Tongue cancer overview

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Overview

Historical Perspective

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Pathophysiology

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Differentiating Tongue cancer from other Diseases

Epidemiology and Demographics

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Natural History, Complications and Prognosis

Diagnosis

Staging

History and Symptoms

Physical Examination

Laboratory Findings

Chest X Ray

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Editor-In-Chief: C. Michael Gibson, M.S., M.D. [1]; Associate Editor(s)-in-Chief: Simrat Sarai, M.D. [2] Mohammed Abdelwahed M.D[3]

Overview

Tongue cancer is cancer that begins in the cells of the tongue. Approximately 25-30% of all oral cavity cancers begin in the tongue. If cancer begins in the proximal two-thirds of the tongue it is described as oral cancer and if it begins on the distal third of the tongue it is described as throat cancer. Approximately 20% of all squamous cell carcinomas of the oral cavity arise from the tongue, and approximately 75% of all tongue squamous cell carcinomas arise from the anterior two-thirds of the tongue. Squamous cell carcinoma of the tongue usually arises from the ventrolateral aspect of the mid and posterior tongue, probably due to adjacent pooling of carcinogens. Tobacco smoking and alcohol ingestion has been identified as the major risk factors in the development of squamous cell carcinoma. There is no classification system established for tongue cancer. Nonsquamous cell cancers comprise fewer than 3% of all lingual malignancies. More than 90% of oral cavity cancers are squamous cell carcinomas. The majority of the other lesions are of minor salivary gland origin. Melanomas, lymphomas and sarcomas rarely occur in the tongue. Genes involved in the pathogenesis of tongue cancer include TP53, c-myc, and erb-b1. On gross pathology, exophytic, ulcerative, and infiltrative growth patterns are characteristic findings of tongue cancer. Tongue cancer may be caused by either tobacco, alcohol, or human papillomavirus. Tongue cancer is caused by a point mutation in the tumor suppressor gene (TP53). Other causes of tongue cancer include areca nuts, the betel nuts or quid, use of slaked lime, and Plummer-Vinson syndrome. Tongue cancer must be differentiated from other diseases that cause malignant lesions of the oral cavity and from few non-neoplastic lesions of the oral cavity, such as lymphoma, adenoid cystic carcinoma, adenocarcinoma, mucoepidermoid carcinoma, rhabdomyosarcoma, liposarcoma, infections at the floor of mouth and mandible, and normal adenoid tissue for lesions at the base of tongue. In 2009, the incidence of tongue cancer was estimated to be 10,530 cases per 100,000 individuals in the United States. Males are more commonly affected by tongue cancer than females. The male to female ratio is approximately 2 to 1. The incidence of tongue cancer increases with age; the median age at diagnosis is 61 years. Approximately one-third of all diagnoses occurred in patients under the age of 55. There is no racial predilection to the tongue cancer. The most potent risk factor in the development of oral cancer is alcohol intake, tobacco use and human papillomavirus transmitted through sexual contact. The other risk factors include history of betel quid intake, male gender, age over 55 years, ultraviolet light, Fanconi anemia, dyskeratosis congenita, lichen planus, graft-versus-host disease (GVHD), immune system suppression, mouthwash and irritation from dentures. Head and neck MRI scan is diagnostic of tongue cancer. On head and neck MRI, tongue cancer is characterized by isointense to hypointense mass on T1-weighted MRI and isointense to hyperintense mass on T2-weighted MRI. The predominant therapy for tongue cancer is surgical resection. Adjunctive chemotherapy, radiation, chemoradiation, or brachytherapy may be required.

Historical perspectives

In 1831, Jaeger first described splitting the Cheek and splitting both cheeks. By 1930s, Hayes Martin was the first to focus on improving cure rates by treating the primary tumor with X-rays. By 1928, V. P. Blair of St Louis was the first to advocate surgery as the best management for oral cancers. A major initiative of the 1970s and 1980s was cytotoxic chemotherapy for patients who unfit for surgeries.

Classification

There is no classification system established for tongue cancer. Nonsquamous cell cancers comprise fewer than 3% of all lingual malignancies. More than 90% of oral cavity cancers are squamous cell carcinomas. The majority of the other lesions are of minor salivary gland origin. Melanomas, lymphomas and sarcomas rarely occur in the tongue.

Pathophysiology

Genes involved in the pathogenesis of tongue cancer include TP53, c-myc, and erb-b1. On gross pathology, exophytic, ulcerative, and infiltrative growth patterns are characteristic findings of tongue cancer.

Causes

Tongue cancer may be caused by either tobacco, alcohol, or human papillomavirus. Tongue cancer is caused by a point mutation in the tumor suppressor gene (TP53). The other genes associated with oral squamous cell cancer of tongue include c-myc and erb -b1. Other causes of tongue cancer include areca nuts, the betel nuts or quid, use of slaked lime, and Plummer-Vinson syndrome.

Differential Diagnosis

Tongue cancer must be differentiated from other diseases that cause malignant lesions of the oral cavity and from non-neoplastic lesions of the oral cavity, such as lymphomasarcoma, metastatic tumormalignant salivary gland tumorstuberculosisscarlet feversyphilispapillomalipoma, leiomyomaneurofibroma, schwannomagranular cell tumor, benign migratory glossitis, Hairy tonguepemphiguserythema multiformemucous membrane pemphigoid, vitamin B deficiencyamyloidosisdiabetes mellitus, hypothyroidismacromegaly.

Epidemiology and Demographics

In 2009, the incidence of tongue cancer was estimated to be 10,530 cases per 100,000 individuals in the United States. Males are more commonly affected by tongue cancer than females. The male to female ratio is approximately 2 to 1. The incidence of tongue cancer increases with age; the median age at diagnosis is 61 years. Approximately one-third of all diagnoses occurred in patients under the age of 55. There is no racial predilection to the development of tongue cancer.

Risk Factors

The most potent risk factors in the development of oral cancer are alcohol intake, tobacco use and human papillomavirus transmitted through sexual contact. The other risk factors include history of betel quid intake, male gender, age over 55 years, ultraviolet light, Fanconi anemia, dyskeratosis congenita, lichen planus, graft-versus-host disease (GVHD), immune system suppression, mouthwash and irritation from dentures.

Screening

According to the United States Preventive Services Task Force, screening for salivary gland tumors is not recommended.

Natural History, Complications and Prognosis

If left untreated, patients with tongue cancer may progress to develop metastasis. Common complications of treatment of tongue cancer include neurotoxicity, bleeding, radiation caries, trismus, osteonecrosis, oral mucositis, chronic dysphagia, anemia, pharyngocutaneous fistula, aspiration, infections, xerostomia, taste alterations, nutritional compromise, and abnormal tooth development. Prognosis is generally good, and the five-year mortality rate of patients with stage I and II tongue cancer is approximately 89 and 95 percent respectively. The five-year disease-specific survival rate of patients with stage III and IV cancers is 39 and 27 percent respectively.

Staging

According to the TNM staging system by the American Joint Committee on Cancer, there are four stages of oral cancer based on the tumor size, lymph nodes involved, and metastasis.

History and Symptoms

Symptoms of tongue cancer include a red or white patch on the tongue, sore throat, an ulcer or lump on the tongue, pain on swallowing, speaking, or moving the tongue, numbness in the mouth, bleeding from the tongue, pain in the ear, and pain in the mouth or tongue.

Physical Examination

Common physical examination findings of tongue cancer include otalgia, submandibular gland asymmetry, and cervical lymphadenopathy.

Laboratory Findings

Laboratory findings consistent with the diagnosis of tongue cancer include reduced CBC levels, abnormal prothrombin time (PT), abnormal activated partial thromboplastin time (aPTT), and abnormal international normalized ratio (INR).

Chest X Ray

Chest and dental x-rays may be performed to detect metastases of tongue cancer to the lungs and mandible.

CT

Head and neck CT scan may be helpful in the diagnosis of tongue cancer. Findings on CT scan suggestive of tongue cancer include soft tissue attenuation of lesions, bony erosions, and increased attenuation of involved nodes.

MRI

Head and neck MRI scan is diagnostic of tongue cancer. On head and neck MRI, tongue cancer is characterized by isointense to hypointense mass on T1-weighted MRI and isotense to hyperintense mass on T2-weighted MRI.

Ultrasound

Ultrasound may be performed to detect metastases of tongue cancer to cervical lymph nodes and to aid in FNAC of suspicious nodes.

Other Imaging Studies

Other diagnostic studies for tongue cancer include bone scan and positron emission tomography.

Other Diagnostic Studies

Other diagnostic studies for tongue cancer include tumor biopsy and panendoscopy. Tumor biopsy helps to evaluate viable tumor cells. The majority of biopsy findings reflect the presence of squamous cell carcinoma. Panendoscopy is highly accurate for evaluation of smaller or more superficial second primary mucosal lesions.

Medical Therapy

The predominant therapy for tongue cancer is surgical resection. It is indicated for patients who have positive resection margins, patients with bone invasion, patients with positive lymph nodes, tumor thickness >4 mm, patients with regional recurrence. For patients who are not surgical candidates but can tolerate chemotherapy, a combined chemotherapy and radiotherapy is appropriate. For patients who are not surgical candidates with bad medical condition and cannot tolerate the chemotherapy, radiotherapy without chemotherapy is more appropriate. Chemotherapy is used in patients who present with extensive primary lesions, in patients with distant metastasis or with poor prognosis. Targeted therapy may be used in combination with chemotherapy or radiation therapy. Targeted therapy drugs, such as monoclonal antibodies, interrupt the spread and growth of specific tongue cancer cells.

Surgery

Surgery is the mainstay of treatment for tongue cancer. A radical approach is required in larger lesions, impaired tongue mobility, deep tongue infiltration, floor-of-mouth extension. A partial glossectomy with negative margins can preserve speech and swallow for most stage I and II lesions of the oral tongue. A Partial glossectomy is commonly required for advanced disease. A total glossectomy is required in cases where bilateral lingual arteries are involved in cancer. In these cases, postoperative radiotherapy or chemoradiotherapy, appears to improve disease control compared with surgery alone. Elective treatment of the neck in patients with stage I and II oral cavity cancer is not well established. Studies recommend a tumor thickness cutoff of 4 mm as a threshold for elective neck dissection.

Primary Prevention

Effective measures for the primary prevention of tongue cancer include avoiding the use of tobacco and excessive use of alcohol. Main methods for prevention are natural components such as: vitamin A, vitamin E, and beta-carotene because they are rich in trace elements and antioxidants. There is a protective effect of diets rich in fresh fruits and vegetables to reduce the incidence of leukoplakia. There is no effective oral cancer screening program for either a general or a selected high-risk population for oral cancer in the United States. Screening high-risk individuals in developing countries could be an effective prevention strategy that lowered the stage of oral cancer at diagnosis and improved 5-year survival. 

Secondary Prevention

Secondary prevention strategies following tongue cancer include monthly follow-ups for the first 12-18 months following therapy. Drugs such as synthetic retinoids, non-steroidal anti-inflammatory drugs, EGFR inhibition, and human papilloma virus related oropharyngeal carcinoma vaccine can be used as a secondary chemopreventive agents.

References

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