Nasopharyngeal carcinoma overview
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Differentiating Nasopharyngeal carcinoma from other Diseases |
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Diagnosis |
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Editor-In-Chief: C. Michael Gibson, M.S., M.D. [1] Associate Editor(s)-in-Chief: Homa Najafi, M.D.[2]Faizan Sheraz, M.D. [3]
Overview
Nasopharyngeal carcinoma (NPC) is a cancer originating in the nasopharynx (the uppermost region of the pharynx), where the nasal passages and auditory tubes join the remainder of the upper respiratory tract. On microscopic histopathological analysis, abundant dense eosinophilic cytoplasm and prominent lymphoid component are characteristic findings of nasopharyngeal carcinoma. Nasopharyngeal carcinoma differs significantly from other cancers of the head and neck in occurrence, causes, clinical behavior, and treatment. Common risk factors in the development of nasopharyngeal carcinoma are Chinese (or Asian) ancestry, Epstein-Barr virus (EBV) exposure, and heavy alcohol intake. Nasopharyngeal carcinoma must be differentiated from normal adenoidal tissue, nasopharyngeal lymphoma and chordoma. It is vastly more common in certain regions of East Asia and Africa than elsewhere, with viral, dietary, and genetic factors implicated in its causation. The prevalence of nasopharyngeal carcinoma is approximately 1 per 100,000 individuals in the USA. Patients of all age groups may develop nasopharyngeal carcinoma. If left untreated nasopharyngeal carcinoma produces few symptoms early in the course of disease. Once the tumor has expanded from its site of origin in the lateral wall of the nasopharynx, it may obstruct the nasal passages and cause nasal discharge or epistaxis. Non-keratinizing nasopharyngeal carcinoma is associated with a 5 year survival rate of 65%. The common complications of nasopharyngeal carcinoma include airway obstruction, dysphagia, and disfigurement of the neck or face. Head and neck MRI may be helpful in the diagnosis of nasopharyngeal carcinoma. The mainstay of therapy for nasopharyngeal carcinoma is external beam radiotherapy. Surgery is not the first-line treatment option for patients with nasopharyngeal carcinoma.
Historical Perspective
The association between EBV and nasopharyngeal carcinoma was made in1970. In 1970, Zur Hausen and et al, were the first to extract EBV DNA from NPC tumors by using DNA hybridization method. In 1970, Henle and et al, revealed the link between stage of NPC tumors and EBV antibody titer. In 1973, Wolf and et al, found EBV DNA in NPC tumor cells by in situ hybridization methods but not in infiltrating lymphoid cells. Babe Ruth, a famous baseball player suffered from nasopharyngeal cancer.
Classification
World health organization classified nasopharyngeal carcinoma into 3 types keratinizing, nonkeratinizing (differentiated, undifferentiated) and basaloid squamous cell carcinoma.
Pathophysiology
On microscopic histopathological analysis, abundant dense eosinophilic cytoplasm and prominent lymphoid component are characteristic findings of nasopharyngeal carcinoma.
Causes
Common causes of nasopharyngeal carcinoma include Epstein Barr virus (EBV infection), Human Papillomavirus (HPV infection), and consumption of salted fish as a source of N-nitrosamine.
Differentiating Nasopharyngeal carcinoma from other Diseases
Nasopharyngeal carcinoma must be differentiated from other congenital abnormalities, inflammatory, and malignant lesions of neck.
Epidemiology and Demographics
The incidence of nasopharyngeal carcinoma is different based on the geographic areas. The incidence in the USA is low, in Alaska and Greenland is moderate and the highest incidenceis seen in southeast Asia, North Africa, southern China and middle east. The incidence of this disease increases with increasing age in low- risk population. However, in high-risk populations, the maximum incidence is seen in individuals around ages 50 to 59 and then the incidence decreases by increasing age. Nasopharyngeal carcinoma usually affects individuals of the Asian race, and is more commonly affected by male than female. The majority of nasopharyngeal carcinoma cases are reported in southern China, Southeast Asia, North Africa and also is more seen in Inuit Indians.
Risk Factors
Common risk factors in the development of nasopharyngeal carcinoma include the family history of cancer, smoking, some disease in ear, nose, and throat, inadequate consumption of fresh fruits and vegetables, heavily alcohol consuming, herbal products and exposure to wood dust.
Screening
Screening for nasopharyngeal carcinoma only is done in endemic areas. Different methods, such as measurement the titre of different types of antibodies against EBV and plasma EBV DNA, and endoscopic examination of nasopharynx can be used for screening.
Natural History, Complications and Prognosis
If left untreated nasopharyngeal carcinoma produces few symptoms early in the course of the disease. Non-keratinizing nasopharyngeal carcinoma is associated with a 5 year survival rate of 65%. The common complications of nasopharyngeal carcinoma's treatment include radiation necrosis of the temporal lobes, cranial nerve palsies, encephalomyelopathy, atrophy and fibrosis of the muscles of mastication, atrophy of salivary glands, hearing loss, and osteoradionecrosis.
Diagnosis
Diagnostic Study of Choice
The staging of nasopharyngeal carcinoma is based on the TNM staging system.
History and Symptoms
Symptoms of nasopharyngeal carcinoma based on the place of involvement are different. Most symptoms are related to existence of mass in nasopharynx, latero-posterior invasion of the tumor to the nasopharyngeal space and dysfunction of eustachian tube, involvement of skull base accompanied by damaging of the 5th and 6th cranial nerves, and neck mass. Most common symptoms are neck mass, nasal symptoms, ear symptoms and headache.
Physical Examination
Patients with nasopharyngeal carcinoma usually appear normal. Physical examination of patients with nasopharyngeal carcinoma is usually remarkable for neck swelling, neck lymphadenopathy, decrease facial sensation, hearing loss and nasal obstruction.
Laboratory Findings
Laboratory findings consistent with the diagnosis of nasopharyngeal carcinoma include an elevated concentration of serum EBV titer. Plasma EBV DNA load, EBV viral capsid antigen, assessment of EBV in the pathologic specimens, Complete blood count, Urea and creatinine, electrolytes, Liver function tests, Calcium and phosphate, and Alkaline phosphatase are the tests which should be done for the diagnosis and assessment of tumor invasion, and differentiation of tumor.
Electrocardiogram
There are no ECG findings associated with nasopharyngeal carcinoma.
X-ray
There are no x-ray findings associated with nasopharyngeal carcinoma. However, it may be helpful for the assessment of metastasis in the chest.
Echocardiography and Ultrasound
There are no ultrasound findings associated with nasopharyngeal carcinoma. However, ultrasonography may be helpful in the assessment of cervical lymph nodes and liver for metastasisevaluation.
CT
CT scan may be helpful in the diagnosis of nasopharyngeal carcinoma and it's metastasis to the lymph nodes, intracranial space, bone, chest, and liver. Findings on CT scan suggestive of nasopharyngeal carcinoma include soft tissue masses which most commonly centred at the lateral nasopharyngeal recess (fossa of Rosenmüller) and heterogeneous enhancement of the tumor in the CT scan with contrast.
MRI
Head and neck MRI may be helpful in the diagnosis of nasopharyngeal carcinoma. It is especially used for the assessment of tumor invasion in the skull base, parapharyngeal spcae, paranasal sinus, middle ear and cervical lymph nodes.
Other Imaging Findings
Positron emission tomography (PET) scan may be helpful in the diagnosis of nasopharyngeal carcinoma. It is useful in the detection of residual or recurrent tumor after treatment and distant metastasis, prediction of clinical cancer outcome and PET/CT scan is used for NPC staging.
Other Diagnostic Studies
Nasopharyngoscopy may be helpful in the diagnosis of nasopharyngeal carcinoma. It is used for assessment of tumor extension, determination of mucosal surface involvement and biopsy of the primary tumor.
Fine needle aspiration (FNA) for biopsy and histopathological analysis is used for diagnosis of nasopharyngeal carcinoma.
Treatment
Medical Therapy
The mainstay of therapy for nasopharyngeal carcinoma is external beam radiotherapy, supplemented in some cases with chemotherapy. Chemotherapy drugs that are used in treatment of nasopharyngeal carcinoma are vast, but the two ones which are used more include Cisplatin and 5-Fluorouracil.
Interventions
The mainstay of treatment for early stages of nasopharyngeal carcinoma is radiotherapy. For the patients in early stages, radiotherapy is used solely most of the time, and in patients with higher stages,it is used in combination with chemotherapy.
Surgery
Surgery is not the first-line treatment option for patients with nasopharyngeal carcinoma.It is used for resistant and locally recurrent types. The methods can be divided into open and minimally invasive nasopharyngectomy.
Primary Prevention
There are no established measures for the primary prevention of nasopharyngeal carcinoma. Although smoking and alcohol cessation may be effective.
Secondary Prevention
Secondary prevention measures of nasopharyneal cancer include routine physical examination and imaging at scheduled intervals after treatment. Dental screening and screening for thyroid cancers are recommended among patients who had received radiation therapy to the oral cavity and cervical region, respectively.