Hypopharyngeal cancer overview
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Editor-In-Chief: C. Michael Gibson, M.S., M.D. [1] Associate Editor(s)-in-Chief: Gertrude Djouka, M.D.[2], Faizan Sheraz, M.D. [3]
Overview
Hypopharyngeal cancer was discovered in 1970 by Dr.Harrison in London, U.K. Hypopharyngeal cancer is a disease in which malignant cells proliferate in the hypopharynx. Most hypopharyngeal cancers form in squamous cells, the thin, flat cells lining the inside of the hypopharynx. It first forms in the outer layer (epithelium) of the hypopharynx, which is split into three areas. Progression of the disease is defined by the spread of cancer into one or more areas and into deeper tissues. Genes involved in the pathogenesis of hypopharyngeal cancer include p16, NOTCH1, cyclin D1, and TP53. Hypopharyngeal cancer is associated with sideropaenic dysphagia and Paterson Brown Kelly syndrome.On gross pathology, flattened plaques, mucosal ulceration, and raised margins of the lesion are characteristic findings of hypopharyngeal cancer. On microscopic histopathological analysis, spindle cells, basaloid cells, and nuclear atypia are characteristic findings of hypopharyngeal cancer.There are no established direct causes for hypopharngeal cancer. The prevalence of hypopharyngeal cancer is estimated to be approximately 10% of all proximal aerodigestive tract malignancies.The incidence of hypopharyngeal cancer is estimated to be 0.78 cases per 100,000 individuals in the United States each year.Hypopharyngeal cancer commonly affects individuals older than 50 years of age. Males are more commonly affected with hypopharyngeal cancer than females. If left untreated, hypopharyngeal cancer produces few symptoms early in the course. Once the tumor has expanded from its site of origin, it may obstruct the aerodigestive tract. Common complications of hypopharyngeal cancer include airway obstruction and disfigurement of the neck or face. The prognosis varies with the type of hypopharyngeal cancer. Squamous cell carcinoma of hypopharynx has the most unfavorable prognosis. The optimal therapy for hypopharyngeal cancer depends on the stage at the time of diagnosis. The feasibility of surgery depends on the stage of hypopharyngeal cancer at the time of diagnosis.
Historical Prospective
Hypopharyngeal Cancer is a rare type of malignant tumor. Hypopharyngeal cancer was discovered by Dr.Harrisson in 1970 with more than half in the postcricoid part.
Classification
Hypopharyngeal cancer may be classified according to the location into 4 subtypes: pyriform sinus cancer, postcricoid area cancer, and posterior wall of hypopharynx cancer. A pyriform sinus cancer subtype is found in 60 to 85 percent of patients who are diagnosed with hypopharyngeal cancer. Hypopharyngeal cancer can also be classified based on the cellular derivatives.
Pathophysiology
Hypopharyngeal cancer arises from squamous cells, which are cells that are normally involved in protection of aerodigestive tract. Hypopharyngeal cancer is a rare type of malignant cancer which has delayed onset of clinical symptoms. Hypopharyngeal cancer is usually found at advanced stage and it is spread to other organs such as lungs, mediastinum,bones, brain, liver, esophagus, and thyroid gland. The metastatic invasion depends on the anatomic location of the hypopharyngeal cancer. Hypopharyngeal cancer is mostly differentiated as squamous cell carcinoma, but the undifferentiated type can be found in the pyriform sinus region. The exact pathogenesis of the hypopharyngeal cancer is not exactly understood, but the p16, NOTCH1, cyclin D1, and TP53 gene mutations have been associated with the development of the hypopharyngeal cancer. Hypopharyngeal cancer is associated with sideropenic dysphagia and Paterson Brown Kelly syndrome. On gross pathology, flattened plaques, mucosal ulceration, and raised margins of the lesion are characteristic findings of hypopharyngeal cancer. On microscopic histopathological analysis, spindle cells, basaloid cells, and nuclear atypia are characteristic findings of hypopharyngeal cancer.
Causes
There are no direct causes for hypopharngeal cancer. However, there are some common risk factors that may lead to gene mutations and cause the hypopharyngeal cancer.Common risk factors for hypopharyngeal cancer can be found here.
Differentiating Hypopharyngeal Cancer from other Diseases
Hypopharyngeal carcinoma must be differentiated from accessory salivary gland tumor, lymphoma, and retropharyngeal abscess.
Epidemiology and Demographics
The prevalence of hypopharyngeal cancer is estimated to be 2,500 new cases annually in U.S and hypopharyngeal cancer is a very rare type of cancer. Hypopharyngeal cancer commonly affects patients in 55 to 65 years of age. Males are mostly affected with a hypopharyngeal cancer compare to women. Hypopharyngeal cancer comprises about 7% of all cancers of the head and neck.
Risk Factors
Common risk factors in the development of hypopharyngeal cancer are tobacco use, and abuse of alcohol consumption.
Screening
According to the National Cancer Institute and American Cancer Society, screening test for hypopharyngeal cancer is not recommended.
Natural History, Complications and Prognosis
The majority of patients with hypopharyngeal cancer are initially asymptomatic. Most patients with hypopharyngeal cancer clinically manisfest symptoms at late stage (III and IV) because of the tumor aggression which metastasizes to lymph nodes and submucosa. Once the tumor has expanded from its site of origin, it may obstruct the aerodigestive tract. Most common clinical presentations are neck mass, dysphagia with weight loss, non healing sore throat, odynophagia,and hoarseness. Common complications of hypopharyngeal cancer include upper airway obstruction and disfigurement of the neck or face. The prognosis varies with the type of hypopharyngeal cancer. Squamous cell carcinoma of hypopharynx has poor prognosis and small survival rate.
Staging
According to the American Joint Committee of Cancer (AJCC) TNM staging system, there are 5 stages of hypopharyngeal cancer based on the tumor size, lymph node involvement, and distant metastasis.
History and Symptoms
The hallmark of hypopharyngeal cancer is dysphagia. A positive history of odynophagia and hoarseness is suggestive of hypopharyngeal cancer. Common symptoms include a lump in the neck, dysphagia, chronic sore throat and hoarseness.
Physical Examination
Patients with hypopharyngeal carcinoma are usually well appearing. Physical examination of patients with hypopharyngeal carcinoma is usually remarkable for neck swelling.
Laboratory Findings
There are no diagnostic laboratory findings associated with hypopharyngeal cancer.
Electrocardiogram
There are no ECG findings associated with hypopharyngeal cancer.
Chest X Ray
Chest X rays may be performed to detect metastasis of hypopharyngeal cancer to the lungs.
CT
Head and neck CT scan may be helpful in the diagnosis of hypopharyngeal cancer. Findings on CT scan suggestive of hypopharyngeal cancer include soft tissue mass, irregular thickening of mucosa, and necrotic region which is a sign of metastasis.
MRI
MRI may be helpful in the diagnosis of hypopharyngeal cancer. Findings on MRI suggestive of hypopharyneal cancer include tumors are hypointense on T1 and hyperintense on T2 for soft tissues.
Other Imaging Findings
Ultrasound may be helpful to assess hypopharyngeal cancer along with endoscopy. Ultrasound may be use to detect, and localize primary tumors that invade neighboring organs such as esophagus, thyroid, and postcricoid area.
Other Diagnostic Studies
Biopsy may be diagnostic of hypopharyngeal cancer. Findings on biopsy diagnostic of hypopharyngeal cancer include spindle cells, basaloid cells, and nuclear atypia.
Medical Therapy
The medical therapy with the combination of the radiotherapy has been used compared to surgical therapy for the treatment of hypopharyngeal cancer.The optimal therapy for hypopharyngeal cancer depends on the stage at the time of diagnosis. The combined treatment helps with organ preservation. swallowing, speech and laryngeal preservation are important to consider during the treatment.
Surgery
The feasibility of surgery depends on the stage of hypopharyngeal cancer at the time of diagnosis. The main goal of the surgery is to clear any margin with tumor cells. The available surgery options are transoral laser surgery, total laryngectomy with partial pharyngectomy surgery, total laryngectomy and circumferential pharyngectomy.
Primary Prevention
Effective measures for the primary prevention of hypopharyngeal cancer include smoking cessation, decrease alcohol consumption, increase vegetables and fruits consumption, and vaccination for HPV.
Secondary Prevention
Secondary prevention measures of hypopharyngeal cancer include routine physical examination and imaging at scheduled intervals after treatment. Dental screening and screening for thyroid cancers are recommended among patients who had received radiation therapy to the oral cavity and cervical region, respectively.