Snapshot A 58-year-old Asian man presents to the clinic with complaints of a painless mass at his right neck. He noticed it about 2 months ago and denies any recent illness, fever, weight changes, or pain at the site. The patient immigrated from Hong Kong 2 years ago. A physical examination was largely unmarkable except for a poorly demarcated, fixed cervical lymph node at the right. Introduction Overview squamous cell cancer of the nasopharynx, which extends from the base of the skull to the upper surface of the soft palate significantly differs from other head and neck cancers in epidemiology, histology, natural history, and treatment Epidemiology incidence marked geographic variation rare in United States, incidence of 1/100000 in U.S. and Western Europe demographics endemic in Southern China, including Hong Kong other common regions include Southeast Asia, North Africa, and Middle East male: female ratio of 2-3: 1 peak incidence in 4th and 6th decades of life risk factors Epstein-Barr virus (EBV) infection diet (food containing volatile nitrosamine) salt-cured food fermented/preserved foods smoking alcohol genetic predisposition human papillomavirus (HPV) Pathogenesis three key etiological factors: environmental (chemical carcinogens), genetic susceptibility, and EBV infection likely multi-factorial as the majority of people who have EBV infections do not have nasopharyngeal carcinoma most common site at the lateral wall of the nasopharynx, followed by superior posterior wall Associated conditions EBV infection Prognosis tumor stage is the most important prognostic factor high plasma/serum EBV DNA associated with advanced stage and active disease Presentation Symptoms headache diplopia facial numbness recurrent otitis media nasal obstruction with epistaxis may remain asymptomatic for prolonged period Physical exam non-tender neck mass indicates cervical node metastasis Imaging Computed tomography (CT) indications best initial imaging test to evaluate for primary tumors at the nasopharynx, skull base, and neck allows for greater spatial resolution with faster acquisition time compared to MRI Magnetic resonance imaging (MRI) indications preferred for assessing extent of disease and intracranial extension specific cranial nerve imaging allows for evaluation of cranial nerve involvement Positron emission tomography (PET) or Flurodexyflucose (FDG) indications preferred modality in evaluating patients with clinical evidence of distant metastasis, advanced nodal disease, or an EBV DNA load of > 4000 copies/mL PET has superior ability to detect lymph node and bone metastasis compared to FDG Studies Labs serum EBV DNA level pretrement plasma levels are used as part of the diagnostic and staging evaluation prognostic indicators and associated with survival outcomes Invasive studies nasal endoscopy with biopsy confirmatory diagnosis with direct visualization histology gross anatomy varies: raised nodule with/without ulceration, smooth mucosal bulge, or infiltrative mass lesion histology interconnecting cords or trabeculae with little or no keratinization variable lymphoplasmacytic infiltrate in background Differential Lymphoma distinguishing factors will have distinct histologic appearance based on the type of lymphoma Treatment Non-operative radiation therapy mainstay treatment can be the used as single-modality treatment for small tumors includes both external (external beam radiation) and internal (brachytherapy) brachytherapy sometimes used in recurrent nasopharyngeal carcinoma chemotherapy chemoradiation therapy often difficult to tolerate due to side effects (e.g., severe sores) adjuvant therapy Operative not a widely used treatment for nasopharyngeal carcinoma radical neck dissection indicated in nodal disease Complications Regional and distal metastasis Death