**1. Introduction**

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

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#### **1.1 Imaging of nasopharyngeal carcinoma**

Nasopharyngeal carcinoma (NPC) is the most common neoplasm to affect the nasopharynx (NP). Arising from the epithelial lining of the nasopharyngeal mucosa, NPC is distinct from squamous cell carcinoma affecting other sites of the pharyngeal space. NPC typically originates in the lateral wall of the nasopharynx and is noted as a locally aggressive neoplasm with a high incidence of metastases to cervical lymph nodes. The primary tumour can extend within the nasopharynx and/or to the base of the skull, palate, nasal cavity or oropharynx. Distant metastases can arise in bone, lung, mediastinum, and, more rarely, the liver (Brennan, 2006).

The etiology of NPC is multifactorial and involves many environmental and genetic risk factors (Henderson *et al.*, 1976). In particular, diets high in salt-preserved foods – such as salted fish, meat, eggs, fruits and vegetables in the Southern Asian diet – have been identified as possible causative factors acting through the carcinogen, *N*nitrosodimethylamine (Yu *et al.*, 1988). In contrast, frequent consumption of fresh fruits and/or vegetables – especially during childhood – is associated with a lower risk of NPC. In addition, studies have indicated a causal role for the Epstein-Barr virus (EBV) in the development of NPC (Chang & Adami, 2006). EBV is a DNA virus responsible for infectious mononucleosis, post-transplantation lymphoproliferative disease, and Burkitt's lymphoma. Elevated IgG and IgA antibody titres against viral capsid antigen, early antigen, and latent viral nuclear antigens have been noted in NPC patients. Furthermore, these antibodies have been shown to precede tumour development by several years. EBV DNA, RNA, and gene products have also been detected in tumour cells (Chang & Adami, 2006). EBV serology is currently used as a screening tool for high-risk populations in southern China (Glastonbury, 2007). Certain genetic haplotypes – HLA A2, Bsn 2, B46, and B58 – are also associated with

Imaging of Nasopharyngeal Carcinoma 97

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

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

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).

**4. Presentation of NPC** 

widespread disease.

opacification.

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

increased risk (Ren & Chan, 1996). Other exposures implicated in NPC include cigarette smoking, other smoke, and occupational exposures including wood dust and industrial heat (Yu *et al*., 2010).
