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Radiological Patterns of Mucosal Spread of Squamous Cell Carcinoma of the Larynx
Updated: Jun 15, 2006
Introduction
Squamous cell carcinoma (SCCA) of the larynx involves the superficial mucosa lining the airway. This tumor predominantly spreads by mucosal pathways, but it can also spread by submucosal routes to exolaryngeal areas by natural foramen and dehiscences of cartilage and bone, by direct invasion of cartilage and bone or by circuitous pathways around cartilage and bone, and to exolaryngeal areas via lymphangitic spread to regional or even distal lymph nodes.
Depending on the site of origin, SCCA of the larynx spreads by distinct patterns, which helps not only in predicting the areas of the larynx to be involved but also in determining the site of origin based on the patterns of the areas involved. In addition, SCCA from a suprahyoid source, such as tumors of the nasopharynx (NP), the oropharynx (OP), the tongue, and the floor of mouth (FOM), may spread inferiorly and enter the endolarynx (see Images 1-2). These patterns are determined by the unique anatomy of the larynx and its relation to the OP and the hypopharynx as well as its connection between the tongue and the FOM via the tongue base at the hyoid bone. From the hyoid to the cricoid, the laryngeal airway and the upper digestive tract coexist; the joint structure is referred to as the aerodigestive tract, with the airway located anterior to the hypopharynx/digestive system.
This article discusses the unique anatomical anatomy of the larynx in relation to the airway and the digestive system, as illustrated by diagrams, CT scans, and MRIs. Patterns of spread of laryngeal SCCA by mucosal, submucosal, and nonmucosal routes are also discussed. The following sites of origin and their patterns of spread are discussed: epiglottis, valleculae, supraglottic, aryepiglottic folds (AEFs), false vocal cord (VC), true vocal cord (TVC), infraglottic, pyriform sinus, OP, tongue, and FOM. This article also addresses certain SCCAs that, by location, have characteristic patterns of adenopathy or involve cartilage and/or bone.
Relevant Anatomy
The larynx is anatomically divided into supraglottic, glottic, and infraglottic regions, with the TVC delineating the margins of separation. The TVC and 1 cm below is defined as the glottic region. The false VC, the epiglottis, and the AEFs with the pyriform sinuses comprise the supraglottic region. Approximately 1 cm below the TVC down to the first tracheal ring comprises the infraglottic region (see Image 3).
The superiormost portion of the larynx at its anterior wall is related to the tongue and the FOM at the hyoid bone. The tongue base inserts onto the hyoid bone located in the midline just above the vallecula and the preepiglottic fat. The mucosal-covered thyroepiglottic ligament is the hyoepiglottic mucosal fold that joins the epiglottis to the hyoid and thus joins the epiglottis to the tongue base. The preepiglottic fat is anterior to all of these structures along the inner surface of the hyoid bone. Its significance on imaging studies is when changes of fatty invasion by the tumor occur (observed well on CT scan and MRI). The base of the epiglottis is attached directly to the anterior wall of the larynx. Mucosal folds from either side of the epiglottis blend with the mucosa of the lateral walls of the larynx, forming the pharyngoepiglottic mucosal fold.
The lateral walls of the OP join the lateral pharyngoepiglottic mucosal fold, which then joins the lateral walls of the larynx at the hyoid bone level. The posterior wall of the OP becomes the hypopharynx (or the back wall) at the level of the hyoid. From the level of the hyoid down to the cricoid, the larynx is anterior and the hypopharynx is posterior. The larynx and the hypopharynx become 2 separate compartments separated by the cricoid. At the level of the inferior cricoid and the cricopharyngeus muscle, the hypopharynx becomes the esophagus. A natural dehiscence referred to as Killian dehiscence is the site where a Zenker diverticulum may occur.
The pyriform sinus and the AEFs are less common but important sites of origin of SCCA; these sites are important because of the unique relationship between the larynx anteriorly and the hypopharynx posteriorly. The AEFs are bilateral paired structures attached to the base of the epiglottis above. The AEFs descend to the level of the arytenoid cartilages, moving from a more anterior location to a more posterior location, and fold back to become the ligamentous support for the false VC. Thus, a tumor can spread from these folds down to the TVC and then spread posteriorly to also involve the hypopharynx.
The pyriform sinus originates in the supraglottic region below the epiglottis, spreading out in a lateral fashion to form a triangle and ending at the level of the false VC. The pyriform sinus is part of the hypopharynx, joining directly to it. The sinus should be considered as an expansion chamber that dilates during deglutition so that solid and noncompressible ingested food can be safely contained without injuring the mucosa of the contracting walls.
The AEFs separate the pyriform sinus from the laryngeal mucosal folds, which are anterior to the AEFs. The lateralmost margin of the pyriform sinus is adjacent to the posterior margin of the thyroid cartilage. Natural dehiscences are present in the cartilage at the hyoid/thyroid membrane level along the anterior larynx and at the bilateral lateral thyroid cartilages for the vessels and the nerves to the larynx, through which a tumor could potentially erode.
Lymphatic drainage of the larynx is rich in certain areas but absent in other areas, most notably the TVC. The epiglottis, the AEFs, and the pyriform sinuses have the richest lymphatic drainage; thus, they are the sites of SCCA with not only the earliest appearance of adenopathy but also the highest likelihood of adenopathy.
Mucosal Patterns Of Spread
SCCA of the larynx primarily involves the TVC (approximately 50-70%). The supraglottic larynx is the second most involved region (20-35%), and the least involved region is the infraglottic larynx (2-6%). Mucosal tumor spread is readily diagnosed by laryngoscopic examination.
Supraglottic region
The supraglottic larynx can be divided into an anterior compartment containing the epiglottis and the false VCs and a posterolateral compartment containing the AEFs, the hypopharynx, and the paraglottic fat.
The most superior located SCCA of the supraglottic larynx is usually an inferior continuation of SCCA from the FOM with involvement of the tongue base. Since the tongue base attaches to the anterior wall of the larynx at the hyoid bone, SCCA may spread to the vallecula and then down to the supraglottic larynx, either along the pharyngoepiglottic folds to the lateral laryngeal wall mucosa or via the thyroepiglottic ligament (hyoepiglottic mucosal fold) to the epiglottis. The tumor may spread from the epiglottis to the anterior wall via the attachment of the base of the epiglottis, via the AEFs down to the TVC and the false VC, or via the laterally located pharyngoepiglottic folds to the lateral walls of the larynx. However, a tumor may primarily arise from the tongue base, the vallecula, or the epiglottis itself.
From the AEFs, SCCA may spread from the ventral surface of the fold to the dorsal surface and, thus, into the region of the pyriform sinus; then, it may even spread more posteriorly to the back wall of the larynx, which is also the hypopharynx. Eventually, SCCA can spread from the supraglottic larynx down to the level of the esophagus at the level of the cricoid cartilage. This region is often referred to as the postcricoid region. However, for SCCA of the larynx to involve the esophagus would be unusual, although the potential does exist.
Likewise, SCCA of the more inferiorly located supraglottic structures (eg, false VC, AEFs) can ascend along the mucosal surfaces, up through the epiglottis, and stay in the midline along the thyroepiglottic ligament (hyoepiglottic mucosal fold) to the anterior wall, or it can ascend along posterior and lateral walls of the larynx and up to the pharynx. Ascension of SCCA of the supraglottic larynx or even the epiglottis into the tongue base or the FOM is unusual, although the potential does exist.
The preepiglottic fat is a constant normal anatomical feature, which is observed well on both MRI and CT scan. Replacement of this fat by the soft tissue intensity or density of a tumor is a grave sign; even if the tumor is locally confined, the fat invasion classifies the tumor as T3 according to the tumor, node, and metastases (TNM) classification system.
The following review of the TNM classification system of supraglottic carcinomas can be of benefit. In the supraglottic region, T1 is a tumor limited to one site without TVC fixation. T2 is a tumor in more than one site but with normal VC mobility. T3 is a tumor that is still limited to the larynx, with one of the following: TVC fixation, postcricoid involvement, medial pyriform sinus involvement, or invasion of the preepiglottic fat. T4 is a tumor that invades cartilage or bone or extends outside of the anatomical confines of the normal larynx.
The epiglottis is like a sieve, such that SCCA involving the dorsal surface readily spreads to the ventral surface. If the tumor spreads along the midline thyroepiglottic ligament (hyoepiglottic mucosal fold), it may then invade the hyoid bone or the tongue base. If the tumor spreads along the pharyngoepiglottic folds, it can spread into the OP and the tonsillar pillar region along the lateral margins of the larynx and the OP. Furthermore, the epiglottis is richly invested in lymphatics, and lymphangitic tumor spread is common.
SCCA of the false VC may produce an additional finding of a laryngocele cyst (air filled) or a saccular cyst (fluid filled) due to obstruction of the laryngeal ventricle opening between the false VC and the TVC. In fact, SCCA should be a consideration in a patient who develops a laryngocele and is not a musician who blows air into a musical instrument, such as a trumpet or a cornet.
Glottic regionBriefly, according to the TNM classification for glottic tumors, T1 is a tumor limited to the VCs with either anterior commissure involvement or posterior commissure involvement but with normal cord mobility. T1 is further subclassified as T1a, which is a tumor limited to one VC, and T1B, which is a tumor that involves both VCs. T2 is a tumor extending to another site (either supraglottic region or subglottic region) or limited to the TVC but with VC impairment. T3 is a tumor in more than 2 sites but still confined to the larynx with normal cord mobility. T4 is a tumor invading the cartilage or beyond the larynx into the OP or the exolaryngeal soft tissues.
SCCA of the TVC usually spreads into the supraglottic region and less often into the infraglottic region. In a superior direction, a tumor from the TVC may spread along the AEFs and up through the epiglottis. In axial CT scan or MRI, the transition from the TVC to the false VC is heralded by the presence of fatty tissue, which forms the medial aspect of the false VC. Thus, evidence from either CT scan or MRI of false VC involvement with a tumor would demonstrate replacement of this fatty tissue with a soft tissue signal tumor (see Image 3).
Determining whether both TVCs are involved is important for voice preservation types of surgeries; 2 common surgeries are the supraglottic laryngectomy and the vertical hemilaryngectomy.
Voice presentation types of surgeries are beyond the scope of this article; however, briefly and simply, the supraglottic laryngectomy is removal of one half of the larynx above the laryngeal ventricle. Thus, both TVCs are preserved, and, by definition, this type of surgery is for SCCA of the supraglottic larynx and not involving the TVC. Therefore, contraindications to this type of surgery are cases in which the TVC or the cartilage is involved; cases in which both arytenoid cartilages can be seen to be involved on imaging studies or VC and, thus, arytenoid cartilage fixation is seen on laryngoscopic examination; and cases in which involvement of the very inferior pyriform sinus or the postcricoid region is present.
The vertical hemilaryngectomy is used if only one VC is involved. Speech can still be preserved with just one VC. This procedure involves removal of the affected TVC, the false VC, the laryngeal ventricle, and the ipsilateral thyroid cartilage with preservation of the outermost perichondrium. Thus, contraindications include contralateral cord involvement of more than one third of the TVC, superior extension of a tumor to the ipsilateral false VC, inferior extension to the subglottic region more than 10 mm along the anterior wall or more than 5 mm along the posterior wall, involvement of the cricoarytenoid joint, spread to the posterior commissure/interarytenoid region, involvement of the contralateral arytenoid, and involvement of the postcricoid. Thyroid cartilage involvement is also a contraindication.
Since most CT scans of the larynx are obtained during respiration, the TVC usually is not fixed to the midline. If the TVC is located in the midline on one side, then VC paralysis should be suspected. If it is observed in conjunction with sclerosis of the ipsilateral arytenoid cartilage, then tumor involvement is implied. Endoscopic confirmation of VC fixation may still be necessary in the presurgical evaluation. Thus, the abnormal findings on imaging may help direct the physical examination, particularly when looking for fixation. Sclerosis of the arytenoid is more significant than sclerosis of other cartilages. Sclerosis of cricoid or thyroid cartilage may not yield tumor on biopsy samples.
Involvement of the contralateral TVC should be suspected when more than 1 mm of soft tissue is crossing either the anterior commissure or the posterior commissure. The mucosa is applied directly to cartilage at the anterior commissure joining both TVCs. The posterior commissure is the mucosa covering the ventral surface of the cricoid cartilage between the arytenoids.
As the tumor spreads in a superior direction along the AEFs, it could spread from the ventral surface to the dorsal surface of the folds and, thus, spread superiorly along the posterior wall or the hypopharynx and up to the posterior OP. The tumor can also spread along the lateral walls from the TVC to the false VC and, eventually, up to the lateral OP or the tonsillar pillar region.
Again, infraglottic spread of a tumor is based on the fact that the mucosa is applied directly to the cricoid cartilage, such that any soft tissue greater than 1 mm in thickness should be suspicious for infraglottic spread. Inferior spread may also occur down to the tracheal rings with the same criteria for mucosal thickening.
Postcricoid spread is also directed inferiorly, with the tumor spreading inferiorly to the TVC and posteriorly to the cricoid. Theoretically, the tumor may then spread to and involve the esophagus. If the esophagus is involved, then other surgical procedures besides a laryngectomy may be indicated, or surgery may be contraindicated.
Infraglottic region
According to the TNM classification for tumors of the subglottic region, T1 is a tumor confined just to the subglottic region. T2 is a tumor extending up to the TVC with normal or impaired mobility. T3 is a tumor limited to the larynx but with VC fixation. T4 is a tumor invading the cartilages and either extending up to the OP or extending into the exolaryngeal soft tissues of the neck.
This region is the least common site for SCCA. In a superior direction, the tumor may spread up to the TVC and, thus, follow pathways similar to those described above in Glottic region. The tumor can also spread in an inferior direction down to the tracheal rings. Unless cricoid invasion occurs, an infraglottic tumor should not spread to the postcricoid region.
Submucosal Patterns Of Spread
The radiologist diagnoses the spread of a submucosal tumor because the otolaryngologist surgeon can assess only the superficial mucosa on laryngoscopic examination. If the submucosal tumor is large, it may be suspected by the mass or bulge it creates.
Supraglottic region
The main site for submucosal spread is from the false VC up to the level of the epiglottis. On imaging studies, this is appreciated by loss of the normal paraglottic fat that abuts the thyroid cartilage being replaced by a soft tissue tumor. On axial CT scan and laryngoscopic examination, a tumor between the false VC and the TVC is difficult to image or inspect. However, direct coronal views of the larynx on MRI can demonstrate the pertinent anatomy without any difficulty. The transition of fatty tissue to muscular tissue related to the false VC and the TVC, respectively, is observed well on MRI (see Image 3).
Glottic region
Unfortunately, a tumor and the thyroarytenoid muscle have the same density on CT scan and, thus, cannot be separated. Very small SCCA of the TVC may not be detected on CT scan. Only those tumors large enough to cause enlargement of the TVC are detected. However, a submucosal tumor in the region of the TVC may be difficult for the otolaryngologist surgeon to visualize.
On either CT scan or MRI, the spread of a submucosal tumor is readily apparent by widening of the so-called thyroarytenoid gap, which is the space between the arytenoid cartilage and the adjacent thyroid cartilage. If this space is widened on one side in conjunction with sclerosis of the ipsilateral arytenoid cartilage, then submucosal spread is highly likely. This pattern of spread is significant in that it can direct a tumor to the natural dehiscences of the thyroid cartilage where the arteries and the nerves penetrate. Thus, a tumor not only can invade the cartilage but also can spread into the adjacent exolaryngeal soft tissues, rendering a T4 classification. Typically, this gap should be no more than 2-3 mm and should be symmetrical (see Image 3).
Spread By Natural Dehiscences/anatomy - Nonmucosal
Normal anatomical structures pass through several natural dehiscences. The natural midline thyroid notch, which is only covered by a membrane, is found in the thyroid cartilage. A natural dehiscence is also found along the anterior larynx between thyroid and cricoid cartilage, which is again covered only by a membrane. A tumor may erode through the notch and the thyroid-cricoid notch and present as an exolaryngeal tumor invading the strap muscles. A tumor can also pass through the bilateral dehiscences of the thyroid cartilage, which are foramen through which the arteries and the nerves to the VC and the larynx pass.
SCCA of the pyriform sinus has a malignant clinical course; patients with these tumors most likely present with exolaryngeal tumors and extensive adjacent adenopathy. SCCA may ascend the hypopharynx (since the pyriform sinus is part of the hypopharynx) and up to the posterior wall of the OP. SCCA can also spread along the hypopharynx down to the postcricoid region (see Image 4).
SCCA in this region tends to be unilateral and does not cross the midline unless it is very advanced. SCCA in the pyriform sinus region also has a propensity to spread by a submucosal route, causing a widening of the thyroarytenoid gap, and along the lateral thyroid cartilage to the natural dehiscences for the arteries and the nerves and into the exolaryngeal tissues.
One of the more significant routes for SCCA of the pyriform sinus is spread around the posterior and lateral margins of the thyroid cartilage into the adjacent soft tissues of the neck, often displacing the common carotid artery in a lateral and sometimes anterior direction. Surgical removal of this tumor should be approached with caution since the carotid artery is very superficial. In addition, a rich lymphatic drainage exists such that adenopathy is often adjacent to SCCA of the pyriform sinus; thus, adenopathy occurs early and frequently.
SCCA of the pyriform sinus also has a propensity to invade the prevertebral space and the muscles. They often present as bulky and large lesions, making it difficult to determine the site of origin. However, if exolaryngeal spread is wrapping around the posterior margin of the thyroid cartilage, then the pyriform sinus becomes obvious as the site of origin (see Image 4).
Lymphangitic Spread Of Tumor
A review of the TNM classification for adenopathy is suggested. Briefly, NX is a situation in which the nodes cannot be evaluated in a clinical setting or from an imaging study. N0 (zero) is no adenopathy. N1 is a single ipsilateral node that is 3 cm or less in its greatest dimension, which may be in a vertical direction. N2 is classified as follows: (1) a single ipsilateral node that is less than 6 cm but greater than 3 cm, (2) multiple ipsilateral nodes that are all less than 6 cm, or (3) bilateral or contralateral nodes that are all less than 6 cm. N2 is further subclassified into N2a, which is a single ipsilateral node greater than 6 cm; N2b, which is multiple ipsilateral nodes all less than 6 cm; and N2c, which is bilateral or contralateral nodes all less than 6 cm. N3 is a lymph node greater than 6 cm.
Also, to simplify the nomenclature of the various lymph nodes, levels have replaced anatomical triangles. Reading more extensive articles about levels of lymph nodes is suggested. Very simply, 7 levels of lymph nodes are identified. Level 1 included the midline and parasagittal submental and submandibular nodes. Levels 2, 3, and 4 are related to the jugular chains of nodes representing high, middle, and lower level nodes related to the internal jugular vein (IJV). The hyoid bone is identified by demarcations on axial CT scan between the second and third levels. In real anatomical terms, the carotid bifurcation separates level 2 and level 3. The top of the cricoid cartilage separates level 3 nodes from level 4 nodes. In real anatomical terms, the belly of the omohyoid muscle separates level 3 nodes from level 4 nodes as it crosses the belly of the sternocleidomastoid muscle.
Level 5 nodes are the same posterior triangle nodes located medial to the sternocleidomastoid muscle and posterior to the carotid arteries. Level 6 nodes are the midline thyroid chain nodes, the largest of which is the delphian node. Level 7 nodes are the IJV chain nodes extending into the thoracic cavity. Recently, this simplistic approach has undergone further modification.
Adenopathy is defined as nodal enlargement greater than 1.0 cm, except for the jugulodigastric (JDG) node located at the angle of the mandible; in this case, the node must be larger than 1.5 cm. However, based on CT scan, a low-density or necrotic center is adenopathy regardless of the size of the node. Caution should be exercised not to mistake a thrombosed jugular vein as a node. Furthermore, a fatty hilum occasionally observed in normal lymph nodes should not be mistaken for adenopathy. The fatty hilum is usually eccentric, and measurement of Hounsfield units on CT scan exhibits negative numbers in the range of fatty tissue.
If the margins of the nodes are shaggy and irregular or if abnormal contrast enhancement of adjacent muscle or other soft tissues contiguous with the lymph node is present, then extracapsular spread exists. This is a grave prognostic sign because the 5-year survival rate is further cut in half (eg, from a 50% 5-year survival rate to a 25% 5-year survival rate). Therefore, identifying this finding is important. Radiation therapists perform addition boost to this node.
If general midline structures, such as the epiglottis, are involved with the tumor, the spread to lymph nodes is bilateral. Unilateral lesions should spread to ipsilateral nodes. However, contralateral adenopathy may be present with no ipsilateral adenopathy. The size of the primary tumor does not correlate well with the size or the numbers of abnormal lymph nodes. Very large bulky lesions may have no adenopathy, and extensive adenopathy may be present with very small or sometimes no definite mucosal lesions to explain the adenopathy. In general, most SCCA of the larynx tends to involve the JDG node located at the angle of the mandible at the simplified classification of level 2.
Supraglottic SCCA tends to spread to the bilateral IJV chain of nodes. The epiglottis, the AEFs, and the pyriform sinuses are most likely to present with adenopathy. The epiglottis and the pyriform sinuses are richly invested with lymphatic drainage, and these 2 structures, when involved with a tumor, exhibit early and frequent adenopathy. Furthermore, the adenopathy associated with SCCA of the pyriform sinus tends to present with extracapsular nodal spread, which further worsens the prognosis.
The TVC has no lymphatic drainage. Therefore, SCCA of the TVC should have no adenopathy. Thus, if adenopathy is found in what appears to be SCCA of the TVC based on clinical findings or even radiographic images, then the tumor is not really confined just to the TVC. The presence of adenopathy indicates spread most likely into the supraglottic region and the infraglottic region.
Subglottic tumors tend to spread to the bilateral middle-to-lower level IJV chain (level 3 or 4). Midline SCCA may spread to the delphian node at level 6 either through the thyroid notch or, less likely, through the thyrocricoid midline membrane.
Multimedia
 | Media file 1: Radiological patterns of mucosal spread of squamous cell carcinoma of the larynx. Various parts of the larynx. |
 | Media file 2: Radiological patterns of mucosal spread of squamous cell carcinoma of the larynx. Normal larynx. |
 | Media file 3: Radiological patterns of mucosal spread of squamous cell carcinoma of the larynx. Various patterns of squamous cell carcinoma spread from the true vocal cord. |
 | Media file 4: Radiological patterns of mucosal spread of squamous cell carcinoma of the larynx. Various pathways of squamous cell carcinoma spread from the pyriform sinus. |
 | Media file 5: Radiological patterns of mucosal spread of squamous cell carcinoma (SCCA) of the larynx. Patient with a bulky SCCA involving the false vocal cord. The false vocal cord without SCCA is shown on the right side with its normal paraglottic fat. |
 | Media file 6: Radiological patterns of mucosal spread of squamous cell carcinoma of the larynx. Enlargement of the aryepiglottic fold on the left side, showing the loss of the normal paraglottic fat (same patient as in Image 5). |
Keywords
radiological patterns of mucosal spread of squamous cell carcinoma of the larynx, SCCA of the larynx, SqCCA of the larynx, lymphangitic spread, laryngeal SCCA
More on Radiological Patterns of Mucosal Spread of Squamous Cell Carcinoma of the Larynx |
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References
Castelijns JA, Gerritsen GJ, Kaiser MC. Invasion of laryngeal cartilage by cancer: comparison of CT and MR imaging. Radiology. Apr 1988;167(1):199-206. [Medline].
Johnson JT. A surgeon looks at cervical lymph nodes. Radiology. Jun 1990;175(3):607-10. [Medline].
Lawson W, BIller HF. Glottic and subglottic tumors. In: Thawley SE, Panje RE, eds. Comprehensive Management of Head and Neck Tumors. 1987;991-1015.
Som PM, Curtin HD. Head and neck imaging. In: Squamous Cell Carcinoma. 1996;1:630-659.
Further Reading
Keywords
radiological patterns of mucosal spread of squamous cell carcinoma of the larynx, SCCA of the larynx, SqCCA of the larynx, lymphangitic spread, laryngeal SCCA
