FRCSEd (ORL), FHKCORL is a member of the following medical societies: Royal College of Surgeons of England
Disclosure: Nothing to disclose.

Vivek Sehgal, MD, Assistant Professor of Radiology, Wayne State University; Director of Magnetic Resonance Imaging, Department of Radiology, Harper University Hospital
Vivek Sehgal, MD is a member of the following medical societies: Radiological Society of North America
Disclosure: Nothing to disclose.

Harold E Kim, MD, Assistant Professor, Department of Radiation Oncology, Wayne State University School of Medicine; Clinical Chief, DMC-Crittenton Radiation Oncology Center, Harper Hospital
Harold E Kim, MD is a member of the following medical societies: American Association for Cancer Research and American Society for Therapeutic Radiology and Oncology
Disclosure: Nothing to disclose.

Arthur J Frazier, MD, Assistant Professor of Radiation Oncology, Residency Program Director, Wayne State University School of Medicine; Radiation Oncologist, Barbara Ann Karmanos Cancer Institute, Gershenson Radiation Oncology Center, Harper Hospital/DMC
Arthur J Frazier, MD is a member of the following medical societies: American Medical Group Association, American Society for Therapeutic Radiology and Oncology, and Michigan State Medical Society
Disclosure: Nothing to disclose.

Medical Editor

David S Levey, MD, PhD, Orthopedic/Spine MRI TeleRadiologist, Radsource, LLC
David S Levey, MD, PhD is a member of the following medical societies: American Roentgen Ray Society, Radiological Society of North America, and Texas Medical Association
Disclosure: Nothing to disclose.

Pharmacy Editor

Bernard D Coombs, MB, ChB, PhD, Consulting Staff, Department of Specialist Rehabilitation Services, Hutt Valley District Health Board, New Zealand
Disclosure: Nothing to disclose.

Managing Editor

C Douglas Phillips, MD, Professor, Departments of Radiology, Neurosurgery, and Otolaryngology, University of Virginia Health Sciences Center
C Douglas Phillips, MD is a member of the following medical societies: American College of Radiology, American Medical Association, American Society of Head and Neck Radiology, American Society of Neuroradiology, Association of University Radiologists, and Radiological Society of North America
Disclosure: Nothing to disclose.

CME Editor

Robert M Krasny, MD, Consulting Staff, Department of Radiology, The Angeles Clinic and Research Institute
Robert M Krasny, MD is a member of the following medical societies: American Roentgen Ray Society and Radiological Society of North America
Disclosure: Nothing to disclose.

Chief Editor

L Gill Naul, MD, Professor and Head, Department of Radiology, Texas A&M University College of Medicine; Chair, Department of Radiology, Chief, Section of Magnetic Resonance Imaging, Scott and White Memorial Hospital and Clinic
L Gill Naul, MD is a member of the following medical societies: American College of Radiology, American Medical Association, American Roentgen Ray Society, Radiological Society of North America, and Texas Medical Association
Disclosure: Nothing to disclose.

Guidelines and clinical trials:

Chemotherapy with radiotherapy for nasopharyngeal cancer. Program in Evidence-based Care - State/Local Government Agency [Non-U.S.].  2003 Jul 22 (revised 2004 Dec).  24 pages.  NGC:004357

Peptide Vaccine to Prevent Recurrence of Nasopharyngeal Cancer

Positron Emission Tomography Scanning and Epstein-Barr Virus DNA levels in the Staging and Follow-Up of Nasopharyngeal Carcinoma.

Proton Radiotherapy With Chemotherapy for Nasopharyngeal Carcinoma

Combination of Gemcitabine and Carboplatin in Metastatic or Recurrent Nasopharyngeal Carcinoma

A Phase 3 Trial of Adjuvant Chemotherapy in Nasopharyngeal Carcinoma Patients With Residual EBV DNA Following Radiotherapy

Fluorouracil, Cisplatin, and Radiation Therapy in Treating Patients With Stage II, Stage III, or Stage IV Nasopharyngeal Cancer

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