Larynx

Squamous papillomas may arise from the true cords, at other sites in the larynx, the oropharynx and the trachea. They may be part of juvenile laryngeal papillomatosis, which may be single or multiple. 'Juvenile' is arbitrarily classified as presenting before the age of 20 years. Multiple is usually defined as more than three lesions.

Most laryngeal papillomas are probably caused by HPV, types 6 and 11 (Travis et al., 1999). These tumours are glistening, nodular, exophytic masses and, depending on their site and size, cause hoarseness, stridor or respiratory distress. A rare complication is squamous cell carcinoma, which may develop in the larynx or lung.

Histologically there are multiple layers of orderly squamous epithelium with no atypia, covering a fibro-vascular core. A few cases may show varying degrees of dysplasia. Prominent surface keratin or intraepithelial dys-keratosis suggests verucca vulgaris or veruccous carcinoma. Squamous carcinomas usually arise in the juvenile lesions. Treatment is by surgery but recurrence is frequent. Solitary adult and juvenile papillomas are often cured by surgery.

Keratosis and Dysplasia

Keratosis is an epithelial area with a marked degree of orthokeratosis or parakeratosis unassociated with underlying epithelial proliferation (AFIP). Typically keratosis is due to long-term tobacco abuse and affects the vocal cords. The mucosa is thickened and white. 'Leucoplakia' is a clinical term meaning 'white plaque' and not a pathological description. Keratotic epithelium usually separates from the vocal cords. This is helpful diagnostically since an intact basal layer helps exclude invasive carcinoma.

Non-dysplastic keratosis shows a normal or increased thickness of squamous epithelium with a prominent granular layer and overlying layers of orthokeratin admixed with parakeratosis. Maturation is orderly and mitoses are basal. If there is no dysplasia there appears to be only a minimal risk of developing a subsequent carcinoma.

Dysplasia is graded into mild, moderate and severe and has similarities to the system used in the cervix except that keratinization is more common in the larynx. Mild dys-plasia involves the basal layer, moderate extends upwards to involve usually two-thirds but does not involve the superficial epithelium. Severe dysplasia shows increased mitoses and involves the full thickness of the epithelium. The more severe the dysplasia, the greater is the chance of an invasive carcinoma co-existing or developing in the larynx. Involvement of the underlying seromucinous glands by dysplastic epithelium is not considered to be evidence of invasion.

Invasive Squamous Cell Carcinoma

Squamous carcinoma of the larynx is associated with cigarette smoking and excess alcohol intake. 'Social' use of alcohol does not appear to cause an increased risk. There is no association between asbestos exposure and carcinoma of this site. Carcinoma of the larynx is divided into supraglottic, glottic and subglottic types. This division has relevance for surgical management. Transglottic carcinoma is a term applied to carcinomas bridging the laryngeal ventricle and involving both the vocal cord and supraglottic regions. Most are glottic carcinomas extending into the supraglottis.

Most carcinomas of the larynx are glottic, arising anteriorly on the mobile part of the cord. They cause hoarseness. The majority of the remaining laryngeal carcinomas are supraglottic and arise from the epiglottis, ventricles, false cords and aryepiglottic folds. These give rise to changes in voice quality and may cause difficulty in swallowing or the feeling of a mass in the throat. Subglottic carcinomas account for 5% or less of all laryngeal carcinomas.

The tumours are usually ulcerated and vary in size from small lesions to large masses, which may almost obstruct the laryngeal lumen (Figure 11; see colour plate section). There are varieties of squamous cell carcinoma, including spindle cell. Since the true cords have a limited lymphatic supply, tumours at this site have a good prognosis. Thus they are often cured by radiation or limited surgical resection. With an increase in size the cords become fixed and the tumour may extend outside the larynx, involving nodes. Subglottic carcinomas are often circumferential and extend beyond the larynx, penetrating the cricothyroid membrane. These cases are likely to involve cervical nodes.

Early carcinomas are usually cured with limited surgery or radiation but laryngectomy is one of the treatments for larger tumours. Recently chemotherapy has been shown to play a role. The size of the tumour and degree of differentiation are important factors in determining prognosis. Patients with laryngeal carcinoma have an increased risk of developing another tumour, especially in the lung or elsewhere in the head or neck.

Genetic Changes in Laryngeal Carcinoma

P53 status over-expression does not result in cell cycle arrest in some studies, although a correlation with this oncogene and early stage glottic cancer as well as those tumours recurring locally has been described (Narayana et al., 1998). It may also relate to decreased survival (Bradford et al., 1997). C-erbB-2 plays no part in prognosis in this tumour (Krecicki et al., 1999). Retinoblastoma protein, however, does relate to survival (Dokiya et al., 1998). Cyclin D1 overexpression identified patients with poor grade laryngeal carcinoma, tumour extension, lymph node involvement and poor histological differentiation (Bellacosa et al., 1996).

Adenosquamous Carcinoma

This may affect the larynx. These are usually high-grade tumours, similar to adenosquamous carcinoma in the lung. Adenocarcinoma is very rare in the larynx and the possibility of a secondary tumour should be considered.

Neural Laryngeal Tumours

Neurilemmomas, neurofibromas, granular cell tumour, paraganglioma, malignant melanoma and carcinoid tumour [this includes all neuroendocrine carcinomas (see the section on the lung) can all be identified in the larynx. These tumours are histologically identical with the pulmonary lesions described below.

Lymphoma

Localized laryngeal non-Hodgkin lymphoma is rare. Extramedullary plasmacytoma has been well described in the larynx, where it causes a subepithelial tumour.

Haemangiomas may arise in the larynx. In infants they present with respiratory distress and affect the subglottic region. Adult haemangiomas are commoner and usually affect the supraglottic and glottic areas. They may cause cough and haemoptysis, as well as hoarseness. Inflammatory myofibroblastic tumour may involve the larynx and in some cases it is caused by 'Mycobacterium avium intracellulari, often in HIV-positive or immunosuppressed patients. The commonest site is on the vocal cords, where they cause hoarseness and stridor.

Carcinomas may metastasize to the larynx, the commonest tumour is melanoma followed by breast, kidney, lung, prostate and gastrointestinal tract carcinomas. Soft tissue laryngeal tumours include liposarcoma, chondro-sarcoma and rarely rhabdomyosarcoma, leiomyosarcoma and malignant fibrous histiocytoma.

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