Nasopharyngeal Carcinoma

In the past, non-keratinising nasopharyngeal carcinomas have been divided into the more common undifferentiated nasopharyngeal carcinoma (ICD-O:8082/3), (synonymous lymphoepithelial carcinoma, lymphoepi-thelioma of Regaud and Schmincke, undifferentiated carcinoma with lymphoid stroma) and the less common differentiated nasopharyngeal carcinoma (ICD-O:8073/3) (or transitional-type carcinoma, intermediate cell carcinoma). The distinction between undifferentiated and differentiated carcinoma is considered unimportant for therapy and prognosis, as these two subtypes represent a spectrum of the same tumour. Nasopharyngeal carcinoma is by far the most common carcinoma in China and Taiwan, accounting for 18% of all carcinomas there, with an incidence of 10-20/100,000 [83]. Nasopharyn-geal carcinomas also occur in endemic forms in Asia, Greenland, Alaska and Africa. In these high-incidence areas, 99% of nasopharyngeal carcinomas are of the non-keratinising subtype. In the western world - a low-incidence area with 0.4-1/100,000 - the non-keratinising nasopharyngeal carcinoma accounts for 75% compared with 25% for keratinising carcinoma [8, 43, 141]. Naso pharyngeal carcinomas show a strong male predilection. While most patients with non-keratinising nasopharyngeal carcinoma are older than 50 years in endemic areas, there is a bimodal age distribution with a peak presentation in the 2nd and 6th decades in intermediate- and low-incidence areas [8, 43, 63, 77, 175]. The causative and aetiological role of EBV is well established in invasive and in situ nasopharyngeal carcinomas, irrespective of the ethnic origin of the patient and the histological subtype [31, 158]. However, environmental factors seem to play a role, since the incidence of non-keratinising na-sopharyngeal carcinoma decreases among second and third generation Chinese living in non-endemic areas [83]. Nasopharyngeal carcinomas arise in the lateral walls of the nasopharynx in the area of the Rosenmuller fossa and presenting symptoms may be nasal obstruction, epistaxis, post-nasal drip, tinnitus and cranial nerve palsy. Hearing loss and unilateral otitis media are related to auditory tube involvement. In more than 50% of patients, however, metastases to cervical lymph nodes are the presenting sign. Since most nasopharyn-geal carcinomas are difficult to visualise on endoscopic examination, "blind" biopsies of the nasopharynx, base of tongue and palatine tonsils are necessary to establish a histological diagnosis of undifferentiated nasopharyngeal carcinoma. In patients presenting with lymph node metastases and clinically occult primary carcinoma, demonstration of EBV in the metastatic carcinoma may be a helpful diagnostic tool to correctly identify the primary nasopharyngeal carcinoma [26, 40, 119, 191]. Nasopharyngeal carcinomas are highly responsive to radiation therapy. The overall 5-year survival has been reported to be between 25 and 50% in the past, but the results of treatment have improved due to refinements in staging and techniques of therapy [4, 115].

Histologically, non-keratinising nasopharyngeal carcinomas lack glandular differentiation. The undifferen-tiated subtype consists of bland uniform undifferentiat-ed cells in large cohesive nests and cords as well as smaller nests and groups of epithelial cells with numerous mitoses. They may be sharply outlined and separated from the surrounding infiltrate or permeated by a dense inflammatory infiltrate consisting of numerous lymphocytes, plasma cells and eosinophilic granulocytes. This pattern often has a distinctly non-carcinomatous and lymphoma-like appearance. The infiltrating lymphocytes are a mixture of plasma cells, B-cells and T-cells, with B-cells usually predominating. Portions of the T-cells are cytotoxic cells. A variant of undifferentiated carcinoma shows extensive acantholysis resulting in a pseudoglandular and pseudovascular pattern. The differentiated subtype shows cellular stratification often in a plexiform growth, reminiscent of transitional cell carcinoma of the urinary bladder (Fig. 6.5). The stroma of non-keratinising nasopharyngeal carcinoma can be fibrous, but is rarely desmoplastic. Coagulative necrosis

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