Nasopharyngeal carcinoma C11.9

Nasopharyngeal carcinoma (NPC) originates from the epithelial cells of the nasopharynx. The tumour expands and grows first inside and later also outside the nasopharyngeal cavity. It reaches the side wall and/or grows towards the base of the skull, palate, nasal cavity and oropharynx. A metastasis typically occurs lymphogenically in the cervical lymph nodes. Enlargement of the cervical lymph nodes is often the first clinical symptom of the tumor disease.

According to the WHO classification 3 subtypes are distinguished:

• WHO type I (frequency of 20%) squamous cell carcinoma, typical in older adults,
• WHO type II (frequency from 30 to 40%) non-keratinising carcinoma
• WHO type III (frequency of 40 to 50%) undifferentiated carcinoma. This is the so-called lymphoepithelial carcinoma (Schmincke-Regaud tumour), which is probably caused or at least promoted by the Epstein-Barr virus.

Prevalence: 1-9 / 100 000; in Central Europe and North America the incidence is < 1/ 100 000 inhabitants. The incidence in South East Asia is 35 new cases/100,000 inhabitants per year. Against those with higher incidence were found in China and Tunisia. In Taiwan this disease is the main cause of death in men.

Multifactorial causes are assumed for the development of nasopharyngeal carcinoma. The following etiological factors are important:

• Genetics: It is assumed that different HLA haplotypes play a role, e.g. A2, B46 and B17 (Tsao SW et al. 2017).
• Environmental factors such as cured fish (nitrosamines), alcohol, cigarette smoke, dust and formaldehyde, herbal teas containing phorbol (phorbol is a tetracyclic diterpene and chemically similar to other toxins of the spurge family such as ingenolmebutate and the daphne family such as daphnetoxin and mezereum), tobacco smoke.
• Viruses: Ebstein-Barr virus, which is particularly strongly associated with the non-cornifying, undifferentiated type, and the human papilloma virus, which occurs in the keratinizing type. The association of NPC and HHV4 results from the detection of EBV DNA in the "lympho-epithelial type" and that malignant epithelial cells express viral antigens. Another reason for the frequent occurrence of the disease in Southeast Asia seems to be the chewing of the betel nut (Jeng J et al. 2001).
• In North Africa children are particularly affected. The cause is not yet clear.

m: w= 4-7:1; Frequency: 45-75 years of age

The following symptoms have been observed in the diagnosis of nasopharyngeal carcinoma: neck swelling (76%), nasal dysfunction (73%), aural dysfunction (62%), headache (35%) (Halperin EC et al. 2013).

Symptoms derived from the primary tumour are:

• Trismus
• Pain
• otitis media
• Nasal regurgitation through paralysis of the soft palate,
• hearing loss and cranial nerve palsy.

Larger tumour masses can lead to blockage of the nasal passages, bleeding and nasal speech. In contrast, hematogenic metastasis is relatively rare.

Metastasis: Haematogenic metastasis is rather rare at the time of diagnosis (3-6%), but increases to 18-50% in the advanced stages of the disease. Bone metastases are more common than liver and lung metastases, although the latter have a better prognosis. Brain and skin metastases rarely occur. The more pronounced the lymph node involvement, the higher the risk of distant metastases.

In serum, viral capsid antigen and DNA of Epstein-Barr virus (EBV) can be detected.

Panendoscopy provides information about the superficial tumor spread in the nasopharynx and the adjacent mucous membranes, but cannot provide information about the deep invasion into the surrounding tissue. Therefore further imaging is indicated. Clinical assessment of the size of the cervical lymph nodes; biopsy of primary tumor and, if necessary, of lymph nodes.

Other possible metastasis sites are detected by neurological examination of the cranial nerves. Furthermore computer tomography and/or magnetic resonance imaging (MRI) of the skull and neck.

Radiotherapy: The treatment of choice for nasopharyngeal carcinoma is radiotherapy (about 70 Gy spread over several sessions). Acute side effects of radiotherapy include mucositits, dermatitis and late complications such as xerostomia, fibrosis (e.g. in the subcutaneous area, temporomandibular joint or larynx) and recurrent otitis media are usually due to the high radiation dose required for adequate tumour control.

Radiotherapy responds very well in the case of non-cornifying and undifferentiated subtypes of nasopharyngeal carcinoma, whereas this is less the case in the cornifying subtype.

Although nasopharyngeal carcinoma is counted among the tumours sensitive to chemotherapy, chemotherapy is currently only "standard therapy" for advanced carcinoma (stage III, IV). The therapy of choice is concomitant chemotherapy, an additional adjuvant or neoadjuvant therapy is possible.

In this case, cisplatin with a dosage of 100mg/m2 is usually used and administered on days 1, 22 and 43 during radiation.

If adjuvant chemotherapy follows, this is usually carried out with cisplatin (100 mg/m2) on day 1 and 5-FU (1000 mg/m2/day) on days 1-4 in 3 cycles every 4 weeks. If ototoxicity occurs during the course of therapy, cisplatin can be replaced by carboplatin.

Alternative: immunotherapeutic use of PD-1 inhibitors (Lam WKJ et al. 2018), if necessary in combination with steel therapy (Yeo ELL et al. 2018)

Prognosis depends on the stage of the tumour. For patients with stage I tumors, the prognosis is between 70 and 80 %; for type III (Schmincke-Regaud tumor), healing rates of > 90 % can be achieved if detected early.

In clinical stage IV the healing rate decreases to 20 to 40 %.

Due to the high radiation sensitivity of the malignant tissue, even if the disease has already established itself in regional lymph nodes, the chances of cure are good. However, the prognosis is significantly worse in the case of cornified nasopharyngeal cancer, as this form is much less radiation-sensitive. In children, metastasis in the cervical lymph nodes at the time of diagnosis does not affect the prognosis.

Originally, the term "lymphoepithelioma" was defined by A. Schmincke and later J. Ewing as a combined clinical and histomorphological tumor entity of the lymphoepithelial organs.

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