Esophagus Cancer

What is Esophageal Cancer

Cancers that start in the area where the esophagus joins the stomach (the GE junction), which includes about the first 2 inches of the stomach (called the cardia), tend to behave like esophagus cancers (and are treated like them, as well); they are grouped with esophagus cancers.

Anatomy, Pathology and Pathogenesis

What is Esophagus ?

The oesophagus also known as the food pipe is a muscular tube measuring 20-25 cm long and 2-3 cm wide that serves as a conduit for moving food and drink from the mouth to the stomach.

Cancer of the esophagus typically occur in one of two forms, squamous cell carcinomas arising from the stratified squamous epithelial lining of the organ, and adenocarcinomas affecting columnar glandular cells that replace the squamous epithelium[6]. Sarcomas and small cell carcinomas generally represent less than 1%-2% of all esophageal cancers [7,8]. On rare occasions, other carcinomas, melanomas, leiomyosarcomas, carcinoids, and lymphomas may develop in the esophagus as well [9].

SCC is the predominant histologic type of esophageal cancer worldwide [10]. The incidence of squamous cell cancer of the esophagus increases with age as well and peaks in the seventh decade of life. The incidence of squamous cell esophageal cancer is three times higher in blacks than in whites, whereas adenocarcinomas are more common in white men.

The natural histories of squamous cell carcinomas and adenocarcinomas of esophagus appear to differ substantially. For squamous cell cancers, transition models have described squamous epithelium undergoing changes that progress to dysplasia and in situ malignant change [11,12]. Most adenocarcinomas, however, tend to arise in the distal esophagus from columnar-lined metaplastic epithelium, commonly known as Barrett’s esophagus[13,14], which replaces the squamous epithelium during the healing reflux esophagitis and may progress to dysplasia. Gastroesophageal reflux disease (GERD), or just reflux[15-17] can damage the lining of esophagus which causes Barrett’ s esophagus[15].

Approximately three quarters of all adenocarcinomas are found in the distal esophagus, whereas squamous-cell carcinomas are more evenly distributed between the middle and lower third[18-24].


  • Esophageal cancer is the eighth most common cancer worldwide, with an estimated 456,000 new cases in 2012 (3.2% of the total), and the sixth most common cause of death from cancer with an estimated 400,000 deaths (4.9% of the total) [1]
  • Much regional variation exists in the incidence and pathology of esophageal cancer [Figure 1]
  • In India, it is the fourth most common cause of cancer-related deaths. [2]
  • Esophageal cancer incidence rates worldwide in men are more than double those in women (male: female ratio 2.4:1)

Signs and symptoms:

  • Difficulty swallowing (dysphagia)
  • Unexplained weight loss
  • Worsening indigestion or heartburn
  • Chest pain, pressure or burning
  • Coughing or hoarseness

Early esophageal cancer typically causes no signs or symptoms.

Risk Factors

  • Gender: The incidence of esophageal squamous cell carcinoma is generally higher in men than women in most countries.
  • Smoking: Smoking is one of the major risk factor for developing esophageal squamous carcinoma. Smokers have a 5-fold risk of developing this disease compared to non-smokers
  • Alcohol: Alcohol is a clear risk factor for squamous carcinoma.
  • Tobacco and nutritional deficit: The “chewers of areca nut” (often mixed with tobacco), are common in regions such as Southeast Asia and India and have been linked to the development of squamous carcinoma.
  • Gastroesophageal reflux disease and Barrett’s esophagus
  • Obesity
  • Drugs
  • Genetics

Risk factors of esophageal cancer are slightly different between the two major subtypes. [25]

Risk factors for squamous cell carcinoma and adenocarcinoma of the esophagus

Risk factor Squamous cell carcinoma Adenocarcinoma
Geography Southeastern Africa, Asia, Iran, South America Western Europe, North America (United States), Australia
Race Black > White White > Black
Gender Male > Female Male > Female
Alcohol ++++
Tobacco ++++ ++
Obesity +++
GERD ++++
Diet: Low fruits and vegetables ++ +
Socioeconomic conditions ++
Genetic aspects ++ +

GERD: Gastroesophageal reflux disease; +: Associated risk; -: No risk associated.


Esophageal cancer is a health problem worldwide with high mortality due to its natural history and diagnosis in advanced stages. There is no sure way to prevent development of esophageal cancer as a variety of physical, lifestyle, and environmental factors can make some people more likely to develop esophageal cancer than others. Still healthy habits such as quitting smoking, stopping consumption of alcohol, exercising regularly and avoiding becoming overweight and seeking medical consultation routinely can help you in reducing the risk.

Since squamous cell carcinoma and adenocarcinoma of the esophagus have different risk factors , they  require different approaches to prevention. For esophageal squamous cell carcinoma, the major environmental risk factors are cigarette smoking and alcohol abuse, smoking cessation and limiting alcohol intake decreases the risk of squamous cell carcinoma. Gastroesophageal reflux disease (GERD) and Barrett esophagus significantly increase the risk for adenocarcinoma of the esophagus. However, eliminating GERD has no documented impact on reducing the subsequent risk of developing adenocarcinoma

Screening for esophageal cancer isn’t done routinely except for patients with Barrett’s esophagus because of a lack of other easily identifiable high-risk groups.

Squamous dysplasia is the precursor lesion of esophageal squamous cell carcinoma; Barrett’s esophagus is the pre-neoplastic lesion preceding adenocarcinoma[26]. Detection and management of these precancerous stages can reduce the incidence/ mortality of esophageal cancer.


  • Endoscopy is the gold standard for the diagnosis of pre-cancerous squamous lesions.

During endoscopy, a flexible tube equipped with a video lens (videoendoscope) is pushed down the throat into the esophagus. Using the endoscope, the doctor examines the esophagus, looking for suspicious areas..

  • Biopsy is done in cases of suspected malignancy on endoscopy or imaging studies. The tissue piece removed during endoscopy is sent to the laboratory for histopathological examination to look for cancerous cells.
  • Bronchoscopy may be done for cancer in the upper part of the esophagus to see if it has spread to the windpipe (trachea) or the tubes leading from the windpipe into the lungs (bronchi).
  • Imaging tests such as X ray, Barium Swallow, CT Scan, MRI Scan, PET Scan are done to evaluate cancer spread


The stages of esophageal cancer range from 0 to IV, with the lowest stages indicating that the cancer is small and affects only the superficial layers of your esophagus. By stage IV, the cancer is considered advanced and has spread to other areas of the body.

Staging is done using the American Joint Committee on Cancer (AJCC) tumor/node/metastasis (TNM) classification system for esophageal  cancer.

Table 1. TNM Classification

Primary tumor (T)
TX Primary tumor cannot be assessed
T0 No evidence of primary tumor
Tis High-grade dysplasia,* defined as malignant cells confined by the basement membrane
T1 Tumor invades lamina propria, muscularis mucosae, or submucosa
T1a Tumor invades lamina propria or muscularis mucosae
T1b Tumor invades submucosa
T2 Tumor invades muscularis propria
T3 Tumor invades adventitia
T4 Tumor invades adjacent structures
T4a Resectable tumor invading pleura, pericardium, or diaphragm
T4b Unresectable tumor invading other adjacent structures, such as the aorta, vertebral body, and trachea
*High-grade dysplasia includes all noninvasive neoplastic epithelial lesions formerly called carcinoma in situ; that term is no longer used for columnar mucosae anywhere in the gastrointestinal tract.
Regional lymph nodes (N)
NX Regional lymph node(s) cannot be assessed
N0 No regional lymph node metastasis
N1 Metastasis in 1-2 regional lymph nodes
N2 Metastasis in 3-6 regional lymph nodes
N3 Metastasis in 7 or more regional lymph nodes
Distant metastasis (M)
M0 No distant metastasis
M1 Distant metastasis




The National Comprehensive Cancer Network (NCCN) provides guidelines for the treatment of esophageal cancer [27].

Treatment options include local mucosal resection or ablation therapies for small tumors, radical surgery for large tumors, chemotherapy, and radiation therapy.

Recommended treatment is primarily dictated by stage, tumor location, and patients’ medical fitness for receiving a particular therapeutic modality.


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