Barrett's Esophagus - Intestinal Metaplasia, Dysplasia and Adenocarcinoma

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.
Gross:Barrett's esophagus shows ulceration and stricture at gastro-esophageal junction.

Immunohistochemistry:

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 .

Note:
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.Hum Pathol. 1999 Dec;30(12):1488-95

Mucin histochemistry of the columnar epithelium of the oesophagus (Barrett's oesophagus): a prospective biopsy study.J Clin Pathol. 1984 Jun;37(6):607-10.

Intestinal metaplasia subtyping: evaluation of Gomori's aldehyde fuchsin for routine diagnostic use.Histopathology. 1997 Sep;31(3):277-83.

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-   IMAGE LINK
- 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.Hum Pathol. 1994 Oct;25(10):982-93.

Length of Barrett's oesophagus: an important factor in the development of dysplasia and adenocarcinoma.Gut. 1992 Sep;33(9):1155-8.

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). IMAGE LINK (WebPath)
-Papillary adenocarcinoma IMAGE LINK (AFIP)
-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.Am J Surg Pathol. 1995 Feb;19(2):183-91.

Adenocarcinoma in the distal esophagus with and without Barrett esophagus. Differences in symptoms and survival rates.Arch Surg. 1996 Jul;131(7):708-13.

Superficial adenocarcinoma of the oesophagus arising in Barrett's mucosa with dysplasia: a clinico-pathological study of 12 patients.Histopathology. 1990 Mar;16(3):213-20.

Problems faced by pathologist:

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

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.

Management:

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. BMJ 2003;326:892-894 ( 26 April )

Optimizing endoscopic biopsy detection of early cancers in Barrett's high-grade dysplasia.Am J Gastroenterol. 2000 Nov;95(11):3089-96.

Short segment Barrett esophagus and specialized columnar mucosa at the gastroesophageal junction.Mayo Clin Proc. 2001 Mar;76(3):331-4.

Helicobacter pylori infection, not gastroesophageal reflux, is the major cause of inflammation and intestinal metaplasia of gastric cardiac mucosa.Am J Gastroenterol. 2002 Feb;97(2) : 302-11.

Barrett's esophagus and Barrett's-related dysplasia.Mod Pathol. 2003 Apr;16(4):316-24.

Defining dysplasia in Barrett esophagus.J Clin Gastroenterol. 2003 May-Jun;36(5 Suppl):S19-25; discussion S26-8.

Dysplasia arising in barrett's esophagus: diagnostic pitfalls and natural history.Semin Diagn Pathol. 2002 Feb;19(1):12-9.

Can extent of high grade dysplasia in Barrett’s oesophagus predict the presence of adenocarcinoma at oesophagectomy ? Gut 2003;52:486-489

Adenocarcinoma of the lower esophagus and the esophagogastric junction.Semin Diagn Pathol. 1991 Aug;8 (3):126-36.