Tongue cancer overview

# 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. 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. More than 90% of oral cavity cancers are squamous cell carcinomas. The majority of the other lesions are of minor salivary gland origin. Nonsquamous cell cancers comprise fewer than 3% of all lingual malignancies. 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 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 incidence of tongue cancer increases with age. The most potent risk factor in the development of oral cancer is alcohol intake, tobacco use and human papillomavirus transmitted through sexual contact. Head and neck MRI scan is diagnostic of tongue cancer. The predominant therapy for tongue cancer is surgical resection. Adjunctive chemotherapy, radiation, chemoradiation, or brachytherapy may be required.

# Historical perspectives
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 unfit for surgery.

# Classification
There is no specific established system for the classification of tongue cancer; however, it's classified as part of the oral cancers. Oral cancer can be classified into three types based on the potential to spread to other parts of the body such as malignant tumors,precancerous conditions, and benign tumors. Most common type of malignant tumor of the mouth is squamous cell carcinoma. Squamous cell carcinoma is further classified based on macroscopic and microscopic features. About 5% of oral cavity cancers are rare malignant tumors that start in different types of cells in the oral cavity. These include salivary gland cancer, melanoma, bone and soft tissue sarcomas, Lymphomas and extramedullary plasmacytomas, Hodgkin lymphoma, and non-Hodgkin lymphoma metastatic cancer.

# Pathophysiology
Leukoplakia and erythroplakia have the greatest potential for malignant transformation in tongue cancer. World Health Organization classified oral cancer into mild, moderate, and severe dysplasia. Genes involved in the pathogenesis of tongue cancer include TP53, c-myc, and erb-b1. On gross pathology, exophytic, ulcerative, and infiltarative growth patterns are characteristic findings of tongue cancer. Tongue cancer constitutes of highly differentiated squamous cells lacking frank cytologic criteria of malignancywith rare mitoses. The surface of the lesion is covered with compressed invaginating folds of keratin layers. A stroma-like inflammatory reaction and a blunt pushing margin may be seen.

# Causes
Tongue cancer is caused by a point mutation in the tumor suppressor gene (TP53). The other oncogenes associated with oral squamous cell cancers of tongue include c-mycand erb -b1.

# 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 lymphoma, sarcoma,, metastatic tumor, malignant salivary gland tumors, tuberculosis, scarlet fever, syphilis, papilloma, lipoma, leiomyoma, neurofibroma, schwannoma, granular cell tumor, benign migratory glossitis, Hairy tongue, pemphigus, erythema multiforme, mucous membrane pemphigoid, vitamin B deficiency, amyloidosis, diabetes mellitus, hypothyroidism, acromegaly.

# 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 with 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.

# 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 tongue cancer is not recommended in the United States. Outside the US, multiple screening programs have been tried in high-risk patients. Screening subjects are tobacco or alcohol consumers.

# 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, a 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
There are no x-ray findings associated with tongue cancer. However, an x-ray may be helpful in the evaluation of metastases 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
There are no other imaging findings associated with tongue cancer.

# 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 can not 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. 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 swallowing for most stage I and II lesions of the oral tongue. Partial glossectomy is commonly required for advanced disease.Total glossectomy is required in cases where bilateral lingual arteries are involved by 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 cavitycancer 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 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 antiinflammatory drugs, EGFR inhibition, and human papilloma virus related oropharyngeal carcinoma vaccine can be used as a secondary chemopreventiveagents.