- 1 What is the histological definition of BO?
- 2 Evidence summary and recommendations
- 3 Issues requiring more clinical research study
- 4 References
- 5 Appendices
What is the histological definition of BO?
The features that should define Barrett’s Oesophagus are not completely understood and this is reflected in the differing definitions given in guidelines from Europe and the USA. It is generally agreed that Barrett’s Oesophagus is characterised by metaplastic columnar mucosa replacing normal oesophageal squamous mucosa, but at this time clinical studies are contradictory about whether histologically-proven intestinal metaplasia (IM) with morphologically typical goblet cells should be necessary for its diagnosis. Further studies are needed to clarify the exact definition to optimise patient screening and follow-up.
Requirement for intestinal metaplasia
It is the aim of guidelines to ensure that screening is directed to those with a significantly increased cancer risk. Because Barrett’s Oesophagus is a precursor to oesophageal adenocarcinoma, a disease that is increasing in incidence, patients with this change are currently recommended to enter surveillance programmes in most clinical guidelines.
It is clear that metaplastic columnar mucosa, usually cardiac or cardio-oxyntic type, may occur in the oesophagus without IM being detected. This often reflects sampling, since longer Barrett’s segments or larger numbers of biopsies are associated with increased detection of IM, as is a longer duration of follow-up with re-biopsy. It is also apparent from several studies that oesophageal adenocarcinoma may arise in a segment of metaplastic columnar mucosa without IM.
Since many studies of cancer risk in Barrett’s Oesophagus were restricted to patients whose diagnosis of Barrett's Oesophagus required the histological identification of IM, further studies will be required to determine the relative risks of intestinalised and non-intestinalised columnar metaplasia as precursors to oesophageal adenocarcinoma. At this time the data are conflicting. One multicentre study of 1751 patients with a median follow up of 3.5 years found a similar carcinoma incidence whether IM was present or not (3.2% and 3.1% respectively). Conversely, interrogating the Northern Ireland Barrett’s Oesophagus Register of 8522 patients with a mean seven years follow-up, a study from Bhat and colleagues found that the presence of IM in the index biopsy was associated with a greater than five-fold increased risk of adenocarcinoma and combined high grade dysplasia/adenocarcinoma compared with those who did not have IM. This suggests that the presence of IM identifies a cohort at significantly increased cancer risk. A smaller multicentre study of 209 patients with oesophageal columnar mucosa under surveillance for a mean of greater than nine years also found a low malignant risk if IM was not detected. Therefore, based on current knowledge there is insufficient evidence to recommend surveillance of patients who have only metaplastic cardiac-type columnar mucosa in the oesophagus.
In routine practice, intestinal metaplasia is diagnosed by the presence of goblet cells. These cells are distended by acidic mucin, which can usually be detected in routine haematoxylin-eosin stained sections and also stains intensely with the alcian blue stain (see figures below). Columnar cells with weaker positive staining and which do not have the characteristic flask shape of goblet cells are not sufficient to diagnose IM.
Biopsies from the tubular oesophagus that have columnar mucosa without IM should be given a descriptive diagnosis (e.g. glandular mucosa without intestinal metaplasia), but it is currently recommended that these are not specifically diagnosed as Barrett’s Oesophagus until the biological significance is clarified.
Intestinal metaplasia at the gastro-oesophageal junction or in the gastric cardia
Intestinal metaplasia occurring in isolation at the gastro-oesophageal junction or cardia without metaplasia in the tubular oesophagus is not diagnosed as Barrett’s Oesophagus. It may be a precursor to carcinoma, but the risk appears to be low and surveillance is not warranted based on current knowledge. However goblet cells noted in a GOJ biopsy can be confirmed to be IM in columnar lined oesophagus if the particular biopsy fragment shows native oesophageal structures such as submucosal glands and/or ducts.
Definitions applied by other Organisations
American Gastroenterological Association
The definition of Barrett's esophagus is the condition in which any extent of metaplastic columnar epithelium that predisposes to cancer development replaces the stratified squamous epithelium that normally lines the distal esophagus. Presently, intestinal metaplasia is required for the diagnosis of Barrett's esophagus because intestinal metaplasia is the only type of esophageal columnar epithelium that clearly predisposes to malignancy.
American College of Gastroenterologists
Barrett’s esophagus is a change in the distal esophageal epithelium of any length that can be recognized as columnar type mucosa at endoscopy and is confirmed to have intestinal metaplasia by biopsy of the tubular esophagus. (Grade B recommendation).
British Society of Gastroenterology
Barrett's oesophagus is defined as an oesophagus in which any portion of the normal distal squamous epithelial lining has been replaced by metaplastic columnar epithelium, which is clearly visible endoscopically (≥1 cm) above the GOJ and confirmed histopathologically from oesophageal biopsies (Recommendation grade C).
Evidence summary and recommendations
Definition of Barrett’s Oesophagus
To identify patients at increased risk of neoplastic progression, Barrett’s Oesophagus is defined as metaplastic columnar mucosa in the oesophagus, with intestinal metaplasia proven histologically.
Issues requiring more clinical research study
- Further studies are needed to clarify the exact definition of Barrett’s Oesophagus to optimise patient screening and follow-up.
- Further studies will be required to determine the relative risks of intestinalised and non-intestinalised columnar metaplasia as precursors to oesophageal adenocarcinoma.
- The biological significance of intestinal metaplasia confined to the gastro-oesophageal junction needs to be clarified.
- Fitzgerald RC, di Pietro M, Ragunath K, Ang Y, Kang JY, Watson P, et al. British Society of Gastroenterology guidelines on the diagnosis and management of Barrett's oesophagus. Gut 2014 Jan;63(1):7-42 Abstract available at http://www.ncbi.nlm.nih.gov/pubmed/24165758.
- Spechler SJ, Sharma P, Souza RF, Inadomi JM, Shaheen NJ, American Gastroenterological Association. American Gastroenterological Association medical position statement on the management of Barrett's esophagus. Gastroenterology 2011 Mar;140(3):1084-91 Abstract available at http://www.ncbi.nlm.nih.gov/pubmed/21376940.
- Spechler SJ, Sharma P, Souza RF, Inadomi JM, Shaheen NJ, American Gastroenterological Association. American Gastroenterological Association technical review on the management of Barrett's esophagus. Gastroenterology 2011 Mar;140(3):e18-52; quiz e13 Abstract available at http://www.ncbi.nlm.nih.gov/pubmed/21376939.
- Wang KK, Sampliner RE, Practice Parameters Committee of the American College of Gastroenterology. Updated guidelines 2008 for the diagnosis, surveillance and therapy of Barrett's esophagus. Am J Gastroenterol 2008 Mar;103(3):788-97 Abstract available at http://www.ncbi.nlm.nih.gov/pubmed/18341497.
- Csendes A. Barrett's esophagus. J Am Coll Surg 2003 Nov;197(5):882-3 Abstract available at http://www.ncbi.nlm.nih.gov/pubmed/14585434.
- Harrison R, Perry I, Haddadin W, McDonald S, Bryan R, Abrams K, et al. Detection of intestinal metaplasia in Barrett's esophagus: an observational comparator study suggests the need for a minimum of eight biopsies. Am J Gastroenterol 2007 Jun;102(6):1154-61 Abstract available at http://www.ncbi.nlm.nih.gov/pubmed/17433019.
- Gatenby PA, Ramus JR, Caygill CP, Shepherd NA, Watson A. Relevance of the detection of intestinal metaplasia in non-dysplastic columnar-lined oesophagus. Scand J Gastroenterol 2008;43(5):524-30 Abstract available at http://www.ncbi.nlm.nih.gov/pubmed/18415743.
- Bhat S, Coleman HG, Yousef F, Johnston BT, McManus DT, Gavin AT, et al. Risk of malignant progression in Barrett's esophagus patients: results from a large population-based study. J Natl Cancer Inst 2011 Jul 6;103(13):1049-57 Abstract available at http://www.ncbi.nlm.nih.gov/pubmed/21680910.
- Takubo K, Aida J, Naomoto Y, Sawabe M, Arai T, Shiraishi H, et al. Cardiac rather than intestinal-type background in endoscopic resection specimens of minute Barrett adenocarcinoma. Hum Pathol 2009 Jan;40(1):65-74 Abstract available at http://www.ncbi.nlm.nih.gov/pubmed/18755496.
- Becker V, Bobardt J, Ott R, Rösch T, Meining A. Long-term follow-up in patients with indeterminate Barrett esophagus. Digestion 2013;88(3):161-4 Abstract available at http://www.ncbi.nlm.nih.gov/pubmed/24080585.
- Jung KW, Talley NJ, Romero Y, Katzka DA, Schleck CD, Zinsmeister AR, et al. Epidemiology and natural history of intestinal metaplasia of the gastroesophageal junction and Barrett's esophagus: a population-based study. Am J Gastroenterol 2011 Aug;106(8):1447-55; quiz 1456 Abstract available at http://www.ncbi.nlm.nih.gov/pubmed/21483461.
- Sharma P, Weston AP, Morales T, Topalovski M, Mayo MS, Sampliner RE. Relative risk of dysplasia for patients with intestinal metaplasia in the distal oesophagus and in the gastric cardia. Gut 2000 Jan;46(1):9-13 Abstract available at http://www.ncbi.nlm.nih.gov/pubmed/10601047.