What is histology?

Histology is the microscopic study of tissue, which is an organized collection of cells and their supporting structures. In Barrett's esophagus, biopsy with histology preserves the normal architecture of the tissue such that not only can the individual Barrett's cells be seen, but also their relationship to other Barrett's cells or "growth pattern" can be seen. In Barrett's esophagus, the growth pattern of cells is in the form of glands.

Biopsy collection and preparation

At the time of EGD (upper endoscopy), biopsies are taken from the esophagus and  placed in a fixative (a chemical mixture) that preserves the biopsies so cells don't start breaking apart and the basic tissue architecture is preserved. A few hours in fixative is usually sufficient for GI biopsies, then the biopsies are embedded in paraffin (wax) to support the tissue so that thin sections or slices can be cut and placed on a microscope slide. The tissue can then be stained with any variety of stains which are used to identify important structures in the tissue.

Endoscopic biopsy The biopsy is ready to be placed into the fixative for processing.

Cutting the paraffin block The biopsy is embedded in a paraffin (wax) block so that thin slices of the biopsy can be made. The long paraffin slice is referred to as a "ribbon."

Close-up view of a paraffin ribbon This paraffin ribbon was cut from a paraffin block that contained four biopsies. Each of the gray strips is a thin slice of a biopsy.

Biopsies mounted and stained The paraffin ribbon containing the thinly sliced biopsies is placed on a microscope slide, stained, and is ready for reading by the pathologist.

Esophageal tissue layers

Endoscopic biopsies only reach the top layer of esophageal tissue called the mucosa. This top layer is made up of surface cells, the basement membrane (the supporting foundation of the cells), the lamina propria (contains small blood vessels and glands), and a thin muscle layer called the muscularis mucosa. Other deeper layers of the esophagus not reached by the forceps include the submucosa, muscularis propria and adventia.

Layers of the esophagus

The esophageal mucosal layer

Histologic definition of Barrett's esophagus

The normal esophagus is lined by squamous cells. In Barrett's esophagus, the normal lining is replaced by an abnormal lining called specialized intestinal metaplasia. Metaplasia is a term used for a tissue that is not normally found in the body. Barrett's metaplasia has characteristics of both stomach tissue and intestinal tissue. Barrett's metaplasia, like stomach and intestinal tissue, produces mucous. The mucous producing cells (goblet cells) stain blue with a special stain (Alcian blue). The Alcian blue stain can be used to differentiate Barrett's tissue from normal stomach tissue that does not have Alcian blue staining goblet cells.

Misdiagnosis of Barrett's esophagus

Occasionally, patients who have stomach-type lining in the bottom of their esophagus and NOT specialized intestinal metaplasia will be given a diagnosis of Barrett's esophagus. Unfortunately, this causes unnecessary anxiety on the part of patients who now believe that they have a pre-malignant condition. A misdiagnosis of Barrett´s esophagus can also lead to unwarranted loss of medical insurance benefits or increase in the cost of medical or life insurance premiums. Based on our present level of knowledge, specialized intestinal metaplasia of the esophagus is the only known columnar esophageal lining at risk for developing esophageal adenocarcinoma (cancer). It is also the only lining for which periodic endoscopic biopsy surveillance is currently recommended.

Under certain conditions, stomach tissue just below the bottom of the esophagus, in the top part of the hiatal hernia (gastric cardia), can have intestinal metaplasia that looks very similar to Barrett's esophagus when the pathologist examines it under the microscope. Intestinal metaplasia of the gastric cardia is very common in the general population and in persons who do not have GERD. At our present level of knowledge, it is not believed to be related to Barrett's esophagus or to the development of esophageal adenocarcinoma. That is why it is important that the gastroenterologist, performing the biopsies, precisely identifies where the bottom of the esophagus begins. This can sometimes be a challenge as the transition from upper stomach (or hiatal hernia) to the lower end of the esophagus can be indistinct and difficult to identify. The problem of accurately and consistently identifying the lower end of the esophagus in every patient is a subject that is quite controversial among Barrett's esophagus experts. This issue is important because it is currently recommended that ONLY specialized intestinalized metaplasia of the esophagus be referred to as Barrett's esophagus and warrants endoscopic cancer surveillance.

The gastroesophageal junction (GE junction) and gastric cardia The GE junction is the region where the esophagus joins the stomach (or hiatal hernia if a hiatal hernia is present). The gastric cardia is located at the top of the stomach or hiatal hernia if present. Specialized intestinal metaplasia in biopsies from the esophageal side of the gastroesophageal junction is Barrett's esophagus. However, intestinal metaplasia in biopsies from the gastric side of the GE junction is intestinal metaplasia of the gastric cardia and NOT Barrett's esophagus.

Endoscopic photo of the GE junction Photo courtesy of the Seattle Barrett's Esophagus Research Program

What if Barrett's esophagus is identified?

If Barrett's esophagus is identified in biopsies examined by the pathologist, then an EGD procedure with multiple systematically obtained biopsies (endoscopic biopsy surveillance) is needed to look for atypical or abnormal changes in the Barrett's tissue that cannot be seen by the GI doctor directly through the endoscope . These atypical changes are collectively known as dysplasia and are used to determine whether a patient is at increased risk for the development of cancer.