PERSPECTIVE, PATTERNS OF SPREAD, AND PATHOLOGY
In the oral cavity, the location of the cancer is a powerful prognosticator of its malignant gradient; a shift of a few centimeters alters the prognosis of the cancer significantly.
PERSPECTIVE AND PATTERNS OF SPREAD
Each specific cancer subsite in the oral cavity has the potential to give rise to different manifestations. Each requires individualized management, dictated by local anatomy and patterns of spread (Fig. 5.2). Thus, lip cancers appear as superficial ulcerations that grow slowly. They rarely enter lymphatic channels or have metastases to lymph nodes, unless there is a deep invasion of the orbicularis oris muscle. By contrast, cancers of the tongue tend to arise along the lateral borders due to irritation of broken teeth and the microtrauma of swallowing foods, alcohol, and smoking tobacco. The underlying musculature is readily invaded and, because of its rich lymphatic network, leads to rapid infiltration and lymph node involvement.
Oral cavity cancers are the most common upper aerodigestive cancers and are predominantly male oriented (88%); lip followed by tongue is the most common site. The malignant gradient in the oral cavity increases from anterior to posterior and from lateral to medial loci. Cancers arising in the posterior portion of the floor of the mouth tend to carry a poor prognosis because the mylohyoid muscle is shorter in its anterior–posterior diameter and is deficient in its posterior part, no longer providing a muscular floor to the oral cavity. Invasion at this particular junction allows the tumor to extend directly into a gap and enter into direct contact with the submandibular salivary gland and tissues of the neck. This leads to the retromylohyoid space and permits the easy propagation of both an infectious and/or neoplastic process directly from the mouth to the neck. The buccal mucosa gives rise to superficial lesions, much as the lip; they tend to be ulcerating, and also arise from irritation due to broken teeth. Deep invasion into the buccinator muscle can lead to swelling of the cheek and access to the deep pterygoid plexus of veins. Unrecognized advancement can become rapidly debilitating, interfering with speech and swallowing and producing a malodorous halitosis. 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. 5.2; Table 5.2).
PATHOLOGY
There are a large variety of carcinomas (Table 5.1), but the most common are squamous cell cancers (Fig 5.1); adenocarcinomas are less common.
Figure 5.1| Cytologic grading of squamous cell carcinoma. Well-differentiated (grade 1) squamous cell carcinoma. The tumor cells bear a strong resemblance to normal squamous cells and synthesize keratin, as evidenced by epithelial pearls.
Figure 5.2 | Patterns of spread. A. Coronal view: The invasion of oral tongue cancer into floor of mouth and alveolar ridges. B. Sagittal view: The invasion of oral tongue into extrinsic floor of mouth musculature and posterior tongue. The primary cancer (oral cavity) 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 2.2.
TNM STAGING CRITERIA
TNM STAGING CRITERIA
These lesions tend to be either exophytic or endophytic, with the greatest concern being cancer of the tongue that, because of the interdigitations of its intrinsic and extrinsic muscles, leads to invasion of the floor of the mouth. Cancers arising in the floor of the mouth tend to be shallow ulcerations, usually in the gutters, and invade into the muscles of the tongue. They can readily attach and destroy the mandible. The lateral angles of the floor are important and precise landmarks for cancer spread in the mouth, because they merge into the alveololingual sulcus of the oropharynx.
In the oral cavity, the location of the cancer is a powerful prognosticator. As noted, a shift of a few centimeters alters the prognosis of the cancer significantly. Buccal cancers, alveolar ridges, and retromolar cancers are more unilaterally localized and are likely to spread into ipsilateral lymph nodes. Structures in the midline, such as the tongue, floor of the mouth, and palate, tend to drain bilaterally and have a poorer prognosis.
SUMMARY OF CHANGES SEVENTH EDITION AMERICAN JOINT COMMITTEE ON CANCER (AJCC)
The TNM stages according to the 7th Edition of AJCC are illustrated in color code of advancement (Fig. 5.3). 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 5.3).
ORAL CAVITY
Figure 5.3 | TNM stage grouping. Oral cavity cancers tend to occur in the lateral gutters. Oral tongue cancers invade the floor of the mouth because of interdigitation of intrinsic and extrinsic musculature. 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.
T-ONCOANATOMY
ORIENTATION OF THREE-PLANAR ONCOANATOMY
The anatomic isocenter of the oral cavity is the C2/C3 level. The anterior bullet enters in the midline at the upper lip (Fig. 5.4A) and the lateral bullet is posterior to the lateral commissure of the lips (Fig. 5.4B).
T-oncoanatomy
The oral cavity extends from the skin–vermillion junction of the lips to the junction of the hard and soft palate anteriorly and the anterior pillar (palatoglossal of the oropharynx) and to the line of the circumvallate papillae inferiorly, which divides the tongue into the anterior two-thirds and posterior one-third of the tongue. The various subsites of the oral cavity are noted. The major structures are the tongue, floor of the mouth, alveolar ridges, gingival, and hard palate within the oral cavity proper; the mandible separates the buccal mucosa and lips.
The deeper and more complex anatomy requires knowledge of the underlying musculature, which suspends the upper aerodigestive tract from the mandible and hyoid bone to the vertebral column and base of the skull. Swallowing, mastication, and the initiation of digestion through salivary gland secretion occur in the oral cavity. The tongue aids in food consumption and the sensation of taste is principally located here. The tongue is vital to social intercourse for verbalization, articulation, conversation, and osculation. All of these complex functions relate to the musculature, namely, the muscles of the lips and cheek, including the orbicularis oris and the deeper muscles of the face, the levator angulioris, the mentalis, and the buccinator muscle of the cheek. The muscles of the tongue and floor of the mouth include the intrinsic muscles of the tongue (longitudinal, transverse, and vertical), the extrinsic tongue muscles (genioglossus, styloglossus, and hyoglossus), and the geniohyoid and mylohyoid muscles, which are the muscles of the floor of the mouth.
The retromolar trigone, when viewed from its superficial mucosa to its deeper underlying structure, shows the complexity of the oral cavity particularly as it relates to the oropharynx. Beneath the retromolar trigone mucosa lies the pterygomandibular raphe, which forms the boundary between the vestibule of the oral cavity and the anterior pillar of the fauces, containing the palatoglossal muscle in its free border. The fibers of the superior pharyngeal constrictor muscle attach laterally and the buccinator anteriorly to the pterygomandibular raphe. When these muscles and the superior constrictor muscle are removed, the various spaces around the tonsillar fossa and the mandible are readily identified with the important underlying nerves. The lingual nerve and buccal nerve are identified, as is the glossopharyngeal nerve and the inferior alveolar nerve. The various spaces are the parapharyngeal space, which lies medial to the lateral pterygoid muscle; the pterygomandibular space, which is occupied by buccal fat and lies lateral to the medial pterygoid muscle; the buccal space, which is lateral to the mandible; and the masseter muscle.
Perhaps no area illustrates the complexity of the underlying anatomy of the oral cavity better than the retromolar trigone. This site is of particular interest to radiation oncologists because cancers in this area tend to be more radiosensitive and carry a better prognosis than cancers of the oropharynx. The retromolar trigone is formed by the posterior boundary of the retromolar space, posterior to the opening of Stensen's (parotid) duct, and extends posteriorly to the anterior surface of the mandible. With the mouth open, the retromolar trigone comes into prominence and assumes a triangular form with a pale mucous membrane. The base of the retromolar trigone is situated superiorly behind the third upper molar tooth, and the apex lies inferiorly behind the third lower molar tooth. The stretching of the mucous membrane in this region results in the lengthening and projection of the underlying elevator muscles. The medial boundary of the trigone forms the border between the oral cavity and the oropharynx.
• Coronal plane (Fig. 5.5A): The coronal plane stratifies the oral tongue and floor of mouth as a set of interdigitating muscles constituted by the intrinsic and extrinsic muscles of the oral cavity.
• Sagittal plane (Fig. 5.5B): This view presents the tongue as a contiguous structure of both the oral cavity and tongue attached to the mandible and hyoid bone, respectively.
• Transverse plane (Fig. 5.5C): Note the pterygomandibular raphe, which defines the retromolar trigone as the buccal mucosa anterior to the anterior tonsillar pillar. The buccinator muscle and medial pterygoid meet at the raphe. The parapharyngeal space and the pterygomandibular space are avenues into lymph nodes, carotid artery encasement, and perineural invasion of the lingual and glossal pharyngeal nerves.
Figure 5.4 | Orientation of three-planar T-oncoanatomy. The anatomic isocenter is at the axial level at C2/C3. A. Coronal. B. Sagittal.
Figure 5.5 | T-oncoanatomy. The Color Code for the anatomic sites correlates with the color code for the stage group (Fig. 5.3) and patterns of spread (Fig. 5.2) and SIMLAP table (Table 5.2). Connecting the dots in similar colors will provide an appreciation for the 3D Oncoanatomy.
N-ONCOANATOMY AND M-ONCOANATOMY
N-ONCOANATOMY
Generally there are two patterns of lymph node involvement that depend on location (Fig. 5.6; Table 5.4). Anterior cancer sites such as the lips, floor of mouth, and mobile oral tongue, are drained by lymph channels into the submental and submandibular lymph nodes. The more posteriorly located cancers drain into the jugulodigastric nodes. Midline tongue cancers can drain and lead to bilateral nodal infiltrations. The gingival and buccal mucosa tend to have unilateral disease (Tables 5.5A and 5.5B; Fig. 5.7A). The incidence and distribution of lymph node metastasis is clinical N0 negative neck (Table 5.5A,B) and clinical N+ positive neck (Fig. 5.7A,B).
M-ONCOANATOMY
Distant metastases are also possible because of the plexus of pharyngeal veins that drain into the jugular vein, and then into the superior vena cava, the right heart, and finally the lungs. The vascular supply of the pharynx arises from the external carotid. The carotid body and sinus located at the bifurcation of the common carotid is an arterial chemoreceptor and baroreceptor area, respectively (see Figs. 5.6).
Figure 5.6 | N-oncoanatomy. The red node highlights the sentinel node, which is the submaxillary and jugulodigastric node. A. Anterior view. B. 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 5.7 | A. Incidence and distribution in node positive neck according to AJCC neck regions. B. Incidence and distribution in node negative (N0) according to AJCC regions. Fig. 5.7A/B correlate with Table 5.5A/B.
STAGING WORKUP
RULES OF CLASSIFICATION AND STAGING
Clinical Staging and Imaging
For all mucosal cancers, careful inspection and palpation of the primary site and all uninvolved subsites are essential. Regional nodes deserve careful evaluation, recognizing that the anterior location of tongue-type cancers can drain into submental areas or pass directly to the supraclavicular region. The mid tongue drains to the mid neck node. Posterior tongue favors the jugulodigastric nodes. Both computed tomography enhancement (CTe) and magnetic resonance imaging (MRI) are recommended for soft tissue and bony involvement; preference is often based on absence of artifacts (teeth fillings and crowns create streaking on CT; see Table 5.6 and Fig 5.8 CT).
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, level of involved nodes, and whether there is extracapsular spread. Specimens taken after radiation and/or chemotherapy need to be so noted, but 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
• The tongue is richly supplied with lymphatics and a high percentage of patients (30%) have bilateral metastatic nodes at the time of initial clinical presentation. Many of these nodes are clinically silent and are detected only on imaging studies.
• With oral cavity tumors, the specific imaging issues to be addressed are those of the bone erosion and degree of submucosal extension.
• To assess perineural spread of tumor, MRI should be performed in patients with adenoid cystic carcinoma of the hard palate.
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 5.8 | Neck and larynx—Axial CT scan. A normal Axial CT at C2/C3 level illustrates the oral cavity, floor of mouth mandible to correlate with anatomy 5.5c. The CT/MRI transverse section can be correlated with the anatomy in Figure 5.5C as an assist to staging.
CANCER STATISTICS AND SURVIVAL
Generally, cancers of the oral cavity, pharynx, and upper digestive passage, account for 36,640 new cases per 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. Thyroid cancers are the exception; long-term survival is high, 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 both normal tissue conservation and reconstructive techniques have added greatly to quality of life. Unfortunately, this patient population abuses ethanol and nicotine; it is difficult to change these habits. Persistence of smoking and drinking contributes to their demise often from second malignant tumors in adjacent sites (see Fig. 1.10).
Specifically, oral cavity cancers encompass six subsites with a wide range of success. Lip cancers are readily recognized in local stages I/II and are successfully controlled in 85% of patients. The buccal mucosa and retromolar trigone spread to ipsilateral nodes and are intermediate; 5-year survival rates are 60% to 65%. Cancers of oral tongue and floor of mouth are more common; they spread rapidly and deeply due to the anatomic interdigitation of the intrinsic and extrinsic muscles of the tongue. Lymphatic drainage is bilateral from these sites. Survival rates range from 45% to 50%. Best chance for a favorable outcome is detection as stage I disease; 70% of patients are alive at 5 years.
Figure 5.9 | Five-year survival rates by stage at diagnosis. (From Edge SB, Byrd DR, and Compton CC, et al, AJCC Cancer Staging Manual, 7th edition. New York, Springer, 2010.)