How Esophageal Cancer Is Diagnosed

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Tests used to diagnose esophageal cancer may include a barium swallow, endoscopy, and endoscopic ultrasound, and are often ordered for people who have difficulty swallowing, a persistent cough, or risk factors for the disease such as long-standing acid reflux. Other procedures and imaging tests such as CT, PET, and bronchoscopy can be helpful in determining the stage of the disease.

Careful staging, in turn, is needed in order to choose the best treatment options.

Labs and Tests

There is no at-home test for esophageal cancer. It's helpful to be aware of both the risk factors for the disease and the potential warning signs and symptoms of esophageal cancer, so that you can make an appointment with your doctor and pursue proper professional testing, if needed.

Lab tests are fairly non-specific with esophageal cancer, but are used along with imaging, a careful review of family and personal health history, and a physical exam to diagnose the disease. A complete blood count (CBC) may show evidence of anemia (a low red blood cell count) if a cancer is bleeding. Liver function tests may be elevated if the cancer has spread to the liver.

Procedures

Procedures are very important in making the diagnosis of esophageal cancer and include:

Endoscopy

Upper endoscopy (esophagoscopy or esophagus-gastric-duodenoscopy) is the primary method of diagnosing esophageal cancer today.

In this procedure, a flexible, lighted tube is inserted through the mouth and down through the esophagus. The tube has a camera at the end that allows physicians to directly visualize the lining of the esophagus. If abnormalities are noted, a biopsy can be performed at the same time.

Before the procedure, people are given a sedative that causes sleepiness, and the procedure is usually well tolerated.

Endoscopic Ultrasound (EUS)

This is procedure done to obtain helpful imaging. During a traditional upper endoscopy, an ultrasound probe at the end of the scope is used to bounce high-energy sound waves off of internal tissues of the esophagus. The echoes form a sonogram, a picture of those tissues. EUS is most helpful in determining the depth of the tumor, which is very important in staging it. It is also very helpful in evaluating nearby lymph nodes and guiding biopsies of any abnormalities. Other imaging tests may also be considered (see below), though this is the most invasive.

Biopsy

A biopsy is often taken during endoscopy, but may also be done via bronchoscopy or thoracoscopy. Pathologists look at this tissue under the microscope to figure out if the tissue is cancerous and, if so, whether it is a squamous cell carcinoma or adenocarcinoma. The sample is also given a tumor grade, a number that describes how aggressive the tumor appears.

Other tissue tests may be done that look at the molecular characteristics of the tumor, such as HER2 status (like breast cancers that can be HER2 positive, esophageal cancers may also be HER2 positive).

Bronchoscopy

bronchoscopy is usually done for esophageal tumors that are located in the middle to upper third of the esophagus.

A bronchoscope (a thin, lighted tube) is inserted through the nose or mouth into the trachea (the tube that connects the mouth to the lungs) and bronchi (the large airways) of the lungs. The procedure allows a physician to directly observe any abnormalities in these areas and collect tissue samples of them (biopsy) if present.

Bronchoscopy is done under sedation, usually as an outpatient procedure. 

Thoracoscopy

During a thoracoscopy, an incision or cut is made between two ribs and a thoracoscope, which is a thin, lighted tube, is inserted into the chest. Doctors use this to look at the organs inside the chest and check abnormal areas for cancer.

Tissue samples and lymph nodes may be removed for biopsy. In some cases, this procedure may be used to remove portions of the esophagus or lung.

Laparoscopy

In a laparoscopy, small incisions or cuts are made in the wall of the abdomen. A laparoscope, another thin, lighted tube, is inserted into the body through one of the incisions to look at the organs inside the abdomen and check for signs of disease. Other instruments may be inserted through the same or other incisions to perform procedures such as removing organs or taking tissue samples for biopsy.

Laryngoscopy

A small lighted tube is inserted down the throat to look at the larynx or voice box. This test can detect any evidence of spread of the cancer to the larynx or pharynx (throat). 

Imaging

Imaging tests may be done initially as part of the diagnostic workup for esophageal cancer, but are more commonly done to stage a cancer that has been found. Tests that may be done include: 

Barium Swallow

The first test done to evaluate a possible esophageal cancer is often a barium swallow or upper endoscopy, although proceeding directly to an endoscopy is preferred if an esophageal cancer is suspected.

In a barium swallow (also called an upper GI series), a person drinks a whitish liquid containing barium and then undergoes a series of X-rays. The barium lines the esophagus and stomach, allowing a radiologist to see abnormalities in the wall of the esophagus on the images taken.

A barium swallow may be helpful in diagnosing strictures (scar tissue within the esophagus), but is used less than in the past because a biopsy cannot be performed at the same time.

CT Scan

A CT scan (computerized tomography) uses a cross-section of X-rays to create a 3D picture of internal organs. With esophageal cancer, the test is not usually used as part of the diagnosis, but is important in staging the disease. CT is particularly good at looking for evidence of any spread (metastasis) of the tumor to lymph nodes or other regions of the body, such as the lungs or liver. 

PET Scan

PET scans are very helpful in looking for evidence of spread with esophageal cancer. A PET scan differs from other imaging studies in that it measures metabolic activity in a region of the body. A small amount of radioactive sugar is injected into the bloodstream and allowed time to be taken up by cells. Cells that are more active, such as cancer cells, show up brighter than areas that are less active metabolically. 

X-Ray

In addition to the above tests for diagnosing and staging esophageal cancer, a chest X-ray to look for spread to the lung  may be conducted.

Differential Diagnoses

There are a number of conditions that may cause symptoms similar to those of esophageal cancer, such as difficulty swallowing. Some of these include:

  • Esophageal stricture: A stricture is scar tissue that forms in the esophagus causing narrowing. It often occurs due to trauma, for example, due to complications of endoscopy for esophageal varices (varicose veins of the esophagus often associated with alcoholism), after a person has had a nasogastric tube (NG tube) in place for an extended period of time, or due to the accidental ingestion of drain cleaner as a child.
  • Stomach cancer (gastric cancer): Cancers in the stomach may cause symptoms similar to those of esophageal cancer.
  • Benign esophageal tumors (such as esophageal leiomyoma): Most tumors of the esophagus (around 99 percent) are cancerous. Benign tumors may, however, occur, and the majority of these are leiomyomas.
  • Achalasia: Achalasia is a rare condition in which the band of tissue between the lower esophagus and stomach (the lower esophageal sphincter) doesn't relax properly, making it difficult for food to pass from the esophagus into the stomach.

Staging

Determining the stage of a cancer is important in choosing the best treatment options, including deciding whether or not surgery is even an option. A combination of imaging tests and biopsy results are usually used to determine the stage.

Doctors use the TNM staging method to classify an esophageal tumor. This system is used for other cancers as well. With esophageal cancer, however, physicians add an additional letter to the acronym—G—to account for tumor grade. The specifics of staging are complex, but learning about them can help you better understand your disease.

T stands for tumor: The number for T is based on how deep into the lining of the esophagus the tumor extends. The innermost layer (closest to food passing through the esophagus) is the lamina propria. The next two layers are known as the submucosa. Beyond that lies the lamina propria, and finally the adventitia, the deepest layer of the esophagus.

  • Tis: This stands for carcinoma in situ, a tumor that involves only the very top layer of cells in the esophagus.
  • T1: The tumor extends through the lamina propria and submucosa.
  • T2: The tumor has spread to the lamina propria, but hasn't penetrated through the muscle of the esophagus.
  • T3: The tumor has spread to the adventitia. It has now penetrated all the way through the muscle in into surrounding tissues.
  • T4: T4a means that the tumor has spread beyond the esophagus to involve structures such as the pleura (lining of the lungs), pericardium (lining of the heart), the azygous vein, the diaphragm, and the peritoneum (the lining of the abdomen). T4b means that the tumor has spread to the aorta, vertebrae, or the trachea.

N stands for lymph nodes:

  • N0: There are no lymph nodes involved.
  • N1: The tumor has spread to 1 or 2 nearby (regional) lymph nodes.
  • N2: The tumor has spread to 3 to 6 nearby lymph nodes.
  • N3: The tumor has spread to 7 or more nearby lymph nodes.

M stands for metastasis (distant spread) of the cancer:

  • M0: Metastases are not present.
  • M1: Metastases are present.

G stands for grade:

  • G1: The cells look like normal cells (well differentiated).
  • G2: The cells look a little different than normal cells (somewhat differentiated)
  • G3: The cells look much different from healthy cells (poorly differentiated).
  • G4: The cells look nothing like healthy esophageal cells and it's almost impossible to tell what organ they originated in (undifferentiated).

Using the results of TNM and G above, oncologists then assign a stage

Stage 0: The cancer is found only in the innermost layer of cells lining the esophagus (Tis, N0, M0). This is also known as carcinoma in situ

Stage I: This stage can be broken down into stage IA and IB.

  • Stage IA: The tumor involves only the innermost layers of tissue (T1, N0, M0, G1).
  • Stage IB: There are two situations in which a tumor could be stage IB. One is similar to stage IA, except the cells are more abnormal appearing (T1, N0, M0, G2 to G3). In the other, the tumor is in the lower esophagus and has spread beyond the first layers of tissue (T2 or T3, N0, M0, G1).

Stage II: Depending on where cancer has spread, stage II esophageal cancer is divided into stage IIA and stage IIB.

  • Stage IIA: There are two basic situations that comprise stage IIA. The tumor may involve the upper or middle part of the esophagus and be T2 or T3 and G1 (but N0 and M0), or the tumor may involve the lower part of the esophagus and be T2 or T3 and G2 or G3, but there is no evidence of lymph node involvement or metastases (N0, M0).
  • Stage IIB: In stage IIB there are also two basic situations. In one, the tumor involves the upper or middle part of the esophagus, but unlike stage IIA, the cells are less differentiated (G2 or G3). Or, the cancer is only in the innermost layers (T1 or T2) but has spread to one or two lymph nodes (N1). There are no metastases.

Stage III: There are three substages of stage III.

  • Stage IIIA: This stage has three possibilities. The tumor may involve the inner layers of cells and three to six lymph nodes (T1 to T2, N2, M0, any G). Alternatively, the tumor may have spread to the outer layer of tissue, but only one to two lymph nodes (T3, N1, M0, any G). Finally, the tumor may have spread to nearby tissue, but no lymph nodes (T4a, N0, M0, any G).
  • Stage IIIB: The cancer has spread to the outer layers of the esophagus, as well as three to six lymph nodes (T3, N2, M0, any G).
  • Stage IIIC: There are three possibilities for this stage as well. The tumor may have spread to nearby tissue, but six or fewer lymph nodes (T4a, N1 or N2, M0, any G). Or, the tumor has spread to nearby tissue such as the aorta, a vertebral body, or the trachea, such that it can't be removed with surgery (T4b, any N, M0, any G). Finally, the tumor has spread to seven or more lymph nodes, but not to distant regions of the body (any T, N3, M0, any G).

Stage IV: The tumor has spread to a distant region of the body (any T, any N, M1, any G).

Screening

Cancer screening tests are those that are done on people who do not have any symptoms of a disease. (If symptoms are present, diagnostic tests are performed.) At present, there is no screening test for esophageal cancer that's available to the general public.

Since the risk of esophageal cancer is elevated in people with Barrett's esophagus, some physicians have recommended periodic screening with endoscopy. The thought behind this is that finding dysplasia (abnormal cells), especially catching severe cases early, could allow for treatments to remove the abnormal cells in the precancerous stage.

That said, thus far, there is minimal to no evidence that this screening reduces the death rate from esophageal cancer. At the same time, screening has the potential for harm, such as bleeding, esophageal perforation, or other problems. There's hope that the future will bring evidence that will help determine if screening high-risk people is advisable.

Sources:

American Society of Clinical Oncology. Esophageal Cancer: Diagnosis. Updated 12/2016.

Bast, R., Croce, C., Hait, W. et al. Holland-Frei Cancer Medicine. Wiley Blackwell, 2017.

National Cancer Institute. Esophageal Cancer Screening (PDQ)—Health Professional Version. Updated 04/06/18.

Rice, T., Patil, D., Blackstone, E. et al. 8th Edition AJCC/UICC Staging of Cancers of the Esophagus and Esophagogastric Junction: Application to Clinical Practice. Annals of Cardiothoracic Surgery. 2017. 6(2):119-130.