Clinical Evaluation and Staging of Oral Cancer

Relevant signs and symptoms
Ulcer
Any ulcer in the oral cavity persisting for more than 3 weeks requires evaluation and biopsy
Pain
Pain is not an initial symptom, but occurs when the mucosa is breached and the submucosal nerve endings are involved
Trismus
A recent onset trismus in an oral cancer patient can be due to severe pain or due to involvement of pterygoid muscles. Longstanding trismus can be due to oral submucous fibrosis
Otalgia
Referred pain to the ear is usually from a lesion in the oral or the base of the tongue or pyriform sinus (requires endoscopic evaluation)
Dental Pain, bleeding gums, loose teeth, ill-fitting dentures
May indicate an early primary lesion of the alveolus
Numbness
Numbness around the lower lip indicates involvement of the mental nerve, inferior alveolar nerve, or mandibular nerve
Numbness in the cheek indicates involvement of the maxillary nerve

1.3 Risk Factors

Tobacco and alcohol are the leading risk factors for the development of OCC. Smoking tobacco confers a two- to fourfold increase in the risk of developing HNSCC and has a dose-response relationship for frequency and duration. Alcohol alone confers a twofold risk in heavy drinkers. Combined use of tobacco and alcohol by the same individual multiply the risk for HNSCC. Furthermore, 40 % of patients who continue to smoke after definitive treatment of an oral cavity lesion will have a recurrence [5].
Patient distribution is different between smokers and nonsmokers. Nonsmokers are represented by a higher percentage of women, more likely to be at the extremes of age (30 < or >80), and tumors are more likely to present in the oral tongue, buccal mucosa, and alveolar ridge. Smokers are more likely to be male, present with tumors of the larynx, hypopharynx, and floor of mouth, with a markedly higher rate of p53 transformation [6].
Smokeless tobacco and snuff are also associated with oral cancer, and they can produce visible changes in the oral mucosa with prolonged use. Similarly, the use of betel or areca nut has been associated with submucosal fibrosis and an increased risk of oral malignancy. The use of these products is more frequently seen in Southeast Asia and India than in western countries [7].
Human papillomavirus (HPV) is not as highly associated with malignant tumors of the oral cavity as in oropharynx, but HPV oncoproteins E6 and E7 have the ability to bind and degrade tumor suppressor gene products of p53 and pRb[8]. This can impair the ability of the cell cycle to arrest for the repair of DNA damage and result in accumulating genetic changes.
Additional factors, which can predispose to carcinoma of the oral cavity, include Plummer-Vinson syndrome, syphilis, ill-fitting dentures, long-term immunosuppression (up to a 30-fold increase with renal transplant) [5], pipe smoking, and UV exposure. Pipe smoking and UV exposure are particularly associated with carcinoma of the lip.

Risk factors associated with oral squamous cell cancer
Smoked tobacco
Smokeless tobacco
Alcohol
Betel nut chewing
Human papillomavirus
Plummer-Vinson syndrome
Long-term immunosuppression
Ill-fitting dentures
Repeated trauma
Pipe smoking (carcinoma of the lip)
Chronic exposure to UV light (for carcinoma of the lip)

1.4 Examination

Thorough evaluation of the oral cavity should yield the practitioner enough information to accurately stage the tumor, exclude a synchronous upper aerodigestive tract lesion, assess the patient’s current functional status from the standpoint of airway and nutrition, and plan for treatment and reconstruction. This evaluation begins with careful inspection of the head and neck and cranial nerves, with emphasis on the oral cavity, pharynx, and larynx. Mirror or video pharyngoscopy may be required to assess lesions extending into the oropharynx. The lesion should be palpated to assess for fixation to the maxillary or mandibular periosteum, underlying musculature, and overlying the skin. The neck should be palpated for the assessment of lymphatic involvement. Prior surgery or radiation treatment effect should be identified and assessed as the reconstruction plan is formulated. A tissue diagnosis should be obtained by either biopsy or fine-needle aspiration. If biopsy was performed at an outside institution, the slides should be obtained and reviewed by a head and neck pathologist in order to confirm the diagnosis. Patients with severe pain or trismus may require examination under anesthesia for both staging and diagnostic purposes (Fig. 1.1).

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Fig. 1.1

Oral cavity subsites
Evaluation of oral cavity subsite:

  1. (a)
    Tongue
     
  2. (b)
    Floor of the mouth
     
  3. (c)
    Alveolus
     
  4. (d)
    Buccal mucosa
     
  5. (e)
    Palate
     
  6. (f)
    Retromolar trigone
     
  7. (g)
    Lip and commissure
     

1.5 Anatomy

The oral cavity extends from the vermillion border of the lip to the hard palate-soft palate junction posterosuperiorly, inferiorly to the circumvallate papillae, and laterally to the anterior tonsillar pillars. The oral cavity is divided into the following subsites: lip, oral tongue, floor of the mouth, hard palate, dentoalveolar ridges, retromolar trigone, and buccal mucosa.
The lips are the transition from the facial skin to the mucous membranes of the oral cavity. The transition begins at the vermillion border and extends proximally to the mucosa of the labiogingival sulcus. Innervation is via the infraorbital nerve (V2) to the upper lip and the mental nerve (V3) to the lower lip. The vascular supply to the lips is derived from branches of the external carotid system, namely, the superior and inferior labial arteries from the facial artery, superficial and deep branches of the submental artery, and the mental branch of the inferior alveolar artery. Lymphatic drainage corresponds to level IB, primarily the submandibular lymph nodes. Midline lower lip lesions may present with submental (IA) spread, and upper lip lesions have the potential to spread to the preauricular, infraparotid, and perifacial lymph nodes.
The dentoalveolar ridge is composed of the mucosa overlying the alveolus, from the transition of buccal mucosa laterally to the floor of the mouth and hard palate medially. Inferiorly, the ascending ramus of the mandible marks the posterior limit of the alveolar ridge. Superiorly the posterior limit is demarcated by the superior aspect of the pterygopalatine arch. The blood supply to the lower alveolus is primarily from the inferior alveolar artery, with supplemental flow from the mandibular periosteum. The blood supply of the hard palate is derived from the greater palatine and the anterior, middle, and posterior superior alveolar arteries. The lymphatic drainage of the buccal sides of the alveolar ridges is to levels IA–B. The lingual surfaces drain to level II and the lateral retropharyngeal nodes.
The hard palate spans from the maxillary alveolar ridges anteriorly and laterally to the soft palate posteriorly and forms the bony boundary between the nasal and maxillary sinus cavities and the oral cavity. Sensation is supplied by the nasopalatine nerve (V2). Lymphatic drainage is to the upper cervical lymphatics and the lateral retropharyngeal nodes. The blood supply to the hard palate is from the greater palatine artery and superior alveolar artery.
The oral tongue is defined as the portion of the tongue anterior to the linea terminalis. It is composed of four intrinsic and four extrinsic muscles and contains a fibrous midline septum. The extrinsic muscles originate outside the body of the tongue. The genioglossus functions to depress and protrude the tongue and provides the majority of the bulk. The hyoglossus depresses the tongue, while styloglossus elevates and retracts. Palatoglossus functions to depress the soft palate and elevate the back of the tongue. The intrinsic muscles of the tongue lie superficial to the genioglossus and function to alter the shape of the tongue. The intrinsic muscles are oriented superoinferiorly longitudinal, transverse, and vertical. There is no distinct plane between these muscles, which can allow a diffuse, infiltrating tumor pattern. Motor innervation is provided by the hypoglossal nerve except for the palatoglossus, which is innervated by a pharyngeal branch of the vagus nerve. General sensory innervation is provided to the anterior two thirds of the tongue by the lingual nerve, which also carries the chorda tympani, providing special sensory innervation. Both functions in the base of the tongue are served by the glossopharyngeal nerve. The lymphatics of the oral tongue can be divided by region. The tip of the tongue drains to the submental nodes and the lateral tongue to levels I–II primarily. There is evidence, however, for a direct drainage pathway from the lateral tongue to levels III/IV. There is little crossover of lymphatics within the oral tongue, and tumors tend to drain to the ipsilateral nodal basins. This is in sharp contrast to the base of the tongue, where tumors frequently metastasize bilaterally.
The retromolar trigone is composed of the mucosa overlying the ascending ramus of the mandible and coronoid process. It is bounded by the buccal mucosa laterally and the anterior tonsillar pillar medially. Superiorly, it is bounded by the maxillary tuberosity, and the anterior margin is the posterior aspect of the mandibular second molar. Periosteal involvement is common given the close proximity of this site to the mandibular ramus, and lower lip paresthesias are common when the inferior alveolar nerve is involved at the mandibular foramen. Sensory innervation is provided by the lesser palatine nerve and branches of the glossopharyngeal nerve. Involvement of CN IX causes referred otalgia by tumors in this subsite. Lymphatic drainage is to levels II and III.
The floor of the mouth is bounded anteriorly and laterally by the mandibular alveolar ridge. The anterior tonsillar pillar is the posterior boundary. The lingual frenulum separates the space into right and left sides. The mylohyoid and hyoglossus muscle provide support for the floor of the mouth and an inferior boundary. The hypoglossal and lingual nerves run within this compartment, and involvement of these nerves may be the presenting complaint for patients with lesions in this subsite, resulting in dysphagia, dysarthria, dysgeusia, paresthesias, or pain. The blood supply to the floor of the mouth is derived from the branches of the submental artery and ascending pharyngeal and lesser palatine arteries. Sensory innervation is derived from branches of the lingual nerve, and lymphatic drainage is to bilateral levels IA–II.
The buccal mucosa extends from the posterior aspect of the lip to the alveolar ridges medially and the pterygomandibular raphe posteriorly. It is pierced by the parotid duct lateral to the second maxillary molar. Sensation is provided by V2 and V3. Lymphatics drain to ipsilateral IA–B.

1.6 Imaging

Appropriate imaging should be obtained to assess the extent of disease, which may either confirm or alter the clinical stage of the patient. Computed tomography is most frequently obtained and is the primary imaging modality for identifying cortical bone erosion and lymph node metastasis. MRI is a useful adjunct for the evaluation of soft tissue extension, nerve, and bone marrow involvement.
Radiograpic assesment of tumor boundaries can be invalueable in treatment planning. Involvement of masticator space is considered advanced local disease (T4b). However, tumors below the mandibular notch (infranotch lesions) or amenable for resection with favorable outcome. In case of tongue cancers, MRI can be helpful to identify features such as tumor extension across the midline, tumor thickness, and involvement of extrinsic muscles. These findings have implications in staging as well as in the management of the primary and neck.
Preoperative chest imaging should be obtained with either plain film or computed tomography. Positron emission tomography (PET) scanning is becoming more frequently employed as a modality to image and assist in staging patients with oral cavity cancer; however, the use of PET and PET-CT varies from institution to institution. Evaluation of distant metastases is one frequently employed use for PET, and suspicious lesions may be confirmed by CT-guided biopsy. While the NCCN recommends routine PET-CT for stage III and IV disease, it may be reserved for patients with recurrent or second primary disease in a resource-constrained setting (Figs. 1.2 and 1.3) [9].

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Fig. 1.2

Right BM with skin involvement
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Fig. 1.3

Gross mandible erosion

1.7 Ancillary Services

Patients scheduled for definitive chemoradiation or major operative head and neck interventions must be carefully screened for factors that have the potential to impact or interrupt treatment. In the oral cavity in particular, the dentition must be evaluated and carefully addressed prior to treatment. In the event that the patient will require dental rehabilitation, skilled dentists and prosthodontists are invaluable additions to the treatment team. Nutritional assessment and appropriate intervention should be completed on every oral cancer patient in the pretreatment period. Malnutrition can predispose the patient to wound complications, failure to complete treatment, and overall higher rates of treatment failure. Early consultation for PEG tube placement is encouraged in all but the most limited tumors, if deglutition is suspected to be or to become a problem. Physical therapy can help to minimize debility in postoperative patients and may avert further trismus in patients with submucosal fibrosis.

1.8 Oral Cavity Lesions

There are several premalignant and malignant entities of the oral cavity, which are discussed in depth elsewhere in this work. Briefly, the premalignant lesions that are often encountered consist of leukoplakia (which can undergo a 2–3 % rate of malignant transformation), erythroplakia (5–10 % rate of transformation), lichen planus (transformation varies by subtype), and submucosal fibrosis (highly associated with transformation to SCCA). Leukoplakia and erythroplakia are characterized as white or red patches of the oral mucosa. They may also be present together as mixed lesion, designated erythroleukoplakia. Biopsy of these lesions is warranted to rule out microinvasive carcinoma. Lichen planus is a cell-mediated immune response which presents as whitish-gray linear or reticular streaking over a violaceous background of the oral mucosa. Lesions may persist for years. Submucosal fibrosis is a chronic fibrotic change of the upper aerodigestive mucosa. Early stages may present with oral burning sensation, vesicle formation, blanching, and leathery changes of the mucosa. Late submucosal fibrosis can result in fibrous bands within the mucosa leading to trismus, oropharyngeal stenosis, uvular distortion, and woody changes to the oral mucosa and tongue. It is most commonly seen in areas where habitual areca nut use is present, and the rates of transformation have been reported as high as 7.6 % [10]. Oral dysplasia is graded from mild to severe and is acknowledged to be part of the premalignant continuum. It can present a treatment challenge in the oral cavity, where wide-field exposure to carcinogens may have been present for years, resulting in field cancerization and dysplasia of a large area of oral mucosa. Verrucous hyperplasia is diagnosed on histology and clinically appears similar to verrucous carcinoma. It does not, however, invade the basement membrane. Necrotizing sialometaplasia is a benign process associated with trauma to the minor salivary glands resulting in an ulcerated area, most commonly at the hard-soft palate junction. This can be seen in the context of an ill-fitting denture. Potentially malignant lesions may be self-limited or progressive and are potentiated by the continuing use of tobacco, alcohol, and betel nut products. The extent of these lesions may not be clear under white light examination in the office or operating theater; therefore, adjuvant examination techniques have been developed. Toluidine blue is an acidophilic metachromatic nuclear stain that will stain carcinoma and some premalignant lesions blue, while normal mucosa is left unstained. Sensitivity and specificity have been reported as high as 95 % and 71 %, respectively [11]. Chemiluminescence has also been investigated as an aid to determine the extent of premalignant lesions. It works by comparing the reflective properties of normal tissues with those of preneoplastic or malignant cells, which have a higher reflective index. Sensitivity and specificity have been reported up to 95 % and 84 %, respectively [12]. These techniques may be helpful in determining the extent of poorly defined premalignant lesions or early carcinomas.

Oral potentially malignant lesions
Leukoplakia (Fig. 1.4)
“A white plaque of questionable risk having excluded (other) known diseases or disorders that carry no increased risk for cancer”
Annual malignant transformation rate 1 %
More common in smokers than in nonsmokers
Clinically classified into homogeneous and nonhomogeneous leukoplakia
Nonhomogeneous leukoplakia is further classified into erythroleukoplakia, verrucous leukoplakia, and proliferative verrucous leukoplakia
Full-thickness biopsy is warranted to rule out microinvasive carcinoma
Lichen planus
Whitish-gray linear or reticular streaking over a violaceous background
Annual malignant transformation rate is <1 %
Reticular, ulcerative, and atrophic are the common morphologies seen in oral cavity
Usually bilateral with more or less symmetrical pattern
Erythroplakia
“A fiery red patch that cannot be characterized clinically or pathologically as any other definable disease”
Associated with tobacco and alcohol consumption
High malignant potential (17 times that of leukoplakia)
Submucous fibrosis
Mostly restricted to Southeast Asia
Most common etiology is areca nut chewing
Characterized by burning sensation, blanching, and stiffness of oral mucosa followed by formation of vertical bands and trismus
Annual malignant transformation rate is approximately 0.5 %
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Fig. 1.4

Extensive leukoplakia
The discussion of oral cavity carcinoma is nearly synonymous with a discussion of squamous cell carcinoma. Variants include sarcomatoid, basaloid, and verrucous carcinoma. Other epithelial malignancies of the oral cavity include mucoepidermoid carcinoma, adenoid cystic carcinoma, and adenocarcinoma orginations in the salivary glands. Sarcomas include osteosarcoma, chondrosarcoma, malignant fibrous histiocytoma, rhabdomyosarcoma, and liposarcoma. They are generally seen overlying the mandible or hard palate. Kaposi sarcoma should be considered in mucosal lesions in HIV-positive patients. Melanoma may present on the lip or in the mucosa. In almost all cases, treatment for these lesions is surgical excision, with adjuvant therapy on an individual bases depending on the pathology and stage of disease.

Malignant lesions of the oral cavity
Squamous cell carcinoma (most common) (Figs. 1.5, 1.6, 1.7, and 1.8)
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Jun 24, 2017 | Posted by in Oral and Maxillofacial Surgery | Comments Off on Clinical Evaluation and Staging of Oral Cancer
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