The Larynx Early Stage Disease

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WILLIAM M. LYDIATT, MD, FACS DANIEL D. LYDIATT, DDS, MD, FACS

The American Cancer Society estimated that in the United States there would be 10,600 cases of laryngeal carcinoma diagnosed in 1999, and 4,200 deaths.1 This accounts for 0.9 percent of cancers from all sites and 0.8 percent of all cancer deaths. Laryngeal carcinoma makes up 1 to 2 percent of cancers worldwide, and the incidence is increasing (Figure 9-1). Spain has one of the highest rates in the world with Basque and Navarra regions reaching a rate of 20 cases per 100,000 persons. There is also a very high incidence in France, Italy, and Poland.2 Men are affected 4 times more frequently than women in the United States and up to 10 times more frequently in other countries.2 This ratio is higher for glottic cancer than supraglottic. Recently, the ratio has decreased in several countries, including the United States, and is thought to be due to an increased incidence in women. Age at diagnosis ranges from the second to tenth decade, with the seventh the most common. Over 90 percent of all laryn-geal cancers are squamous cell carcinoma, which will be the primary focus of this chapter. Other histologic types include lymphoma, spindle-cell carcinoma, neuroendocrine carcinoma, minor salivary gland carcinomas, mucosal melanoma, and various sarcomas. Metastatic lesions and direct extension of thyroid carcinoma are other rare possibilities.

Early laryngeal carcinoma is an excellent paradigm for examining the role of competing and complementary therapies. While we will define early

Cancer Larynx Disease Pathophysiology
Figure 9-1. Bar graph of world incidence of laryngeal cancer.

stage as stage I (T1N0M0) and II (T2N0M0), there is controversy about what constitutes early laryngeal cancer. Ferlito and colleagues point out that early laryngeal cancer is more accurately called minimally invasive cancer without muscle or cartilage invasion.3 Most T2 and many T1 cancers of the larynx have more extensive invasion. Stage I glottic cancer with only superficial invasion may be best treated endo-scopically, while a bulky stage I lesion will require more aggressive resection or radiation therapy. We will discuss therapeutic options and their rationale with respect to stage and site later in this chapter.

ANATOMY

Embryologically, the larynx begins as a slit-like groove in the pharyngeal floor. Anterior to this slit the epiglottis develops from the ventral ends of the third and fourth branchial arches. Lateral to this swelling the arytenoids develop from the sixth branchial arches. The ventral fourth and fifth arches form the laryngeal cartilages.4 The supra-glottic larynx develops from the buccopharyngeal anlage and the glottic (each side unilaterally) and subglottic portions from the tracheopulmonary anlage.5 The lymphatics follow this pattern with areas above the ventricle, (the junction of the supraglottic and glottic larynx), draining superiorly through the thyrohyoid membrane and areas below the ventricle draining inferiorly through the cricothyroid membrane to regional lymph nodes.5,6 This embryology forms the rationale for the vertical partial laryngectomy, and the supraglottic horizontal laryngectomy. The need for bilateral neck dissections in most supraglottic laryngectomies is based on the midline development of the epiglottis and consequent bidirectional lymphatic flow. If neck dissection is indicated for a lesion of the true vocal cord, unilateral dissections are usually adequate based on this embryology. The marked edema seen after supraglottic laryngectomies for radiotherapy failure results in part from the lymphatic differences between the arytenoids (sixth arch) and the remainder of the larynx (fourth and fifth arches). Conversely, surgical salvage by a vertical partial laryngectomy after failed radiation therapy is possible due to this embryology.

The larynx is also divided roughly along embry-ologic lines for staging purposes (Figure 9-2). The supraglottic larynx is composed of the epiglottis, aryepiglottic folds, arytenoids, and false cords. The glottis consists of the true vocal cords, and the anterior and posterior commissures. The subglottis involves the remaining portion of the larynx to the inferior border of the cricoid cartilage.7

Intralaryngeal barriers to tumor spread consist of ligaments, fibroelastic membranes, and perichondrium.5 The conus elasticus (triangular membrane) has a base that attaches to the thyroid and cricoid cartilages and an apex that attaches to the vocal process of the arytenoid and the vocal ligament. The conus elasticus, along with the vocal ligament, may limit early invasive cancer and make it amenable to conservative treatment.5 The paraglottic space is the area between the conus elasticus and the perichondrium of the thyroid ala and is occupied by the thyroarytenoid muscle. This space may also limit spread of early true vocal cord cancer.

Whole organ sections have failed to consistently demonstrate a barrier between the supraglottic and glottic larynx. Cancer tends to remain confined

Figure 9-2. Anatomic diagram of the larynx.

between these embryologic areas. Cancer of the supraglottic larynx tends to invade anteriorly into the preepiglottic space, and recurrences after supra-glottic laryngectomy are much more common at the base of the tongue than the anterior commissure.5,8

Diagnosis

Risk Factors

The most important risk factor for squamous cell carcinoma of the larynx is tobacco.9-13 It is also the primary preventable risk factor, accounting for 90 to 95 percent of glottic and supraglottic carcinomas. Other factors increasing its carcinogenic potential are hand-rolled versus commercially produced cigarettes, black versus blond tobacco, number of cigarettes smoked per day, number of years of smoking, and constant daily smoking versus intermittent smoking.2,14 Alcohol is a significant cofactor with tobacco in supraglottic carcinoma—creating a more than additive risk13,15,16 (Figure 9-3). Alcohol is an independent risk factor as well.

A diet deficient in fruits and vegetables increases the risk of laryngeal cancer and, conversely, one rich in fruits and vegetables may be preventive.17,18 Exactly which compounds in this diet are protective remain elusive. Occupational exposures which appear relevant include diesel fumes, mists containing sulfuric acid, coal dust, and machining fluids.2,19,20 The role of human papillomavirus (HPV) as a causative agent in laryngeal cancer has been investigated, and while the type of cancer associated with HPV appears more aggressive and there is a higher than expected rate of paired incidence of cervical cancer, a causative role has not been proved.21,22 Finally, family history appears to be relevant beyond the obvious link with smoking.23

Presenting Signs and Symptoms

The diagnosis of laryngeal carcinoma should be considered when hoarseness is present for more than 2 to 3 weeks. Glottic carcinoma presents early with hoarseness due to vocal cord involvement. Other signs of glottic carcinoma are hemoptysis, airway embarassment—especially with exertion, halitosis, and the so-called hot potato voice. Cancers of the supraglottic larynx generally present later due to a lack of symptoms in the early stages. Common signs and symptoms include difficulty swallowing, otalgia, and odynophagia. Following the history, the next step in diagnosis is a careful examination of the larynx by a qualified specialist.

Laryngeal Cancer Staging

Figure 9-3. Relationship of tobacco and alcohol to the genesis of laryngeal cancer. Data from Tuyns AJ, et al. Cancer of the larynx/hypopharynx, tobacco and alcohol: IARC international case-control study in Turin and Varese (Italy), Saragoza and Navarra (Spain), Geneva (Switzerland) and Calvados (France). Int J Cancer 1988;41:483-91.

Figure 9-3. Relationship of tobacco and alcohol to the genesis of laryngeal cancer. Data from Tuyns AJ, et al. Cancer of the larynx/hypopharynx, tobacco and alcohol: IARC international case-control study in Turin and Varese (Italy), Saragoza and Navarra (Spain), Geneva (Switzerland) and Calvados (France). Int J Cancer 1988;41:483-91.

A laryngeal mirror provides an excellent panoramic view of the larynx, oropharynx and hypophar-ynx in most people. A flexible or rigid endoscope provides an alternate view which can be done in the office (Figures 9-4A and B). By having the patient perform a Valsalva's maneuver, the pyriform sinuses can often be examined in better detail. These studies may be videotaped for documentation or a more sophisticated stroboscopic examination can be done to document dysfunction from the tumor. The neck must be carefully palpated for adenopathy. Chest radiography and liver function tests will suffice for a metastatic survey in the absence of any systemic complaints. A computed tomography scan provides detail of cartilage invasion but should be reserved for those cases when management would be changed—

Figure 9-4. A, Larynx during quiet breathing. S, Larynx during phonation.

as in the case of large lesions or fixed vocal cords. Biopsies can be done in the clinic or in the operating room at the time of direct laryngoscopy.

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