Malignant Tumors of the Mobile Tongue

Frequency

The tongue is the most common intraoral site of cancer in most countries. The worldwide incidence of oral cancer varies widely, in view of the spectrum of risk factors. Because of this variability, cancer of the tongue is a serious public health problem with significant mortality and morbidity.

Indications are that the incidence of squamous cell carcinoma of the mobile tongue has been rising among younger women in industrialized nations. This was supported by a study by Satgunaseelan et al, using the 2017 Australian Cancer Incidence and Mortality database and information from the National Registry of Diseases Office, Singapore. The report found that the incidence of primary mobile tongue squamous cell carcinoma has significantly risen in persons under age 45 years within the populations of Australia and Singapore, with the rate of increase being significantly higher in females. Similarly, data from four tertiary Australian institutions revealed the number of females with this mobile tongue cancer to have increased, even with a reduction in the proportion of female smokers under 45 years.[3]

It was estimated that 18,040 new cases of tongue cancer would occur in the United States in 2023, with an estimated 2940 deaths from the disease. These figures represented 0.9% of all new cancer cases and 0.5% of all cancer deaths.[4]

It was estimated that in 2023, cancers of the oral cavity and pharynx overall would make up 2.8% of all new cancers in the United States, and 1.9% of all cancer deaths.[5]

In Europe and Australia, the incidence of oral cavity cancer is also very low, accounting for less than 5% of all cancers. In France (male incidence rates up to 8 per 100,000 per annum), it is the third most common cancer in males and the second most common cause of death from cancer.

This incidence variability may relate to different societal habits, such as chewing betel nuts and habitual reverse smoking observed in Asia and the higher incidence of smoking and alcohol intake in certain European countries.

In a study examining the global incidence of oral and oropharyngeal cancer in patients under age 45 years, Hussein et al determined that the incidence of oral tongue cancer has notably risen among white women in this age group.[6]

Race

A study by Joseph et al found that the incidence of squamous cell carcinoma of the oral tongue has risen among white females in the United States while at the same time decreasing among African American women. The study, which used data from 1973 to 2010 from the Surveillance, Epidemiology, and End Results (SEER) program, found an upward annual percentage change of 0.53 among white females, although the rise appears to have been limited to women under age 50 years. The report also found the estimated 1-, 5-, and 10-year relative survival rates for squamous cell carcinoma of the oral tongue to be greater in white women than in African American females, but following multivariable analysis, the investigators attributed the higher survival rate not to race but to such factors as lower stage, younger age, married status, and receipt of surgical treatment.[7]

Tobacco

Tobacco is the leading preventable cause of death in the United States and is responsible for 1 out of every 5 deaths. Of all potential etiologic factors, cancer of the tongue is correlated the closest with the use of tobacco products. Numerous studies have shown that up to 90% of patients with oral cavity cancers use tobacco products and that the relative risk of such cancers increases with the amount smoked and the duration of the habit. The incidence of oral cavity cancers in persons who smoke is approximately 6 times that of those who do not smoke. Exposure to tobacco causes progressive sequential histological changes to the oral mucosa. Over a prolonged period of exposure, these changes eventually lead to neoplastic transformation, in particular changes in the expression of p53 mutations. These changes may be reversible if tobacco exposure is discontinued.

The evidence supporting the benefit for head and neck cancer patients to cease smoking after treatment for their cancer is compelling. In a study by Moore, 40% of patients who continued to smoke after definitive treatment for an oral cavity malignancy went on to recur or develop a second head and neck malignancy. For patients who stopped smoking after treatment, only 6% went on to develop a recurrence.

The recent increase in the incidence of oral cavity cancer in young adults is significant. The explosive use of snuff, or smokeless tobacco, in certain regions of the United States has lead to increased numbers of buccal mucosa, mandibular alveolus, and tongue cancers.

Alcohol

The correlation between alcohol consumption, particularly hard liquor, and oral cavity cancer is also significant, especially in patients taking more than 4 consumptions per day. Approximately 75% of patients who develop oral cavity cancers consume alcohol, and the disease occurs 6 times more often in persons who drink than in those who do not drink. The role of alcohol consumption in the development of tongue cancer appears to be independent of cigarette smoking. The use of alcohol has a synergistic rather than cumulative effect on the risk of carcinogenesis. The risk for a person who smokes tobacco and drinks alcohol is 15 times that of an individual with neither habit.

Other factors

A number of other factors have been associated with an increased incidence of tongue cancer. The use of the product of the Areca catechu tree,the betel nuts or quid as well as the use of slaked lime is a habit practiced by as many as 220 million people in India and the continent of Asia. This mixture is highly irritating to the oral mucosa, as well as carcinogenic.

The detection of mutations in tumor suppressor genes has been reported in patients with cancers of the oral cavity. Nitrosamines constitute the most abundant carcinogens present in tobacco. These agents can damage DNA, leading to point mutations. These point mutations lead to deregulation of tumor suppressor genes, the best characterized being TP53, which is located on chromosome 17. Other oncogenes associated with oral squamous cell cancers include c-myc and erb -b1.

The human papillomavirus, an epitheliotropic DNA virus, is another etiologic agent for carcinogenesis, transforming cells to a malignant phenotype. Human papillomavirus (HPV) has been detected in various amounts in persons with oral dysplasia, leukoplakia, and malignancy. In the subset of patients without other risk factors, HPV should be considered as an etiologic factor, and proper handling is needed for biopsy specimens to be sent for analysis. See also Human Papillomavirus.

Plummer-Vinson syndrome (achlorhydria; iron deficiency anemia; and mucosal atrophy of the mouth, pharynx, and esophagus) has been associated with an increased risk of cancer of the oral cavity. Increasing amounts of data suggest that vitamins A and C, along with the carotenoids, may be protective against epithelial cancers. Riboflavin and iron deficiencies are known to produce dysplastic changes to the oral mucosa. This may partly explain its relationship to alcoholism, which may result in riboflavin deficiency and oral cancer.

The role of occupational and environmental exposures in the development of cancer is an expanding field of study and may eventually be more important once the underlying molecular biology of cancer is better understood.

As with other areas of the upper aerodigestive tract, more than 90% of oral cavity cancers are squamous cell carcinomas. Most of the other lesions are of minor salivary gland origin. Lymphomas, melanomas, and sarcomas rarely occur in the tongue. The following information, unless otherwise stated, is related to squamous cell carcinomas.

Premalignant lesions

Leukoplakia and erythroplakia are the lesions with the greatest potential for malignant transformation. The term leukoplakia is defined as a clinical white patch of the mucosa that cannot be characterized clinically or pathologically as any other disease. Leukoplakia is considered a premalignant condition from the chronic irritation of the mucous membranes, resulting in increased rates of epithelial and connective tissue proliferation. Onset of leukoplakia generally occurs after the age of 40 years, with the incidence peaking before age 50 years. It is 2-3 times more common in men than in women. Many other systemic and local inflammatory conditions will result in the presentation of leukoplakia (candidal infection, pemphigus, pemphigoid, lichen planus, lupus, ill-fitting dentures, oral hairy leukoplakia) making proper evaluation and management imperative in identifying patients at risk of oral cancer.

The fate of leukoplakic lesions has been the subject of much controversy. The rates of malignant transformation range from less than 1% to as high as 17.5%, averaging 4.5-6%. In one of Banoczy's studies, a cohort of 670 patients was monitored for 3 years; of the patients, 7.5% had spread of leukoplakia in the oral cavity and 6% of the lesions became malignant. Leukoplakia erosiva (erythroleukoplakia) and nodular leukoplakia exhibited the highest rate of malignant transformation.

Erythroplakia is defined as a red, velvety plaque that is found on the oral mucosa and cannot be ascribed to any other predetermined condition. No sex predilection is recognized, and it is rarely found on the tongue compared with other sites in the oral cavity. Mashberg has considered erythroplakia the earliest sign of asymptomatic cancer.[8]

Squamous cell carcinoma

Squamous cell carcinoma is by far the most common malignancy of the tongue, typically having 3 gross morphologic growth patterns: exophytic, ulcerative, and infiltrative. The infiltrative and ulcerative types are observed most commonly on the tongue. Early carcinomas smaller than 1 cm may be detected only during a routine clinical examination. In the case of symptomatic tumors, the most common finding is an indurated, ulcerated area of the tongue. The induration may extend deep into the tongue musculature and root of the tongue. In many cases, regional lymphadenopathy may be present. Generally, a correlation is recognized between tumor size, nodal presence, metastasis, and eventual prognosis. The relationship between histological differentiation and clinical stage of the illness has been the subject of debate. Currently, the site and size of the primary tumor are well recognized as factors that are more important.

Malignancies of the tongue may grow to significant size before they cause symptoms. Approximately three fourths of the cancer occurs in the mobile tongue and is most often well differentiated. Because of the relative laxity of the tissue planes separating the intrinsic tongue musculature, cancer cells may spread easily and become symptomatic only when tumor size interferes with tongue mobility. Squamous cell carcinoma of the tongue may arise in apparently normal epithelium, in areas of leukoplakia, or in an area of chronic glossitis. These lesions are usually larger than 2 cm at presentation, with the lateral border being the most common subsite of origin. At this point, the patient may develop speech and swallowing dysfunction. Pain occurs when the tumor involves the lingual nerve, and this pain may also be referred to the ear.

Carcinomas of the tongue base are clinically silent until they deeply infiltrate the tongue musculature. They are usually less differentiated. Because of the difficulties with direct visualization, they may extend into the oral tongue or have clinical lymph metastases before the diagnosis is established.

The evaluation of a patient with tongue cancer begins with a detailed history, specifically inquiring about tobacco and alcohol use, pain, weight loss, dysphagia and odynophagia, referred otalgia, hemoptysis, neck mass, hoarseness, and articulation difficulties. During a complete head and neck examination, specific attention is directed at the site and size of the lesion and infiltrating characteristics. Furthermore, the physician should perform a thorough bimanual examination of the tumor, the surrounding floor of mouth, and the submandibular triangles. Submandibuklar gland asymetry and nodal adenopathy are carefully noted with the bimanual examination of the neck and is compared to imaging studies obtained as part of the evaluation. Nodal masses may become painful as they enlarge and develop central necrosis. When they extend beyond the lymphatic system, nodal masses may cause cranial nerve, respiratory, swallowing and upper extremity symptoms.

A dental evaluation is also performed, with attention to dental hygiene, dentition status, and integrity of the mandible. Patients with additional medical problems or those who will likely have complications should be referred for evaluation by an internist or an appropriate subspecialist. Because surgery is often part of the therapy of these lesions, an opinion from a medical internist may be obtained to aid in the perioperative treatment of the patient.

It is important to evaluate the patient's swallowing and dietary status. Many of these patients present with malnutrition associated with an alcoholism history or as a result of dysphagia from the enlarging tumor. An inquiry of the patient's change in speech will give an indication of the location, functional impairment and severity of the tumor extent. As these tumors enlarge, they may cause deformity of the anatomy of the oral contents, and a mass effect which can lead to respiratory compromise when the patient presents late in their illness.

The oral tongue is the freely mobile portion of the tongue. It is bordered anteriorly by the lingual frenulum and posteriorly by the circumvallate papillae. The root is the undersurface of the tongue at its junction with the floor of the mouth. The junction of the tongue with the floor of the mouth forms a gutter, the gingivolingual sulcus, where food and liquids flow to the oropharynx. The oral tongue consists of 4 anatomic regions: the tip, the lateral borders, the dorsum, and the undersurface. Posterior to the circumvallate papillae, the base of the tongue is anatomically part of the oropharynx. It is covered by squamous epithelium composed of circumvallate, filiform, and fungiform papillae.

The muscular portion of the tongue is composed of 3 paired intrinsic and 3 paired extrinsic muscle groups. The extrinsic muscles, made up of the genioglossus, hyoglossus, and styloglossus, alter the shape and position of the tongue. The trilaminar group of intrinsic muscles, which is composed of the inferior lingual, vertical, and transverse muscles, originates and inserts within the tongue substance. They are responsible for the changes in the shape of the tongue during speech, mastication, and swallowing.

The lingual artery provides blood supply to the tongue. A branch of the external carotid artery, it arises at the level of the hyoid, where it travels forward to lie deep to the hyoglossus muscle. At this point, it divides into various branches to supply the ipsilateral tongue. Its only anastomosis is with its contralateral artery at the tongue tip. A plexus of veins follows the artery, and the main lingual vein drains into the internal jugular vein.

The hypoglossal (cranial nerve XII) nerve runs anteriorly between the submandibular gland and the hyoglossus muscle. Nerve fibers are sent to the extrinsic muscles; then, the terminal branches plunge into the tongue substance to supply the intrinsic muscles. The lingual branch of the mandibular nerve (cranial nerve V3) provides the sensory nerve supply to the mobile tongue. Taste is provided by the chorda tympani, a branch of the facial nerve, traveling with the lingual nerve.

Because of its different embryological origin, the glossopharyngeal (cranial nerve IX) nerve and the superior laryngeal nerve provide sensation, motor supply, and taste sensation to the base of the tongue.

An extensive submucosal lymphatic plexus provides lymphatic drainage to the tongue. All vessels ultimately drain into the deep jugular lymph nodes, between the levels of the digastric and omohyoid muscles. Various lymphatic collection channels originate near the tongue tip, pierce the mylohyoid, and drain into first echelon submental and submandibular lymph nodes. Lymph node channels from the tongue base pass through the pharyngeal wall laterally below the tonsil to reach the jugulodigastric nodes. Because the lymphatic plexus freely communicates across the midline, cancer of the tongue frequently metastasizes bilaterally. Understanding the lymphatic anatomy is critical when making a decision about the proper surgical management of the neck in patients with tongue cancer.

Contraindications to surgery for tumors of the mobile tongue include patients who are unable to tolerate anesthesia for such a procedure because of medical illness. In certain cases, patients may not be suitable for surgery if the tumor is deemed unresectable on the basis of its extent. Surgery would also be contraindicated in a patient refusing a surgical procedure.

Because of the difficulty in tolerating anesthesia, these patients would also not be suitable candidates for brachytherapy. In these cases, such patients should be considered for external beam radiation therapy, or palliative therapy.

Because the incidence of distant metastases at presentation is low, the only laboratory workup needed should be directed at the evaluation of the patients' underlying chronic medical conditions. A complete blood count (CBC) is a useful general screen that helps the consulting internist establish if further testing is warranted.

In a patient with a suspected bleeding diathesis, investigations may also include tests of prothrombin time (PT), activated partial thromboplastin time (aPTT), and international normalized ratio (INR).

See the list below:

• Dental radiographs: Periapical dental films provide fine details and are the most useful for detecting minimal invasion of the mandible, compared with CT scans and panoramic radiographs showing gross bony destruction.

• Bone scan: Bone scanning has no role in the evaluation of mandibular involvement by tumors, nor has it been considered useful in the patient's general survey for bony metastases.

• Chest radiograph: This may be used as the sole radiographic study in the evaluation for distant metastases because the incidence of distant metastases at presentation is low.

• CT and MRI scans: Radiologic evaluation with a CT scan and MRI has revolutionized the assessment of patients with head and neck tumors. Because of the higher soft tissue resolution with an MRI scan, the assessment of the mobile tongue may be facilitated with this modality. Computerized tomography is an excellent modality to evaluate the patient's nodal status. The evaluation of nodal number, size, location, contour and necrosis is helpful in staging. Due to its imaging characteristics tongue cancer may be difficult to pick up on computerized tomography, unless the tumor leads to deformity of the extrinsic tongue musculature or the anatomy of the floor of mouth or tongue base.

• Involvement of the extrinsic tongue musculature and direct extension in the submandibular glands and the base of tongue can be revealed with MRI.

  • Response to therapy also may be evaluated more thoroughly.

  • As part of the staging and management processes, confirmation of nodal disease, vascular distortion or involvement, bony destruction, or potential space involvement aids in the diagnosis.

  • In his 1991 paper, Shaha demonstrated that physical examination findings were accurate at predicting the extent of mandibular involvement 90% of the time in patients with floor of the mouth cancer.[9] Radiographs and CT scans were not as accurate and correctly predicted mandibular involvement in only 70% of patients.

• MRI: Both CT scan and MRI are generally reliable for detecting the extent of soft tissue and bony involvement in persons with oral cavity carcinoma. However, MRI has several potential advantages in staging tumors of the oral cavity.

  • Tissue contrast between tumor and normal musculature is higher on T2-weighed images.

  • No beam artifact from amalgam or other dental material is noted.

  • Imaging can be performed in sagittal, coronal, and axial planes.

  • Contrast between postirradiation fibrosis and recurrent tumor is improved on T2-weighed images.

• Positron emission tomography-CT imaging:

  • The combination of positron emission tomography (PET) and CT is a new diagnostic and staging modality in the evaluation of the patient with head and neck cancer.

  • PET scans are used most often to reveal cancer and to examine the effects of cancer therapy by characterizing biochemical changes in the cancer. These scans can be performed on the whole body or can be localized to the head and neck.

  • A PET scan demonstrates the biological function of the body before anatomical changes take place, while the CT scan provides information about the body's anatomy, such as size, shape, and location. By combining these 2 scanning technologies, a PET-CT scan enables physicians to more accurately diagnose and identify cancer and its extent.

  • These can be used as a tool in the initial evaluation of the patient who presents for initial staging, as well as for evaluating response to treatment.

Tumor biopsy

A sample of the lesion may be obtained in the clinical setting or as part of the endoscopic evaluation of the tumor. Proper sampling is required in order to allow the pathologist to evaluate viable tumor cells. The vast majority of biopsy findings reflect the presence of squamous cell carcinoma. In fewer instances, minor salivary gland malignancies and sarcomas are discovered.

Panendoscopy

The routine use of this procedure, which includes a bronchoscopy, an esophagoscopy, and a laryngoscopy, has been the subject of much controversy.[2] It allows for the complete evaluation of the upper aerodigestive tract and helps rule out the presence of a metachronous tumor. The mucous membranes of the upper aerodigestive tract are carefully evaluated, and biopsy samples of any abnormal-looking areas are taken for assessment. An intermediate view is obtained by performing a tumor-specific endoscopy, whereby the anesthetized patient in a relaxed state can have the oral cavity examined with less difficulty. After completing the evaluation, the tumor is staged.

Squamous cell carcinoma is by far the most common epithelial malignancy of the tongue, and nonsquamous cell cancers comprise fewer than 3% of all lingual malignancies. Also, the 2 prominent variants of oral squamous cell carcinomas that may be present are referred to as verrucous carcinoma and sarcomatoid squamous cell carcinoma.

Verrucous cell carcinomas have been described as a unique form of squamous cell carcinoma related to human papillomavirus infection. In its early phases, the tumor may be subclinical and asymptomatic as a verruciform growth phase that lasts several years. In other patients, the lesion may appear suddenly or as a slowly growing lesion that has a sudden and rapid growth phase.

The macroscopic appearance of these lesions depends on the duration of the lesion, the amount of keratinization, and the changes in the adjoining mucosa. A fully developed lesion has the appearance of an exophytic bulky lesion that is gray to grayish-red and has a rough, shaggy, or papillomatous surface.

Microscopically, these tumors are broadly based and invasive through papillary fronds. They are composed of highly differentiated squamous cells lacking frank cytologic criteria of malignancy with rare mitoses. The surface of the lesion is covered with compressed invaginating folds of keratin layers. Typically, a blunt pushing margin and astromalike inflammatory reaction are seen.

Sarcomatoid carcinomas are also referred to as pseudosarcoma, pseudosarcomatous squamous cell carcinoma, pleomorphic carcinoma, metaplastic carcinoma, and the spindle variant of epidermoid carcinoma. The tumor manifests as a rapidly growing, polypoid, and bulky mass, often in a site exposed to prior irradiation. The histogenesis of these tumors is not clear. In general, because of their heterogeneous nature, microscopic interpretation of these tumors is highly subjective. In addition, sampling limitations are inherent to any fine structural analysis. Electron microscopy findings from these tumors are likely to be of value only if epithelial features are present within the spindle cells.

Malignancies of salivary gland origin also may occur, with adenoid cystic carcinomas[10] and mucoepidermoid carcinomas predominating in histological subtypes. Relative to the palate, minor salivary gland malignancies of the tongue are rare.

Oral mucosal melanomas to the tongue are rare relative to other oral cavity sites such as the palate, alveolar gingivae, and lips. Virtually any malignancy can metastasize to the tongue. Statistically, carcinomas of the breast, lung, kidney, and adrenal gland are the most common.

As described in the June 5, 2018, update of the American Joint Committee on Cancer (AJCC) Cancer Staging Manual, Eighth Edition, primary oral cavity tumors are staged as follows.[11]

Criteria for primary tumor (T) classification

These include the following[11] :

• T1 - Tumors are 2 cm or smaller, with a depth of invasion of 5 mm or less
• T2 - Tumors are 2 cm or smaller, with a depth of invasion of over 5 mm, or tumors are greater than 2 cm but do not exceed 4 cm, with a depth of invasion of 10 mm or less
• T3 - Tumors are larger than 2 cm but no bigger than 4 cm, with a depth of invasion of over 10 mm, or tumors are over 4 cm in size, with a depth of invasion of 10 mm or less
• T4 - This involves moderately or very advanced local disease
• T4a - This involves moderately advanced local disease; tumors are over 4 cm, with a depth of invasion of over 10 mm, or tumors have invaded only adjacent structures (eg, having advanced through the cortical bone of the mandible or maxilla or demonstrated maxillary sinus or facial skin involvement)
• T4b - Tumors have invaded the masticator space, pterygoid plates, or skull base and/or encased the internal carotid artery.

Criteria for clinical nodal classification

These include the following[11] :

• N0: No nodal metastasis is present
• N1: The metastasis occupies a single ipsilateral node and is no more than 3 cm in the greatest dimension; no extranodal extension is present
• N2a: The metastasis occupies a single ipsilateral lymph node; exceeds 3 cm, but not 6 cm, in the greatest dimension; and does not involve extranodal extension,
• N2b: Metastases, none beyond 6 cm in the greatest dimension, occupy multiple ipsilateral lymph nodes, with no extranodal extension
• N2c: The metastases occupy bilateral or contralateral lymph nodes, with none exceeding 6 cm in the greatest dimension and with no extranodal extension present
• N3a: The metastasis occupies a lymph node and is over 6 cm in the greatest dimension, and no extranodal extension is present
• N3b: Metastasis is present in any node(s), and clinically overt extranodal extension exists

Stage groupings, also defined by the AJCC, are delineated in the table below.

Table. (Open Table in a new window)

A number of generalities predominate as philosophic tenets of tongue malignancy management. The general beliefs are that superficial lesions are treated with single-modality therapy (eg, radiation or surgery) and that large lesions are treated with multiple modalities (eg, combined surgery and radiation). Additionally, cervical nodes are treated with either surgery or radiation therapy, and survival increases if microscopically positive nodes are present. The therapeutic decision must take into consideration the patient's age, lifestyle, and willingness to participate in the therapeutic regimen. The treatments have substantially different morbidities and may result in significant differences in quality of life.

If possible, a younger patient is treated surgically to avoid radiation therapy because of the known late adverse effects of radiation. Additionally, premature use of radiation therapy eliminates this modality from future consideration if the disease recurs. In an older patient, either modality may be chosen if the lesion is superficial and small.

Avoid using a modality that preserves greatest function but places the patient at a greater risk of local or regional recurrence.

Radiation therapy

Radiation therapy may be used as a single-modality treatment for small or superficial tongue lesions. The local control rates for T1 and T2 oral tongue cancers are similar for surgery and radiation therapy. However, radiation therapy has the advantage of preserving normal anatomy and tongue function.

Three main techniques of radiation therapy administration may be used. External beam radiotherapy using a single ipsilateral portal or bilateral-opposed portals may be selected, depending on tumor size and location, nodal status, and the possible inclusion of interstitial implants.[12]

A second technique is brachytherapy, whereby the tumor is treated by implanting a series of hollow needles, through which radioactive seeds are injected during the length of the treatment.[13, 14] This may be used as a single modality or can be used following a partial glossectomy with controlled frozen sections. One of the advantages of this technique is the almost direct administration of the radiation to the tumor bed. Often, this technique is used after the tumor bed has been preliminarily treated with external beam radiotherapy. Brachytherapy may result in significant tongue edema, necessitating an elective tracheotomy.

A third technique is orthovoltage radiotherapy. Most successful in cooperative patients with well-marginated and exophytic lesions, cone therapy is administered prior to external beam radiation therapy. An intraoral cone is placed against the tumor bed. Either orthovoltage or electrons may be given with equal control rates.

In early or moderately advanced tumors (ie, T1, T2, early T3), postoperative radiation therapy is considered if adverse histological features are noted in the pathology specimen of the primary tumor or the specimen from elective neck dissection.

For advanced lesions, combined treatment with surgery is advisable. Most patients initially undergo surgical resection; however, many patients have recently been treated with high-dose (therapeutic) preoperative radiation therapy with either external beam radiotherapy alone or external radiation therapy plus interstitial radiotherapy followed by surgical resection of the residual tumor. The latter technique results in a less-extensive tongue resection, hopefully without compromising the prognosis.

Radiation therapy is considered a valid option for the primary management of small oral tongue cancers in patients who refuse surgery or those who are poor surgical candidates.

Chemotherapy

The role of chemotherapy in the management of cancer of the oral tongue is still unclear. Early tumors are not treated with this modality, because of the high success of either radiation therapy or surgery. Patients who present with extensive primary lesions or with distant metastases and poor prognoses are good candidates for chemotherapy. Factors to consider if contemplating chemotherapy include stage of disease, general medical status, potential efficacy, and tolerance to adverse effects.

A newer strategy for using chemotherapeutic agents is concomitant chemoradiation. With this modality, chemotherapy is administered at the same time as radiation therapy. This approach has multiple benefits, which include synergism, radiosensitization, beneficial antiproliferative effects, possible improved locoregional control, and possible improved survival.

The ideal surgical approach to oral tongue tumors depends on the tumor size and the involvement of adjacent structures. For most small T1 and T2 lesions confined to the tongue, peroral horizontal wedge excision with primary anterior-to-posterior closure may be achieved quite easily.

With larger lesions and impaired tongue mobility, implying deep tongue infiltration or floor-of-mouth extension, a more radical approach is required. The tongue may be approached through a lateral pharyngotomy. If more exposure is necessary, a mandibulotomy may be required for access if the mandible is free of tumor. When the tumor involves or extends to the gingiva, consider resection of the mandible.

Another strategy is to use the combination of a glossectomy and brachytherapy. In this setting, controlled margins of excision are obtained, followed by the use of brachytherapy needles prior to awakening from general anesthesia. The patient is then monitored postoperatively for 48 hours, during which the radiation oncologist proceeds with the brachytherapy dosimetry and implantation of radioactive seeds for periods of up to 72 hours. The needles are then removed and the patient's recovery proceeds in-hospital until the patient meets discharge goals.

The patient's preoperative evaluation is initiated by obtaining consent for the procedure. The discussion includes the goals of the procedure, the estimated operative time, and a description of the postoperative course. This often necessitates presenting the information to family members who will assist in the patient's recovery.

The surgeon presents a detailed plan of surgical management. With smaller tumors, peroral resections may impair tongue mobility, resulting in dysphagia or speech difficulties. With larger tumors for which a mandibulotomy or a mandibulectomy is required, the patient's airway may become an issue and the physician may need to consider a tracheotomy. The goal remains to excise the tumor in its entirety from a tridimensional standpoint, including a margin of normal-looking tissue. In these settings, a preoperative assessment by a speech therapist is beneficial to the patient so that expected difficulties can be discussed.

Educate patients who present with clinical lymphadenopathy or those whose surgical plan includes a neck dissection about the procedure and about the expected difficulties, depending on which neck structures must be resected.

In more extensive procedures, advise the blood bank about the potential need for a transfusion and request that the blood bank personnel type and cross-match the appropriate number of units. Obtain autologous blood from the patient preoperatively. In most cases, to expedite surgical management, usually the patient does not have enough time to build back sufficient reserves.

Use information obtained from the preoperative evaluation under anesthesia and the radiological imaging to plan the excision. Unless the tumor is very small, general anesthesia is necessary. In patients with more complex medical problems, a preoperative evaluation by the anesthesiologist provides additional information regarding potential medical issues that may arise during the surgery.

Prophylactic antibiotics at the time of surgery are a good means of limiting the risk of infection in the perioperative period. Consider agents that cover microorganisms in the oral flora, especially anaerobes. The antibiotic dosage may depend on the patient's medical status, especially kidney function.

For peroral resections, once the patient is under general anesthesia, all the edges of the tumor are carefully visualized. Palpation of the tumor helps assess the depth of infiltration and how much of the tongue substance must be resected. The area of excision includes a 5- to 10-mm margin of normal-looking soft tissue. Perform the excision with either a scalpel blade or electrocautery. The advantage of electrocautery is that bleeding is controlled as the resection is performed. Larger vessels may need to be controlled with ligatures. Once the resection is completed, samples of the wound bed are submitted to the pathologist for frozen section and tumor clearance. Because the defects are smaller, the tongue is usually closed in multiple layers on itself from posterior to anterior.

For larger tumors (ie, T3, T4 lesions) that require a mandibulotomy, perform a tracheotomy early in the resection to allow for postoperative airway protection and care. Tracheotomy also improves the visibility of the tumor and helps define the margins of excision more precisely. If the tumor approaches or involves the gingiva, perform a mandibulectomy. McGregor and MacDonald demonstrated the mechanisms of mandibular involvement.[15, 16] In nonirradiated patients, the tumor crawls up the lingual plate and enters through the occlusal surface of both dentulous and edentulous mandibles.

If the mandibular invasion is limited, the inferolateral mandible usually remains uninvolved and marginal mandibulectomy may be performed. The lingual cortex becomes the lateral margin, with local control rates similar to those achieved with a segmental mandibulectomy. The preservation of mandibular continuity markedly improves postoperative form and function. When the mandibular invasion is through the cortex, segmental mandibulectomy and appropriate glossectomy are required, followed by postoperative radiation therapy.

Surgical reconstruction for smaller defects may be accomplished by primary closure and insertion of a skin graft. Larger defects may require a free flap.[17, 18] If limited mandibular involvement is present, a radial forearm flap provides proper bulk while not tethering the tongue to the floor of the mouth. Anterior mandibular segmental defects must be reconstructed to avoid the so-called "Andy Gump" deformity, a term coined in 1978 in a dental publication referring to the appearance of a chinless cartoon character from the early 20th century. This is best accomplished by using a fibula free flap with skin paddle, if needed. The fibula free flap has excellent bone stock that can support osseointegrated implants for dental restoration. Alternatives include a scapular or iliac crest free flap. The decision to use one or multiple microvascular and/or pedicled flaps depends on the functional status of the patient and the size of the defect.

Final wound closure is accomplished with meticulous attention to the approximation of the wound edges after adequate hemostasis is completed. Place suction drains in the wound when indicated, and use irrigation to remove small clots and debris.

Following a limited glossectomy, most patients require sufficient analgesia and may require a short course of postoperative antibiotics. Carefully examine the patient's wounds, and intensively monitor patients who underwent free flap reconstruction to assess for early flap failure. In cases in which a neck dissection is part of the surgical plan, carefully evaluate the skin flaps for wound dehiscence. Monitor the drain sites for the amount and type of drainage.

Patients usually have postoperative odynophagia as a result of tongue pain and may require energy supplementation if unable to tolerate a soft diet. In cases of extensive resections, percutaneous feedings via a nasogastric or gastrostomy tube are advisable, at least until the wound edges have had sufficient time to epithelialize.

For patients dependent on a tracheostomy, proper nursing care is necessary to prevent crust accumulation and tube obstruction. The nursing team may want to teach the patient tracheotomy tube care early in the recovery, familiarizing the patient and other caregivers with long-term care.

All patients are monitored regularly following surgery to assess wound healing, the development of complications, and for recurrence of disease. If an ulcer develops in the surgical site, perform a biopsy because of the limited morbidity associated with this procedure.

For patients with larger tumors for whom radiation therapy is part of treatment, consider early referral to a radiation therapist. Radiation therapy also may be considered for patients who are not surgical candidates but who experience disease recurrence.

For excellent patient education resources, visit eMedicineHealth's Cancer Center. Also, see eMedicineHealth's patient education article Cancer of the Mouth and Throat.

Complications may be classified by type and timing of occurrence. Early postoperative complications include collection of blood or serum under the neck flaps or site(s) of reconstruction. Drains on high suction evacuate these fluids and keep the neck flaps in close apposition for faster wound healing. Wound dehiscence may result from infection, malnutrition, poor wound healing, or tissue necrosis. Gentle handling of the tissue and meticulous wound closure may prevent this.

Proper donor and recipient site selection, perioperative use of anticoagulants, and close monitoring of the site of vascular anastomosis help prevent flap failure. Monitoring the vascular anastomoses may be difficult, and subtle changes in flow characteristics also may herald early signs of flap failure. Sometimes, signs of flap failure can be detected with the use of a portable Doppler ultrasound unit. Later changes may include an alteration in the turgor or color of the skin paddle of the flap. Early intervention by wound reexploration and revision of the vascular anastomosis may allow salvage of a failing flap.

Salivary leaks or air leakage may occur when the mucosal incisions are not well approximated, potentially leading to fistulae and wound infection. Aggressive management of fluid collections minimizes the risk of fistulization, and small collections may be aspirated. Larger accumulations require reopening the wound and irrigating and cleaning the wound surfaces, followed by packing the surgical site.

Late complications include skin or mucosal slough, exposure of the mandibulotomy site, nonunion, osteonecrosis, and fistula formation. Others include poor speech and swallowing function. If exposure of the carotid artery occurs as a result of tissue sloughing, bring in regional or distant tissue when the wound is clean to prevent carotid rupture.

Management of mandibular exposure or nonunion depends on the severity of the problem. Solutions range from local wound care in limited cases to mandibular restabilization and reconstruction if hardware is exposed.

For T1 and T2 lesions, radiotherapy using interstitial implants with or without external beam radiotherapy and surgical excision have equivalent results. The 5-year disease-free survival rate ranges from 80-90% for lesions treated with either modality. The long-term complications of radiation implants, including local necrosis and bone exposure, are more frequent than those associated with surgery. Surgery also reserves the option of radiation for the treatment of second primary lesions, which occur in up to 40% of cases. The 5-year survival rates for patients in stages III and IV are 30-50%, with lymph node metastasis decreasing the survival rate 15-30%. A 2011 study by Bonnardot et al reports that concurrent or previous diagnosis of oral lichen planus significantly increased the risk of disease-specific death and disease recurrence. In this cohort of patients, the 5-year survival rate was less than 25%.[19]

A retrospective study by Marra et al indicated that in patients with oral tongue squamous cell carcinoma, high cure rates can be realized through treatment with radical surgery and subsequent radiotherapy or chemoradiotherapy. However, the disease-free survival rate tends to be diminished in association with perineural invasion and extranodal extension. In the study, 106 patients (none of whom had distant metastases at baseline imaging) underwent resection, with adjuvant radiotherapy or chemoradiotherapy administered to those at particular risk of relapse. The 5-year disease-free survival rate was 87.4%, while the hazard ratios for disease recurrence in patients with extranodal extension or perineural invasion were 2.87 and 3.85, respectively.[20]

In a study of oral tongue squamous cell carcinoma, Zhang et al reported that in patients in whom positive margins were detected intraoperatively, immediate resection of these margins led to a local recurrence–free 3-year survival rate (92%) comparable to that of patients with negative margins (91%) and superior to that of patients with positive margins who did not undergo margin resection (73%). Invasive carcinoma/high-grade dysplasia situated less than 1 mm from the inked edge was designated as a positive margin.[21]

Treatment failure often occurs in the cervical lymph nodes, even for patients with an N0 neck. The incidence of occult cervical metastasis in carcinoma of the tongue correlates with the T stage. In a study from Spiro and Strong, the incidence of cervical metastasis increases progressively as the T stage advances.[22] Of patients with T1 cancers, 20% had occult metastases, compared to 43% and 77% of patients with stages T2 and T3 disease, respectively.

Elective radiation therapy is an option for the treatment of the N0 neck. Mendenhall et al demonstrated that elective neck radiation significantly reduces the rate of neck recurrence. Others have published conflicting studies. Meoz et al reported a 16.6% neck recurrence rate for patients receiving the traditional 50 Gy dose to the upper neck. Decroix and Ghossein reported a 14% rate of neck recurrence among 50 patients with squamous cell carcinoma of the oral tongue staged N0 who received radiation therapy.

For patients with cancer of the oral tongue, elective treatment of the N0 neck is better than no treatment. This may take the form of either radiation therapy or surgery. Radiation therapy is preferable in individuals with poor health, but it has the associated adverse effects of mucositis and xerostomia and the risk of osteoradionecrosis. Surgery appears to provide better overall cure rates and allows for pathologic evaluation of the specimen for prognostication.

To better evaluate prognosis and outcome, many studies have looked at the expression of various growth factors and tumor markers. In studying the overexpression of epidermal growth factor (EGFR) and cerb-B2, these 2 growth factors have not been found useful in predicting outcome and survival.

A study by Yu et al indicated that overexpression of the cancer-associated biomarker CD147 in combination with a high Ki-67 labeling index correlates with a poor prognosis in patients with squamous cell carcinoma of the oral tongue.[23]

A study by Minami et al found that in patients with oral tongue cancer who underwent surgical resection as their primary treatment, a significantly better cause-specific survival rate was experienced by those whose tumors were positive for the p16 tumor-suppressor protein than by those who were p16-negative.[24]

A number of issues remain controversial in the management of tongue cancer. The optimal radiation therapy schedule for managing small lesions in order to limit xerostomia, mucositis, and potential late complications (eg, osteoradionecrosis, fibrosis) is an ongoing debate. The addition of new chemotherapy agents may provide increased tumor sensitization to the radiation and may allow for dose limitation.

The management of the N0 neck continues to be a source of open debate. Because of the relatively high incidence of occult disease, the preferred treatment of these patients is either of the 2 modalities. Possibly with newer imaging techniques on the horizon, physicians will be better able to identify smaller tumor foci and the number of patients staged as N0 will decrease.

Finally, the greatest challenge remains in the field of tongue reconstruction. Numerous microvascular flaps have been described to give bulk and also sensation to the neotongue. Some even use motor reinnervation as a means to give some mobility to these tissues. Because of the complexity of integration of the intrinsic and extrinsic tongue musculature and the crucial role the tongue has in speech, taste, and deglutition, the ideal flap has yet to be identified.