MRI and CT of Nasopharyngeal CA

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AJR:198 , January 2012 11

and has the worst prognosis. It is analogous

to squamous cell carcinoma elsewhere in the

pharynx and is associated with cigarette and

alcohol use. Nonkeratinizing carcinoma (type

2) behaves in a fashion similar to type 3. Both

types are radiosensitive and have a much bet-

ter prognosis. Undifferentiated carcinoma

(type 3) was previously called B lymphoep-

ithelioma because of the mix of undifferen-

tiated epithelial and nonmalignant T lym-

phocytes. In North America, around 25% of

patients with NPC have type 1, 12% have type

2, and 63% have type 3. The histologic distri-

bution in southern China is 2%, 3%, and 95%,

respectively [2–6].

Imaging Techniques

MRI

The protocol for routine MRI of a naso-

pharyngeal mass includes unenhanced T1-

weighted images to detect skull base involve-

ment and fat planes (in at least an axial and

sagittal plane). A T2-weighted fast spin-echo

sequence in axial plane is used for the ad-

ditional assessment of early parapharyngealtumor spread, paranasal sinus invasion, mid-

dle ear effusions, and detection of cervical

lymph nodes. Axial and coronal contrast-en-

hanced T1-weighted images (with and with-

out fat suppression) are used to detect tumor

extent, including perineural spread and in-

tracranial extension of the tumor. The slice

thickness is 3–5 mm [3–7].

Additional MRI sequences may be used in

evaluation of NPC but, at present, are of lim-

MRI and CT of NasopharyngealCarcinoma

Ahmed Abdel Khalek Abdel Razek1

Ann King2

Abdel Razek AAK, King A

1Department of Diagnostic Radiology, Mansoura

University Hospital, Faculty o f Medicine, ElghomheryiaSt, Mansoura DK, Egy pt. Address correspondence to

A. A. K. Abdel Razek ([email protected]).

2Department of Diagnostic Radiology and Interventional

Radiology, Chinese University of Hong Kong, Hong Kong,

China.

Neuroradio logy/Head and Neck Imaging • Review

AJR 2012; 198 :11–18

0361–803X/12/1981–11

© American Roentgen Ray Society

Nasopharyngeal carcinoma (NPC)

is a unique disease with clinical

behavior, epidemiology, and his-

topathology that is different from

that of squamous cell carcinomas of the head

and neck. NPC accounts for 0.25% of all ma-

lignancies in the United States and 15–18% of

malignancies in southern China. It also ac-

counts for 10–20% of childhood malignan-

cies in Africa. The male to-female ratio is 3:1.

It is most common among patients 40–60

years old, and bimodal age peaks occur in the

second and sixth decades of life [1–5]. NPC is

caused by the interaction of genetic suscepti-

bility, environmental factors (e.g., exposure to

chemical carcinogens), and infection with Ep-

stein-Barr virus. High antibody titers to Ep-

stein-Barr virus antigens are useful diagnostic

markers, and there are many tests to detect

both IgG and IgA titers. In China, dietary fac-

tors for NPC include nitrosamine-rich salted

food [2–5]. Patients often present with local

symptoms, such as epistaxis and a blocked

nose, but may also present with hearing loss,

otalgia, headache, or cranial nerve (CN) in-volvement. However, the nasopharynx is a rel-

atively clinically silent area; therefore, the

first presentation may be with cervical nodal

or distant metastasis [1–6].

Pathology

The World Health Organization classifica-

tion of NPC recognizes three histologic types.

Keratinizing squamous cell carcinoma (type

1) is found more often in nonendemic areas

Keywords: cancer, imaging, lymph node, MRI,

nasopharynx

DOI:10.2214/AJR.11.6954

Received March 25, 2011; accepted after revision

August 8, 2011.

This article was presented as educational exhibit at

RSNA 2010.

F O C U S O N :

OBJECTIVE. This article reviews the MRI and CT of nasopharyngeal carcinoma. Ex-

tension of nasopharyngeal tumors, especially into the skull base and the deep facial spaces,

is well illustrated on imaging. Assessment of retropharyngeal and cervical lymphadenopa-

thy is important for treatment planning. MRI is commonly used for monitoring patients af-

ter therapy.

CONCLUSION. Imaging can detect effect of radiation on surrounding structures. The

imaging findings that help to differentiate nasopharyngeal carcinoma from simulating lesionsare discussed.

Abdel Razek and KingImaging of Nasopharyngeal Carcinoma

Neuroradiology/Head and Neck ImagingReview


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Imaging of Nasopharyngeal Carcinoma

lies above the roof of the nasopharynx. The

ethmoid and sphenoid are less commonly

involved. Sinus involvement is recognized

by the loss of contiguity of the sinus walls.

Intrasinus extension of tumor may be seen.

Tumor can be differentiated from reactive

mucosal thickening on MRI, where inflam-

matory mucosal thickening is seen as uni-form T2-weighted signal greater than that

of tumor, also enhancing to a greater degree

than tumor [1, 10].

Category T4 NPC— Meningeal involve-

ment appears as nodular enhancement, often

along the floor of middle cranial fossa or pos-

terior to the clivus. Direct invasion of the brain

is rare. Invasion of cavernous sinus can lead to

multiple cranial palsies. NPC may spread into

the cavernous sinus from tumor surrounding

the horizontal portion of the internal carotid

artery, foramen ovale, orbital fissures, or di-

rectly through the skull base [1, 6, 10].

The frequency of diagnosed CN palsy in

NPC ranges from 8.0% to 12.4%, and the

clinical and MRI findings are not always

consistent. Nerves are resistant to tumor, and

perineural tumor spread is an insidious and

often asymptomatic process by which NPC

can invade upward and backward through

the skull base to the cavernous sinus and

middle cranial fossa and invade CN II to VI

(upper CN palsy). It may also involve the ca-

rotid space, where it may compress or invade

CN XII as it exits through the hypoglossal

canal, CN IX to XI as they emerge from the

jugular foramen (lower CN palsy), and the

cervical sympathetic nerves.

CN involvement on MRI is seen when

there is either enhancement of soft-tissue tu-

mor along the course of the ipsilateral related

nerve, replacing the normal structures of the

CN on gadolinium-enhanced T1-weighted

images; or perineural spread, with enlarge-ment or abnormal enhancement of the nerve,

obliteration of the neural fat pads adjacent to

the neurovascular foramina, or neuroforam-

inal enlargement. Maxillary and mandibu-

lar nerve involvement is best seen on coronal

T1-weighted contrast-enhanced MRI with

fat saturation. Hypoglossal nerve involve-

ment may also occur [13, 19] (Fig. 5).

Orbital invasion is a marker of extensive dis-

ease. Direct orbital invasion is rare, but when

present it can invade via the inferior orbital fis-

sure (from tumor in the pterygopalatine fossa),

optic canal, and superior orbital fissure.

Anatomic masticator space involvement

affects the overall survival and local relapse-

free survival of patients with NPC. The fre-

quency of masticator space involvement in

NPC is 19.7%. Infiltration of the medial and

lateral pterygoid muscles, infratemporal fat,

and temporalis muscle is found when tumors

extend laterally from the parapharyngeal

space, pterygoid base, or the pterygomaxil-

lary fissure [4, 20]. Hypopharynx is the most

inferior site of tumor invasion included in the

staging classification, but it is very rarely in-

volved at diagnosis [1–3].

N Category

NPC has a propensity to spread to nodes

(Fig. 6) and, in about 75–90% of cases, is

found by imaging to have a tendency for bi-

lateral neck spread [21]. Nodal metastases

are diagnosed if the shortest nodal axial di-

ameter reaches 5 mm or greater in the lateral

retropharyngeal region, 11 mm in the jugu-lodigastric region, or 10 mm in other non-

retropharyngeal nodes of the neck; if there

is a group of three or more nodes that are

borderline in size; or if the nodes display ne-

crosis or extracapsular spread. Extracapsular

spread has also been shown to be an indepen-

dent prognostic factor [8, 22].

Retropharyngeal Lymph Nodes

The diagnosis of enlarged retropharyngeal

lymph nodes in patients with NPC can only

be made by imaging, and MRI has an ad-

vantage over CT in being better able to sep-

arate the lateral retropharyngeal nodes from

the primary tumor in the adjacent postero-

lateral nasopharynx. Lateral retropharyngeal

nodes are among the most common sites of

nodal spread from NPC and have been con-

sidered the first echelon of metastatic spread

[21] (Fig. 7). However, nodal spread may by-

pass these nodes and spread to other nodes of

the upper neck. Metastatic lateral retropha-

ryngeal nodes can be identified from the skull

base to the level of C3. Retropharyngeal node

involvement is now classified as category N1,

whether unilateral or bilateral [1, 23]. PET/CT

Fig. 1—49-year-old woman with nasopharyngealcarcinoma (NPC) localized to nasopharynx (T1). Axialcontrast-enhanced T1-weighted image shows smallNPC (short arrows ) centered in left Rosenmüllerfossa (long arrow ), which is the most common sitefor this cancer, and involving posterior wall. Tumoris confined to nasopharynx, and there is smallmetastatic left retropharyngeal node (curved arrow ).

Fig. 2—50-year-old man with nasopharyngealcarcinoma (NPC) with parapharyngeal extension(T2). Axial contrast T1-weighted image shows NPC(white arrows ) with left parapharyngeal extensionand involvement of parapharyngeal fat space. Notenormal levator palatini muscle (red arrow ), tensorpalatini muscle (blue arrow ), pharyngobasilar fascia(black arrow ), and fat space (yellow arrow ) on normalright side

Fig. 3—58-year-old man with nasopharyngealcarcinoma with prevertebral extension (T2). AxialT1-weighted contrast-enhanced image showsnasopharyngeal carcinoma (straight arrows ) withextensive spread predominantly posteriorly intolongus muscles (arrowheads ) and clivus (curvedarrows ).


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14 AJR:19 8, January 2012

Abdel Razek and King

reveals increased FDG uptake in metastatic

cervical lymph nodes, but MRI appears to be

superior to PET/CT for the assessment of ret-

ropharyngeal nodal metastasis because of the

better discrimination of nodes from the adja-

cent primary tumor [24].

Other Cervical Lymph Nodes

Metastatic nodes posterior to the jugu-

lar vein in the upper neck are the most com-

mon sites for nonretropharyngeal nodes [22]

and are designated as high internal jugular

nodes, although at this site, the internal jug-

ular and spinal accessory nodal chains con-verge. Nodes then usually spread in an or-

derly sequence down the neck. Nodes in the

submandibular and parotid or periparotid re-

gion are far less common at diagnosis. Nodal

metastases at supraclavicular fossa increase

the incidence of distant metastases [1].

M Category

NPC shows a high frequency of distant me-tastases (5–41%). The most common sites of

metastases include bone (20%), lung (13%),

and liver (9%). Patients with supraclavicu-

lar lymphadenopathy or tumors extension

into the parapharyngeal and retropharyngeal

space have a significantly higher risk of dis-

tant metastases. PET/CT is sensitive to detect

bony and soft-tissue metastatic deposits [8].

Whole-body MRI shows a diagnostic capac-

ity similar to that of FDG PET/CT in assess-

ing distant-site status in patients with untreat-

ed NPC; in one reported study, the combined

interpretation of whole-body MRI and FDG

PET/CT showed no significant benefit over ei-

ther technique alone [24].

Tumor Volume

Tumor volume is a significant prognostic

factor in the treatment of malignant tumors.

However, it is not used presently in staging

because technical considerations have pre-

vented tumor volume measurement from be-

ing routinely used in a clinical setting and be-

cause methods for volume measurement are

not standardized. The measurement of tumor

volume has always been tedious and often in-

volves tracing the tumor outline. The resultsare often affected by both intra- and interop-

erator performance. To overcome this prob-

lem, several investigators have developed

semiautomated systems to reduce inter- and

intraoperator variability. Errors encountered

by computer-based techniques are thus likely

to be classified as systematic errors and not as

resulting from the experience of the operator.

Semiautomated tumor volume measurementis now possible for NPC [25, 26].

Pediatric NPC

Pediatric NPC is rare and usually poorly dif-

ferentiated. It has a predilection for adolescents

and teenagers. Unfortunately, these tumors

tend to be locally advanced by the time they

are diagnosed, mainly because the clinical pre-

sentation is nonspecific. Gross parapharyngeal

space invasion is common, and tumor can also

extend to the pterygopalatine fossa. Metastasis

to liver and spleen in NPC commonly presents

as solitary or multiple solid masses. Lymphoid

hyperplasia, which is more common in the

younger population, can be differentiated from

pediatric NPC by the symmetric configuration

and a striped pattern on both T2-weighted and

contrast-enhanced images. Also, rhabdomyo-

sarcoma can be differentiated from pediatric

NPC by lower peak incidence (3–10 years) and

inhomogeneous enhancement with necrotic in-

tratumoral foci [27].

After Treatment

The primary treatment for NPC is radia-

tion therapy, but induction chemotherapy

with 5-fluorouracil cisplatin is sometimescombined with radiation therapy. NPC is

Fig. 4—Patient with nasopharyngeal carcinoma(NPC) with skull base invasion and pterygoid sclerosis(T3). A xial CT bone window shows large NPC fillingnasopharynx and nasal cavity with bony destructionof sphenoid bone, including right pterygoid base,which also shows sclerosis (arrow ). Right middle eareffusion is present.

A

Fig. 5—68-year-old man with nasopharyngeal carcinoma (NPC) with skull base foraminal invasion . A, Coronal T1-weighted contrast-enhanced MRI shows NPC (straight arrows ) with skull base invasion at foramen ovale (arrowhead ) with invasion into cavernous sinus(curved arrow ).B, Coronal T1-weighted contrast-enhanced MRI shows invasion of NPC (straight arrows ) into foramen lacerum (arrowheads ), where it encases carotid artery andextends into cavernous sinus (curved arrow ).C, Axial T1-weighted contrast-enhanced MRI shows NPC invading pterygopalatine fossa (circle ), pterygomaxillary fissure (arrow ), and vidian canal (arrowhead ).

CB


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treated primarily by a high radiation dose (>

60 Gy), and in conventional (2D) radiothera-

py, the nasopharynx and adjacent region are

treated by radiation beams from the left and

right sides and sometimes also with an an-

terior radiation beam. The neck lymphatics

are usually irradiated by a separate anterior

radiation beam. Intensity-modulated radio-

therapy offers the opportunity of dose es-

calation to the tumor without increasing the

dose to other organs at risk. These treatmentsrequire very accurate delineation of the gross

tumor volume [3, 28].

Tumor Recurrence

It is advantageous to obtain a scan 3–6

months after radiation therapy to provide a

baseline study against which any future im-

aging can be compared. Regular surveil-

lance imaging is also desirable, but its value

has not been proven, especially for patients

with early-stage disease in whom the radio-

therapy response rates are high. Therefore,

follow-up scans are often guided by clini-

cal factors, such as suspicion of tumor recur-rence or development of a radiation-induced

complication. Any enlarging posttreatment

soft-tissue mass or any new deep lesion or

intracranial enhancement is concerning for

recurrent disease [1, 3].

Differentiating fibrosis from tumor re-

currence is difficult on routine CT. PET/

CT often provides an easier method for dif-

ferentiating tumor recurrence from fibrosis.

Typically, recurrent tumors show uptake of

radionuclide tracer, but fibrosis does not.

MRI can differentiate mature scar tissue,

which shows retraction, low T2 signal, and

no contrast enhancement from tumor, which

is expansile and of intermediate T2 signal

with moderate contrast enhancement on non-

fat-saturated images (Fig. 8). However, there

may be an overlap between partially treated

tumor and immature scar tissue. MRI shows

a trend toward higher accuracy in detecting

disease at the primary site than does PET/

CT, although the latter shows a trend toward

higher accuracy in detecting nodal disease

[28–30].

Nonmalignant Pharyngeal MassNonmalignant pharyngeal masses are

seen in less than 1% of MRI examinations

performed 2–14 years (mean, 8 years) after

radiation therapy. It has two patterns. The

first is a nasopharyngeal polyp (1–5 cm) that

shows mixed heterogeneous T2 signal inten-

sity and marked contrast enhancement (Fig.

9), with the larger polyps having stellate ar-

eas of reduced enhancement. The second is

a sphenoid sinus mass, which consists of a

nonenhancing mass filling a nonexpanded

sinus and a heterogeneous-enhancing mass

expanding the sinus or nonenhancing rhino-

liths in the sphenoid sinus. This appearance

in sphenoid sinus, as well as the larger polyps

with a stellate appearance, can be similar to

that of radiation-induced sarcomas [31].

Trismus With Masticator Space Abnormalities

Trismus is most commonly due to abnor-

mality of masticator muscles as a result of

the effects of radiation and rarely is second-

ary to damage of the mandibular nerve. It

may be due to osteoradionecrosis of the man-

dibular ramus and temporomandibular joint

Fig. 6—Patient with metastatic cervical lymphnode (N2). Axial T1-weighted contrast-enhancedMRI shows metastatic node (arrow ) posterior to leftupper internal jugular vein, which is common site formetastatic node with or without retropharyngealnodal involvement.

Fig. 7—Patient with retropharyngeal metastaticcervical lymph node (N1). Axial T1-weighted contrast-enhanced MRI shows metastatic node (arrow ) inleft retropharyngeal region, which is frequently firstechelon for nodal spread.

A

Fig. 8—Patient with nasopharyngeal carcinoma (NPC) recurrence.A, Image obtained before treatment shows NPC involving nasopharyngeal mucosa, centered in rightRosenmüller fossa (straight arrow ) with deep posterior extension into longus muscles (curved arrow ).B, Image obtained 3 months af ter treatment shows that mucosal component of tumor has resolved (straightarrow ) leaving behind mild symmetric post treatment mucosal thickening in nasopharynx. Deep component issmall residual mass (curved arrow ), which is nonspecific and could represent early scar tissue or residual cancer.

B


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or abnormality in the perimasticator tissues

as a result of radiation fibrosis or inflamma-tion spreading from sinusitis. One half of

patients have no significant abnormality on

MRI [4, 32] (Fig. 10).

Temporal Lobe Injury

Temporal lobe injury occurs in 3% of pa-

tients of NPC with a latent period of 1.5–13

years. Depending on the radiation field, it may

be bilateral or unilateral. It can involve the gray

and white matter simultaneously or the gray

matter alone; however, isolated white matter

lesions are rare. Temporal lobe injury result-

ing from radiation is not always an irrevers-

ible and progressive process but is one that canregress or resolve at MRI. In the evolution of

radiation injury, white matter lesions are seen

first and are followed by contrast-enhanced le-

sions, which have an increasing tendency to be-

come necrotic with increasing size. Cysts are

the least frequent manifestation and arise in the

late stages (Fig. 11). MRI spectroscopy in early

delayed phase of injury shows reduced N-ace-

tyl aspartate and creatine levels and increasedcholine levels as a result of demyelination. The

late delayed phase of radiation injury shows the

decrease of N-acetyl aspartate, choline, and

creatine levels [33].

Osteoradionecrosis

Osteoradionecrosis may occur 1 year after

irradiation. It is believed to be secondary to os-

teoblastic destruction with subsequent vascu-

lar damage. The skull base, cervical spine, and

the mandible are commonly affected. Imaging

findings include areas of osteolysis and mixed

sclerosis (Fig. 12) within the irradiation por-

tal. Fragmentation and sloughing of necroticbone may also be found. There is surrounding

inflammatory soft-tissue mass that may mimic

tumor recurrence or osteomyelitis [34].

Radiation-Induced Tumors

Radiation-induced tumors ar ise 5–10 years

after irradiation of NPC in 0.4–0.7% of cas-

es. Sarcomas and squamous cell carcinomas

arise in the high-dose field zone and involvesites around the maxillary region, such as the

palate, maxillary sinus, alveolar process, and

nasal cavity. Squamous cell carcinomas also

arise in the low-dose field, may occur many

years after radiotherapy, and may involve pe-

ripheral sites such as the temporal bone. The

presence of a heterogeneous tumor or rapidly

growing large destructive mass that displays

different signal intensity from NPC should

suggest the possibility of a radiation-induced

sarcoma. The presence of calcification or os-

sification points strongly to a diagnosis of ra-

diation-induced sarcoma [2, 35].

Differentiation of NPC From

Simulating Lesions

Lymphoma

The nasopharynx is one of the most com-

mon sites of extranodal non-Hodgkin lympho-

ma in the head and neck region. It usually oc-

curs in the sixth decade of life and is associated

A

Fig. 12—61-year-old man with osteoradionecrosis.A, Axial CT scan bone window showsosteoradionecrosis in skull base with sclerosis andosteolysis.B, Sagittal CT scan bone window showsosteoradionecrosis in anterior arch of C1 (long arrow )and tip of dens (short arrow ).

B

Fig. 9—54-year-old man with nonmalignantpharyngeal mass. Axial T1-weighted contrast-enhanced MRI shows small markedly enhancinginflammatory polyp (arrow ) arising from posteriorwall of nasopharynx.

Fig. 10—Patient with changes to pterygoid muscleafter radiation therapy. Axial T2-weighted MRIshows increased T2 signal in pterygoid muscles(arrows ) mainly involving left side.

Fig. 11—50-year-old man with radiation-inducedinjury to temporal lobe. Coronal T2-weighted MRIshows bilateral radiation-induced injury to whitematter in temporal lobes (arrows ).


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with gastrointestinal tract lymphoma in up to

10% of patients at either the time of diagno-

sis or relapse. Lymphoma is frequently located

in the midline, unlike NPC, which often arises

laterally. Bone invasion is not common even in

large tumors, and as with NPC, nodes are fre-

quent but these may involve sites such as the

submandibular and parotid nodes, which areless frequently involved at presentation in pa-

tients with NPC. Also, lymphoma has a lower

apparent diffusion coefficient value than does

NPC because of its higher cellularity [6–8].

Adenoid Cystic Carcinoma

Adenoid cystic carcinoma usually affects

patients during middle age and there is no re-

ported sex predilection. Unlike patients with

NPC, patients with adenoid cystic carcino-

mas rarely present with cervical lymphade-

nopathy. This tumor has a greater propensity

for perineural spread than does NPC. The tu-

mor exhibits higher apparent diffusion coef-

ficient value on diffusion-weighted MRI be-

cause of its cystic component [6, 7].

Extramedullary Plasmacytoma

Extramedullary plasmacytoma is a rare ma-

lignant soft-tissue tumor, but 80% of these tu-

mors occur in the head and neck with the na-

sopharynx being a common site. It is most

commonly seen in the sixth and seventh decades

and has an 80% male preponderance. The tu-

mor transgresses into a multiple myeloma in 20–

30% of cases. The lesion may present as a sub-

mucosal homogeneous and enhancing polypoidnasopharyngeal mass several centimeters in di-

ameter, with or without bone destruction [6].

Pleomorphic Adenoma

Pleomorphic adenoma occurs in the pha-

ryngeal mucosal space, arising from minor

salivary gland tissue. When associated bone

changes are present, benign-appearing bone

remodelling is the typical pattern. However,

slowly progressive bone destruction with an

aggressive appearance can be observed [36].

Tuberculosis

Nasopharyngeal tuberculosis is rare andis thought to result from direct infection of

the upper respiratory tract. It mimics NPC,

especially in Asian patients. It has two pat-

terns. The first pattern is a discrete polypoid

mass in the adenoids, and the second pattern

is a more diffuse soft-tissue thickening of

one or two of the walls of the nasopharynx.

Extension outside the confines of the naso-

pharynx is not usually a major feature [37].

Pseudotumor

Fibrosing inflammatory pseudotumor is

a nonspecific inflammatory process of un-

certain cause that rarely involves the naso-

pharynx. MRI findings that help to differen-

tiate pseudotumors from NPC are ill-defined

less likely contour bulging features, with lo-

cal infiltration, hypointensity on T2-weight-ed images, relatively weak enhancement, no

significant regional lymphadenopathy, and

good response to steroid therapy [38].

Amyloidosis

On CT, amyloidosis appears as a well-de-

fined submucosal homogeneous calcified

mass without bone destruction with or with-

out lymphadenopathy. The lesion exhibits

minimal enhancement. On MRI, the submu-

cosal location, distinctive hypointensity on

T2-weighted imaging, and early enhancement

on dynamic contrast-enhanced MRI helps to

differentiate amyloidosis from NPC [39].

Conclusion

In conclusion, MRI is essential for detec-

tion of early NPC, staging of the primary tu-

mor, and evaluation of associated retropha-

ryngeal and cervical lymphadenopathy. It has

been used for monitoring patients after thera-

py to detect tumor recurrence and radiation-

associated changes in the soft tissue and bone.

Imaging is valuable for the differentiation of

NPC from other simulating lesions.

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MRI and CT of Nasopharyngeal CA