The larynx is divided into 3 anatomical regions. The supraglottic larynx includes the epiglottis, false vocal cords, ventricles, aryepiglottic folds, and arytenoids. The glottis includes the true vocal cords and the anterior and posterior commissures. The subglottic region begins about 1 centimeter below the true vocal cords and extends to the lower border of the cricoid cartilage or the first tracheal ring.

The supraglottic area is rich in lymphatic drainage. After penetrating the pre-epiglottic space and thyrohyoid membrane, lymphatic drainage is initially to the jugulodigastric and midjugular nodes. About 25% to 50% of patients present with involved lymph nodes. The precise figure depends on T stage. The true vocal cords are devoid of lymphatics. As a result, vocal cord cancer confined to the true cords rarely, if ever, presents with involved lymph nodes. Extension above or below the cords may, however, lead to lymph node involvement. Primary subglottic cancers, which are quite rare, drain through the cricothyroid and cricotracheal membranes to the pretracheal, paratracheal, and inferior jugular nodes, and occasionally to mediastinal nodes.[1]

A clear association has been made between smoking, excess alcohol ingestion, and the development of squamous cell cancers of the upper aerodigestive tract.[2] If a patient with a single cancer continues to smoke and drink alcoholic beverages, the likelihood of a cure for the initial cancer (by any modality) is diminished, and the risk of second tumor is enhanced. Second primary tumors, often in the aerodigestive tract, have been reported in up to 25% of patients whose initial lesion is controlled. A study has shown that daily treatment of these patients with moderate doses of isotretinoin (13-cis-retinoic acid) for 1 year can significantly reduce the incidence of second tumors.[3] No survival advantage has yet been demonstrated, however, in part because of recurrence and death from the primary malignancy. Additional trials are ongoing.

Supraglottic cancers typically present with sore throat, painful swallowing, referred ear pain, change in voice quality, or enlarged neck nodes. Early vocal cord cancers are usually detected because of hoarseness. By the time they are detected, cancers arising in the subglottic area commonly involve the vocal cords; thus symptoms usually relate to contiguous spread.

The most important adverse prognostic factors for laryngeal cancers include increasing T stage and N stage. Other prognostic factors may include sex, age, performance status, and a variety of pathologic features of the tumor, including grade and depth of invasion.[4]

Prognosis for small laryngeal cancers that have not spread to lymph nodes is very good, with cure rates of 75% to 95% depending on the site, tumor bulk,[5] and degree of infiltration. Although most early lesions can be cured by either radiation therapy or surgery, radiation therapy may be reasonable to preserve the voice, leaving surgery for salvage. Patients with a preradiation hemoglobin level greater than 13 grams per deciliter have higher local control and survival rates than patients who are anemic.[6] This observation is being evaluated in a randomized clinical trial.

Locally advanced lesions, especially those with large clinically involved lymph nodes, are poorly controlled with surgery, radiation therapy, or combined modality treatment. Distant metastases are also common even if the primary tumor is controlled.

Intermediate lesions have intermediate prognoses, depending on site, T stage, N stage, and performance status. Therapy recommendations for patients with these lesions are based on a variety of complex anatomic, clinical, and social factors, which should be individualized and discussed in multidisciplinary consultation (surgery, radiation therapy, and dental and oral surgery) prior to prescribing therapy.

Patients treated for laryngeal cancers are at highest risk of recurrence in the first 2 to 3 years. Recurrences after 5 years are rare and usually represent new primary malignancies. Close, regular follow-up is crucial to maximize the chance for salvage. Careful clinical examination and repetition of any abnormal staging study are included in follow-up, along with attention to any treatment-related toxic effect or complication.

References

1. Spaulding CA, Hahn SS, Constable WC: The effectiveness of treatment of lymph nodes in cancers of the pyriform sinus and supraglottis. Int J Radiat Oncol Biol Phys 13 (7): 963-8, 1987.  [PUBMED Abstract]
   
   
2. Spitz MR: Epidemiology and risk factors for head and neck cancer. Semin Oncol 21 (3): 281-8, 1994.  [PUBMED Abstract]
   
   
3. Hong WK, Lippman SM, Itri LM, et al.: Prevention of second primary tumors with isotretinoin in squamous-cell carcinoma of the head and neck. N Engl J Med 323 (12): 795-801, 1990.  [PUBMED Abstract]
   
   
4. Yilmaz T, Hoşal S, Gedikoglu G, et al.: Prognostic significance of depth of invasion in cancer of the larynx. Laryngoscope 108 (5): 764-8, 1998.  [PUBMED Abstract]
   
   
5. Reddy SP, Mohideen N, Marra S, et al.: Effect of tumor bulk on local control and survival of patients with T1 glottic cancer. Radiother Oncol 47 (2): 161-6, 1998.  [PUBMED Abstract]
   
   
6. Fein DA, Lee WR, Hanlon AL, et al.: Pretreatment hemoglobin level influences local control and survival of T1-T2 squamous cell carcinomas of the glottic larynx. J Clin Oncol 13 (8): 2077-83, 1995.  [PUBMED Abstract]
   
   

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