Nasopharyngeal carcinoma (NPC) is a malignant tumor arising from the mucosal epithelium of the nasopharynx, and the incidence of nasopharyngeal carcinoma in China ranks first in the world. The location of nasopharynx is located at the back of the nasal cavity, which is deep and hidden (Figure 1). Compared with other malignant tumors of the head and neck, nasopharyngeal cancer often occurs in relatively young people, mostly between 30 and 50 years old, and more men than women.
The location of normal nasopharynx and mucous membrane under endoscopy
What are the factors related to the occurrence of nasopharyngeal cancer?
EpsteinBarr (EB) virus infection: EB virus is a kind of herpes virus, which has special affinity with human upper respiratory tract lymphocytes, and EBV-encoded RNA (EBER) can be found in the nucleus of nasopharyngeal cancer cells. VCA), membrane antigens (MA), and nuclear antigens (NA). Therefore, joint detection of EBV EA-IgA and VCA-IgA antibodies can be used as serological markers for screening and diagnosis of nasopharyngeal carcinoma.
2.Genetic factors: There are racial and family clusters of nasopharyngeal cancer patients, which may be related to family members carrying certain nasopharyngeal cancer susceptibility genes (it is still unclear what exactly they are).
3.Environmental and dietary factors: Consumption of salted fish and pickled food is a high-risk factor for nasopharyngeal cancer in southern China, and it is related to the age of eating salted fish, the duration and frequency of consumption and the cooking method. This is related to the high concentration of nitrosamine compounds in salted fish and pickled products. Environmental factors are also a cause of nasopharyngeal cancer. It has been reported that among Chinese Americans, the second generation born in the United States has a lower risk of developing nasopharyngeal cancer than the first generation born in Asia, while Caucasians born in California in Southeast Asia have a higher risk of developing nasopharyngeal cancer than those born in the United States.
What are the clinical symptoms of nasopharyngeal cancer?
1.Nasal bleeding and aspiration of blood: Mostly in the morning after waking up, blood discharge will be sucked out from the mouth, and as the disease progresses, blood snot will appear.
2. Enlarged lymph nodes in the neck: Most patients with nasopharyngeal carcinoma will have neck masses (enlarged lymph nodes) when they visit the hospital, and most of them have no other symptoms but come to the hospital with neck masses and are diagnosed with nasopharyngeal carcinoma after examination. The enlarged lymph nodes may be painless or slightly painful, and they are mostly fixed and cannot be pushed.
3.Tinnitus, ear blockage, hearing loss and other symptoms of secretory otitis media.
4.Nasal congestion: caused by the tumor blocking the posterior nostril, starting from one side, and in severe cases, both sides are blocked.
5.Headache: caused when the tumor destroys the skull base or spreads intracranially and involves the nerves, the pain is partial to the temporal top of the affected side.
6. Advanced tumor may show symptoms such as difficulty in opening mouth, tongue extension and obliquity, vision loss, protruding eyes, diplopia and hoarseness.
Screening means of nasopharyngeal cancer
Currently, the widely used clinical screening method for nasopharyngeal carcinoma is EBV serological test, which is an immunoenzymatic method to detect VCA-IgA and EA-IgA antibody titers of EBV. The former is more sensitive and less accurate, while the latter is the opposite. Therefore, simultaneous testing of both antibodies is recommended for suspected nasopharyngeal carcinoma, which is helpful for early diagnosis. For cases with VCA-IgA titer ≥ 1:40 and/or EA-IgA titer ≥ 1:5, they belong to the high-risk group for nasopharyngeal cancer, and further examination of the nasopharynx should be performed to clarify whether there are suspicious lesions in the nasopharynx.
Misconceptions about EBV
Nowadays, many medical check-up reports contain the results of serum EBV tests. When the check-up patients find that their EBV serological indexes are elevated, they are immediately “creeped out and alarmed” when they check online that there is a close relationship between EBV and nasopharyngeal cancer. EBVs are related to nasopharyngeal cancer, but not necessarily to nasopharyngeal cancer, because EBVs are relatively common influenza viruses (herpes viruses) that are most often found in colds and when resistance to EBVs decreases, resulting in increased EBV antibody serology. The relationship between EBV infection and nasopharyngeal cancer is far from clear.
However, the presence of one of the following three conditions should be taken seriously and considered as a high-risk target for nasopharyngeal carcinoma.
(1) A more pronounced elevated VCA-lgA titer, such as greater than 1:40.
(2) Those who are positive for both VCA-IgA and EA-IgA antibodies.
(3) Persistent elevation in either of the two indicators, VCA-IgA and EA-IgA, was seen after several months of continuous monitoring.
What is the next step to be taken to rule out nasopharyngeal carcinoma after being defined as a high-risk patient in this situation?
(1) Electronic nasopharyngoscopy: It can best reflect the condition of nasopharyngeal mucosa, and is the most effective means to detect early nasopharyngeal cancer.
(2) MRI: MRI is significantly better than CT in the observation of nasopharynx, which can observe whether the mucosa of nasopharynx is thickened, whether the nasopharynx is symmetrical on both sides, and whether the regional lymph nodes are enlarged.
(3) Neck ultrasound: The purpose of neck ultrasound examination is to clarify whether there is enlargement or metastasis of lymph nodes in the neck, because nasopharyngeal cancer can have metastasis of lymph nodes in the neck at an early stage, so the situation of the neck has an important reference value in determining whether it is nasopharyngeal cancer.
Diagnostic means of nasopharyngeal carcinoma
In clinical practice, we often encounter patients who come to the clinic with symptoms such as nasal bleeding, retractable blood, tinnitus, ear blockage, hearing loss and nasal congestion, asking whether they have nasopharyngeal cancer. It is true that these are some symptoms that often appear in nasopharyngeal cancer, but the appearance of these symptoms does not necessarily mean nasopharyngeal cancer, which may be related to the nasopharynx. Because of the special location of nasopharynx and the closest relationship with nasal cavity and ear, the local inflammation and other manifestations of nasopharynx will also lead to related symptoms.
How to diagnose nasopharyngeal cancer? There are mainly the following methods.
(1) MRI: MRI is significantly better than CT in the observation of nasopharynx, which can observe whether the mucous membrane of nasopharynx is thickened, whether the nasopharynx is symmetrical on both sides, and whether there is enlargement of regional lymph nodes.
(2) Electronic nasopharyngoscopy: It is a commonly used examination for the diagnosis of nasopharyngeal cancer and can best reflect the condition of nasopharyngeal mucosa.
(3) Neck ultrasound: The purpose of neck ultrasound examination is to clarify whether there is enlargement or metastasis of lymph nodes in the neck.
Difficulties in the Differential Diagnosis of Nasopharyngeal Carcinoma
It is easier to diagnose typical nasopharyngeal carcinoma clinically, but for some patients with suspected nasopharyngeal carcinoma that are not, it is necessary to fully analyze the patient’s condition and examination results before making a diagnosis. For example, we often encounter patients with obvious symptoms, such as nasal congestion, tinnitus, hearing loss, and aspiration of blood; imaging examinations (CT or MRI) reveal obvious thickening of mucous membrane in the nasopharynx and suspected masses; nasopharyngoscopy reveals thickening and elevation of mucous membrane in the nasopharynx, and basic disappearance of the left and right pharyngeal fossa; EBV examination reveals elevated antibody titers. All the evidence and manifestations point directly to nasopharyngeal cancer, and patients may go to many hospitals for treatment, but no diagnosis can be confirmed. How to differentiate between inflammatory hyperplasia and nasopharyngeal cancer? My personal experience is as follows.
(1) First of all, observe whether there are enlarged or metastatic lymph nodes in the neck. It is best to have a clear ultrasound examination of the neck, which is not accurate by hand. If there are suspicious metastatic enlarged lymph nodes in the neck, it is highly suspected to be nasopharyngeal carcinoma, and the pathological nature must be clarified through nasopharyngoscopic biopsy at the same location as the enlarged lymph nodes in the nasopharynx. Because more than 80% of nasopharyngeal carcinoma will have metastatic enlarged lymph nodes, nasopharyngeal carcinoma without metastasis in the neck is very rare in clinical practice, so this is the key clinical information to be referred to in the diagnosis of nasopharyngeal cancer.
(2) Use new endoscopic techniques to assist in observing whether there are imaging features of nasopharyngeal carcinoma. Currently, I use narrow band imaging (NBI) endoscopy to observe whether there are twisted serpentine/earthworm-shaped tan microvessels in the mucosa of the nasopharynx (Figure 2). The presence of such typical features is basically certain to be nasopharyngeal carcinoma and helps to detect some early and occult nasopharyngeal carcinoma.
If the nasopharyngeal manifestation is progressing or severe, it is necessary to take biopsy again to clarify the nature and further exclude whether it is nasopharyngeal cancer.
(4) EBV testing is not very useful in detecting nasopharyngeal cancer, but it can be monitored dynamically.