Introduction
Background
Laryngeal cancer is the most common cancer of the upper aerodigestive tract. The incidence of laryngeal tumors is closely correlated with smoking, as head and neck tumors occur 6 times more often among cigarette smokers than among nonsmokers. The age-standardized risk of mortality from laryngeal cancer appears to have a linear relationship with increasing cigarette consumption. Death from laryngeal cancer is 20 times more likely for the heaviest smokers than for nonsmokers.
Furthermore, active smoking by patients with head and neck cancer is associated with significant increases in the annual rate of second primary tumor development compared to former smokers or nonsmokers. The use of unfiltered cigarettes or dark, air-cured tobacco is associated with further increases in risk.
Although alcohol is a less potent carcinogen than tobacco, alcohol consumption is a risk factor for laryngeal tumors. In individuals who use both tobacco and alcohol, these risk factors appear to be synergistic, and they result in a multiplicative increase in the risk of developing laryngeal cancer.
For excellent patient education resources, visit eMedicine's Cancer and Tumors Center. Also, see eMedicine's patient education article Cancer of the Mouth and Throat.
Pathophysiology
Most squamous cell carcinomas of the larynx result from an exposure to carcinogens, such as tobacco and alcohol, which cause diffuse mucosal changes (field effect).
Frequency
United States
Laryngeal cancers account for approximately 1.2% of all new cancer diagnoses in the United States. According to the most up-to-date data from the Surveillance, Epidemiology, and End Results (SEER) Program (National Cancer Institute), the age-adjusted rate for larynx cancer was 4.0923 cases per 100,000 (in 9 SEER registries) in 1973-2000. The age-adjusted rates for larynx cancer were 4.0375 cases per 100,000 and 6.6844 cases per 100,000 for whites and African Americans, respectively. In the United States, more than half of the cases involve glottic cancer.
International
Age-standardized incidence rates ranged from 2.5 to 17.1 per 100,000 person-years at risk in men and from 0.1 to 1.3 per 100,000 person-years at risk in women in European and Asian countries (Scottish Health Statistics).
Mortality/Morbidity
- The prognosis for small laryngeal cancers that do not have lymph node metastases is good, with cure rates of 75-95%, depending on the site, the size of the tumor, and the extent of infiltration.
- Advanced disease has a worse prognosis. Supraglottic cancers usually manifest late and have a poorer prognosis.
- Patients with a hemoglobin level greater than 13 g/dL before radiation have rates of local control and survival that are higher than those of patients who are anemic.
Race
Laryngeal carcinoma is more common in African Americans than in whites, with a ratio of 3.5:1.
Sex
In the 1950s, the male-to-female ratio in patients with laryngeal cancer was 15:1. This number had changed to 5:1 by the year 2000, and the proportion of women afflicted by the disease is projected to increase in years to come. These changes are likely a reflection of shifts in smoking patterns, with women smoking more in recent years.
Age
Laryngeal cancer most commonly affects men middle-aged or older who are smokers and who use alcohol. The peak incidence is in those aged 50-60 years.
Anatomy
Cartilage
The cartilaginous framework of the larynx includes the thyroid cartilage, cricoid cartilage, arytenoid cartilage, and corniculate cartilage (see Images 1-8).
The conus elasticus (cricovocal ligament) is an elastic membrane that joins the upper surface of the cricoid cartilage, the vocal process of the arytenoid, and the lower thyroid cartilage. It serves as a barrier against inferior invasion of pre-epiglottic fat disease. The anterior commissure tendon extends from the anterior commissure and inserts into the thyroid cartilage.
Regions of the larynx
The larynx is divided into 3 anatomic regions: the supraglottic larynx, the glottis, and the subglottic region.
The supraglottic larynx consists of epiglottis, false vocal cords, ventricles, aryepiglottic folds, and arytenoids. The anatomic borders are as follows: superior, epiglottis; inferiorly, point at which the vocal cord epithelium turns upward to form the lateral wall of the ventricle; anterior, posterior edge of the vallecula superiorly and anterior false cord inferiorly; and posterior, the arytenoids.
The glottic larynx consists of the true vocal cords and anterior commissure. The anatomic borders are as follows: superior, point at which the vocal cord epithelium turns upward to form the lateral wall of the ventricle; inferior, 5 mm below the free margin of the vocal cords; anterior, the anterior commissure, which is usually located within 1 cm of the skin surface (an important consideration in planning for radiation therapy); and posterior, the posterior commissure.
The subglottic larynx consists of the region between the vocal cords and the trachea. The anatomic borders are as follows: superior, 5 mm below the free margin of the vocal cords, and inferior, the inferior aspect of the cricoid cartilage.
Pre-epiglottic fat space
The pre-epiglottic fat is located in the anterior and lateral aspects of the larynx and is often invaded by advanced cancers. The anatomic borders are as follows: superior, hyoid bone and hyoepiglottic ligament; inferior, conus elasticus; anterior, thyrohyoid membrane; posterior, anterior wall of the pyriform sinus; and lateral, thyroid cartilage wall. Invasion of the pre-epiglottic fat has significant surgical implications, so evaluation of this space should be part of any radiologic analysis.
Nerves
The recurrent laryngeal nerve innervates the intrinsic laryngeal muscles. Damage to this nerve causes hoarseness clinically and medialization of the arytenoid cartilage radiographically. Enlargement of the pyriform sinus is an important secondary sign of recurrent laryngeal nerve paralysis. The superior laryngeal nerve innervates the cricothyroid muscle, an extrinsic laryngeal muscle that tenses the true vocal cords. Damage to this nerve produces bowing of the vocal cord.
Lymphatics
The first-echelon lymphatics for the supraglottic larynx are the subdigastric nodes and the middle anterior cervical nodes (level 3), and the second-echelon lymphatics are the lower anterior cervical nodes (level 4).
The glottic larynx contains few lymphatics, and nodal spread occurs only with primary extension to the supraglottis or subglottis. For tumors with spread to the supraglottis, the subdigastric nodes are at risk. For tumors with spread to the anterior commissure and anterior subglottis, the middle and lower anterior cervical nodes, the Delphian node, and the lateral paratracheal nodes are at risk.
The first-echelon lymphatics for the subglottic larynx are the Delphian node, the lower anterior cervical nodes and paratracheal nodes, and the supraclavicular nodes, and the second-echelon lymphatics are the mediastinal nodes.
Glottic and subglottic tumors metastasize to ipsilateral lymph nodes, but supraglottic tumors often spread to nodes on both sides of the neck.
Levels of the neck
The anatomy of the cervical lymph nodes is relevant to the treatment of all laryngeal cancer. The American Joint Committee on Cancer (AJCC) and the American Academy of Otolaryngology–Head and Neck Surgery classification systems are widely used.
The neck is divided into 5 levels: level I includes the submental and submandibular triangles; level II, the superior jugular chain nodes extending from the skull base down to the carotid bifurcation and posteriorly to the posterior border of the sternocleidomastoid muscle; level III, the jugular nodes from the carotid bulb inferiorly to the omohyoid muscle; level IV, the jugular nodes from the omohyoid muscle to the clavicle; and level V, the posterior triangle bounded by the sternocleidomastoid anteriorly, the trapezius posteriorly, and the omohyoid inferiorly.
Radiologists use the hyoid bone as a marker for the carotid bifurcation, and the inferior cricoid cartilage as a marker for the omohyoid muscle, which may be difficult to discern radiographically. The Radiation Therapy Oncology Group, in collaboration with 2 European research groups, has established guidelines for delineation of nodal levels.
Presentation
Most laryngeal cancers arise in the glottic region and are symptomatic early as a result of hoarseness and changes in the voice.
Clinical presentation
For supraglottic tumors, common symptoms include mild odynophagia, mild dysphagia, and mass sensation. Uncommon symptoms include severe dysphagia and aspiration and referred ear pain. The mechanism of the referred ear pain is through the activation of the internal branch of the superior laryngeal branch of cranial nerve X with referral to the auricular nerve of Arnold. The pain is located in the posterior wall of the external auditory canal and posterior pinna.
For glottic and subglottic tumors, the most common presenting symptom is hoarseness of the voice. Uncommon symptoms include odynophagia, referred ear pain, thyroid cartilage pain, and airway obstruction.
Staging system
The AJCC has designated staging by using the tumors, nodes, and metastases (TNM) classification. Definitions for the stages are described below.
Primary tumor, T stage
TX indicates that the primary tumor cannot be assessed; T0 means no evidence of primary tumor; and Tis indicates carcinoma in situ.
In the supraglottis, the T stages are as follows: T1, tumor limited to 1 subsite of the supraglottis with normal vocal cord mobility; T2, tumor invasion of the mucosa of more than 1 adjacent subsite of the supraglottis or glottis or of a region outside the supraglottis (eg, mucosa of base of tongue, vallecula, medial wall of pyriform sinus), without fixation of the larynx; T3, tumor limited to the larynx with vocal cord fixation and/or invasion of any of the postcricoid area or pre-epiglottic tissues; T4, tumor invasion through the thyroid cartilage and/or extension into soft tissues of the neck, thyroid, and/or esophagus.
Subsites include the following: false cords, arytenoids, suprahyoid epiglottis, infrahyoid epiglottis, and aryepiglottic folds (laryngeal aspect).
In the glottis, the T stages are as follows: T1, tumor limited to the vocal cord (may involve anterior or posterior commissure) with normal mobility; T2, tumor extension to the supraglottis and/or subglottis and/or impaired vocal cord mobility; T3, tumor limited to the larynx with vocal cord fixation; and T4, tumor invasion through the thyroid cartilage and/or other tissues beyond the larynx (eg, trachea or soft tissues of the neck, including the thyroid and pharynx).
Stage T1 can be subdivided into T1a, in which the tumor limited to 1 vocal cord and T1b, in which the tumor involves both vocal cords.
In the subglottis, the T stages are as follows: T1, tumor limited to the subglottis; T2, tumor extension to a vocal cord with normal or impaired mobility; T3, tumor limited to the larynx with vocal cord fixation; T4, tumor invasion through cricoid or thyroid cartilage and/or extension to other tissues beyond the larynx (eg, trachea or soft tissues of neck, including the thyroid and esophagus).
Regional lymph nodes, N stage
The N stages are as follows NX, regional lymph nodes cannot be assessed; N0, no regional lymph node metastasis; N1, metastasis in a single ipsilateral lymph node, 3 cm or less in greatest dimension; N2, metastasis in a single ipsilateral lymph node more than 3 cm but not more than 6 cm in greatest dimension, metastases in multiple ipsilateral lymph nodes with none more than 6 cm in greatest dimension, or metastases in bilateral or contralateral lymph nodes none more than 6 cm in greatest dimension; and N3, metastasis in a lymph node more than 6 cm in greatest dimension.
Stage N2 may be further subdivided as follows: N2a, metastasis in a single ipsilateral lymph node more than 3 cm but not more than 6 cm in greatest dimension; N2b, metastasis in multiple ipsilateral lymph nodes, none more than 6 cm in greatest dimension; and N2c, metastasis in bilateral or contralateral lymph nodes, none more than 6 cm in greatest dimension.
Distant metastasis, M stage
MX indicates that distant metastasis cannot be assessed; M0, no distant metastasis; and M1, distant metastasis.
Preferred Examination
Diagnostic workup
The diagnostic workup of an individual with a suspected laryngeal carcinoma should include history taking, physical examination, laboratory tests, and radiologic examination.
History taking should include an inquiry into hoarseness, odynophagia, dysphagia, referred ear pain, thyroid cartilage pain, aspiration, and dyspnea.
Physical examination should include a complete head and neck examination with fiberoptic endoscopy for an assessment of vocal cord fixation and the extent of primary disease. Subglottic disease is usually not well visualized endoscopically. Fullness between hyoid bone and thyroid cartilage suggests involvement of the pre-epiglottic space. Ulceration of the infrahyoid epiglottis or fullness of the vallecula suggests involvement of the pre-epiglottic space. Disappearance of a laryngeal click suggests postcricoid involvement. Localized pain over 1 ala of the thyroid cartilage suggests thyroid cartilage invasion.
Laboratory tests should include determination of the complete blood count and alkaline phosphatase level, and liver function tests should be performed.
Radiologic examination should include cross-sectional imaging (CT or MRI) of the head and neck to delineate the extent of primary disease, the presence of bone or cartilage invasion, and the presence of nodal disease. Imaging is particularly useful for submucosal regions such as the pre-epiglottic space and subglottis. T1 tumors of the glottis may not require imaging, though CT is often used to exclude nodal metastases. Plain chest radiography or chest CT may be used to rule out pulmonary metastasis. Although some authors claim that MRI provides a more accurate depiction of tumor extent, most institutions continue to use CT as the primary cross-sectional modality. Advances in high-resolution multi-channel helical CT have kept CT competitive with MRI. MRI is more sensitive, but less specific, than CT for the diagnosis of cartilage invasion.
Further assessment of carcinomas
Approximately 95% of all laryngeal and hypopharyngeal malignant tumors are squamous cell cancers. Almost all squamous cell carcinomas are diagnosed by means of direct visualization because they arise from the mucosal surface of the larynx. Biopsy performed with direct laryngoscopy can help confirm the diagnosis, but the otolaryngologist is usually sure of the diagnosis by simply visualizing the abnormality, even before the biopsy is performed. In the case of small tumors, the clinician can not only diagnose the problem but also obtain enough information by means of direct visualization to obviate the need for imaging. In some cases, however, landmarks important to therapeutic planning are deep to the mucosa; in these cases, imaging can be helpful.
The information sought at imaging depends on the size and position of the primary tumor and the type of therapy planned. A small tumor without evidence of deep extension does not require imaging because all information needed for the therapeutic decision may be obvious at endoscopy. Treatment options include cord stripping, laser excision or radiation therapy. Alternatively, the lesion may be so large that a total laryngectomy is the only option considered; thus, imaging of the primary lesion is of limited usefulness.
For intermediate-sized lesions, imaging can provide useful information. Radiation therapy remains an option. If surgery is considered, a decision must be made as to whether a patient is a candidate for a voice-sparing partial laryngectomy or whether total laryngectomy is required.
Supraglottic carcinomas are associated with a high incidence of nodal metastases at diagnosis; therefore, complete evaluation of the internal jugular lymph nodes with imaging studies is needed. The reported incidence of clinically positive lymph nodes is 55% at initial diagnosis, with a 16% incidence of bilateral involvement.
Differential Diagnoses
Other Problems to Be Considered
Hyperkeratosis
Papillomas
Polyps
Fibromas
Granulomas
Laryngoceles
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References
Castelijns JA, Gerritsen GJ, Kaiser MC, et al. Invasion of laryngeal cartilage by cancer: comparison of CT and MR imaging. Radiology. Apr 1988;167(1):199-206. [Medline].
Castelijns JA, van den Brekel MW, Niekoop VA, Snow GB. Imaging of the larynx. Neuroimaging Clin N Am. May 1996;6(2):401-15. [Medline].
Curtin HD. Imaging of the larynx: current concepts. Radiology. Oct 1989;173(1):1-11. [Medline].
Horowitz BL, Woodson GE, Bryan RN. CT of laryngeal tumors. Radiol Clin North Am. Mar 1984;22(1):265-79. [Medline].
Som PM, Curtin HD. Larynx. Head and Neck Imaging. 4th ed. St Louis: Mosby-Year Book;. 2003: 1595-699.
Further Reading
Keywords
cancer of the larynx, laryngeal cancer, laryngeal tumor, glottic tumor, glottic cancer, subglottic tumor, head and neck cancer, smoking, throat cancer
