PERSPECTIVE, PATTERNS OF SPREAD, AND PATHOLOGY
The malignant gradient is vertical in reference to the horizontal midplane through the true glottis; it is greater above and below the vocal cords.
PERSPECTIVE AND PATTERNS OF SPREAD
Cancers of the larynx are among the most commonly occurring cancers in the upper respiratory passage and present the challenge of preservation of phonation. The larynx is a critical structure in the respiratory tract and is the major sphincter through which air enters and exits from the lung. It performs the essential function of closure to the airway entrance during deglutition. Once involved the laryngeal cancer can be an isolated nodule, but is often part of a field cancerization process due to habitual smoking. The likelihood of a recurrence or second primary in lung is inevitable if the host is either unwilling or unable to give up tobacco. Persistent hoarseness demands an otologic examination.
The malignant gradient is from anterior to posterior, from superior to inferior, and from medial to lateral. Most important is sparing of the vocal cords and voice preservation. A number of randomized studies have confirmed that chemoradiation regimens are able to yield comparable survival with laryngeal preservation versus radical laryngectomy.
Cancers arising in the different subsites of the larynx have patterns of spread that reflect the anatomy of a larynx in its development and function. The malignant gradient is in reference to the horizontal midplane through the true glottis. Cancers above have a favorable outcome and cancers below have a better prognosis for readily apparent reasons relating to the ease of detection of supraglottic compared to subglottic cancers that are obscured by the vocal cords. Cancers of the true vocal cord are detected early because they alter voice quality and lead to hoarseness. They tend to arise from the free margin, but frequently cross to the opposite cord via the anterior commissure. The vocal cords are relatively avascular and are poor in lymphatics. Consequently, lymph node involvement and distant metastases are rare.
Subglottic cancers are very uncommon because inhaling carcinogens (i.e., smoking tobacco) results in exposure of supraglottis and glottis to a larger degree. The subglottis is a relatively protected site.
A true subglottic cancer needs to arise a centimeter below the vocal cords or glottis and invade the cricoid cartilage predominantly because there is not a muscle layer and the mucosa is juxtaposed to the cartilage. Subglottic origin is clinically obscured by the vocal cords and would become symptomatic by invading the glottis. Clinically, a transglottic cancer would be interpreted to be a vocal cord cancer unless the tumor bulk was mainly in the region below the glottis. Most subglottic cancers, when discovered, tend to be bilateral and circumferential. Patterns of Spread are presented as a cancer crab that can invade in six basic directions Superior-Inferior, Medial-Lateral, Anterior-Posterior (SIMLAP) of adjacent anatomic sites (Fig. 10.2; Table 10.2).
Figure 10.1| Squamous cell carcinoma. An infiltrative neoplasm is composed of cohesive nests of tumor.
Figure 10.2 | Patterns of spread. A. Coronal. Note transglottic invasion and invasion fixing cord B. Sagittal. Note invasion of pre-epiglottic fat pocket invasion and subglottic extension. The primary cancer (glottic larynx) invades in various directions, which are color-coded vectors (arrows) representing stage of progression: Tis, yellow; T1, green; T2, blue; T3, purple; T4a, red; and T4b, black. The concept of visualizing patterns of spread to appreciate the surrounding anatomy is well demonstrated by the six directional pattern i.e. SIMLAP Table 10.2.
PATHOLOGY
The larynx is lined by pseudostratified ciliated columnar epithelium except on the superior surface of the epiglottis and vocal cords, which are covered by stratified squamous, nonkeratinized epithelium (Fig. 10.1). Most cancers are squamous cell cancers but a variety of malignancies can occur (Table 10.1). Vocal cord cancers tend to be well differentiated and supraglottic; subglottic cancers tend to be more undifferentiated.
TNM STAGING CRITERIA
TNM STAGING CRITERIA
Glottic cancers are the most common laryngeal cancers and are three times more common than others. Glottic cancers are most often confined to the true cords along its anterior free border. However, the cancerous nodule usually is part of a field cancerization and is an alert signal to stop smoking. To halt future cancers from developing elsewhere in the respiratory and upper digestive passage, it is essential to abstain from smoking. Cancers of the true cord tend to be confined to one cord, but one third of the cases involve both cords, most often spreading across the anterior commissure where it may extend along anterior attachment (Broyles ligament) to the thyroid cartilage. Invasion of thyroid cartilage can follow with destruction of its calcified body. Posterior involvement of arytenoid cartilage is uncommon and obscures their normal double-beaded appearance.
Supraglottic cancers can arise from a variety of different locations and tend to cause few symptoms until advanced. The free surface of the epiglottis, the false cords, and the ventricles can all be involved. Transglottic cancers are usually advanced and extend from the supraglottic area, invade the vocal cords, and impair their function. These tumors spread rapidly because of the rich lymphatic network in this region. Bilateral neck nodes are often encountered. Another favored area of spread is the pre-epiglottic fat space.
Subglottic cancers, in terms of prognosis, are worse than other types. This is probably due to their tendency to invade the trachea and to reach a more advanced state before detection.
Subglottic cancers are often vocal cord lesions beginning on the inferior surface of the true cords but growing unrecognized. True subglottic cancers are really tracheal cancers and begin 1 cm below the vocal cords. Such cancers are rare and tend to involve the cricoid cartilage early because there is no muscle layer beneath the mucous membrane. Difficulty in breathing rather than hoarseness may be the critical complaint.
The larynx was initially staged with the development of the TNM system and appeared in the joint first edition of American Joint Committee on Cancer/International Union Against Cancer (AJCC/UICC) (1978). The basis of progression of laryngeal cancers is related to their spread patterns to subsites (T2) as well as advancement from any one major site: glottic, supraglottic, subglottic to another, and (T2) if cord mobility is preserved. Loss of cord mobility indicates T3.
SUMMARY OF CHANGES SEVENTH EDITION AJCC
The TNM stages according to the 7th Edition of AJCC are illustrated in color code of advancement (Fig. 10.3). T4 lesions have been divided into T4a (moderately advanced local disease) and T4b (very advanced local disease), leading to the stratification of Stage IV into Stage IVA (moderately advanced local/regional disease), Stage IVB (very advanced local/regional disease), and Stage IVC (distant metastatic disease).
The TNM Staging Matrix is color coded for identification of Stage Group once T and N stages are determined (Table 10.3).
GLOTTIC LARYNX
Figure 10.3 | TNM stage grouping. Glottic cancers are commonly confined to vocal cords producing hoarseness early, which leads to their detection. Vertical presentations of stage groupings, which follow the same color code for cancer stage advancement, are organized in horizontal lanes: Stage 0, yellow; I, green; II, blue; III, purple; IVA, red; and IVB, black. Definitions of TN on left and stage grouping on right. Note inferior box on T-oncoanatomy provides a key to vocal cord mobility.
SUBGLOTTIC CANCER LARYNX
Figure 10.2A | Patterns of spread. A. Coronal: Note paralaryngeal invasion and cricoid cartilage. B. Sagittal: Note posterior invasion into pharynx and esophagus. The primary cancer (glottic larynx) invades in various directions, which are color-coded vectors (arrows) representing stage of progression: Tis, yellow; T1, green; T2, blue; T3, purple; T4a, red; and T4b, black. The concept of visualizing patterns of spread to appreciate the surrounding anatomy is well demonstrated by the six directional pattern i.e. SIMLAP Table 10.2A.
SUBGLOTTIC LARYNX
Figure 10.3A | TNM stage grouping. Subglottic cancers are tracheal tumors and are often life-threatening because of their vital location and present as advanced cancers. Vertical presentations of stage groupings, which follow the same color code for cancer stage advancement are organized in horizontal lanes: Stage 0, yellow; I, green; II, blue; III, purple; IVA, red; and IVB, black. Definitions of TN on left and stage grouping on right. Note inferior box on T-oncoanatomy provides a key to vocal cord mobility.
T-ONCOANATOMY
ORIENTATION OF THREE-PLANAR ONCOANATOMY
The anatomic isocenter of the true glottis is at the C5 level. The anterior surface bullet enters midway below the anterior notch of the thyroid cartilage and its inferior border (Fig. 10.4A) and the lateral bullet enters through the body of the thyroid cartilage (Fig. 10.4B).
T-oncoanatomy
The introduction to three-dimensional planar view of the larynx is best appreciated from the posterior coronal view with the constrictor musculature split.
• Coronal plane (Fig. 10.5A): The larynx is divided into three parts: (i) the supraglottis, (ii) the glottis, and (iii) the subglottis; these three parts are known as the vestibule, ventricle (glottis), and infraglottic cavity, respectively. The epiglottis is readily visualized at its vestibule. The opening of the larynx, referred to as the aditus larynges or the superior laryngeal aperture, can be traced from the epiglottis to the arytenoids. The aryepiglottic folds start at the free edge of the epiglottis and terminate at the corniculate and arytenoids cartilages. The false cords and true cords are separated by the ventricle. Each acts as a sphincter that closes off the airway.
• Sagittal plane (Fig. 10.5B): The cartilaginous skeleton of the larynx consists of the epiglottis, thyroid, cricoid, arytenoids, corniculate cartilages, and hyoid bone. A set of fine membranes and muscles hold this cartilage together, forming a rigid structure, which is not easily destroyed by cancer invasion. The cricothyroid muscle tenses the vocal cords. The intrinsic muscles include the posterior cricoarytenoid, thyroarytenoids, vocalis, thyroepiglottis, and aryepiglottis. The essential function of these muscles is to open and close the glottis during breathing and to regulate cord tension during speaking. The true cords and false cords are separated by a ventricle. The pre-epiglottic fat-filled space can be readily infiltrated from a cancer in the supraglottic region at its base because the epiglottic cartilage sits as an upside-down paddle. These features are best appreciated in the sagittal view.
• Transverse view (Fig. 10.5C): The axial view illustrates the paralaryngeal space between the thyroid and epiglottal cartilage and the position of the larynx to the pharynx. The prevertebral space is separated from the larynx by the hypopharynx, and the prevertebral fascia is rarely invaded by true laryngeal malignancies.
Refer to Figure 10.5 for T-oncoanatomy for three planar sections.
Figure 10.4 | Orientation of three-planar T-oncoanatomy. Glottic (Top). Subglottic (Bottom). The anatomic isocenter is at the axial level at C5/6 for Glottis, and C6/7 for Subglottis. A. Coronal. B. Sagittal.
Figure 10.5 | Glottic (Top) and Subglottic (Bottom): T-oncoanatomy. The color code for the anatomic sites correlates with the color code for the stage group (Fig. 10.3 and 10.3A) and patterns of spread (Fig. 10.2 and 10.2A) and SIMLAP table (Table 10.2 and 10.2A). Connecting the dots in similar colors will provide an appreciation for the three-dimensional oncoanatomy.
N-ONCOANATOMY AND M-ONCOANATOMY
N-ONCOANATOMY
Each segment of the larynx drains to a different sentinel node (Fig. 10.6; Table 10.4). The glottis or true vocal cords are not rich in lymphatics and drain to pretracheal or paralaryngeal lymph nodes. The supraglottis is richer in lymphatics and vascularization, with drainage favoring midjugular and jugulodi-gastric nodes.
Subglottic cancers drain to deeper cervical nodes, the jugulo-omohyoid, and even the scalene nodes. The incidence and distribution of clinically negative neck node (N0) Figure 10.7A and Table 10.5A, and clinically positive (N+) Fig. 10.7B and Table 10.5B.
Orientation of N Oncoanatomy for Subglottic: The sentinel node is different than the glottis and is the jugulo-omohyoid. However, as the cancer advances, transglottic, the mid deep cervical nodes become involved.
M-ONCOANATOMY
The venous drainage of the larynx is by way of laryngeal veins into the internal jugular vein, brachiocephalic vein, and then into the superior vena cava. Metastases are most likely to target the lung (Figs. 10.6 and Fig. 7.7B as in Oropharynx).
Figure 10.6 | N-oncoanatomy. Glottic (A,B). The red node highlights the sentinel node, which is the paralaryngeal node. Subglottic (C,D). The red node highlights the sentinel node, which is the jugulo-omohyoid node. A,C.Anterior view. B,D. Lateral view. M-oncoanatomy is determined by the jugular vein, which joins with the subclavian vein to form the superior vena cava on the right, and the innominate vein, which drains into the right side of the heart and then into lung.
Figure 10.7 | A. Incidence and distribution for N0 neck according to AJCC neck node regions. B. Incidence and distribution for N0 neck according to AJCC neck regions.
STAGING WORKUP
RULES OF CLASSIFICATION AND STAGING
Clinical Staging and Imaging
Assessment of the larynx in its three compartments—supraglottis, glottis, and subglottis—is optimally performed with a fiberoptic laryngoscope and often requires general anesthesia, which is advised often after completion of diagnostic imaging studies. Determining vocal cord motion, namely, partial or complete paralysis, is difficult because the normal cord can cross over to meet the involved cord. Imaging studies do not supplant endoscopy and are viewed as complementary. Distinction between the three compartments is essential to staging. Computed tomography (CT) (Fig. 10.8) and magnetic resonance imaging (MRI) are often complementary (see Table 10.6).
Pathologic Staging
The gross specimen should be evaluated for margins. Unresected gross residual tumor must be included and marked with clips. All resected lymph node specimens should describe size, number, and level of involved nodes and whether there is extracapsular spread. Specimens taken after radiation, chemotherapy, or both need to be noted; specimen shrinkages may occur up to 30% after resection itself. Designations pT and pN should be used after histopathologic evaluation. Perineural invasion deserves special notation.
Oncoimaging Annotations
• After contrast administration, cross-sectional CT studies of the larynx should be performed, extending from C1 to the thoracic inlet.
• MRI should be performed before and after gadolinium enhancement.
• Extralaryngeal tumor spread, sclerosis, erosion, and lysis suggest cartilaginous cancer invasion. The negative predictive value of this combination of findings is high, but the specificity is low.
• A positive diagnosis of cartilage invasion on MRI should be made with caution because the positive predictive value of the altered signal behavior as a sign of invasion is low.
• Pretreatment CT imaging is predictive of local tumor control in patients treated with definitive radiation therapy. Tumor diameters less than 2 cm have a high likelihood of local control, whereas tumors with diameters greater than 2 cm have only a 50% chance of control.
• Both positron emission tomography with fluorine-18-labeled-deoxyglucose (FDG) and thallium-201 single photon emission computed tomography have useful potential in differentiating posttreatment radiation changes from recurrent tumor.
PROGNOSIS AND SURVIVAL
PROGNOSTIC FACTORS
• Size of lymph nodes
• Extracapsular extension from lymph nodes for head and neck
• Head and neck lymph nodes levels I-III
• Head and neck lymph nodes levels IV-V
• Head and neck lymph nodes levels VI-VII
• Other lymph node group
• Clinical location of cervical nodes
• Extracapsular spread (ECS) clinical
• Extracapsular spread (ECS) pathologic
• Human papillomavirus (HPV) status*
CANCER STATISTICS AND SURVIVAL
The survival rates for subglottic cancers are poorer than similar stage glottic and subglottic cancers. Prognostic factors are similar to glottic. Glottic cancers are found in early stage I. Therefore, survival is at 90% level. Subglottic cancers are found late stage III/IV with survival rates under 50% (Fig. 10.9).
*The foregoing passage is from Edge SB, Byrd DR, and Compton CC, et al, AJCC Cancer Staging Manual, 7th edition. New York, Springer, 2010, p. 65.
Figure 10.8 | Glottic (left) and Subglottic (right). Neck and Larynx—Axial CT scan. A. Note Thyroid cartilage encompasses true glottis and anterior commisure invasion (Broyle's ligament) erodes the calcified thyroid cartilage. B.Note cricoid cartilage encompasses subglottic region. The CT/MRI transverse section can be correlated with anatomy in Figure 10.5C as an assist to staging.
Figure 10.9 | Five-year survival rates by stage diagnosis of subglottis. (Data from Edge SB, Byrd DR, and Compton CC, et al, AJCC Cancer Staging Manual, 7th edition. New York, Springer, 2010.) *The foregoing passage is from Edge SB, Byrd DR, and Compton CC, et al, AJCC Cancer Staging Manual, 7th edition. New York, Springer, 2010, p. 65.