PERSPECTIVE, PATTERNS OF SPREAD, AND PATHOLOGY
The malignant gradient is in reference to the horizontal mid-plane through the true glottis. Cancers above have a better outcome and cancers below have a poorer prognosis.
PERSPECTIVE AND PATTERNS OF SPREAD
Cancers of the larynx are among the 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, 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 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. The malignant gradient is greater 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 less favorable outcome and cancers below have a better prognosis for readily apparent reasons relating to the ease of detection of supraglottic compared with subglottic cancers 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. 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. 9.2; Table 9.2).
PATHOLOGY
Most cancers are squamous cell cancer (Fig. 9.1), but a variety of malignancies can occur (Table 9.1). Vocal cord cancers tend to be well differentiated, and supraglottic and subglottic cancers tend to be more undifferentiated.
Figure 9.1| Squamous cell carcinoma. An infiltrative neoplasm is composed of cohesive nests of tumor.
Figure 9.2 | Patterns of spread. A. Coronal. Transglottic invasion B. Sagittal. Pre-epiglottic fat pocket invasion allows for paralaryngeal spread. The primary cancer (supraglottic 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 9.2.
TNM STAGING CRITERIA
TNM STAGING CRITERIA
Supraglottic cancers can arise from a variety of different locations and tend to cause few symptoms until advanced (Fig. 9.3). The free surface of the epiglottis, false cords, and ventricles can all be involved. Transglottic cancers are usually advanced cancers that extend from the supraglottic area and invade the vocal cords and impair their function. These tumors spread rapidly because of the rich lymphatic network of this region. Bilateral neck nodes are often encountered. Another favored area of spread is the pre-epiglottic fat space.
Epilaryngeal cancers arise from the free border of the larynx where they come into contact with the pharynx. Cancers of the tip of the epiglottis can spill into the valleculae and can appear like a golf ball on a tee. Another common point of origin is the aryepiglottic fold, from which the cancer can spread into the supraglottic larynx or into the piriform sinus. Arytenoids cancers are unusual and obscure the normal double-beaded appearance of the posterior cartilages of the larynx.
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.
The larynx was initially staged with the development of the TNM system and appeared in the joint first edition of the American Joint Committee on Cancer/International Union Against Cancer guidelines (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, 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. 9.3). 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 9.3).
SUPRAGLOTTIC LARYNX
Figure 9.3 | TNM stage grouping. Supraglottic cancers spread insidiously and may not be detected until surrounding structures are invaded as vocal cords or spill into piriform fossa. 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 supraglottic larynx is at the C5 level. The anterior surface bullet is at the level of the thyroid cartilage notch (Fig. 9.4A) and the lateral surface bullet is at the same level anterior to the greater horn of the thyroid cartilage (Fig. 9.4B).
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. 9.5A): The larynx is divided into three parts: (i) supraglottis, (ii) glottis, and (iii) 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 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 arytenoid cartilages. The false cords and the true cords are separated by the ventricle. The true cords act as a sphincter that closes off the airway.
• Sagittal plane (Fig. 9.5B): The cartilaginous skeleton of the larynx consists of the epiglottis, thyroid, cricoid, arytenoids, cuneiform and corniculate cartilages and hyoid bone. A set of fine membranes and muscles hold this cartilage together, forming a rigid structure that is not easily destroyed by cancer invasion. The crieothyroid muscle tenses the vocal cords. The intrinsic muscles include the posterior and lateral 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 the 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 coronal and sagittal views.
• Transverse view (Fig. 9.5C): 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.
Figure 9.4 | Orientation of three-planar T-oncoanatomy. The anatomic isocenter is at the axial level at C5. A. Coronal. B. Sagittal.
Figure 9.5 | T-oncoanatomy. The Color Code for the anatomic sites correlates with the color code for the stage group (Fig. 9.3) and patterns of spread (Fig. 9.2) and SIMLAP tables (Table 9.2). Connecting the dots in similar colors will provide an appreciation for the 3D Oncoanatomy.
N-ONCOANATOMY AND M-ONCOANATOMY
N-ONCOANATOMY
Each segment of the larynx drains to a different sentinel node (Fig. 9.6; Table 9.4). 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 jugulodigastric nodes. Infraglottic cancers drain to deeper cervical nodes, the jugulo-omohyoid, and even the scalene nodes. The incidence and distribution of clinically negative neck nodes (N0) Table 9.5A and clinically positive (N+) Table 9.5B according to AJCC levels (Fig. 8.7A,B).
M-ONCOANATOMY
The venous drainage of the larynx is by way of laryngeal veins into the internal jugular vein and ultimately into the superior vena cava. Metastases are most likely to target the lung.
The target organ for supraglottic spread is classically the lung (Fig. 9.7B).
Figure 9.6 | N-oncoanatomy. The red node highlights the sentinel node, which is the jugulodigastric node. A. Anterior view. B. Lateral view. M-oncoanatomy is determined by the right internal jugular vein which joins with the right subclavian vein to form the right brachiocephalic vein, which drains into the superior vena cava on the right, and the left brachiocephalic vein, which drains into the superior vena cava and then the right side of the heart and then into lung.
Figure 9.7 | A. Incidence and distribution of 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 infraglottis—is optimally performed with fiberoptic laryngoscope and often requires general anesthesia, which is advised often after completion of diagnostic imaging studies. Determining vocal cord motion, either partial or complete paralysis, is difficult; 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. 9.8) and magnetic resonance imaging (MRI) are often complementary (see Table 9.6).
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-section 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 can cause cartilage sclerosis, erosion, and lysis, suggestive of cartilaginous cancer invasion on CT.
• 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 of less than 2 cm have a high likelihood of local control, whereas tumor diameters greater than 2 cm have only a 50% chance of control.
• Both positron emission tomography with fluorine-18-labeled-deoxy-glucose and thallium-201 single photon emission computed tomography have useful potential in differentiating posttreatment radiation changes from recurrent tumor.
PROGNOSIS AND CANCER SURVIVAL
PROGNOSTIC FACTORS
The seventh edition of the AJCC Cancer Staging Manual lists the following prognostic factors for nasal ethmoid sinus cancers:
• 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
• Tumor thickness*
*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. 99.
Figure 9.8 | Neck and Larynx—Axial CT scan. The CT/MRI transverse section can be correlated with the anatomy in Figure 9.5C as an assist to staging.
CANCER STATISTICS AND SURVIVAL
Generally, cancers of the oral cavity, pharynx, and upper digestive passage account for 36,540 new cases each year. In addition, cancer of the larynx affects another 12,720 patients and thyroid cancers, 44,670.
Approximately 25% of head and neck cancer patients die annually, often due to other causes. Long-term survival in thyroid cancers is exceptional, with only 1,500 deaths (5%). The improvement in oral cavity and pharyngeal tumors from 1950 to 2000 was modest at 14% and matches larynx at 15%. A multidisciplinary approach is vital, and normal tissue conservation and reconstructive techniques have both added greatly to quality of life. Unfortunately, this patient population abuses ethanol and nicotine and it is difficult to change these habits. Persistence of smoking and drinking contributes to their demise, often from second malignant tumors in adjacent sites.
Specifically, laryngeal cancers are a more favorable site in head and neck cancers because hoarseness allows for early detection. With early detection, stage I glottic cancers have 95% survival at 5 years and overall stages at 85%. Success in advanced stages in both survival and preservation of voice is due to chemoradiation regimens, which yield high complete response rates (i.e. 50% 5 years survival and somewhat better for stages I and II).
Figure 9.9 | Five-year survival rates by stage at diagnosis. (Data from Edge SB, Byrd DR, and Compton CC, et al, AJCC Cancer Staging Manual, 7th edition. New York, Springer, 2010.)