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MR Imaging of Nasopharyngeal Carcinoma

      Keywords

      Key points

      • Most nasopharyngeal carcinomas arise in endemic regions and are a radiosensitive undifferentiated carcinoma with a strong genetic basis and close association with the Epstein-Barr virus.
      • MR imaging can detect early cancers that cannot be detected by endoscopy, including those identified by plasma Epstein-Barr virus–related marker screening.
      • Primary and nodal MR staging is aided by a structured report and forms the cornerstone for radiation field planning and determining the need for chemotherapy.
      • Distant metastases most commonly present after treatment.

      Introduction

      Nasopharyngeal carcinoma (NPC) is prevalent in distinct geographic regions, including southern China, Southeast Asia, North Africa, Greenland, and Alaska, and most commonly affects middle-aged men. Unlike most squamous cell carcinomas of the head and neck, those that develop in the nasopharynx of patients from endemic and certain nonendemic regions are mostly of the nonkeratinizing undifferentiated subtype. Several etiologic factors have been implicated in undifferentiated NPC,
      • Tsao S.W.
      • Yip Y.L.
      • Tsang C.M.
      • et al.
      Etiological factors of nasopharyngeal carcinoma.
      the most predominant of which is the Epstein-Barr virus (EBV). NPC also has a strong genetic basis; nearly 12% of patients have a first-degree relative with NPC,
      • Ouyang P.Y.
      • Su Z.
      • Mao Y.P.
      • et al.
      Prognostic impact of family history in southern Chinese patients with undifferentiated nasopharyngeal carcinoma.
      and the risk of NPC remains even after emigration.
      NPC has a propensity for local invasion and for spreading to lymph nodes in the neck and at distant sites. Early-stage NPCs can be asymptomatic or can cause nonspecific symptoms such as nasal stuffiness, epistaxis, and hearing loss due to middle ear effusion from eustachian tube obstruction. Therefore, patients often present at a later stage with symptoms such as neurologic deficits or a lump in the neck. Distant metastases are uncommon at presentation (approximately 8% of patients),
      • Chua M.L.K.
      • Ong S.C.
      • Wee J.T.S.
      • et al.
      Comparison of 4 modalities for distant metastasis staging in endemic nasopharyngeal carcinoma.
      and most are detectable only after treatment. Undifferentiated NPC is sensitive to radiotherapy. Intensity-modulated radiotherapy is used for locoregional disease, and chemotherapy is added for advanced cancers.
      For several decades, MR imaging has been the technique of choice for staging of NPC in the head and neck.
      • Ng S.H.
      • Chang T.C.
      • Ko S.F.
      • et al.
      Nasopharyngeal carcinoma: MRI and CT assessment.
      • King A.D.
      • Lam W.W.M.
      • Leung S.F.
      • et al.
      MRI of local disease in nasopharyngeal carcinoma: Tumour extent vs tumour stage.
      • King A.D.
      • Ahuja A.T.
      • Leung S.F.
      • et al.
      Neck node metastases from nasopharyngeal carcinoma: MR imaging of patterns of disease.
      • Ng S.-H.
      • Chang J.T.-C.
      • Chan S.-C.
      • et al.
      Nodal metastases of nasopharyngeal carcinoma: patterns of disease on MRI and FDG PET.
      • Abdel Khalek Abdel Razek A.
      • King A.
      MRI and CT of nasopharyngeal carcinoma.
      MR imaging maps the sites and boundaries of the primary tumor and nodal metastases when planning for radiation therapy, and it also provides indicators of the need for chemotherapy. It remains the cornerstone of treatment planning because of its advantages over 18F-fluorodeoxyglucose positron emission tomography (PET)/computed tomography (CT) in mapping the extent of the primary tumor.
      • King A.D.
      • Ma B.B.
      • Yau Y.Y.
      • et al.
      The impact of 18F-FDG PET/CT on assessment of nasopharyngeal carcinoma at diagnosis.
      ,
      • Chen W.
      • Li J.
      • Hong L.
      • et al.
      Comparison of MRI , CT and 18F-FDG PET/CT in the diagnosis of local and metastatic of nasopharyngeal carcinomas : an updated meta analysis of clinical studies.
      MR images are fused with those from the planning CT scan for three-dimensional radiation planning.
      • Emami B.
      • Sethi A.
      • Petruzzelli G.J.
      Influence of MRI on target volume delineation and IMRT planning in nasopharyngeal carcinoma.
      An advanced stage, especially N3 nodal disease, and high plasma EBV DNA levels are often considered in NPC endemic regions to select patients at risk of distant metastases who would benefit from a whole-body PET/CT scan. Whole-body MR imaging and, more recently, PET-MR imaging are promising techniques with some advantages over PET-CT scanning.
      • Ng S.H.
      • Chan S.C.
      • Yen T.C.
      • et al.
      Pretreatment evaluation of distant-site status in patients with nasopharyngeal carcinoma: accuracy of whole-body MRI at 3-Tesla and FDG-PET-CT.
      • Ng S.-H.
      • Chan S.-C.
      • Yen T.-C.
      • et al.
      Comprehensive imaging of residual/recurrent nasopharyngeal carcinoma using whole-body MRI at 3 T compared with FDG-PET-CT.
      • Chan S.C.
      • Yeh C.H.
      • Yen T.C.
      • et al.
      Clinical utility of simultaneous whole-body 18F-FDG PET/MRI as a single-step imaging modality in the staging of primary nasopharyngeal carcinoma.
      After treatment, MR imaging is used to detect and map residual or recurrent locoregional disease (which tends to have the same signal intensity as the original tumor) and to identify long-term radiation-induced complications.
      • King A.D.
      • Ahuja A.T.
      • Yeung D.K.
      • et al.
      Delayed complications of radiotherapy treatment for nasopharyngeal carcinoma: imaging findings.
      PET-CT scanning has greater value in the posttreatment setting for the detection of locoregional recurrence and distant metastases; the latter are now the major cause of death from this disease. However, posttreatment imaging is beyond the scope of this article, which instead focuses on the use of MR imaging at the initial diagnosis for detection or early cancer, staging, and management and briefly covers differential diagnoses.

      Normal anatomy

      The nasopharynx lies behind the nasal cavity and just below and in front of the sloping skull base. It comprises a roof, lateral and posterior walls, and a floor formed by the soft palate. Fig. 1 shows an MR image of the anatomy of the nasopharynx in a patient with early NPC. In brief, the lining of the nasopharynx comprises mucosa and submucosa and contains abundant lymphoid tissue, with focal accumulation in the center of the roof and the upper posterior wall of the site of the adenoids. The pharyngeal recess, also known as the fossa of Rosenmüller, is a posterolateral outpouching from each side of the nasopharynx that lies posterior to the eustachian tube and its expanded distal cartilaginous portion, known as the torus tubarius. The nasopharynx is bounded by fascia, which is best appreciated as a thin line on MR images along the lateral aspect of the nasopharynx and curving around the deep aspect of the pharyngeal recess. The levator veli palatini muscle and the eustachian tube enter the nasopharynx through a gap in the fascia. Lateral to the fascia is the tensor palatini muscle, the parapharyngeal fat space that contains the pterygoid venous plexus and the mandibular branch (V3) of the trigeminal nerve, and the medial and lateral pterygoid muscles. The retropharyngeal region contains the prevertebral muscles, Batson’s venous plexus, lymph nodes, and lymphatic channels. The internal carotid artery lies posterolateral to the nasopharynx near the deep aspect of the pharyngeal recess. The anatomy of the skull base and other closely related structures is discussed in the section on Staging.
      Figure thumbnail gr1
      Fig. 1Anatomy of the nasopharynx and primary stage T1 focal NPC. Axial T1-weighted postcontrast MR image shows a small focal cancer confined to the right pharyngeal recess (open straight arrow) and normal anatomy; pharyngeal recess on the left (open curved arrow), levator palatini muscle (1), torus tubarius (2), eustachian tube orifice (3), tensor palatini muscle (4), medial pterygoid muscle (5), lateral pterygoid muscle (6), parapharyngeal fat space (7), prevertebral muscles (8), internal carotid artery (9), and fascia (arrow heads).

      Imaging protocols

      MR imaging is performed with a head and neck coil on a 1.5-T or 3.0-T MR imaging system. The optimal choice of sequences and planes is compromised by the scanning time. Table 1 shows a suggested protocol. Two-dimensional sequences should be obtained with a slice thickness of 3 or 4 mm, with the scan coverage separated into upper and lower regions. It is suggested that at least one T1-weighted postcontrast sequence should be a spin-echo sequence without fat saturation and that diffusion-weighted imaging (DWI) should include a high b-value (ie, at least 800). The addition of a three-dimensional T1-weighted fat saturation after contrast gradient echo scan in the coronal plane allows for volumetric scanning with thin contiguous slices (0.8 mm with 0.4-mm overlap) and multiplanar reconstruction (0.4 mm).
      Table 1MR imaging protocol for nasopharyngeal carcinoma
      RegionSequences and Planes
      Coverage may need to be extended for the most advanced cases.
      Coverage
      Plane Tilt
      Two-dimensional sequences
       Head/upper neckAxial T2WFS, DWI, T1W before and after contrastAbove the skull base (level of superior orbital rim/inferior frontal sinuses) to lower margin of mandible or C3.Perpendicular to posterior nasopharyngeal wall
      Sagittal T1WInclude medial half of maxillary sinus on each side.Parallel to midline
      Coronal T2W and T1W after contrastMid portion of the hard palate to posterior spinal canalParallel to posterior nasopharyngeal wall
       NeckAxial T1W after contrast (±T2WFS)Several sections above the lower margin of the mandible or C3 (overlap with the head/upper neck) to several sections below the suprasternal notchPerpendicular to cervical spine
      Three-dimensional sequences
       Nasopharynx and whole neckCoronal volumetric T1WFS after contrast with reconstruction into coronal, axial, and sagittal planesMid portion of hard palate to posterior spinal canalParallel to posterior nasopharyngeal wall
      Abbreviations: DWI, diffusion-weighted imaging; FS, Fat saturation; W, weighted.
      a Coverage may need to be extended for the most advanced cases.

      Imaging findings

      Early Detection

      NPC is one of the few cancers for which a blood test exists that can successfully screen for early-stage disease. Plasma EBV DNA screening for NPC was recently shown to successfully detect early-stage cancers in asymptomatic patients
      • Chan K.C.A.
      • Woo J.K.S.
      • King A.
      • et al.
      Analysis of plasma epstein–barr virus DNA to screen for nasopharyngeal cancer.
      ; 70% of NPCs were stage I or II carcinomas (compared with 21% from the literature data).
      • Chan K.C.A.
      • Woo J.K.S.
      • King A.
      • et al.
      Analysis of plasma epstein–barr virus DNA to screen for nasopharyngeal cancer.
      However, small cancers may be hidden from the endoscopic view in the pharyngeal recess (see Fig. 1), the corner of the roof, or the submucosa. Detection via endoscopy is also hampered by coexisting benign hyperplasia. Prospective studies on the performance of endoscopic examination and MR imaging have shown that MR imaging is highly sensitive
      • King A.D.
      • Vlantis A.C.
      • Bhatia K.S.S.
      • et al.
      Primary nasopharyngeal carcinoma: diagnostic accuracy of MR imaging versus that of endoscopy and endoscopic biopsy.
      and that 11% of all NPCs in symptomatic patients were detected only by MR imaging,
      • King A.D.
      • Vlantis A.C.
      • Bhatia K.S.S.
      • et al.
      Primary nasopharyngeal carcinoma: diagnostic accuracy of MR imaging versus that of endoscopy and endoscopic biopsy.
      ,
      • King A.D.
      • Vlantis A.C.
      • Yuen T.W.C.
      • et al.
      Detection of nasopharyngeal carcinoma by MR imaging: diagnostic accuracy of MRI compared with endoscopy and endoscopic biopsy based on long-term follow-up.
      and this figure increased to between 17% and 35% in asymptomatic patients screened for the disease, a high proportion of whom had early-stage cancer.
      • King A.D.
      • Woo J.K.S.
      • Ai Q.Y.
      • et al.
      Complementary roles of MRI and endoscopic examination in the early detection of nasopharyngeal carcinoma.
      ,
      • Liu Z.
      • Li H.
      • Yu K.
      • et al.
      Comparison of new magnetic resonance imaging grading system to conventional endoscopy for the early detection of nasopharyngeal carcinoma.
      MR imaging can also detect early NPCs as long as 3 years before they are visible on endoscopy.
      • King A.D.
      • Vlantis A.C.
      • Yuen T.W.C.
      • et al.
      Detection of nasopharyngeal carcinoma by MR imaging: diagnostic accuracy of MRI compared with endoscopy and endoscopic biopsy based on long-term follow-up.
      ,
      • King A.D.
      • Woo J.K.S.
      • Ai Q.Y.
      • et al.
      Complementary roles of MRI and endoscopic examination in the early detection of nasopharyngeal carcinoma.
      Primary tumors tend to be nonnecrotic, homogeneous, or mildly heterogeneous, and the signal characteristics, that is, intermittent T2 signal intensity, low signal on the apparent diffusion coefficient (ADC) map (restricted diffusion), and moderate contrast enhancement on non–fat-saturated images, although early cancers may show less contrast enhancement,
      • King A.D.
      • Wong L.Y.S.
      • Law B.K.H.
      • et al.
      MR imaging criteria for the detection of nasopharyngeal carcinoma: discrimination of early-stage primary tumors from benign hyperplasia.
      are similar to those of other carcinomas (Fig. 2). Detection of NPC is straightforward when the tumor invades beyond the nasopharynx or when early-stage tumors form a focal mass on one side of the nasopharynx (see Fig. 1), but it is more challenging when an early-stage tumor forms a focal mass in the midline of the roof or spreads in a diffuse manner to involve both sides of the nasopharynx (see Fig. 2). In these cases, early-stage NPC must be differentiated from benign hyperplasia, which also causes enlargement of the adenoid and/or diffuse thickening of the nasopharyngeal walls.
      • King A.D.
      • Wong L.Y.S.
      • Law B.K.H.
      • et al.
      MR imaging criteria for the detection of nasopharyngeal carcinoma: discrimination of early-stage primary tumors from benign hyperplasia.
      • Bhatia K.S.S.
      • King A.D.
      • Vlantis A.C.
      • et al.
      Nasopharyngeal mucosa and adenoids: appearance at MR imaging.
      • Wang M.-L.
      • Wei X.-E.
      • Yu M.-M.
      • et al.
      Value of contrast-enhanced MRI in the differentiation between nasopharyngeal lymphoid hyperplasia and T1 stage nasopharyngeal carcinoma.
      • Surov A.
      • Ryl I.
      • Bartel-Friedrich S.
      • et al.
      MRI of nasopharyngeal adenoid hypertrophy.
      NPC and benign hyperplasia may also coexist. Detection of NPC in these cases relies heavily on asymmetry in the thickness or signal intensity when comparing the right and left halves of the nasopharynx (see Fig. 2A), excluding asymmetry caused by cysts. In addition, alternating septa of enhancement and columns of lower enhancement, which give adenoidal hyperplasia a stripped appearance, is lost in NPC (see Fig. 2B). Tumors that arise in the corner of the roof adjacent to benign hyperplasia in the adenoid may also displace the normal adenoidal striped pattern toward the opposite side. A four-grade system for MR imaging detection of NPC was first proposed in 2011
      • King A.D.
      • Vlantis A.C.
      • Bhatia K.S.S.
      • et al.
      Primary nasopharyngeal carcinoma: diagnostic accuracy of MR imaging versus that of endoscopy and endoscopic biopsy.
      and was recently updated in 2020 to a five-grade system to achieve a sensitivity of 98% and a specificity of 90% for NPC detection.
      • King A.D.
      • Woo J.K.S.
      • Ai Q.-Y.
      • et al.
      Early detection of cancer: evaluation of MR imaging grading systems in patients with suspected nasopharyngeal carcinoma.
      Figure thumbnail gr2
      Fig. 2Stage T1 NPC causing (A) diffuse asymmetrical thickening with low enhancement along the nasopharyngeal walls that is greater on the left (open straight arrow) than on the right (solid straight arrow) and (B) a central roof mass with moderate enhancement at the site of the adenoid without the normal adenoidal stripped pattern.
      An MR imaging grading system was recently evaluated for use with a non–contrast-enhanced scan,
      • King A.D.
      • Woo J.K.S.
      • Ai Q.-Y.
      • et al.
      Early detection of cancer: evaluation of MR imaging grading systems in patients with suspected nasopharyngeal carcinoma.
      and studies on DWI
      • Ai Q.Y.
      • King A.D.
      • Chan J.S.M.
      • et al.
      Distinguishing early-stage nasopharyngeal carcinoma from benign hyperplasia using intravoxel incoherent motion diffusion-weighted MRI.
      and automatic discrimination using artificial intelligence
      • Ke L.
      • Deng Y.
      • Xia W.
      • et al.
      Development of a self-constrained 3D DenseNet model in automatic detection and segmentation of nasopharyngeal carcinoma using magnetic resonance images.
      ,
      • Wong L.M.
      • King A.D.
      • Ai Q.-Y.H.
      • et al.
      Convolutional neural network for discriminating nasopharyngeal carcinoma and benign hyperplasia on MRI.
      have shown promise for expanding the role of MR imaging in EBV-related marker screening programs.

      Staging

      All sites of local invasion and sites of nodal metastases should be indicated in the MR imaging report for radiation field planning, and the stage also indicates when additional chemotherapy is required. The use of a structured report based on tumor, node, and metastasis staging
      ensures that all relevant structures in the head and neck are scrutinized systematically and presented clearly and concisely to facilitate the transfer of information to the referring radiotherapist and oncologist. These sites are illustrated in the following paragraphs, and a basic template for evaluation is shown in Box 1.
      Suggested template for staging nasopharyngeal carcinoma

        Primary Tumor

      • (T1) Nasopharyngeal carcinoma measuring (X × X cm) and predominantly arising from (left/right side). Nasal cavity and oropharynx
      • (T2) Parapharyngeal, retropharyngeal, and carotid sheath
      • (T3) Skull base bones (clivus, right and left pterygoid processes, right and left petrous apices and body of the sphenoid); foramina (rotundum, ovale, and lacerum); canals (vidian, pterygopalatine, and hypoglossal); fissures (pterygomaxillary, orbital [inferior and superior] and petroclival); pterygopalatine fossa; large tumors, jugular foramen, optic canal, infraorbital canal, sphenoid wings, and occipital condyles. Upper cervical spine, sphenoid, ethmoid, and maxillary sinus
      • (T4) Cavernous sinus, cranial nerves (especially V3, V2, infraorbital, auriculotemporal, and 12th), middle and posterior cranial fossa dura orbit, infratemporal fossa, parotid gland, and hypopharynx

        Nodal Metastases

      • General description for staging. Unilateral/bilateral (N1/N2); size of the largest node/conglomeration of nodes (>6 cm N3); groups below the level of the cricoid cartilage (N3). Necrosis and extranodal tumor spread
      • Sites of metastatic nodes (right and left sides). retropharyngeal; parotid/periparotid; submental (level IA); submandibular (level IB); upper, middle, and lower internal jugular chain (levels II, III, IV); posterior triangle (levels VA, VB); and paratracheal (level VI). Mediastinal and axillary (if partially covered on the scan)

        Distant metastases (M1) and second primary tumors

      • Lung apices and bones
      • Additional findings
      • Middle ear/mastoid effusion
      • Mucosal inflammatory changes in the paranasal sinuses
      • Other findings

        Conclusion

      • Nasopharyngeal carcinoma with unilateral/bilateral cervical nodal metastases (Head and neck scan stage T_N_M_ according to the 8th edition of AJCC)

      Local staging

      The primary tumor size is only a weak predictor of outcome
      • Feng M.
      • Wang W.
      • Fan Z.
      • et al.
      Tumor volume is an independent prognostic indicator of local control in nasopharyngeal carcinoma patients treated with intensity-modulated radiotherapy.
      and is not a criterion for NPC staging, but the size should be indicated on the report (using at least two dimensions; a single dimension does not reflect the volume of NPCs with irregular shapes
      • King A.D.
      • Zee B.
      • Yuen E.H.Y.
      • et al.
      Nasopharyngeal cancers: which method should be used to measure these irregularly shaped tumors on cross-sectional imaging?.
      ).

      Stage T1 (nasopharynx, nasal cavity, and oropharynx)

      NPCs confined to the nasopharynx tend to form a focal mass in the pharyngeal recess or roof, but they may also be diffuse and involve both sides of the nasopharynx and fill the nasopharyngeal cavity (Figs. 1 and 2B).
      • King A.D.
      • Wong L.Y.S.
      • Law B.K.H.
      • et al.
      MR imaging criteria for the detection of nasopharyngeal carcinoma: discrimination of early-stage primary tumors from benign hyperplasia.
      Superficial spread outside the nasopharynx is included in stage T1; spread into the nasal cavity along the nasal septum and/or lateral walls is common but is often limited to the posterior aspect. NPC tends to spread in a superior direction rather than an inferior direction, so superficial spread to the oropharynx is usually accompanied by deep spread elsewhere.
      • King A.D.
      • Lam W.W.M.
      • Leung S.F.
      • et al.
      MRI of local disease in nasopharyngeal carcinoma: Tumour extent vs tumour stage.

      Stage T2 (parapharynx and retropharynx)

      Deep invasion of the soft tissues that lie lateral and posterior to the nasopharynx involves the parapharynx, retropharynx, and carotid sheath (Fig. 3). The parapharyngeal fat space may be compressed by tumor confined within the nasopharynx (TI) instead of being invaded (T2). In either scenario, middle ear or mastoid effusion is common. Spread to the prevertebral muscles in the retropharynx can be subtle or bulky providing the main route of inferior spread.
      Figure thumbnail gr3
      Fig. 3Primary stage T2 NPC. Axial T1-weighted postcontrast MR image shows a case of (A) NPC in the right pharyngeal recess with early invasion through the levator palatini muscle (∗) into the parapharynx (open straight arrow) and into the retropharynx (open curved arrow) compared with (B) stage T1 NPC causing a focal mass in the right pharyngeal recess that is confined to the nasopharynx and displaces and thins the levator palatini muscle (∗).

      Stage T3 (skull base, paranasal sinuses, and cervical spine)

      Skull base invasion is common (approximately 65%)
      • King A.D.
      • Lam W.W.M.
      • Leung S.F.
      • et al.
      MRI of local disease in nasopharyngeal carcinoma: Tumour extent vs tumour stage.
      ,
      • Li Y.Z.
      • Cai P.Q.
      • Xie C.M.
      • et al.
      Nasopharyngeal cancer: impact of skull base invasion on patients prognosis and its potential implications on TNM staging.
      and may be the only site of invasion outside the nasopharynx (Fig. 4, Fig. 5, Fig. 6, Fig. 7). The skull base should be assessed systematically at the most common sites of invasion, which comprise six bony sites (clivus, right and left pterygoid processes, right and left petrous apices, and body of the sphenoid, especially the floor of the sphenoid sinus); three foramina (rotundum, ovale, and lacerum); three canals (vidian, pterygopalatine, and hypoglossal); three fissures (pterygomaxillary, orbital, and petroclival); and one fossa (pterygopalatine fossa). Tumor in the pterygopalatine fossa spreads in many sites, including the nasal cavity (via the sphenopalatine foramen), middle cranial fossa (via foramen rotundum), orbit (via the inferior orbital fissure), infratemporal fossa (via the pterygomaxillary fissure), and oropharynx (via the pterygopalatine canal). Larger tumors invade beyond these sites such as to the jugular foramen, optic canal, infraorbital canal, wings of the sphenoid, occipital condyles, and upper cervical spine. The roof of the nasopharynx forms the floor of the sphenoid sinus, so the sphenoid sinus frequently undergoes invasion by NPC, whereas invasion of the ethmoid sinus and maxillary sinus is less frequent.
      Figure thumbnail gr4
      Fig. 4Primary stage T3 NPC with invasion into skull base bones. Axial T1-weighted MR images of the skull base superior to the roof of the nasopharynx show (A) a normal skull base with high T1 signal intensity of the fatty bone marrow in five of the six bones invaded commonly by NPC: clivus (1), right pterygoid process (2), left pterygoid process (3), right petrous apex (4), and left petrous apex (5); (B) invasion into the clivus (1), left pterygoid process (3), and left petrous apex (4); and (C) subtle invasion of the pterygoid process and left pterygopalatine fossa (open straight arrow) with early invasion on the right side as well. The floor and walls of the sphenoid sinus are best assessed in the coronal plane (not shown).
      Figure thumbnail gr5
      Fig. 5Primary stage T3 NPC with invasion into skull base foramina. Coronal T1-weighted postcontrast MR images show the foramina invaded commonly by NPC (open straight arrows) and normal foramina on the opposite side (open curved arrows). From anterior to posterior: (A) foramen rotundum, which contains the maxillary nerve, the vidian canal is also invaded (solid straight arrow); (B) foramen ovale, which contains the mandibular nerve and invasion of cavernous sinus (solid straight arrow) and dura of the middle cranial fossa (solid curved arrow); (C) foramen lacerum just below the horizontal portion of the internal carotid artery, the artery is encased (solid straight arrow) and intracranial invasion into the cavernous sinus (solid curved arrow).
      Figure thumbnail gr6
      Fig. 6Primary stage T3 NPC with invasion into skull base canals. Axial T1-weighted postcontrast MR images with fat saturation show the canals invaded commonly by NPC (straight open arrows). From superior to inferior: (A) vidian canal (connects the pterygopalatine fossa (∗) and foramen lacerum), tumor is also spreading from the pterygopalatine fossa (∗) to the infratemporal fossa via the pterygomaxillary fissure (open curved arrow); (B) pterygopalatine canal (connects the pterygopalatine fossa and palate); and (C) hypoglossal canal. Note also extensive parapharyngeal invasion (solid straight arrow) and perineural spread into the parotid gland along the auriculotemporal nerve (open curved arrow).
      Figure thumbnail gr7
      Fig. 7Primary stage T3 NPC with invasion into skull base pterygopalatine fossa/fissures. Coronal T1-weighted postcontrast MR images show tumor in the pterygopalatine fossa (∗) with spread into the inferior orbital fissure (open straight arrow) to the orbit; the sphenopalatine foramen (open curved arrow) to the nasal cavity; pterygopalatine canal to the palate (solid straight arrow). Tumor in the pterygopalatine also spreads along the pterygomaxillary fissure to the infratemporal fossa (A), vidian canal to the foramen lacerum (see A), and foramen rotundum to the middle cranial fossa (not shown).

      Stage T4 (brain, cranial nerves, orbits, parotid gland, infratemporal fossa, and hypopharynx)

      Intracranial invasion most commonly involves the cavernous sinus and dura of the middle and posterior cranial fossa (see Figs. 5 and 6). Spread into the cavernous sinus may occur through the foramina, along the internal carotid artery, or directly through the bone. The cranial nerves are frequently surrounded and may be invaded by tumor in the parapharyngeal region, skull base foramina, cavernous sinus and orbital fissures, especially the mandibular nerve (foramen ovale and parapharyngeal region), the maxillary nerve (foramen rotundum), and the hypoglossal nerve (hypoglossal canal). Perineural spread distal to the main tumor bulk is less common, but it is important to scrutinize distal pathways such as the auriculotemporal nerve in the parotid gland (via the mandibular nerve) and the infraorbital nerve in the floor of the orbit (via the maxillary nerve) which lie outside the standard radiation field. Muscle denervation in the tongue or in the muscles of mastication provides clues regarding cranial nerve involvement. Invasion of the infratemporal fossa (defined for NPC staging purposes as anterior to the anterior margin of the lateral pterygoid muscle) is usually via the pterygomaxillary fissure or through the lateral pterygoid muscle. The parotid gland, orbit, and hypopharynx are further indicators of the most advanced patterns of local disease.

      Nodal staging

      Nodal metastases occur in approximately 80% of patients,
      • Au K.H.
      • Ngan R.K.C.
      • Ng A.W.Y.
      • et al.
      Treatment outcomes of nasopharyngeal carcinoma in modern era after intensity modulated radiotherapy (IMRT) in Hong Kong: a report of 3328 patients (HKNPCSG 1301 study).
      but even though small early T-stage tumors can have extensive nodal metastases, they are not necessarily present in late T-stage tumors (Fig. 8). Diagnosis of a metastatic NPC node by MR imaging relies on criteria similar to those used for other carcinomas of the head and neck, such as size, necrosis, and extracapsular extension.
      Figure thumbnail gr8
      Fig. 8Nodal metastases. Axial T1-weighted postcontrast MR images of nodal metastases (open straight arrows). (A) Lateral retropharyngeal nodes and (B) upper internal jugular nodes (level II), including those posterior to the internal jugular vein (level IIA/B), are both common groups for the first echelons of nodal spread, and (C) bilateral nodes, extranodal spread, and necrosis are common. (Bilateral nodal metastases increase the stage from N1 to N2, except for bilateral retropharyngeal nodes, which are still classified as N1.) Coronal T1-weighted postcontrast image shows (D) orderly spread down the neck with bilateral nodal metastases and the most advanced nodal stage comprising bulky matted nodes larger than 6 cm in maximum dimension (N3) and involvement of groups in the lower neck (N3).
      Nodes are frequently bilateral and may show necrosis and extranodal spread. The first groups of metastatic spread are either the lateral retropharyngeal or the upper internal jugular chain (level II), especially those that lie posterior to the vein (IIA and IIB).
      • King A.D.
      • Ahuja A.T.
      • Leung S.F.
      • et al.
      Neck node metastases from nasopharyngeal carcinoma: MR imaging of patterns of disease.
      ,
      • Ng S.-H.
      • Chang J.T.-C.
      • Chan S.-C.
      • et al.
      Nodal metastases of nasopharyngeal carcinoma: patterns of disease on MRI and FDG PET.
      ,
      • Liu L.-Z.
      • Zhang G.-Y.
      • Xie C.-M.
      • et al.
      Magnetic resonance imaging of retropharyngeal lymph node metastasis in nasopharyngeal carcinoma: patterns of spread.
      ,
      • Wang X.S.
      • Hu C.S.
      • Ying H.M.
      • et al.
      Patterns of retropharyngeal node metastasis in nasopharyngeal carcinoma.
      The lateral retropharyngeal nodes are located between the internal carotid artery and the anterolateral margin of the prevertebral muscle and extend from approximately the level of the lateral recess of the nasopharynx to the third cervical vertebra.
      • King A.D.
      • Ahuja A.T.
      • Leung S.F.
      • et al.
      Neck node metastases from nasopharyngeal carcinoma: MR imaging of patterns of disease.
      The minimum axial dimension for retropharyngeal nodes is controversial, and 5 mm and 6 mm have both been advocated.
      • King A.D.
      • Ahuja A.T.
      • Leung S.F.
      • et al.
      Neck node metastases from nasopharyngeal carcinoma: MR imaging of patterns of disease.
      ,
      • Zhang G.
      • Liu L.
      • Wei W.
      • et al.
      Radiologic criteria of retropharyngeal lymph node metastasis in nasopharyngeal carcinoma treated with radiation therapy.
      The nodes that lie immediately deep to the lateral margin of the recess are separated from the primary tumor by a thin line of fascia that is best appreciated on an MR image,
      • King A.D.
      • Ma B.B.
      • Yau Y.Y.
      • et al.
      The impact of 18F-FDG PET/CT on assessment of nasopharyngeal carcinoma at diagnosis.
      but the fascia may be disrupted or totally lost if direct spread occurs between the two sites. The medial retropharyngeal nodes lie in the midline anterior to the prevertebral muscles. Discrete nodes at this site are rarely seen, but it is likely that spread along the abundant lymphatic channels in this region contributes to the extensive retropharyngeal pattern of inferior spread seen in some patients. Orderly spread down the neck occurs along the internal jugular chain and/or spinal accessory chain in the posterior triangle to the lower neck and the supraclavicular fossa. Involvement of the parotid/periparotid, submandibular, and submental nodes is less common.
      • King A.D.
      • Ahuja A.T.
      • Leung S.F.
      • et al.
      Neck node metastases from nasopharyngeal carcinoma: MR imaging of patterns of disease.
      Nodal staging differs from that of other head and neck cancers. It is based on (1) laterality, unilateral or bilateral disease (N1 or N2, respectively, except for bilateral retropharyngeal nodes, which are staged as N1); (2) size, any node larger than 6 cm (N3); and (3) involvement of nodes in the lower neck below the level of the cricoid cartilage (N3). The best method for measuring the maximum size for staging purposes is controversial, but a recent study showed that the maximum measurement of matted or contiguous nodes may be the best predictor of outcome.
      • Ai Q.Y.
      • King A.D.
      • Mo F.K.F.
      • et al.
      Staging nodal metastases in nasopharyngeal carcinoma: which method should be used to measure nodal dimension on MRI?.
      The nodal volume
      • Chen F.P.
      • Zhou G.Q.
      • Qi Z.Y.
      • et al.
      Prognostic value of cervical nodal tumor volume in nasopharyngeal carcinoma: analysis of 1230 patients with positive cervical nodal metastasis.
      • Ai Q.-Y.
      • King A.D.
      • Mo F.K.F.
      • et al.
      Prediction of distant metastases from nasopharyngeal carcinoma: improved diagnostic performance of MRI using nodal volume in N1 and N2 stage disease.
      • Yuan H.
      • Ai Q.Y.
      • Kwong D.L.W.
      • et al.
      Cervical nodal volume for prognostication and risk stratification of patients with nasopharyngeal carcinoma, and implications on the TNM-staging system.
      and extracapsular extension
      • Mao Y.P.
      • Liang S.B.
      • Liu L.Z.
      • et al.
      The N staging system in nasopharyngeal carcinoma with radiation therapy oncology group guidelines for lymph node levels based on magnetic resonance imaging.
      ,
      • Ai Q.-Y.
      • King A.D.
      • Poon D.M.C.
      • et al.
      Extranodal extension is a criterion for poor outcome in patients with metastatic nodes from cancer of the nasopharynx.
      also show promise for prediction of the outcome.

      Staging of distant metastases

      Identification of distant metastases on the head and neck staging MR scan is uncommon, but they may sometimes be found in the lung apices, while bony metastases in the cervical spine are rare.

      Functional MR Imaging Markers for the Prediction of Response

      Several promising pretreatment and intratreatment functional MR imaging markers are available for the prediction of short-term and long-term treatment response, including markers from DWI,
      • Hong J.
      • Yao Y.
      • Zhang Y.
      • et al.
      Value of magnetic resonance diffusion-weighted imaging for the prediction of radiosensitivity in nasopharyngeal carcinoma.
      • Zhang Y.
      • Liu X.
      • Zhang Y.
      • et al.
      Prognostic value of the primary lesion apparent diffusion coefficient (ADC) in nasopharyngeal carcinoma: a retrospective study of 541 cases.
      • Tu N.
      • Zhong Y.
      • Wang X.
      • et al.
      Treatment response prediction of nasopharyngeal carcinoma based on histogram analysis of diffusional kurtosis imaging.
      • Qamar S.
      • King A.D.
      • Ai Q.Y.H.
      • et al.
      Pre-treatment intravoxel incoherent motion diffusion-weighted imaging predicts treatment outcome in nasopharyngeal carcinoma.
      dynamic contrast-enhanced MR imaging (DCE-MR imaging),
      • Qin Y.
      • Yu X.
      • Hou J.
      • et al.
      Prognostic value of the pretreatment primary lesion quantitative dynamic contrast-enhanced magnetic resonance imaging for nasopharyngeal carcinoma.
      • Zheng D.
      • Yue Q.
      • Ren W.
      • et al.
      Early responses assessment of neoadjuvant chemotherapy in nasopharyngeal carcinoma by serial dynamic contrast-enhanced MR imaging.
      • Chan S.-C.
      • Yeh C.-H.
      • Chang J.T.-C.
      • et al.
      Combing MRI perfusion and 18F-FDG PET/CT metabolic biomarkers helps predict survival in advanced nasopharyngeal carcinoma: a prospective multimodal imaging study.
      and amide proton transfer imaging (APT imaging).
      • Qamar S.
      • King A.D.
      • Ai Q.Y.H.
      • et al.
      Pre-treatment amide proton transfer imaging predicts treatment outcome in nasopharyngeal carcinoma.
      ,
      • Qamar S.
      • King A.D.
      • Ai Q.Y.
      • et al.
      Amide proton transfer MRI detects early changes in nasopharyngeal carcinoma: providing a potential imaging marker for treatment response.
      High pretreatment ADC from DWI or pure diffusion coefficient (D) from intravoxel incoherent motion is an indicator of poor treatment response
      • Zhang Y.
      • Liu X.
      • Zhang Y.
      • et al.
      Prognostic value of the primary lesion apparent diffusion coefficient (ADC) in nasopharyngeal carcinoma: a retrospective study of 541 cases.
      • Tu N.
      • Zhong Y.
      • Wang X.
      • et al.
      Treatment response prediction of nasopharyngeal carcinoma based on histogram analysis of diffusional kurtosis imaging.
      • Qamar S.
      • King A.D.
      • Ai Q.Y.H.
      • et al.
      Pre-treatment intravoxel incoherent motion diffusion-weighted imaging predicts treatment outcome in nasopharyngeal carcinoma.
      (Fig. 9). These results are in keeping with those from other head and neck cancers where high ADC/D is associated with histologic findings seen in resistant tumors, such as low cell density and high stromal content. In the early intratreatment period, the ADC rises as cell death and blood supply increase. Similar to other head and neck cancers, NPC with a higher rise in ADC indicates a better response based on short-term outcomes.
      • Hong J.
      • Yao Y.
      • Zhang Y.
      • et al.
      Value of magnetic resonance diffusion-weighted imaging for the prediction of radiosensitivity in nasopharyngeal carcinoma.
      Figure thumbnail gr9
      Fig. 9The pretreatment pure diffusion maps derived from intravoxel incoherent motion diffusion weighted imaging and contrast-enhanced MR images of a primary nasopharyngeal carcinoma in two patients with NPC; one without relapse (A, B) in whom the pure diffusion coefficient was 0.62 × 10−3 mm2/s and one with relapse (C, D) in whom the pure diffusion coefficient was higher at 0.81 × 10−3 mm2/s.
      There are only limited DCE data. Two studies found poor long-term response in tumors with a large extracellular extravascular volume, as indicated by a high Ve,
      • Qin Y.
      • Yu X.
      • Hou J.
      • et al.
      Prognostic value of the pretreatment primary lesion quantitative dynamic contrast-enhanced magnetic resonance imaging for nasopharyngeal carcinoma.
      ,
      • Chan S.-C.
      • Yeh C.-H.
      • Chang J.T.-C.
      • et al.
      Combing MRI perfusion and 18F-FDG PET/CT metabolic biomarkers helps predict survival in advanced nasopharyngeal carcinoma: a prospective multimodal imaging study.
      while another found poor short-term response in tumors with a low Ktrans.
      • Zheng D.
      • Yue Q.
      • Ren W.
      • et al.
      Early responses assessment of neoadjuvant chemotherapy in nasopharyngeal carcinoma by serial dynamic contrast-enhanced MR imaging.
      APT imaging is a fairly new chemical exchange-saturation transfer MRI technique that has recently been applied to NPC. Preliminary results show high pretreatment APT values or a rise in APT in the early-intratreatment period may be an indicator of poor response.
      • Qamar S.
      • King A.D.
      • Ai Q.Y.H.
      • et al.
      Pre-treatment amide proton transfer imaging predicts treatment outcome in nasopharyngeal carcinoma.
      ,
      • Qamar S.
      • King A.D.
      • Ai Q.Y.
      • et al.
      Amide proton transfer MRI detects early changes in nasopharyngeal carcinoma: providing a potential imaging marker for treatment response.
      Parametric imaging has the potential to provide more comprehensive treatment prediction, for example, diffusion may have predictive advantages for NPC locoregional resistance and APT for distant metastases.
      • Qamar S.
      • King A.D.
      • Ai Q.Y.H.
      • et al.
      Pre-treatment intravoxel incoherent motion diffusion-weighted imaging predicts treatment outcome in nasopharyngeal carcinoma.
      ,
      • Qamar S.
      • King A.D.
      • Ai Q.Y.H.
      • et al.
      Pre-treatment amide proton transfer imaging predicts treatment outcome in nasopharyngeal carcinoma.

      Diagnostic Criteria and Differential Diagnosis

      Other malignant and nonmalignant diseases produce abnormalities centered in the nasopharynx with or without spread to adjacent structures. The MR imaging appearance of NPC may overlap with that of these other processes, so diagnosis requires biopsy and histologic examination in most cases. The most common differential diagnosis for NPC is non-Hodgkin’s lymphoma (Fig. 10). Lymphoma is commonly exophytic, but it may be invasive and mimic early- or late-stage NPC. The diagnosis of lymphoma relies on clues such as multifocal disease, involvement of unexpected nodal groups,
      • King A.D.
      • Lei K.I.K.
      • Richards P.S.
      • et al.
      Non-Hodgkin's lymphoma of the nasopharynx: CT and MR imaging.
      ,
      • Liu X.W.
      • Xie C.M.
      • Mo Y.X.
      • et al.
      Magnetic resonance imaging features of nasopharyngeal carcinoma and nasopharyngeal non-Hodgkin's lymphoma: are there differences?.
      and differences in functional MR imaging parameters. Notably, the ADC and Ktrans of lymphoma are lower than those of undifferentiated NPC.
      • Fong D.
      • Bhatia K.S.S.
      • Yeung D.
      • et al.
      Diagnostic accuracy of diffusion-weighted MR imaging for nasopharyngeal carcinoma, head and neck lymphoma and squamous cell carcinoma at the primary site.
      • Song C.
      • Cheng P.
      • Cheng J.
      • et al.
      Differential diagnosis of nasopharyngeal carcinoma and nasopharyngeal lymphoma based on DCE-MRI and RESOLVE-DWI.
      • Lee F.K.
      • King A.D.
      • Ma B.B.-Y.
      • et al.
      Dynamic contrast enhancement magnetic resonance imaging (DCE-MRI) for differential diagnosis in head and neck cancers.
      Other tumors that originate in the nasopharynx include adenoid cystic carcinoma, sarcoma and radiation-induced sarcoma, plasmacytoma, melanoma, and (rarely) pleomorphic adenoma. Inflammatory and infectious disease processes include skull base osteomyelitis,
      • Goh J.P.N.
      • Karandikar A.
      • Loke S.C.
      • et al.
      Skull base osteomyelitis secondary to malignant otitis externa mimicking advanced nasopharyngeal cancer: MR imaging features at initial presentation.
      nasopharyngeal tuberculosis, sarcoid granulomatosis with polyangiitis, and amyloid and IgG4-related disease.
      • Liu J.
      • Zhang B.
      • Sun H.
      • et al.
      Immunoglobulin G4-related disease in the skull base mimicking nasopharyngeal carcinoma.
      Discussion of these pathologies is beyond the scope of this article, but diseases other than NPC should be suspected when the nasopharyngeal abnormality is very heterogeneous or necrotic or when the scan shows calcification (amyloid or sarcoma), high T2 signal intensity (sarcoma and infection), low T2 signal intensity (IgG4-related disease), high signal intensity on the ADC map (infection, inflammation, pleomorphic adenoma), marked contrast enhancement (granulomatous polyps, infection, vascular tumors), multifocal disease, or prominent perineural spread (adenoid cystic carcinoma).
      Figure thumbnail gr10
      Fig. 10Non-Hodgkin’s lymphoma (open straight arrows). (A) Nasopharyngeal lymphoma is indistinguishable from NPC on this axial T1-weighted postcontrast MR image, although (B) very low signal intensity on the apparent diffusion coefficient map is a clue to the diagnosis. Diagnosis requires biopsy, but other features on MR images of the head and neck that suggest lymphoma include multisite involvement or nodes outside the expected pathway of metastatic spread for NPC (such as parotid/periparotid, submandibular, and external jugular chain nodes).

      Pearls, pitfalls, and variants

      Detection

      • The pharyngeal recess and lateral aspect of the roof are common sites of early NPC and require scrutiny in the axial and coronal planes, respectively, to ensure that no small tumors are missed.
      • The contrast-enhanced striped appearance of adenoidal hyperplasia is best appreciated on a scan dedicated to the nasopharynx.
      • Benign hyperplasia is common in the general population and may be mildly asymmetrical on an MR image, so the MR grading systems should be applied only to patients in whom NPC is suspected.

      Staging

      T1 and T2 staging

      • Tumor sites within the nasopharynx do not influence staging or radiation planning.
      • The C1/2 junction is a useful landmark for demarcating the junction of the nasopharynx and oropharynx and can overcome difficulties with the use of the soft palate.

      T3 staging

      • For skull base invasion, it is helpful to begin by assessing the five of the six major bones on the axial T1-weighted image immediately above the level of the nasopharynx (see Fig. 4) for any loss of high T1 signal intensity of fatty bone marrow. One must also verify that signal loss in the pterygoid processes or petrous apices is not due to fluid in aerated bone.
      • Assessment of all skull base bones, foramina, canals, fissures, and pterygopalatine fossae requires multiple sequences and planes. In addition to the axial plane, the coronal plane is valuable for assessment of the body of the sphenoid (including the sphenoid sinus floor), foramina, vidian canals, and orbital fissures, and the sagittal plane is valuable for assessment of the clivus.
      • Skull base invasion may be of small volume and easily missed, so one must check for sites of anterior spread into the medial aspect of the pterygoid processes or pterygopalatine fossa and for spread into the floor of the sphenoid sinus and clivus. The presence of tumor in the pterygopalatine fossa requires systematic scrutiny of all connecting sites, including subtle superior spread to the inferior orbital fissure.
      • Red marrow hyperplasia or edema may cause heterogeneous or generalized loss of the fatty bone marrow signal, especially in the clivus. To identify tumor invasion, one must look for a signal intensity similar to that of tumor on all sequences that are in direct continuity with the primary tumor in the nasopharynx.
      • Sites of bony sclerosis adjacent to the tumor should be included in the report because they are usually covered in the radiation field.
      • Even large areas of bone invasion will be overlooked on the postcontrast T1-weighted MR image without fat saturation.

      T4 staging

      • Compared with local invasion, the emissary veins in the hypoglossal nerve canal and inferior petrosal sinus and basilar plexus posterior to the clivus show more marked contrast enhancement.
      • Denervation in the pterygoid muscles adjacent to the tumor is characterized by less diffusion restriction and preservation of muscle striations.

      N staging

      • The minimum axial diameter is used to identify a metastatic node, but the maximum diameter is used to designate the nodal stage.
      • The difficulty in defining the supraclavicular fossa boundary has been overcome by using the lower border of the cricoid cartilage as the landmark to define N3 disease.
      • A nodule in the parotid gland has a high chance of being a benign salivary gland tumor than a metastatic node.
      • Superior cervical sympathetic ganglia occur in a location similar to that of metastatic retropharyngeal nodes. The ganglia, however, are usually bilateral and more fusiform in shape, show greater contrast enhancement and less restriction of diffusion, and contain a small T2 hypointense spot. These ganglia also tend to have a more posterolateral location, and the minimum axial dimension is usually smaller than that of a metastatic node.
        • Yokota H.
        • Mukai H.
        • Hattori S.
        • et al.
        MR imaging of the superior cervical ganglion and inferior ganglion of the vagus nerve: structures that can mimic pathologic retropharyngeal lymph nodes.

      What the referring physician needs to know

      Detection

      • In a patient in whom NPC is suspected and who has normal results on an endoscopic examination or an indeterminate submucosal bulge or enlarged adenoid, the detection of a small cancer on an MR image guides the site and depth of biopsy (which is especially important for tumors in the pharyngeal recess near the internal carotid artery). Small suspected tumors in the pharyngeal recess may require biopsy under navigation and general anesthesia or close surveillance via MR imaging.
      • Normal MR imaging reassures the physician that the patient does not have NPC and that sampling biopsies are not required.

      Staging

      • The MR imaging report should indicate all sites of local tumor invasion and nodal metastases for radiation planning. Special note should be made when the NPC (1) approaches or invades the orbit, neurologic structures (ie, the cavernous sinus, temporal lobes, brain stem, cervical cord, or brachial plexus), or salivary glands (which are normally spared from the radiation field to reduce xerostomia) or (2) spreads to sites distal to the main tumor bulk (ie, perineural spread especially along the infraorbital and auriculotemporal nerves).
      • Indications for the addition of chemotherapy may vary between centers, but in general, advanced local disease (T3/T4, and in some institutions, bulky T2) or nodal disease (N2/3) is an indication for concurrent chemoradiation. Neoadjuvant chemotherapy is also used to shrink the tumor before concurrent chemoradiation when a bulky primary or nodal metastasis lies close to neurologic structures, when extensive perineural spread is found, or when the oropharynx is involved (to reduce the severity of radiation-induced mucositis).
      • Advanced-stage disease (especially N3) is a marker for distant metastases and an indication for PET/CT scanning at centers where it is not routinely performed. The detection of distant metastases may lead to a change in the treatment of primary and nodal disease from curative to palliative.

      Summary

      MR imaging plays a major role in the imaging of head and neck NPC because of its ability to detect and depict the boundaries of the primary tumor site and regional nodal metastases. The staging report is critical for staging and for planning radiation or chemoradiation therapy. A structured approach ensures that all sites that influence management in this complex region are covered in the report. New morphologic and function parameters for MR imaging show promise for improving outcome prediction. MR imaging also plays a new role in the detection of early-stage cancers that cannot be detected via endoscopy, and this role is likely to expand in regions in which NPC is endemic as the use of NPC screening programs becomes more widespread. Distant metastases tend to present after treatment, but PET-MR imaging shows promise for whole-body evaluation of patients in whom distant metastases are detected at the initial presentation.

      Acknowledgments

      The author would like to acknowledge Dr Qi-Yong Ai from the Department of Imaging and Interventional Radiology, The Chinese University of Hong Kong, for literature search, content editing, and image preparation.

      Disclosure

      The author declares no conflicts of interest.

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