BARRETTS ESOPHAGUS

& TUMORS OF ESOPHAGUS

Prof. Samina Rizvi

Pathology
13.4.2020
Esophageal Disorders
• Motility
• Anatomic & Structural
• Reflux
• Infectious
• Neoplastic
• Miscellaneous
 Anatomy of The Esophagus
• The esophagus is a hollow muscular organ, approximately
25cm in length that extend from the pharynx to the
stomach.
• The esophagus has 2 muscle layers: the inner circular
layer and the outer longitudinal layer. The longitudinal
muscle shortens the esophagus, while the circular muscle
forms lumen-occluding ring contractions. The
combination of these localized contractions is responsible
for peristalsis. The proximal esophagus contains striated
muscle and the distal esophagus smooth muscle, with a
long transition zone between. Striated muscle is “faster”.
 Esophageal
Anatomy/functional
Upper Esophageal
Sphincter (UES)

Esophageal Body 18 to 24 cm
(cervical & thoracic)

Lower Esophageal
Sphincter (LES)
Normal esophagus
 Normal Esophageal Histology
Stratified squamous, non-keratinized, epithelium

Lumen

• Suprabasal layer

• Basal cell layer

Lamina propria
 Ly = lymph nodule
Gastroesophageal junction Ep*=infolded epithelium

Esophagus Stomach

Ly

Ep*

University of Michigan Virtual Microscopy slide collection, slide #155

Inferior esophageal sphincter = a physiological sphincter

• Pressure difference between esophagus and stomach
• Diaphragmatic contraction
• Unidirectional peristalsis
Prevents reflux of stomach contents into esophagus
Gastroesophageal junction
Transition from stratified squamous to simple columnar epithelium

Bloom and Fawcett, 12th ed. Fig. 25-6, p.599

Gastroesophageal junction
A medically important region:
1. Pyrosis (heartburn) –acid reflux

2. Dysphagia (difficulty in swallowing)

Generic term used to describe ANY difficulty in swallowing
Could be something “extrinsic:” mediastinal mass, vascular anomaly
Could be “intrinsic:” e.g. esophageal tumor, inflammation, motility
disorder

3. Achalasia (“failure to relax”)

Lack of peristalsis in the lower esophagus due to loss of myenteric
neurons (chalasis = relaxation)

4. Barrett’s esophagus/Intestinal metaplasia

Change in esophageal mucosa from squamous to “intestinal” (i.e.
columnar)
Result of prolonged injury: e.g. chronic reflux, noxious agents (smoking,
etc.)
“pre-cancerous:” 10% risk of progression to adenocarcinoma
5. Esophageal cancer
Squamous cell carcinoma –carcinogenesis of basal cells
Adenocarcinoma –progression of Barrett’s esophagus into cancer
 Barrett Esophagus

Barrett esophagus is a complication of chronic GERD that is characterized by

intestinal metaplasia within the esophageal squamous mucosa.

The greatest concern in Barrett esophagus is that it

confers an increased risk of esophageal adenocarcinoma.

Genomic sequencing of biopsies involved by Barrett

esophagus has revealed the presence
of mutations that are shared with esophageal
adenocarcinoma,
 BARRETT’S ESOPHAGUS
• A change in the lining of the esophagus from the
normal squamous lining to an intestinal type lining
called intestinal metaplasia.
• Intestinal metaplasia, characterized by goblet cells,
is biologically unstable with greatest risk of
neoplastic progression
 Metaplasia
One adult cell type replaces another type
Response to Chronic Tissue Injury

GERD
Reflux
Esophagitis

Stratified Squamous Specialized Intestinal

Epithelium Metaplasia
(Normal Esophagus) (Barrett’s Esophagus)
 *
• Most common in white males.
• typically presents between 40 and 60 years of age.

• Diagnosis suspected on endoscopy but requires

confirmation by pathology examination of biopsies.
• Vast majority of cases caused by acid reflux and
secondary injury to the normal lining.
• Incidence appears to have increased substantially.
 MORPHOLOGY
• Barrett esophagus can be recognized as one
or several tongues or patches of red, velvety
mucosa extending upward from the
gastroesophageal junction. This metaplastic
mucosa alternates with residual smooth, pale
squamous (esophageal) mucosa and
interfaces with light-brown columnar 
(gastric) mucosa distally 
 Me
Co tapl
Ep lum asti

Stratified
ith na c

Squamous
Epithelium
eli r
um
Metaplastic
Columnar
Epithelium
Barrett’s Metaplasia

Esophageal
Adenocarcinoma
 Fig 17-7 Barrett esophagus.(ROBINS)

A,  Normal  gastroesophageal  junction. 

B,  Barrett  esophagus.

 
Note  the  small  islands  of  residual 
pale  squamous mucosa within the 
Barrett mucosa
 MICROSCOPIC
• Note  the  transition  between 
esophageal squamous mucosa 
(left) and Barrett metaplasia, 
with abundant 
metaplastic goblet cells (right). 
 
 Fig 17-8  Dysplasia in Barrett esophagus
A, Abrupt transition from Barrett metaplasia to low-grade
dysplasia (arrow). Note the nuclear stratification and
hyperchromasia. 

Atypical mitoses, nuclear hyperchromasia, 

irregularly clumped chromatin, increased  nuclear-to-
cytoplasmic ratio, and a failure of epithelial cells to
mature as they migrate 
to the esophageal surface are present in both 
grades of dysplasia  
Fig 17-8 Dysplasia in Barrettes oesphagus
• B, Architectural irregularities, including gland-
within-gland, or cribri form, profiles in high-
grade dysplasia

• Gland architecture is abnormal and is 

characterized by budding, irregular shapes, 
and cellular crowding.  High-grade  dysplasia
Fig : 17.8
Intestinal Metaplasia
Low Grade Dysplasia
Higher Power
BARRETT’S WITHOUT DYSPLASIA
REGULAR Z - Line Irregular Z - Line

Wallner B, Sylvan A, Janunger KG. Endoscopic assessment of the "Z-line" (squamocolumnar junction) appearance: reproducibility
of the ZAP classification among endoscopists. Gastrointest Endosc 2002;55:65-69.
 Endoscopic Images

Normal Squamo- LA Grade A LA Grade D

columnar junction Esophagitis Esophagitis
TUMORS OF OESOPHAGUS

Prof. Samina Rizvi

 Types

 Benign (10%)
 Epithelial
 Mesenchymal

 Malignant (90%)
 Epithelial
 Mesenchymal
 Others
 Etiology

 Alcohol and smoking

 Other carcinogens
 Damage of the
oesophagus
 Deficiency of Mb, Zn and
vitamin A
 GERD
 HPV
 Other illnesses
 Cancer of the Esophagus
 Relatively uncommon, cancer of the esophagus narrows
the lumen, causing the principal symptom, dysphagia.
The obstruction causes vomiting, and the person may
experience a bad taste in his or her mouth or bad
breath. There is accompanying weight loss because of
the inability to eat.
 The carcinoma spreads into adjacent organs and to
remote sites through the lymph vessels. It frequently
metastasizes before it is detected. Prognosis for cancer
of the esophagus is poor. Like mouth cancer, tobacco
and alcohol use are major risk factors.
 Classification
• Benign tumors of the esophagus are generally
1. mesenchymal, arise within the esophageal wall.
2. Leiomyomas being most common
• Fibromas,
• lipomas,
• hemangiomas,
• neurofbromas, and
• lymphangiomas also occur.
 Site:
Upper third: 20%
Middle third: 30%
Lower third: 50%
 Pathology

 Macrosopic
 Superficial
form
 Polyp
 Ulcer
 Infiltrative  Microscopic
form  Squamous cell cancer
 Adenocarcinoma
 CARCINOMA OF THE ESOPHAGUS
• Esophageal cancer is the fastest growing cancer
in the western countries
• Squamous cell carcinoma still accounts for
most esophageal cancers diagnosed
• However, in the US, esophageal
adenocarcinoma is noted in up to 70% of
patients presenting with esophageal cancer
 Oesophageal tumours
Key facts and pathological features
• There are several types of oesophageal tumours.
• Adenocarcinoma
• Rapidly increasing incidence in Western world: 5:1
(M:F)
• Commonest in Japan, northern China, and South
Africa,
• Associated with dietary nitrosamines, GERD, and
Barrett's metaplasia.
• Typically occurs in the lower half of the oesophagus.
 Esophageal Tumors

Squamous carcinoma
• Incidence slightly reducing in Western world: 3:1
(M:F)
• Associated with smoking, alcohol intake, diet poor
in fresh fruit and vegetables, chronic achalasia,
chronic caustic strictures.
• May occur anywhere in the oesophagus.
 esophageal tumours
Rhabdomyo(sarco)ma
• Malignant tumour of skeletal muscle wall of the
oesophagus. Very rare.
• Lipoma and gastrointestinal stromal tumours
• GIST (gastrointestinal stromal tumours) are rare.
Fig 17.8 A, Esophageal adenocarcinoma
organized into back-to-back glands.
B, Squamous cell carcinoma composed of nests of malignant cells
 Symptoms
• Early-stage cancers may be asymptomatic
or mimic symptoms of GERD
• Most patients with esophageal cancer
present with dysphagia and weight loss
• Because of the distensibility of the
esophagus, a mass can obstruct two
thirds of the lumen before symptoms of
dysphagia are noted
 Signs and symptoms
• 90% - dysphagia and weight loss
• Aspiration pneumonia and cough
• Hoarseness
• Horner syndrome
• Palpable neck lymph nodes
• Hypercalcaemia
• Bleeding
• Infection
 Diagnostics
• X rays
• Oesophagoscopy (histology and cytology)
• Endoscopic ultrasound
• CT and PET
• Bronchoscopy
 Endoscopy
• The diagnosis of esophageal cancer is made
best from an endoscopic biopsy
• any patient undergoing surgery for
esophageal cancer must have an endoscopy
performed by the operating surgeon before
entering the operating room for a definitive
resection
Oesophageal cancer
 Assingment
• Q1. Define epigenetic changes in body
• Q2. Explain the changes occuring in epigenetic
changes
• Q3. How does an epigenetic change differ
from a mutation?