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Triangular Space Larynx

Fig. 3.2 A Diagram of the larynx and pre-epiglottic space. B Diagram and boundaries of the oropharynx and hypopharynx, with relationship to oral cavity and larynx, respectively.

conus elasticus inferiorly, the thyroid cartilage laterally, the quadrangular membrane medially and the pyriform sinus posteriorly. The pre-epiglottic space, also filled with adipose and connective tissue, is triangular shaped. It is bounded anteriorly by the thyroid cartilage and thyrohyoid membrane, posteriorly by the epiglottis and thyroepiglottic ligament, and superiorly by the hyoepiglottic ligament which forms its base. Both para-glottic and pre-epiglottic spaces contain lymphatics and blood vessels, but no lymph nodes. Suprahyoid epiglottic tumours are distinct from the more common infrahyoid tumours in that they are superior to the pre-epiglottic space, and often spread to the base of the tongue. Tumours that invade the pre-epiglottic and paraglottic spaces may spread without impedance through the loose connective tissue and eventually invade the extralaryngeal tissues. The supraglottic larynx is well endowed with lymphatics draining primarily into the upper, middle and lower jugular lymph nodes (levels II, III and IV, respectively). The glottis, in contrast, has a limited lymphatic supply, but also drains to the same group of lymph nodes. If a glottic carcinoma extends more than one centimeter inferi-orly, the paratracheal lymph nodes are at risk for metastasis. The lymphatic drainage of the subglottis is mainly to the paratracheal lymph nodes and, only infrequently, to the middle and lower jugular lymph nodes (levels III and IV). Early in life, the larynx is entirely lined by ciliated respiratory epithelium. With time, this epithelium is gradually replaced by non-keratinizing stratified squamous epithelium. The adult larynx is lined entirely by squamous epithelium, with the exception of the ventricles and the subglottis - which continue to be lined by respiratory epithelium. Infrequently, one may see small patches of persistent ciliated respiratory epithelium in an otherwise typical adult supraglottis. The nonkeratinized squamous mucosa of the true vocal cords is normally about 5-10 cells thick. Although mucoserous glands are abundant in the supraglottis and subglottis, they are essentially absent in the true vocal cords.


The pharynx is a hollow muscular tube extending from the skull base to the lower border of the cricoid cartilage. It is arbitrarily divided into three regions: nasopharynx, oropharynx, and hypopharynx. The hypopharynx (also known as laryngopharynx) lies behind the larynx and partially surrounds it on either side, commencing from a plane of the superior border of the hyoid bone (or floor of the vallecula) to the inferior border of the cricoid cartilage. It is continuous with the oropharynx above and with the cervical esophagus below. The junction of hypopharynx with the cervical esophagus corresponds to the sixth cervical vertebra. The lumen of the hypopharynx is cone-shaped, wide superiorly and rapidly narrowing in the postcricoid and cervical esophageal areas. The hypopharynx has three components: right and left pyriform sinuses, postcricoid area, and lateral and posterior pharyngeal walls. The pyriform sinuses are extralaryngeal gutters nestled against the thyroid lamina. Each pyriform sinus is shaped like an inverted pyramid with the apex pointed toward the lower limit of the cricoid cartilage. The superior border corresponds to the pharyn-goepiglottic fold. Each sinus has three walls, medial, lateral and anterior. The postcricoid area forms the anterior wall of the hypopharynx and connects the two pyriform sinuses. It extends from the level of the arytenoid cartilages to the inferior border of the cricoid cartilage {947}. The lateral pharyngeal wall merges with the pyriform sinus. The posterior pharyngeal wall extends from the level of the superior surface of the hyoid bone to the inferior border of the cricoid cartilage.

The hypopharynx is richly supplied with lymphatics. The major drainage is along the jugular chain (levels II, III and IV), retropharyngeal lymph nodes and the node of Rouviere at the skull base. The hypopharynx is typically lined by nonker-atinizing squamous epithelium, although areas of parakeratin or orthokeratin can be seen secondary to chronic irritation. The lamina propria contains scattered lymphoid aggregates as well as mucoserous glands.


The trachea extends from the lower border of the cricoid cartilage to the carina and averages 11 cm long in adults, varying roughly in proportion to an individual's height {1660}. It is 20-27 mm transversely and 16-20 mm sagitally {64}. There are approximately two tracheal cartilaginous rings per centimeter of trachea, with a total of about 18-22.

Although usually referred to as rings, the cartilages are incomplete posteriorly, and form about two-thirds of a circle. The tracheal cartilages are connected to each other by fibroelastic annular ligaments. Sometimes the first tracheal ring may be fused to the cricoid cartilage. The trachea is continuous with the larynx superiorly and the bronchi inferiorly. Anteriorly, it is intimately associated with the thyroid gland and posteriorly with the esophagus. The trachea is lined entirely by ciliated respiratory epithelium and contains abundant mucoserous glands in the lamina propria. Posteriorly, the non-cartilaginous or membranous portion of trachea contains prominent smooth muscle. The submucosal lymphatics drain toward the posterior part of the trachea and connect with the paratracheal lymph nodes. They also anastomose with sub-carinal, peribronchial and esophageal lymph nodes {64}.

Neck dissections

A neck dissection is a tissue mass containing the cervical lymphatics. In its classical form, it extends from the submandibular soft tissues to the supraclavicular fatty tissue, laterally bordered by the platysma, and medially by the internal jugular vein. The lymph nodes in this area are divided into 6 different compartments, referred to as levels {2183}. Level I is subdivided in two compartments, the submental area (level IA) that lies between both anterior bellies of the digastric muscle and the hyoid bone dor-sally, and the submandibular area (level 1B) that lies between the anterior belly of the digastric muscle medially and the mandibular bone laterally. Dorsally, this area is bordered by the tendon between the anterior and posterior belly of the digastric muscle that is attached to the

Fig. 3.3 Schematic drawing to show the various lymph node levels in the neck. Drawing by John A.M. de Groot.

hyoid bone, and the stylohyoid muscle. Thus, the triangle of soft tissue enclosed anteriorly and laterally by the mandible and dorsally by the hyoid is subdivided into one median compartment, the submental area and 2 lateral compartments, the submandibular areas. Level II represents the upper jugular (cervical) group of lymph nodes. This area extends from the base of the skull superiorly to the level of the inferior border of the hyoid bone inferiorly. The lymph nodes in this area mainly cluster in the vicinity of the internal jugular vein and are laterally covered by the body of the sternocleidomastoid muscle. Level III represents the middle jugular (cervical) group of lymph nodes. These lymph nodes are located around the middle third of the internal jugular vein that superiorly begins where the upper jugular compartment ends; the lower border lies at the inferior border of the cricoid cartilage.

Level IV comprises the lymph nodes located around the lower third of the internal jugular vein extending from the inferior border of the cricoid cartilage superiorly to the clavicle inferiorly. Level V is the lymph nodes collectively taken together as the posterior triangle group. This is a triangular area lying between the anterior border of the trapezius muscle posteriorly, the posterior border of the sternocleidmastoid muscle anteriorly and the clavicle caudally. It is subdivided into a superior compartment, level VA that contains the spinal accessory lymph nodes and a lower compartment (level VB) that contains the transverse cervical and the supraclavic-ular lymph nodes. A horizontal plane through the inferior border of the anterior cricoid arch separates both sublevels. Level VI is the anterior compartment. This compartment has the hyoid bone as its cranial and the suprasternal notch as its caudal border. Both lateral borders are the common carotid arteries. This area is rectangular and lies between the area defined as level I above and the sternum below.

Four different types of neck dissections are recognized {2183}. A radical neck dissection consists of lymph nodes from level I through V. The internal jugular vein, sternocleidomastoid muscle, and spinal accessory nerve also form part of it. A modified radical neck dissection comprises all lymph nodes from levels I-V while preserving one or more of the non-lymphoid structures that should be specified, e.g. modified radical neck dissection with preservation of spinal accessory nerve. If less than level I-V is removed, the neck dissection is referred to as selective, while specifying the levels that are included. The use of terms such as supra-omohyoid neck dissection is less preferable due to ambiguities about the extent of the surgical procedure. Extended radical neck dissection is the fourth type. This term refers to any type of neck dissection that consists of a radical neck dissection together with additional structures either lymphatic or non-lymphatic that have to be identified specifically. These structures may be additional lymph node compartments, nerves, or blood vessels. Examination of a neck dissection should be done with the following questions in mind: (1) does the specimen contain lymph nodes with metastatic deposits, (2) if so, how many lymph nodes with metastases are present, specified for each level (3) what is the size of the largest positive lymph node, necessary for staging, and (4) is there extracapsular tumour spread?

Dissection of the specimen starts with determination of the type of neck dissection and identification of the various lymph nodes levels and any additional non-lymphoid structures that may have been removed. As the anatomical boundaries that are used by the surgeons to identify the lymph node levels are not present in the specimen, these cannot be used by the pathologist. Optimal processing of a neck dissection therefore requires that the surgeon submit the specimen with all lymph node levels properly labelled.


Age and sex distribution

Laryngeal and hypopharyngeal squa-mous cell carcinoma (SCC) occur most frequently in the sixth and seventh decades, but some cases have been described in children {123,1934}. They are more common in men {344,2113} though the male:female ratio is decreasing in some countries; women are becoming increasingly affected because of increased prevalence of smoking over the last two decades {584}. Tracheal SCC occurs predominantly

Global Cancer Incidence
Fig. 3.5 Global incidence rates of cancer of the larynx (all ages) in males. Age-standardized rates (ASR, world standard population) per 100,000 population and year. From: Globocan 2000 {730}.

between 40 and 60 years of age, men are affected at least twice as often as women {1040}.


SCC comprises about 95% of laryngeal malignancies. The majority originate from the supraglottic and glottic regions, although there are geographic variations in the relative ratio between these two sites. The incidence in men is high (10/100,000 pa or more) in southern and central Europe, southern Brazil, Uruguay and Argentina and among Blacks in the United States. The lowest rates (<1/100,000 pa) are recorded in SouthEast Asia and central Africa. The incidence in women is below 1/100,000 pa in most populations. An estimated 140,000 new cases occurred worldwide in 1990, 86% of these patients were men {1980,1981}. The incidence is slightly more common in urban that in rural areas {344,2113}.

There are also geographic differences in the topographic distribution of the laryn-geal SCC {126}. In France, Spain, Italy, Finland and the Netherlands, supraglot-tic SCC predominates, while in the United States, Canada, England and Sweden glottic SCC is more common. In Japan, SCC is approximately equally distributed between the two sites. Interpretation of incidence rates of hypopharyngeal cancer is probably complicated by absence or misclassifi-

cations within subsites of the pharynx. Recorded incidence is highest among men (>2.5/100,000 pa) in India, Brazil and Central and Western Europe, and is lowest (<0.5/100,000 pa) in East Asia, Africa and Northern Europe. Incidence among women is low (<0.2/100,000 pa) in most populations except India, where rates up to 1/100,000 pa are recorded {1981}. This is probably due to the fact that tobacco is more often chewed than smoked in India.

Tracheal carcinoma is rare with approximately one tracheal carcinoma per 75 laryngeal carcinomas. It accounts for less than 0.1% of cancer deaths {1040}. SCC is the most frequent malignant tumour of the trachea representing 5673% of all tracheal carcinomas {1040}.


The incidence of laryngeal and hypopha-ryngeal SCC is increasing in much of the world, both in men and in women. This increase is related to changes in tobacco and alcohol consumption {344}. Primary prevention of laryngeal and hypopharyngeal SCC could be achieved by cessation of smoking and reduction of alcohol consumption {344}.


Tobacco and alcohol - Larynx

Most cases of laryngeal cancer in Western countries are related to smoking and alcohol abuse {90}. The combined effect follows a multiplicative rather than additive model {285,772,1607,1608, 1800,1943,2647,2885}. The increased relative risk (RR) for alcohol consumption differs by site, and is higher for the supraglottis and hypopharynx and lower for the glottis and subglottis {2647}. The impact of increased RR (10x) for smoking is stronger for glottic than supraglot-tic SCC {2647}. Studies in several populations have shown a direct dose-related response between smoking and SCC and the benefits of cessation. Smoking black tobacco cigarettes entails a stronger risk than smoking blond tobacco {2235}. Other smoking habits that increase the RR of laryngeal SCC include: smoking at a young age, long duration, high number of cigarettes per day, and deep smoke inhalation {195,1035}. The influence of tobacco on RR of laryngeal SCC is confirmed even for non-drinkers {308,2833}. Case controlled studies from Italy and Switzerland show an increased RR of 2.46 for heavy drinkers and laryngeal SCC. The RR for current smokers who do not drink is 9.38 {238}. Avoiding cigarettes and alcohol could prevent about 90% of laryngeal and hypopharyngeal SCC {718}.

Tobacco and alcohol - Hypopharynx

Studies from India have also reported an association between chewing tobacco-containing products {968} and hypopha-ryngeal SCC. Tobacco and alcohol are also the main risk factors for hypopha-ryngeal SCC. The effect of alcohol is stronger and the impact of tobacco is weaker than for laryngeal SCC.

Asbestos and occupational exposure

There is controversy regarding occupational asbestos exposure and increased risk for developing laryngeal SCC {247, 1255,1982,2484}. A recent review has not supported a causative role for asbestos exposure {283}. However, there is evidence supporting other occupational exposures and increased risk of laryn-geal SCC, such as polycyclic aromatic hydrocarbons, metal dust, cement dust, varnish, lacquer, etc {1608}. After adjustment for alcohol and tobacco consumption, the increased risk ranged from 1.8 for cement dust to 2.7 for polycyclic aromatic hydrocarbons. Significant associations are also found with ionizing radiation, diesel exhausts, sulphuric acid mists and mustard gas {1608,2821}.

Asbestos Smoking
Fig. 3.6 Multiplicative increase in relative risk of laryngeal cancer as a consequence of both alcohol drinking and active smoking (colour coding approximates progressive doubling of risk as exposure increase). From A.J. Tuyns et al. {2647}.

Human papillomavirus (HPV)

There is conflicting evidence implicating HPV16, in 3-85% of laryngeal SCC {1523}. The prevailing opinion is that HPV has a minor causative role, if any, in laryngeal carcinogenesis {853,1253, 1510,1523,1999,2330}. Additionally, HPV DNA has been detected in 12-25% of individuals with clinically and histologically normal larynges {1912,2172}, suggesting that the occasional demonstration of HPV in laryngeal SCC may be incidental.

Diet and nutritional factors

A protective effect is probably exerted by high intake of fruits and vegetables {238, 565,1405,1910,1951,2003,2885,2901}. Specific evidence regarding carotenoids and vitamin C, is inadequate for a conclusion {2821}. Maté drinking has been suggested to be a risk factor in studies from Brazil and Uruguay {90}.

Gastroesophageal reflux Gastroesophageal reflux has been related to increased risk of laryngeal SCC, especially among patients who lack other major risk factors {80,812,1782, 2724}. Gastroesophageal reflux may act as a promoter in the presence of tobacco and alcohol {812}.

Genetic susceptibility

There is no evidence of strong genetic factors in laryngeal carcinogenesis; however, polymorphisms for enzymes implicated in the detoxification of alcohol and tobacco, such as alcohol and aldehyde dehydrogenases, are likely to represent weak susceptibility factors, with relative risks in the order of 1.5-2 {200,1590}. Bloom syndrome is an inheritable condition with a predisposition towards laryn-geal and hypopharyngeal SCC.

Pathology overview and principles

Compartmentally, the supraglottis is distinct from the glottis and subglottis. The supraglottis is embryologically derived from the buccopharyngeal anlage (branchial arches III and IV) while the glottis is derived from the laryngotra-cheal anlage (branchial arches V and VI). The fascial compartmentalization, as well as the lymphatic drainage is distinct for the supraglottis and glottis and is the oncologic basis for the supraglottic horizontal laryngectomy. Dye injected into the supraglottis remains confined and does not travel to the ventricular or glottic tissues. Likewise, glottic dye injections do not pass superiorly to the ventricle or interiorly to the mucosa overlying the cricoid cartilage. In tact, the mucosa overlying the lamina propria ot the glottis (Reinke's space or laryngeal bursa) may burst from fluid distention rather than allowing injected dye to extend into the ventricle or cross the anterior commissure. These studies also confirm that the larynx is divided into right and left compartments {2087}.

The anatomic site of occurrence of tumour within the larynx can influence 1) the type of presenting symptoms, 2) stage at presentation, 3) treatment, and 4) prognosis. The vast majority of malignancies of the supraglottis and glottis are SCC. However the relative distribution of SCC per laryngeal compartment varies worldwide. Non-squamous tumours comprise a small subset of laryngeal malignancies, and are more likely encountered in the supraglottis and infraglottis than the glottis.

Glottic tumours present with hoarseness and are typically small when detected. In contrast, the supraglottis is a clinically silent area and, as such, tumours in this site are often large at the time of diagnosis. Epiglottic tumours may present with a change in vocal quality (a muffled or "hot potato voice"), airway obstruction, dysphagia and/or cervical metastasis.

Tumours at the base of the epiglottis may escape visualization at indirect laryngoscopy ("Winkelkarzinom" or "cancer in the corner"). Primary ventricular tumours are rare and often remain obscured on laryngeal examination, merely forming a bulge beneath the false vocal cord. Tumours of the pyriform sinus are usually large when discovered and typically present as odynophagia or referred otalgia. If the tumour involves the medial wall or the apex of the pyriform sinus, vocal cord dysfunction may result.

Content of surgical pathology report, including cervical lymph nodes

The surgical pathology report of a laryngectomy specimen should indicate the type of procedure (hemi-, supraglottic-, or total laryngectomy), and whether any additional tissues are attached (neck dissection, thyroid gland, parathyroid gland). Additional features that should be addressed include 1) site of origin, size and extent of the tumour; 2) histologic type and grade; 3) presence of perineural, lymphovascular, cartilaginous and/or extralaryngeal invasion and 4) status of the resection margins {3,290}. The neck dissection should include the details as stated above (see 'Anatomy -Neck dissections').

Surgical pathology report of a hypopha-ryngectomy specimen should indicate whether the tumour is arising from the

Table 3.1 Histologic diagnoses for 479 patients with laryngeal malignancies*


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  • virpi
    Can peribronchial lymph node adenocarcinoma metastisise to the oropharnx or vocalchords?
    4 years ago

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