The three histologic variants are keratinizing squamous cell carcinoma, nonkeratinizing squamous cell carcinoma, and undifferentiated carcinoma; the last-mentioned is the most common and the one most closely linked with EBV. The undifferentiated neoplasm is characterized by large epithelial cells with indistinct cell borders (reflecting “syncytial” growth) and prominent eosinophilic nucleoli. In nasopharyngeal carcinomas, the tumor cells are often accompanied by a striking influx of T cells, which are believed to be responding to viral antigens. Nasopharyngeal carcinomas invade locally, spread to cervical lymph nodes, and then metastasize to distant sites. They tend to be radiosensitive, and 5-year survival rates of 50% are reported, even for patients with advanced cancers. Responses to immune checkpoint inhibitors also have been reported, providing a new therapeutic strategy for tumors that do not respond to conventional therapy.
A variety of nonneoplastic, benign, and malignant neoplasms of epithelial and mesenchymal origin may arise in the larynx, but only vocal cord nodules, papillomas, and squamous cell carcinomas are sufficiently common to merit comment. In all of these conditions, the most common presenting feature is hoarseness.
Vocal cord nodules (“polyps”) are smooth, hemispherical protrusions (usually <0.5 cm in diameter) located, most often, on the true vocal cords. The nodules are composed of fibrous tissue and covered by stratified squamous mucosa that usually is intact but can be ulcerated from contact trauma with the other vocal cord. These lesions occur chiefly in heavy smokers or singers (singer’s nodes), suggesting that they are the result of chronic irritation or over use.
Laryngeal papilloma or squamous papilloma of the larynx is a benign neoplasm, usually located on the true vocal cords, that forms a soft, raspberry like excrescence rarely more than 1 cm in diameter. Histologically, it consists of multiple slender, fingerlike projections supported by central fibrovascular cores and covered by an orderly, typical, stratified squamous epithelium. When the papilloma is on the free edge of the vocal cord, trauma may lead to ulceration that can be accompanied by hemoptysis.
Papillomas usually are single in adults but often are multiple in children, in whom the condition is referred to as recurrent respiratory papillomatosis (RRP), since they typically tend to recur after excision. These lesions are caused by human papillomavirus (HPV) types 6 and 11 and often spontaneously regress at puberty. Cancerous transformation is rare. The most likely cause for their occurrence in children is vertical transmission from an infected mother during delivery. Therefore, the recent availability of an HPV vaccine that can protect women of reproductive age against infection with types 6 and 11 provides an opportunity for prevention of RRP in children.
Carcinoma of the Larynx
Carcinoma of the larynx represents only 2% of all cancers. It most commonly occurs after 40 years of age and is more common in men than in women (with a gender ratio of 7:1). Environmental influences are very important in its causation; nearly all cases occur in smokers, and alcohol and asbestos exposure also may play roles. Human papillomavirus sequences have been detected in about 15% of tumors, which tend to have a better prognosis than other carcinomas.