Nasopharyngeal Carcinoma- Imaging Diagnosis and Recent Progress

Review:Nasopharyngeal Carcinoma: I magi ng Diagnosis and Recent Progress

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Nasopharyngeal Carcinoma: Imaging Diagnosis and Recent Progress

Rakesh Maharjan, Zhanwang Xiang, Feng Shi, M.D. Ketong Wu, M.D, Chuanxing Li

1. Department of Medical Imaging & Interventional Radiology, Cancer Center and State Key Laboratory of Oncology in South
China, Sun Yat-sen University, Guangzhou, 510060, P.R. China
ADD: 651 Dongfeng Road, East, Guangzhou, P. R. China
2. Corresponding author: Chuanxing Li,MD

Abstract
With continuous development of imaging techniques, medical imaging plays an important role in
diagnosis of Nasopharyngeal Carcinoma (NPC). Computed tomography (CT) is the basic mean for diagnosis of
NPC and has an advantage over diagnosis of those involving the skull base. Magnetic resonance imaging(MRI)
has an excellent soft tissue contrast resolution and it is superior to CT for detecti ng areas involving early
primary focal invasion and retropharyngeal lymph node metastasis. With positron emission tomography(PET)
imaging alone, the anatomical localization is unclear but when combined with CT, it shows high sensitivity in
the identification of primary tumor, lymph node metastasis ,distant metastasis and efficacy assessment. I n
this article, we review the current imaging methods commonly used in clinical diagnosis of nasopharyngeal
carcinoma and discuss the most recent advances.

Keywords: Nasopharyngeal carcinoma; Imaging diagnosis; CT; MRI; PET/CT

Chuanxing Li

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Nasopharyngeal carcinoma is the most common head and neck cancer. It is of epithelial origin and 90%
are poorly differentiated squamous cell carcinoma followed by well-differentiated squamous cell carcinoma
and undifferentiated carcinoma. Due to its anatomy and pathology, radiotherapy is preferred and is the most
effective means of treatment. Local invasion and lymph node metastasis of nasopharyngeal carcinoma had
higher incidence, early detection, early diagnosis, accurate staging and evaluation after treatment had been
the key to improve the efficacy of treatment and prolong survival period
[1]
. Moreover, CT, MRI and PET/CT
play significant role in the diagnosis of NPC, its TNM staging and post treatment assessment as well as
provides improved efficacy together in order to provide an important basis for further clinical treatment.

Computed Tomography
Nasopharyngeal carcinoma usually occurs in lateral nasopharyngeal recess. Local soft tissue obviously
thickens and forms a lobulated ri m of soft tissue mass. CT value about 35~45Hu, density is more or less
uniform with adjacent muscle tissue. Necrosis may be seen in a few places. With the contrast scan, there is
moderate enhancement. CT has features of good density resolution and overlapping of unorganized images.
It can clearly show the nasopharynx and parapharyngeal and other deep soft tissue and is significant for
qualitative diagnosis and positioning of nasopharyngeal carcinoma. With the progression of NPC, the
surrounding bone tissue is easily invaded. Moreover, the biggest advantage of CT imaging is that the
surrounding bony destruction by NPC can be clearly visualized on CT image. Zheng et al
[2]
found that
radiologists should pay attention to bony structures invaded by nasopharyngeal carcinoma on CT images. In
addition, CT scan is very quick and abundant information can be achieved ,it is also relatively cheaper and
therefore is still an effective imaging method for diagnosis and follow-up of nasopharyngeal carcinoma.

New CT Techniques and diagnostic for Nasopharyngeal Carcinoma: Modern technologies of CT in
nasopharyngeal carcinoma include perfusion imaging (CTP) and virtual endoscopy (CTVE),which are
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increasingly used in clinical diagnosis.The technology of CTP utilizes perfusion parameters (such as :blood
perfusion , bl ood volume and so on) to get an i mage which shows vascular characteristics and hemodynamic
changes in nasopharyngeal lesion. It can find more early recurrent nasopharyngeal carcinoma lesions than
conventional CT. Jin et al
[3]
found the technology of CTP can provide ti mely hemodynamic changes in the
physiological and pathological situations and evaluate the efficacy of the treatment process, it can also
further infer biological characteristics of the tumor and prognosis
[4]
. Meanwhile, studies from Liu et al
[5]
also
showed that multi-slice spiral CT can more clearly reflect the tumor bl ood flow, blood volume and other
characteristics of tumor blood supply. Moreover, they can be correlated with TNM staging of nasopharyngeal
carcinoma. Also with rapid development of spiral CT, its scan data can be used for reconstructi on in variety of
ways and image fusion as per clinical need. Its benefits are that it can measure the size of tumor, determine
the biological target for radiotherapy and can be used to further standardize radiation dose.CT virtual
endoscopy (CTVE) technol ogy, also known as endovascular reconstructi on techniques, applies a continuous
spiral CT scans to adjust the threshold value of CT and organizational transparency, eliminate unwanted
organization, and then show the change of lumen according to the navigation. It is able to objectively display
the surface and extent of the lesion and is good for guiding treatment and prognosis.Zhao et al
[6]
found
Multislice spiral CT virtual endoscopy(MSCTVE) and endoscopy had good correlation. Song
[7]
also found that
spiral CT image reconstruction was a reliable method to study the anatomy of facial nerve and other cranial
nerve canals.

Magnetic Resonance Imaging
MRI shows a good soft tissue resolution. Due to its multi -faceted, multi-parameter function of medical
imaging and molecular characteristics, it is currently consi dered to be the most effective method for
nasopharyngeal carcinoma. It can clearly show the infiltration to surrounding structures of nasopharynx such
as the parapharyngeal space, masticator space, pterygopalatine fossa,etc. It can also detect the skull base
Chuanxing Li

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and cranial nerve involvement as well as relatively smaller cervical and retropharyngeal lymph nodes. In
comparison to CT, MRI can cause staging changes about more 33.9% patients with NPC, 19.5% to adjust
treatment strategy. Sun
[8]
found that in X92 staging, MRI made 32.0% of the T stage change, 11.6% N staging
change, 30.4% change in clinical staging. According to the sixth edition of the UICC/AJCC staging, MRI makes
39.6% of the T stage change (36.0% upgrade, 3.6% downgrade); 9.2% N stage change(5.6% upgrade, 3.6%
downgrade); 37.6% of the clinical stage change(33.6% upgrade, 4.0% downgrade). At the same time, MRI can
detect the bone marrow infiltration by tumor before the local bone trabecula has been destroyed and
distinguish fibrotic lesion and tumor recurrence after radiotherapy.

MRI Manifestations of Nasopharyngeal Carcinoma: NPC typically manifests the lesion of
nasopharyngeal soft tissue, mainly originated in the pharyngeal recess, followed by nasopharyngeal wall and
roof. It causes local mucosal thickening or formation of small lumps and finally leads to toasymmetrical
narrowing of nasopharynx. Tumor tissue signal intensity is uniform, On T1W1 the tumor is isointense to the
adjacent muscles, while on T2-weighted images, the tumor shows high signal intensity. Gd-DT PA enhanced
scan shows significant strengthening of the mass. The tumor margins are partially visible and can intrude into
pharyngonasal cavity by forming mass or the parapharyngeal space by submucosal growth. Some sections
may be infiltrative growth and form unclear boundaries with the surrounding structures. Fat stripe
disappears. Most of the researches show
[9]
that MRI is the modality of choice for detecting local invasion of
tumor. With the growth of tumor, it spreads anterolaterally or posteriorly invading the sorrounding tissue.
Even the meninges behind the invaded structures may be seen thickened or formation of lumps. NPC can
also be dissected along the adjacent channels (such as the carotid sheath, oval foramen, etc) into invading
the brain, it results in local thickening of the meninges or the cavernous sinus and forming lumps.
In addition, submucosal nasopharyngeal carcinoma mainly spreads from nasopharyngeal epithelial
submucosal growth, forming deep submucosal mass. The signal intensity is similar to that of typical
Review:Nasopharyngeal Carcinoma: I magi ng Diagnosis and Recent Progress

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naospharyngeal carcinoma but nasopharyngeal mucosa is still intact and smooth, T2W1 shows continuous
hyperintense linear shadow. Most of the biopsies were negative, only by taking deep biopsy of the
submucosal tumor as displayed in MRI images, diagnosis is possible.

New MRI Techniques for Nasopharyngeal Carcinoma: Modern technol ogies of MRI include
diffusion-weighted imaging(DWI), magnetic resonance spectroscopic imaging(MRS), magnetic resonance
perfusion imaging (PWI )and diffusion tensor i maging(DTI). Diffusion-weighted imaging can sensitively detect
nasopharyngeal pri mary tumor and metastatic lymph nodes
[10]
and also through the apparent diffusion
coefficient (ADC) value differentiate between the nasopharyngeal lymphoma and cervical lymphoma. Fong et
al
[11]
reported that DWI can be used to differentiate between nasopharyngeal carcinoma and
nasopharyngeal lymphoma. ADC value of nasopharyngeal lymphoma is about (0.75±0.19)× 10-3mm
2
/s while
that of NPC is approximately (0.98±0.16)× 10-3mm2/s. ADC value for nasopharygeal lymphoma is lower than
that of NPC. Ozgen et al
[12]
found that in NPC skull base invasion, the ADC value of skull base was lower than
that of osteomyelitis. ADC value was about （0.74± 0.18）×10-3mm
2
/s in NPC invasion while（1.26 ±
0.19)×10-3mm
2
/s in osteomyelitis. Magnetic resonance spectroscopic imaging, by measuring the content of
metabolites between the tumor and normal tissues , can evaluate the content of metabolites changes in the
tumor tissue
[13]
, it mainly detects choline(Cho), creatinine (Cr), lactate (Lac) and N-acetyl asparate(NAA)
among other metabolites in the tissue. Jansen et al
[14]
found that 1 H MRS combined with PET can better
predict short-term efficacy of NPC. Li et all
[15]
also proved that the Cho was increasing, the NAA was declining
and the rate of Cho/NAA was also increasing 3 weeks before radiotherapy. The peak value of Cho of damaged
brain tissue was higher than that of normal brain tissue, peak NAA value was less and with treatment the
peak values gradually returned to normal. Thus, there is a significant value of MRS assessment for evaluation
of curative effect of NPC, early detection of recurrenance and assessment of temporal lobe damage due to
radiation. Magnetic resonance perfusion imaging can distinguish between the tumor tissue and fibrosed
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tissue after radiotherapy and can be used for the detection of recurrent lesions of NPC. The studies from
Quon
[16]
showed that the residual tumor area showed a high perfusion in PWI but noted that to confirm
whether the high perfusion area is due to tumor antiogenesis or not needs further investigations. Magnetic
resonance diffusion tensor imaging can be used to assess radiation damage to the brain tissue as well as to
monitor the changes of brain during the curative process. Early changes after radiotherapy can be displayed
with DTI which is not possible with conventional MRI
[17]
, therefore, it can prevent or delay radiation induced
brain tissue damage and provide more imaging evidences for clinical early intervention treatment.
In conclusion, advances in MRI technology with its unique advantages to NPC imaging has opened a new
chapter in its diagnostic imaging. In clinical practice, every new imaging technique plays a different role and
can also be used in together according to the requirment, it can complement each other and thus improve
comprehensive diagnostic capabilities of NPC.

Advances in TNM Staging of Nasopharyngeal Carcinoma: In 2009, a collaborative project of UICC and
AJCC formed 7th edition of TNM classification(Table.1) by modifying the 6th edition formed in 2003. In
compare to 6th edition, the 7th edition of UICC/AJCC has staged that the oropharynx and nasal involvement
down to T1 and the retropharyngeal lymph nodes is regarded as N1. Moreover, MRI for pri mary tumor
invasion , skull base involvement as well as retropharyngeal lymph nodes is preferred than CT .

Primary tumor staging of nasopharyngeal carcinoma: Primary tumor staging of nasopharyngeal
carcinoma (T stage), according to the size of the primary tumor nasopharyngeal carcinoma and its
surrounding tissue invasions, is divided into 4 stages(Table 1). Assessment of primary nasopharyngeal tumors
and its surroundi ng tissue structure is the most important factor for treatment and prognosis of NPC.
Parapharyngeal space from the base of the skull to the crescent-shaped hyoid bone mainly contains fat tissue,
on MRI it is usually characterized by high signal intensity. TNM classification of parapharyngeal space involved
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is defined as infiltration posterolaterally beyond the fascia of nasopharyngeal skull base. On T1W1 and T2W2
imaging, pharyngobasilar fascia is expressed as hypointense linear signal, early involvement is expressed as
interrupted line. It can be taken to identify tumors confined to parapharyneal cavity, parapharyngeal space
invasion and pharyngeal lymph nodes after fusion. 7th edition of UICC/AJCC staging defined parapharyngeal
involvement which contains masticator space as T2, Teo P et al
[18]
found that parapharyngeal involvement
was associated with distant metastasis and prognosis in NPC patients. Masticator space is located outside the
parapharyngeal space, containing palate venous plexus, mandibular nerve and the muscles of mastication,
the muscles mainly include the temporalis muscle, masseter, medial and lateral pterygoid muscles.7th
edition of UICC/AJCC staging defined invasion of medial pterygoid muscles in masticator space as T4. Studies
by Chong VF et al
[19]
have shown that the specific imaging findings that will directly affect the stage and
treatment of NPC. Lateral pterygoid muscle involvement means neurovascular tissue within the gap has been
involved. The studies from Chen YB
[20]
also showed that 69.14% medial pterygoid muscle involvement was
associated with characteristics of nerve involvement in T4 NPC. MRI has significant advantage to show tumor
involving cranial nerve lesions over CT. On MRI, the circular structures or disappearance of fat around the
patent foramen can serve as a reliable sign of nervous around early infiltration. Early detection of cranial
nerve involvement is possible with MRI. Studies from Cheng SH et al
[21]
showed that MRI diagnosis of cranial
nerve involvement enables more patients with T-stage upgrade. NPC with cranaial nerve involvement usually
indicates poor prognosis ,the survival and control rates in these patients were significantly reduced
[22]
. It has
been reported
[23]
that among the T3, T4 NPC patients, the 3 year overall survival rate of no distant metastasis
was significantly higher than those with cranial nerve invasion in MRI. In 3 year overall survival group with
cranial nerve palsy, there was no significant difference in survival in patients without distant metastasis, local
recurrence free survival and the group without cranial nerve palsy .
Lymph Nodes Staging: According to the 7
th
edition of UICC/AJCC criteria（Table 1）, unilateral
retropharyngeal lymph nodes are classified as N1, bilateral cervical lymph nodes metastases as N2 and for
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N2 or N3, the main difference lies in the size of lymph nodes and site involved. N staging of NPC lymph node
metastasis depends on the evaluation of retropharyngeal and cervical lymph node metastasis which acts as
the key factor affecting the clinical staging, treatment planning and prognosis. NPC firstly metastasized to
the retropharyngeal lymph nodes, MRI is superior to CT for detecting rtropharyngeal lymph nodes<4mm and
can distinguish from primary tumor site. The studies from King and Lam
[24,25]
showed that lateral
retropharyngeal lymph nodes which the minimum of diameter was 5mm can be considered as metastases
and medially any visible lymph node be considered as malignant. When retropharyngeal or cervical lymph
node showed necrosis or extracapsular spread, it would be malignant regardless of the size of lymph node.

Positrone Mission Tomography-computed Tomography
PET/CT Manifestation of NPC: The characteristics of PET/CT imaging of NPC show irregular or spherical
shape of primary nasopharyngeal tumor. The soft tissue mass of NPC has specific characteristics with
metabolic sharp edges, invasion and metastasis. It can roughly divided into two types; mucosal and
submucosal invasive type. Mucosal type are small, mostly unilateral, bulky shadow and cord li ke shadow
(cross-section), less radioactive concentration and indistinct boundaries. Oval mass shadow is common in
submucosal type, mostly unilateral. Bilateral invasions are connected together with multiple cervical lymph
node metastases forming "pea shaped". Radioactivity concentration is significantly increased. It can clearly
show the pri mary tumor location, size, shape, relations with the surrounding tissue and cancer tissue
metabolism.

TMN staging: NPC patients are prone to lymph node metastasis and distant metastasis. The most
common metastasis is to the mediastinal lymph nodes, which is followed by lung, liver and finall y bone
metastasis. Distant metastasis is an important indicator for prognosis of NPC but only about 1/6 of the
patients are diagnosed with distant metastasis on examination. Meta-analysis by Chang MC et al
[26]
found
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that the good diagnostic performance of the whole-body FDG-PET or PET/CT in M staging of NPC. Researches
from Liu et al
[27]
suggested that PET/CT carried a higher diagnostic accuracy in the depiction of distant
metastases of cervical lymph node metastases than enhanced CT and MRI. It was also more sensitive and
accurate than enhance CT and MRI for diagnosing residual or recurrent NPC. In addition, PET/CT can detect
metastatic lymph nodes of ≤10mm. A study from Antoch et al
[28]
compared MRI and PET/CT findings in 98
cases of malignant tumors in which accuracy was 79% and 93% respectively in N staging.

Radiotherapy and Efficacy Assessment: Currently, due to the special nature of nasopharyngeal anatomy
and pathology, radiotherapy is preferred and is the most effective means of treatment. PET/CT has an
irreplaceable role before the radiotherapy of nasopharyngeal lesion, it can confirm the size and scope of
lesion, make radiation treatment planning,and provide the basis for clinical treatment and prevention of
further complications after radiotherapy provi de the basis. Zhuang etc
[29]
found PET/CT can help determine
the tumor target volume and clinical target volume, it can also devote to build appropriate programs and
three-di mensional radiotherapy program. Meantime, Shankar LK
[30]
also thought that PET/CT is the first step
before radiotherapy planning.
The partial residual tumor and recurrence after comprehensive treatment of NPC is very common ,the
suitable evaluation of the local and systemic conditions of the patients which in turn is very important for
timely and effective treatment to i mprove the patient life quality and prolong survival. The study by Ng SH et
al
[31]
suggested that it was difficult to accurately distinguish between the residual/ recurrence of tumor from
radiotherapy fi brosis, edema and scar by CT, MRI. Analysis of 21 studies done between 1990 to 2007 by Liu T
et all
[32]
showed that PET had an upper hand over CT, MRI in diagnosis of local recurrence, moreover, PET
which was combined with CT would be the most perfect. Thus, PET/CT has a higher sensitivity and specificity
in early detection of nasopharyngeal tumor recurrence after radiotherapy
[33,34]
. TSA IM H et al
[35,36]
also found
that, in the follow-up of patients after radiotherapy, those patients on MRI suggested residue and recurrence
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of NPC, the sensitivity of undergoing PET/CT scan was 90% ~100%, specificity was 88.9%~100% and accuracy
was 85.7%~97%, the result was that PET/CT should be better than MRI in early detection of nasopharyngeal
tumor residue and recurrence after radiotherapy. Therefore, PET/CT can be used effectively to compensate
the limitations of CT and MRI in detection of residual and recurrent tumor.

Summary
At present, the imaging methods for clinical diagnosis of NPC include CT, MRI and PET/CT and they do
have their own characteristics. Radiological diagnosis of NPC should be done by a combination of CT,MRI and
PET/CT for comprehensive analysis and estimation. Since different forms of imaging are complementary to
each other, only through multi-mode imaging can we get broader and comprehensive information. MRI is
superior in depiction and delineation of local invasion of primary tumor,when combined with diagnostic
characteristics of distant metastasis on PET/CT ,it will be the best clinical strategy to guide diagnosis and cure.
However, for early diagnosis, relapsing tumor after treatment and recessive forms of metastases still remains
difficult and requires more clinical trial data analysis and research.



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Table 1 Seventh edition of UICC staging system for nasopharyngeal carcinoma
Classifications UICC (2009) staging system
T1 Nasopharynx, oropharynx or nasal cavity without
parapharyngeal extension
T2 Parapharyngeal extension
T3 Bony structures of skull base and/or paranasal sinuses
T4 Intracranial,cranial nerves, hypopharynx, orbit,
Infratemporal fossa/masticator space
N1 Unilateral cervical, unilateral or bilateral retropharyngeal
lymph nodes, above supraclavicular fossa; < 6 cm
N2 Bilateral cervical above supraclavicular fossa;< 6 cm
N3 N3a > 6 cm
N3b Supraclavicular fossa