NPC is one of the most common epithelial malignancies of the head and neck in southern China and it also has a high morbidity rate in some Southeast Asia countries, where the incidence of this disease is 20-30 per 100 000 (1, 2). Nasopharyngeal region is rich in lymphatic plexus and the epithelium is commonly infiltrated by many small lymphoid cells. Lymphoid metastases are found in almost 90% of patients at diagnosis (3, 4). Radiotherapy has proved to be the most effective therapeutic approach, nevertheless, chemotherapy is also needed in advanced disease (5, 6). This article deals with a patient with dysphagia and limitation of neck movement resulting from a huge cervical metastasis of NPC. We describe this case in details regarding clinical presentation, histology, medical imaging and therapeutic regimen.
In March 2011, a 23-year-old Chinese man with severe malnutrition was admitted to the Department of Oral and Maxillofacial Surgery Sun Yat-sen Memorial Hospital of Sun Yat-sen University, Guangzhou, China. He had a 19-month and 16-month history of progressively enlarging mass in the left neck and right neck, respectively. The cervical mass had undergone a rapid increase in size and firmness over the previous 1.5 months and was accompanied by presence of dysphagia and limitation of neck movement but no symptoms of headache, dyspnea, nasal occlusion or blood-stained nasal discharge.
On physical examination,a firm, fixed, non-tender, and lobulated tumor was palpable in left cervical levels II, III, which was measured 15×10×7 cm with non-defined boundary. Meanwhile, physical examination revealed the other hard tumor on the right cervical level II which was measured 7×6×6 cm (Figures 1A and B). There was a slight flushing of the skin in the cervical region but no papules were found and there were no phanerous lesions in the oral cavity, parotid glands and submaxillary glands.
The usual pre-operative work-up was implemented. Computerized tomography (CT) of the head and neck showed thickening of the soft tissue in posterior nasopharynx and enlarging nodes in the left parapharyngeal space. In two sides of the neck, multiple cystic lesions were found; most of them were 14×10 cm in size (Figures 2A and B). The CT scans of the chest, abdomen, and pelvis found no evidence of primary malignancy or metastatic disease. Therefore, NPC as the initial diagnosis was considered. Then, pharyngorhinoscopy was applied and showed neoplasm in the nasopharynx, while biopsy revealed undifferentiated non-keratinizing carcinoma (Figure 4A). For blood test, moderate anemia was found and no infectious disease was detected, such as HIV.
To relieve symptoms, a selective neck dissection was performed on the neck bilaterally. In the left neck, dissection included levels I, II, III and IV, while the sternocleidomastoid (SCM) muscle and internal jugular vein was sacrificed because of tumor infiltration (Figure 3). Meanwhile, lympho adipose tissue and cervical mass of levels I, II and III were dissected away in the right neck. Subsequently, histopathological examination of bilateral cervical mass revealed undifferentiated non-keratinizing carcinoma (Figure 4B), which was later proven CKs, CK5/6, P63, Epstein–Barr virus-encoded RNA in situ hybridization (EBER ISH) positive (Figures 4C, D, E and F), thus supporting NPC cervical lymph node metastasis. The final diagnosis of this case was nasopharyngeal non-keratinizing carcinoma pT3N2M0 according to the 2002 American Joint Committee on Cancer (AJCC) staging system.7 The patient then underwent concurrent chemo radiotherapy during a two-month period. The CT-based three-dimensional radiotherapy was given with a total dose of 66 Gy delivered to the primary tumor and 60 Gy to bilateral neck metastatic areas, while concurrently a 40 mg/m2 dose of cisplatinum was administered weekly.
There was no evidence of persistent malignancy in primary tumor or any recurrence in cervical areas, one month after completion of the definitive treatment. The patient was in good condition at the time of the last follow up in December 2016 and was living a normal life.
The majority (75–90%) of newly diagnosed NPC patients have loco-regionally advanced disease, commonly with nodal metastases (1). Retropharyngeal nodes are the first echelons of nodal metastases for NPC while internal jugular nodes are the most frequently involved non-retropharyngeal nodes (72%), (3, 7). Superior deep cervical lymph nodes are the most common area of involvement, with directed spread reaching or occasionally jumping to the supraclavicular region. In a study of 101 patients, Ng et al. reported that the incidence of level II, III and IV cervical lymph node metastases was 95.5%, 60.7% and 34.8%, respectively (8). In a study of 104 cases, Chow et al. reported that the largest size of metastatic cervical lymph nodes of NPC was 10cm.9 Therefore, the case of the patient with bilateral enormous cervical lymph nodes metastasis described in this report is extremely rare and the patient was only complaining about dysphagia and limitation of neck movement.
Histologically, NPC is subdivided into three types: keratinizing squamous cell carcinoma differentiated non-keratinizing carcinoma, undifferentiated non-keratinizing carcinoma and basal-like squamous cell carcinoma. Undifferentiated non-keratinizing carcinoma is the most common in Southern China(95% of patients, which has been shown to have high correlation with EBERISH positivity (8, 10). EBER ISH has been well-described and used to confirm systemic metastases of NPC (10, 12). Ngan et al. propose one could argue about another unknown primary cancer as a potential source of metastasis if there is no EBER ISH confirmation (11). In the present case, the final histopathological examination showed that the bilateral enormous cervical lymph nodes metastasis was EBER positive and supported the NPC metastasis. Generally, non-keratinizing carcinomas have better primary tumor control rates and nodal control rates than keratinizing squamous cell carcinoma, while the latter group has a poorer survival rate than former group because of higher incidence of deaths from uncontrolled primary tumors and nodal metastases (13). The present case was identified undifferentiated non-keratinizing carcinoma in primary tumor and cervical mass. The patient received concurrent chemo radiotherapy after bilateral neck dissection and no tumor recurrence or metastasis was found in a 67 months fellow-up. Nevertheless, metastatic cervical nodes from NPC are more readily controlled than cervical nodes of similar size arising from other head and neck squamous cell carcinomas (9). Most of recent studies have clearly demonstrated that NPC is no longer a problematic disease from a loco-regional control, based on the current standard treatment approach which consists of concurrent chemo-radiotherapy with cisplatin-based regimens, generally followed by adjuvant chemotherapy (14-17).
Although surgical resection has a limited role in metastasis of NPC, there are some cases of advanced disease with a reasonable outcome after resection (11, 18, 19). The patient in our report presented with dysphagia and a limitation of neck movement at diagnosis. We performed a selective neck resection of metastatic cervical mass as primary treatment. He received a good symptomatic relief which was helpful for improving defective nutrition condition and for building confidence for further treatment.
In conclusion, our patient had a bilateral enormous cervical metastasis from NPC which was resulting in significant clinical symptoms at the time of diagnosis. First, we performed an aggressive surgical resection for cervical mass, followed by concurrent chemo-radiotherapy; the comprehensive treatment regimen reached a reasonable outcome in such a case of advanced disease.