**3. Histopathology of NPC**

Three histologic subtypes are recognized by the World Health Organization (WHO) classification system:

	- Type 1 is further subdivided into poorly, moderately, and well-differentiated

In contrast to Type 1, Type 2 and 3 are associated with elevated EBV titres. In addition, Type 2 and 3 may also be accompanied by lymphoepithelioma, which is an inflammatory infiltrate of lymphocytes, plasma cells, and eosinophils. Histopathologic typing has prognostic significance, as Type 2 and Type 3 exhibit a more favourable prognosis and greater radiosensitivity than Type 1. Risk factors for Type 1 include cigarette smoke and ethanol consumption, whereas Type 2 and 3 are the endemic forms (Brennan, 2006).

In NPC, two histological patterns may be recognized: (1) the Regaud type which is a welldefined collection of epithelial cells surrounded by lymphocytes and connective tissue, and (2) the Schmincke type, which appears as diffuse tumours intermingled with inflammatory cells (Brennan, 2006).

## **4. Presentation of NPC**

96 Carcinogenesis, Diagnosis, and Molecular Targeted Treatment for Nasopharyngeal Carcinoma

increased risk (Ren & Chan, 1996). Other exposures implicated in NPC include cigarette smoking, other smoke, and occupational exposures including wood dust and industrial heat

NPC is a rare malignancy that exhibits a distinct ethnic and geographic variation (Chang & Adami, 2006). While in most regions of the world, age standardized incidence rates for both males and females are <1 per 100,000 person-years (Chang & Adami, 2006; Chong, 2006)), higher rates are observed in a few well-defined populations. Studies have demonstrated intermediate incidence rates in several indigenous populations in Southeast Asia, the Arctic, and the Middle East/North Africa (ranging from 0.5 to 31.5 per 100,000 person-years in males and 0.1 to 11.8 person-years in females) (Chang & Adami, 2006; Parkin *et al*., 2002), and endemic rates in the natives of southern China reaching 20-30 per 100,000 person-years and 15-20 per 100,000 person-years amongst males and females, respectively, in the province of Guangdong (Ho, 1978; Yoshizaki *et al.*, 2011). In addition, within geographic regions, a distinct ethnic variation also exists. For example, in the US, rates are highest amongst Chinese Americans, followed by Filipino Americans, Japanese Americans, Blacks,

Globally, there are more than 80,000 incident cases and 50,000 deaths annually due to NPC (Parkin *et al*., 2005). NPC shows a male predilection of 2-3:1 (Parkin *et al*., 2002). In low risk populations, incidence increases with age, while in high risk populations, incidence peaks in the 6th decade of life and declines thereafter. NPC is rare in pediatric populations. Thus, the

Three histologic subtypes are recognized by the World Health Organization (WHO)

Type 1 is further subdivided into poorly, moderately, and well-differentiated

lymphoepithelioma and anaplastic variants; comprises most cases of childhood and

In contrast to Type 1, Type 2 and 3 are associated with elevated EBV titres. In addition, Type 2 and 3 may also be accompanied by lymphoepithelioma, which is an inflammatory infiltrate of lymphocytes, plasma cells, and eosinophils. Histopathologic typing has prognostic significance, as Type 2 and Type 3 exhibit a more favourable prognosis and greater radiosensitivity than Type 1. Risk factors for Type 1 include cigarette smoke and

In NPC, two histological patterns may be recognized: (1) the Regaud type which is a welldefined collection of epithelial cells surrounded by lymphocytes and connective tissue, and (2) the Schmincke type, which appears as diffuse tumours intermingled with inflammatory

ethanol consumption, whereas Type 2 and 3 are the endemic forms (Brennan, 2006).

highest incidence rates are observed in middle-aged men (Chang & Adami, 2006).

Type 1 – squamous cell carcinoma; typically found in older adult populations

Type 3 – undifferentiated or poorly differentiated carcinoma, including

(Yu *et al*., 2010).

**2. Epidemiology of NPC** 

**3. Histopathology of NPC** 

Type 2 – non-keratinizing carcinoma

classification system:

adolescent NPC

cells (Brennan, 2006).

Hispanics, and finally Caucasians (Burt *et al*., 1992).

While some patients are asymptomatic, 50% to 70% of patients initially present with cervical lymphadenopathy in the form of a neck mass and are diagnosed by lymph node biopsy (Glastonbury, 2007). Symptoms at presentation may include trismus, pain, otitis media due to Eustachian tube dysfunction, nasal regurgitation due to paresis of the soft palate, and hearing loss. Depending on the degree of local infiltration, patients may also suffer from cranial nerve dysfunction and headache. Cranial nerve neuropathies (most often CN5 and CN6) are an indication of skull base infiltration. Larger growths may also produce nasal obstruction or bleeding and a "nasal twang". Metastatic spread may result in bone pain or organ dysfunction. Rarely, a paraneoplastic syndrome of osteoarthropathy may occur with widespread disease.

#### **5. Role of imaging in the management of NPC**

All stages of NPC patient management, from diagnosis and staging to treatment and followup, involve imaging. On presentation, a full diagnostic work-up for NPC involves a physical examination (including neurological examination of the cranial nerves), laboratory testing (including a complete blood count, liver function tests, and alkaline phosphate levels), an endoscopic-guided biopsy, as well as imaging studies. Since 6% of NPC is submucosal and cannot been seen on endoscopy (King *et al*., 2006), cross-sectional imaging studies, such as magnetic resonance imaging (MRI) or computed tomography (CT), are required to help confirm the diagnosis, as well as accurately demarcate the exact limits of pharyngeal wall involvement and tumour invasion into surrounding structures. Currently, MRI and CT are not routinely used for screening purposes; however, the radiologist should consider NPC whenever head and neck imaging is obtained, especially in high-risk patients – such as those of Asian descent – being evaluated for otitis media or with incidental findings of middle ear opacification.

Early findings of NPC on imaging include asymmetry of the nasopharynx and an obstructed Eustachian tube (ET) **(Figure 1)** (Glastonbury, 2007)**.** Most NPC masses originate in the fossa of Rosenmuller, otherwise known as the lateral pharyngeal recess. Furthermore, involvement of the lateral pharyngeal recess may cause dysfunction of the ET – either directly or indirectly by infiltrating the surrounding musculature – leading to stasis of middle ear secretions and unilateral hearing loss **(Figure 2).** In cases of head and neck imaging for neck masses of "unknown primary," careful attention should be paid to the possibility of NPC since cervical lymphadenopathy is the most common presentation.

Like other neoplasms, a mainstay in NPC treatment is staging. Staging contributes information regarding prognosis and helps guide treatment planning, facilitate stratification of treatment, and coordinate clinical studies (Mao *et al*., 2009; Yu *et al*., 2010). While in the past, CT was preferred, MRI is currently the imaging modality of choice for NPC staging using the American Joint Committee on Cancer (AJCC) tumour, node, metastasis (TNM) staging system (King *et al.*, 1999; Liang, 2009; Ng *et al*., 1997). CT still has a role in the assessment of bony skull base involvement (Olmi, 1995), but MRI is considered superior to CT for assessing primary tumour invasion into surrounding soft tissue and bony structures, pharyngobasilar fascia invasion, invasion into the sinus of Morgagni, skull base invasion, as well as cavernous sinus extension and perineural disease (Liao *et al.*, 2008; Sakata, 1999).

Imaging of Nasopharyngeal Carcinoma 99

MRI is also more reliable for differentiating between the primary tumor and retropharyngeal adenopathy (Chang, 2005; Chong, 1996; Chung, 2004; King, 2000). For patients with clinical or biochemical evidence of advanced disease, additional investigations – including bone scintigraphy, chest x-ray, CT of thorax, abdomen, and pelvis, and/or fluorodeoxyglucose (FDG)-positron emission tomography (PET)-CT imaging – may be indicated (Caglar, 2003; Chen *et al.,* 2006; Chiesa & De Paoli, 2001; Chua *et al*., 2009;

The mainstay of treatment in NPC is radiation therapy (RT) with the addition of concurrent and/or adjuvant chemotherapy reserved for higher stages of disease. Surgical salvage (nasopharyngectomy) has also been used in cases of recurrent disease (Yu *et al.,* 2010). The goal of treatment is to be curative. To be effective, RT must target the primary lesion as well as any associated neck adenopathy. Thus, cross-sectional imaging, in particular MRI, is needed to determine areas of disease infiltration. NPC has been shown to spread in a stepwise pattern along privileged pathways, such as the neuroforamina (Liang *et al.,* 2009). In addition, involvement of critical structures located near the NP – including the cavernous sinus, pituitary gland, orbit and brainstem – must be evaluated to guide appropriate treatment and to spare these structures of the radiation dose if they are clear of disease (Yu *et al.*, 2010). In the case of intensity-modulated RT (IMRT), CT is also required to correctly

Follow-up evaluation involves a baseline imaging study that is typically performed 2 to 3 months after completion of radiation treatment, followed by imaging every 3 to 6 months for the first 2 post-treatment years (Glastonbury, 2007). Any soft tissue signal abnormalities on MRI in the nasopharynx, deep face, or skull base should remain stable over this period or show further reduction in volume. Recurrent disease is seen as any increase in the bulk of abnormal signal from baseline imaging. Most recurrences, local or systemic, occur within the first 2 years after treatment (Glastonbury, 2007). Of patients with recurrences, 10% to 20% may be curable with additional treatment (Glastonbury, 2007). After 2 years without evidence of recurrence, the imaging interval is typically extended to every 6 to 12 months. Although not yet the mainstay of treatment, one meta-analysis demonstrated that FDG-PET/CT is more sensitive and specific than CT and MRI for the diagnosis of local residual

The staging MRI protocol for NPC varies from center to center. In general, the images should cover the area from above the frontal sinuses to the thoracic inlet on axial studies and from the tip of the nose to the fourth ventricle on coronal sequences. At our institution, axial and coronal T1- and T2-weighted images, as well as a sagittal T1 or T2 fat saturation series covering the entire head and neck are obtained. A head and neck imaging coil is routinely used for both the 1.5T and 3.0T MRI scanners. The axial, coronal and sagittal T1 series are performed using a T1-FLAIR technique. Postgadolinium-enhanced axial images with fat saturation and coronal images without fat saturation are also acquired using a conventional spin echo T1 technique. Lau *et al.* found that the axial precontrast and postcontrast series were the most informative MRI sequences for evaluating primary tumour extension and achieved approximately 100% diagnostic accuracy in T-staging of NPC (Lau *et al.,* 2004). We find that axial and coronal noncontrast T1-weighted images are

Comoretto *et al.,* 2008; Lee, 1992).

or recurrent NPC (Liu *et al.,* 2007).

**5.1 MRI technique** 

calculate dose based on absorption rates (Glastonbury, 2007).

Fig. 1. Axial T2 weighted image shows a mass filling the left fossa of Rosenmuller (\*).

Fig. 2. Axial T2 weighted image shows a right sided NPC that is resulting in right Eustachian tube dysfunction and fluid build up in the right mastoid.

Fig. 1. Axial T2 weighted image shows a mass filling the left fossa of Rosenmuller (\*).

Fig. 2. Axial T2 weighted image shows a right sided NPC that is resulting in right

Eustachian tube dysfunction and fluid build up in the right mastoid.

MRI is also more reliable for differentiating between the primary tumor and retropharyngeal adenopathy (Chang, 2005; Chong, 1996; Chung, 2004; King, 2000). For patients with clinical or biochemical evidence of advanced disease, additional investigations – including bone scintigraphy, chest x-ray, CT of thorax, abdomen, and pelvis, and/or fluorodeoxyglucose (FDG)-positron emission tomography (PET)-CT imaging – may be indicated (Caglar, 2003; Chen *et al.,* 2006; Chiesa & De Paoli, 2001; Chua *et al*., 2009; Comoretto *et al.,* 2008; Lee, 1992).

The mainstay of treatment in NPC is radiation therapy (RT) with the addition of concurrent and/or adjuvant chemotherapy reserved for higher stages of disease. Surgical salvage (nasopharyngectomy) has also been used in cases of recurrent disease (Yu *et al.,* 2010). The goal of treatment is to be curative. To be effective, RT must target the primary lesion as well as any associated neck adenopathy. Thus, cross-sectional imaging, in particular MRI, is needed to determine areas of disease infiltration. NPC has been shown to spread in a stepwise pattern along privileged pathways, such as the neuroforamina (Liang *et al.,* 2009). In addition, involvement of critical structures located near the NP – including the cavernous sinus, pituitary gland, orbit and brainstem – must be evaluated to guide appropriate treatment and to spare these structures of the radiation dose if they are clear of disease (Yu *et al.*, 2010). In the case of intensity-modulated RT (IMRT), CT is also required to correctly calculate dose based on absorption rates (Glastonbury, 2007).

Follow-up evaluation involves a baseline imaging study that is typically performed 2 to 3 months after completion of radiation treatment, followed by imaging every 3 to 6 months for the first 2 post-treatment years (Glastonbury, 2007). Any soft tissue signal abnormalities on MRI in the nasopharynx, deep face, or skull base should remain stable over this period or show further reduction in volume. Recurrent disease is seen as any increase in the bulk of abnormal signal from baseline imaging. Most recurrences, local or systemic, occur within the first 2 years after treatment (Glastonbury, 2007). Of patients with recurrences, 10% to 20% may be curable with additional treatment (Glastonbury, 2007). After 2 years without evidence of recurrence, the imaging interval is typically extended to every 6 to 12 months. Although not yet the mainstay of treatment, one meta-analysis demonstrated that FDG-PET/CT is more sensitive and specific than CT and MRI for the diagnosis of local residual or recurrent NPC (Liu *et al.,* 2007).

#### **5.1 MRI technique**

The staging MRI protocol for NPC varies from center to center. In general, the images should cover the area from above the frontal sinuses to the thoracic inlet on axial studies and from the tip of the nose to the fourth ventricle on coronal sequences. At our institution, axial and coronal T1- and T2-weighted images, as well as a sagittal T1 or T2 fat saturation series covering the entire head and neck are obtained. A head and neck imaging coil is routinely used for both the 1.5T and 3.0T MRI scanners. The axial, coronal and sagittal T1 series are performed using a T1-FLAIR technique. Postgadolinium-enhanced axial images with fat saturation and coronal images without fat saturation are also acquired using a conventional spin echo T1 technique. Lau *et al.* found that the axial precontrast and postcontrast series were the most informative MRI sequences for evaluating primary tumour extension and achieved approximately 100% diagnostic accuracy in T-staging of NPC (Lau *et al.,* 2004). We find that axial and coronal noncontrast T1-weighted images are

Imaging of Nasopharyngeal Carcinoma 101

The nasopharynx is at the superior and posterior aspect of the aerodigestive tract. The nasopharyngeal mucosa is lined with squamous epithelium and surrounded by a muscular and fascial sling consisting of the superior constrictor muscle and the buccopharyngeal fascia derived from the middle layer of the deep cervical fascia. The space has three walls and a roof. It opens anteriorly to the posterior nasal cavity via the posterior nasal choanae, and inferiorly into the oropharynx at the level of the hard palate. On imaging, the C1/2 junction is also an accepted marker between the nasopharynx and oropharynx (Dubrulle *et al*., 2007). The roof of the nasopharynx abuts the sphenoid sinus floor, and slopes posteroinferiorly along the clivus/basiocciput to the upper cervical vertebrae. Remains of adenoid tissue may persist into adulthood and exist as tags in the roof of the nasopharynx. The pharyngobasilar fascia (PBF), a tough aponeurosis connecting the superior constrictor muscles to the skull base, is perhaps the most important structure of the nasopharynx. The tough fibers of the pharyngobasilar fascia create a framework that determines the configuration of the nasopharynx and the support by which the entire pharynx hangs from the skull base (Dillon *et al.*, 1984). The parallel lateral walls of the pharyngobasilar fascia extend from the posterior margin of the medial pterygoid plate anteriorly to the occipital pharyngeal tuber and prevertebral muscles posteriorly. The foramen lacerum, which is

Treatment-related edema, fibrosis, inflammation, and scarring limit ability to diagnose residual or recurrent disease

involvement of the nasopharynx, skull base, intracranial disease, perineural spread,

Inferior to MRI for detecting retropharyngeal lymph node metastases (Ng *et al.*, 2009; Ng *et al*., 2010,

False-positive and falsenegative related to

inflammatory hyperplastic nodes, nodes with large areas of necrosis, small nodes that are beyond the spatial resolution limits of PET (Ng *et al.*, 2009; Zhang

Su *et al.*, 2006)

*et al.,* 2006)

parapharyngeal space, and brain (due to high FDG uptake by the brain) (Comoretto *et al*., 2008; King *et al.*, 2008; Ng *et al.*, 2009)

disease versus posttherapy changes due to treatmentrelated edema, fibrosis, inflammation, and scarring (Comoretto *et* 

*al*., 2008)

**6. Anatomy of the nasopharynx** 

the best for providing detailed views of the local NP anatomy and surrounding structures, whereas postcontrast images allow for accurate assessment of perineural disease along major nerves, such as the maxillary and mandibular divisions of the trigeminal nerve, as well as the cavernous sinus (Yu *et al*., 2010).


#### **5.2 Comparison of imaging methods**

the best for providing detailed views of the local NP anatomy and surrounding structures, whereas postcontrast images allow for accurate assessment of perineural disease along major nerves, such as the maxillary and mandibular divisions of the trigeminal nerve, as

**MRI CT PET/CT** 

Relatively inexpensive Superior to MRI and CT for assessing lymph node metastasis, especially cervical nodal metastases, and distant metastases, especially occult metastatic disease (i.e., N- and Mstaging of NPC) (Comoretto *et al.,* 2008; King & Bhatia, 2010; King *et al*., 2008; Lin *et al*., 2008; Ng *et al.,* 2009, Wang *et al*., 2007)

Screens the entire patient for local recurrence, lymph node metastases and distant metastases during a single whole-body examination using a single injection of

Significantly better sensitivity and specificity compared to CT and MRI for diagnosis of local residual or recurrent nasopharyngealcarcinoma

(Liu *et al.*, 2007)

Exposure to ionizing

regions)

Expensive

radiation

undermaps the

Accessibility issues (in some

Compared to MRI, PET/CT

FDG

Rapid image acquisition time

Widely available

Less accurate than MRI and PET/CT for evaluating tumour invasion into surrounding tissues (Ng *et al*., 2009)

Exposure to ionizing

radiation

well as the cavernous sinus (Yu *et al*., 2010).

PET/CT for assessing primary tumour invasion into

surrounding soft tissue and boney structures, pharyngobasilar fascia invasion, invasion into the sinus of Morgagni, skull base invasion, intracranial invasion, as well as cavernous sinus

extension and

perineural disease (Liao *et al.,* 2008; Ng *et al*., 2009 Sakata *et al.*, 1999)

Superior to CT and PET/CT for evaluating retropharyngeal adenopathy

No exposure to ionizing radiation

Long image acquisition times compared to CT

Less readily available compared to CT not always reliable in distinguishing between enhancing residual

**Weaknesses** Expensive

**5.2 Comparison of imaging methods** 

**Strengths** Superior to CT and


#### **6. Anatomy of the nasopharynx**

The nasopharynx is at the superior and posterior aspect of the aerodigestive tract. The nasopharyngeal mucosa is lined with squamous epithelium and surrounded by a muscular and fascial sling consisting of the superior constrictor muscle and the buccopharyngeal fascia derived from the middle layer of the deep cervical fascia. The space has three walls and a roof. It opens anteriorly to the posterior nasal cavity via the posterior nasal choanae, and inferiorly into the oropharynx at the level of the hard palate. On imaging, the C1/2 junction is also an accepted marker between the nasopharynx and oropharynx (Dubrulle *et al*., 2007). The roof of the nasopharynx abuts the sphenoid sinus floor, and slopes posteroinferiorly along the clivus/basiocciput to the upper cervical vertebrae. Remains of adenoid tissue may persist into adulthood and exist as tags in the roof of the nasopharynx.

The pharyngobasilar fascia (PBF), a tough aponeurosis connecting the superior constrictor muscles to the skull base, is perhaps the most important structure of the nasopharynx. The tough fibers of the pharyngobasilar fascia create a framework that determines the configuration of the nasopharynx and the support by which the entire pharynx hangs from the skull base (Dillon *et al.*, 1984). The parallel lateral walls of the pharyngobasilar fascia extend from the posterior margin of the medial pterygoid plate anteriorly to the occipital pharyngeal tuber and prevertebral muscles posteriorly. The foramen lacerum, which is

Imaging of Nasopharyngeal Carcinoma 103

known as the nodes of Röuviere, are the first nodes in the lymphatic drainage of the nasopharynx and, along with the cervical Level II nodes, are reported to be the most common site of nodal metastases (Wang *et al.,* 2009). The lateral retropharyngeal lymph nodes can be identified on MRI from the skull base to the level of C3 (King & Bhatia, 2010). The medial retropharyngeal nodes do not form a discrete nodal chain, and thus, are less

Fig. 4. Axial T1 image shows the torus tubarius (\*). The solid arrow points to the opening of the Eustachian tube. Dashed arrow is the fossa of Rosenmuller. The dashed area shows the

Other important structures include the foramen rotundum and pterygoid (or Vidian) canal, which communicate with the pterygopalatine fossa and are potential routes of tumour

After the initial diagnosis of NPC is made on history, physical examination, and biopsy, cross-sectional imaging is required for cancer staging. Currently, the 7th edition of the International Union Against Cancer (UICC) and American Joint Committee on Cancer (AJCC) TMN staging system is used, which was recently revised and released on 1 January 2010. As previously described, most cases of NPC originate in the lateral pharyngeal recess and spread submucosally with early infiltration into deeper neck spaces. NPC tends to have

fat in the left prestyloid parapharyngeal space.

spread.

**7. Staging of NPC** 

well-defined patterns of spread.

often visible on imaging.

within the confines of the pharyngobasilar fascia, is a fibrocartilaginous structure that forms part of the floor of the horizontal carotid canal and roof of the nasopharynx. It provides a route for nasopharyngeal tumors to access the cavernous sinus and intracranial cavity. The pharyngobasilar fascia is a fibrous structure and occasionally can be seen as a thin dark line on T2-weighted axial MR images, deep to the submucosal tissues of the nasopharynx (**Figure 3**).

Fig. 3. Axial T2 weighted image at the level of the nasopharynx. The arrow shows the pharyngobasilar fascia on the left side.

The paired Eustachian tubes, along with the medial fibers of the levator veli palatini muscle pass into the nasopharynx via the sinus of Morgagni, a posterolateral defect in the pharyngobasilar fascia. The opening of the Eustachian tube is anterior (on axial images) and inferior (on coronal images) to the torus tubarius, the distal cartilaginous end of the eustachian tube that forms a mucosal-lined structure projecting into the lumen of the nasopharynx from the superior aspect of the posterior lateral nasopharyngeal walls. The fossa of Rosenmüller, otherwise known as the lateral pharyngeal recess, is posterior (on axial images) and superior (on coronal images) to the torus tubarius. The fossa of Rosenmüller is the most common site of origin of NPC (Goh & Lim, 2009) (**Figure 4**). However, asymmetry of the lateral pharyngeal recesses is a common and normal incidental finding, and should not be mistaken as tumours.

Lateral to the nasopharynx is the parapharyngeal space (PPS), a fibrofatty space which separates the nasopharynx from the masticator space (**Figure 4).** Involvement of the parapharyngeal fat serves as an important marker of tumour infiltration used in staging. The posterolateral boundary of the nasopharynx consists of the carotid space (post-styloid parapharyngeal space), which is located posterior to the parapharyngeal space. Located posterior to the nasopharynx, between the nasopharyngeal mucosal space and the prevertebral muscles, is the retropharyngeal space, a potential space that contains the medial and lateral retropharyngeal lymph nodes. The lateral retropharyngeal nodes, also

within the confines of the pharyngobasilar fascia, is a fibrocartilaginous structure that forms part of the floor of the horizontal carotid canal and roof of the nasopharynx. It provides a route for nasopharyngeal tumors to access the cavernous sinus and intracranial cavity. The pharyngobasilar fascia is a fibrous structure and occasionally can be seen as a thin dark line on T2-weighted axial MR images, deep to the submucosal tissues of the nasopharynx

Fig. 3. Axial T2 weighted image at the level of the nasopharynx. The arrow shows the

The paired Eustachian tubes, along with the medial fibers of the levator veli palatini muscle pass into the nasopharynx via the sinus of Morgagni, a posterolateral defect in the pharyngobasilar fascia. The opening of the Eustachian tube is anterior (on axial images) and inferior (on coronal images) to the torus tubarius, the distal cartilaginous end of the eustachian tube that forms a mucosal-lined structure projecting into the lumen of the nasopharynx from the superior aspect of the posterior lateral nasopharyngeal walls. The fossa of Rosenmüller, otherwise known as the lateral pharyngeal recess, is posterior (on axial images) and superior (on coronal images) to the torus tubarius. The fossa of Rosenmüller is the most common site of origin of NPC (Goh & Lim, 2009) (**Figure 4**). However, asymmetry of the lateral pharyngeal recesses is a common and normal incidental

Lateral to the nasopharynx is the parapharyngeal space (PPS), a fibrofatty space which separates the nasopharynx from the masticator space (**Figure 4).** Involvement of the parapharyngeal fat serves as an important marker of tumour infiltration used in staging. The posterolateral boundary of the nasopharynx consists of the carotid space (post-styloid parapharyngeal space), which is located posterior to the parapharyngeal space. Located posterior to the nasopharynx, between the nasopharyngeal mucosal space and the prevertebral muscles, is the retropharyngeal space, a potential space that contains the medial and lateral retropharyngeal lymph nodes. The lateral retropharyngeal nodes, also

pharyngobasilar fascia on the left side.

finding, and should not be mistaken as tumours.

(**Figure 3**).

known as the nodes of Röuviere, are the first nodes in the lymphatic drainage of the nasopharynx and, along with the cervical Level II nodes, are reported to be the most common site of nodal metastases (Wang *et al.,* 2009). The lateral retropharyngeal lymph nodes can be identified on MRI from the skull base to the level of C3 (King & Bhatia, 2010). The medial retropharyngeal nodes do not form a discrete nodal chain, and thus, are less often visible on imaging.

Fig. 4. Axial T1 image shows the torus tubarius (\*). The solid arrow points to the opening of the Eustachian tube. Dashed arrow is the fossa of Rosenmuller. The dashed area shows the fat in the left prestyloid parapharyngeal space.

Other important structures include the foramen rotundum and pterygoid (or Vidian) canal, which communicate with the pterygopalatine fossa and are potential routes of tumour spread.
