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Barrett's Esophagus -

Intestinal Metaplasia,

Dysplasia and Esophagus

Dr Sampurna Roy MD


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Barrett's esophagus is defined as replacement of  the lower esophageal squamous mucosa  by specialized columnar epithelium as a result of chronic gastroesophageal reflux.

[Histologically, specialized columnar epithelium consists of two cell types i) goblet cell ii) columnar cells. ]

- Long segment Barrett's esophagus (LSBE)- Replacement of 3cms or greater than 3cm of the distal esophagus by specialized columnar epithelium.

- Short segment Barrett's esophagus (SSBE)-Replacement of less than 3cm of distal esophagus by specialized columnar epithelium.               

- Ultrashort segment Barrett's esophagus (USSBE)- Intestinal metaplasia within the Z-line of the esophago-gastric junction (intestinal metaplasia of gastric cardia).

The shorter length of Barrett's esophagus are at an increased risk of adenocarcinoma.  

It has been suggested that there is a close relationship between USSBE and gastric Helicobacter pylori infection.

The patient with cardia intestinal metaplasia should be evaluated in context of endoscopic finding , histologic and serologic findings for H pylori infection and findings from the biopsies of distal stomach.

Histologically, Barrett's esophagus may show specialized metaplastic mucosa, cardiac or junctional type mucosa, atrophic fundic type mucosa.


CK7 and CK20-  Helps in distinguishing  intestinal metaplasia of distal esophagus from that of proximal stomach. 

In Barret's esophagus there is superficial and deep CK7 positivity and only superficial CK20 staining.

Intestinal Metaplasia                       

Intestinal metaplasia in Barrett's esophagus is often of type 3.

Sulphated sialomucin expression is associated with the development  of dysplasia and subsequent carcinoma.     


Sulphated mucins or sulphomucin and nonsulphated mucins or sialomucin are acid mucins. 

Histochemistry: High iron diamine/ Alcian Blue pH2.5 : 

Sialomucin stains blue and sulphomucin stains brown.

What are the different types of intestinal metaplasia?

Type1- Complete: Goblet cells-Sialomucins and sulphomucin.
Columnar cells - Nonsecretary

Type2 - Incomplete: Goblet cells- Sialomucins and sulphomucin
Columnar cells- Sialomucin

Type3 - Incomplete:Goblet cells- Sialomucins and sulphomucins
Columnar cells- Sulphomucin

Significance of acid-mucin-positive nongoblet columnar cells in the distal esophagus and gastroesophageal junction.

Mucin histochemistry of the columnar epithelium of the oesophagus (Barrett's oesophagus): a prospective biopsy study.

Intestinal metaplasia subtyping: evaluation of Gomori's aldehyde fuchsin for routine diagnostic use.

Dysplasia in Barrett's Esophagus

Dysplasia in Barrett's esophagus is defined as presence of neoplastic epithelium that is confined within the basement membrane of the gland within which it arises.

Dysplasia in Barrett's esophagus is reported as-

1. Negative for dysplasia   

2. Positive for dysplasia- i)Low grade ii)High grade 

3. Indefinite for dysplasia.

Low grade dysplasia-

-Minimal distortion of crypt architecture

-Atypical nuclei present in the basal half of the crypts

-Nuclear character- variable hyperchromasia
                                  - irregular nuclear contour
                                  - nuclear crowding

- Marked reduction in the number of goblet cells in the dysplastic area

High grade dysplasia-  

- Severe cytological atypia characterized by nuclear hyperchromatism , pleomorphism & nuclear stratification towards the luminal surface.

- Severe architectural atypia characterized by complex
branching or cribriform patterns. Sometimes villiform architecture of the mucosal surface is identified.

Barrett's esophagus, dysplasia, and adenocarcinoma.

Length of Barrett's oesophagus: an important factor in the development of dysplasia and adenocarcinoma.

Site:  Usually lower esophagus. Commonly arise from Barrett's metaplastic mucosa. (rarely from gastric heterotopic mucosa).

Age:  Usually in middle aged white male . Average age is 57 years.

Macroscopic features:  Flat, ulcerating , infiltrative lesion.

Microscopic features:  Wide range of glandular features are noted (resemble gastric adenocarcinoma).

-Papillary adenocarcinoma
-Tubular adenocarcinoma
-Mucinous adenocarcinoma (mucin production)

The backround Barrett's type mucosa may demonstrate areas of high grade dyspalsia.

The tumour usually penetrates through the muscle coat.

Perineural invasion is noted.

Lymphnode metastasis is present.

The tumour has a poor prognosis.

What is intramucosal carcinoma of the esophagus?
Intramucosal carcinoma is characterized by tumour cells penetrating through the basement membrane and infiltrating into the lamina propria as single cells or in clusters.

Sometimes it can be extremely difficult to distinguish between high grade dysplasia and intramucosal carcinoma.

Surgical pathology of adenocarcinoma arising in Barrett's esophagus. Analysis of 67 cases.

Adenocarcinoma in the distal esophagus with and without Barrett esophagus. Differences in symptoms and survival rates.

Superficial adenocarcinoma of the oesophagus arising in Barrett's mucosa with dysplasia: a clinico-pathological study of 12 patients.

Problems faced by Pathologist:

1. Sampling error- Dysplastic changes is sometimes limited to a small area which may be  left unsampled.               

2. There may be interobserver variation among pathologists, in the diagnosis of dysplasia.

Sometimes the distinction of regenerative changes and true dysplasia can be very difficult specially in the presence of inflammation or ulceration.



Indefinite dysplasia - Rebiopsy after medical therapy.
(antireflux therapy to reduce the intensity of inflammation and reactive epithelial change).

Low grade - Rebiopsy to exclude a worse lesion and then regular follow up.

High grade - Most regard this as an indication for esophagectomy (this is controversial). The slide should be reviewed by experienced pathologist.

A four quadrant, 1cm endoscopic biopsy protocol performed at closely timed intervals, consistently detect early cancers arising in HGD in Barrett's esophagus and should be used in patients with high grade dyplasia who do not undergo surgical resection.

Managing Barrett's oesophagus. 

Optimizing endoscopic biopsy detection of early cancers in Barrett's high-grade dysplasia.

Short segment Barrett esophagus and specialized columnar mucosa at the gastroesophageal junction.

Helicobacter pylori infection, not gastroesophageal reflux, is the major cause of inflammation and intestinal metaplasia of gastric cardiac mucosa.

Diagnosis and grading of dysplasia in Barrett's oesophagus.

Barrett's esophagus and Barrett's-related dysplasia.

Defining dysplasia in Barrett esophagus.

Dysplasia arising in barrett's esophagus: diagnostic pitfalls and natural history.

Can extent of high grade dysplasia in Barrett’s oesophagus predict the presence of adenocarcinoma at oesophagectomy ? 

Adenocarcinoma of the lower esophagus and the esophagogastric junction.

Prospective multivariate analysis of clinical, endoscopic, and histological factors predictive of the development of Barrett's multifocal high-grade dysplasia or adenocarcinoma.  

Histologic classification of patients based on mapping biopsies of the gastroesophageal junction.




Dr Sampurna Roy  MD

Consultant  Histopathologist (Kolkata - India)







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