1. A detailed clinical history with clinical impression must be provided by the clinician.This should include age of the patient, sex, clinical findings and their duration,history of previous surgery, history of immunosuppression,drug history, history of systemic or dermatologic disorders.

2. Site of the biopsy (upper, middle or lower third of the esophagus).

3. Endoscopic finding plays a critical role in the diagnosis of esophageal lesions.    Endoscopic images

1. Is the esophageal biopsy is normal or abnormal? Normal esophageal biopsy

2. Is the abnormality non-neoplastic or neoplastic in nature?
3. In case of non-neoplastic lesion:
        - What type of epithelium is included in the biopsy (squamous , glandular or junctional)?
        - What is the type and severity of inflammation?
        - Is it associated with ulceration?
        - Is the inflammation due to fungal or viral organisms?
        - How to differentiate between regenerative changes  and true  epithelial dysplasia in Barrett's esophagus?
         - How to grade the epithelial dysplastic changes?
4. If the lesion is neoplastic in nature:         
         - What is the tumour type and differentiation?
         - Does the biopsy include normal esophageal mucosa?
         - Is there any overlying squamous dysplasia , glandular dysplasia or Barrett's metaplasia?
         - Is it possible to comment on the submucosal invasion in the biopsy specimen?
 

1. Inflammation throughout esophagus suggests infective cause specially in immunocompromised patients.
The histopathologist must carefully search  for organisms and viral inclusions .
- In suspected case of  Cytomegalovirus infection , biopsy should be taken from the ulcer base to sample infected fibroblasts and endothelial cells. Microscopic features include  large cells in the subepithelial layer with intranuclear inclusions, a halo around the nucleus and multiple small cytoplasmic inclusions.   IMAGE  
- In Candida oesophagitis PAS and Grocott stains are useful in demonstrating the organisms. IMAGE  
- In Herpes simplex virus esophagitis biopsy should be taken from the squamous epithelium at the margins of the ulcer. Microsocpically there are multinucleated giant cells and intranuclear ground glass inclusions.

(GROSS)IMAGE 1 ;  2   (MICRO) IMAGE 3  ;  4

2. Acid or bile reflux is common in the lower third of the esophagus.   
When reflux esophagitis is suspected the histopathologist should look for the following features-
    Basal cell hyperplasia ; vascular prominence ; elongation of lamina propria increased intraepithelial eosinophils and varying degree of chronic inflammation.
    Reflux esophagitis may progress to superficial ulceration and spread of  inflammation to the wall.

3. In Barrett's esophagus (columnar lined esophagus) the biopsy  may show any of the following features-
    - Fundic type mucosa (with parietal and chief cells)
    - Cardiac or junctional type mucosa (composed of mainly mucous glands).
    - Flat mucosa with specialised (incomplete) intestinal metaplasia   
Mucin histochemistry is useful in  the identification of immature intestinal metaplasia. 
Presence of submucosal glands with ducts beneath distorted glandular mucosa is diagnostic of Barrett's esophagus.   
In many cases the histopathologists report the case as : " If the biopsy is truely from esophagus , it corroborates with an endoscopic diagnosis of Barrett's esophagus."
Glandular dysplasia in Barrett's esophagus is reported as indefinite, low grade or high grade. 

Low magnification view is very important.

In true dysplasia ,due to consistent presence of nuclear hyperchromasia attention is immediately drawn to the dysplastic area.
To diagnose true dysplasia the full length of the gland must be assessed. In dysplasia,  the cytological changes are present throughout the crypt from the base to the surface epithelium and there is abrupt interphase with adjacent epithelium.  In reactive hyperplasia there is surface maturation and gradual transition with adjacent epithelium.

Often the case is reported as: " Indefinite for dyplasia. A repeat biopsy is advised after the inflammation has subsided." IMAGE LINK(AFIP)

Invasive carcinoma developing in Barrett's esophagus is usually adenocarcinoma in type. Carcinoma is reported only  when there is unequivocal  evidence of  invasion into the lamina propria.  

 An endoscopic biopsy protocol can differentiate high-grade dysplasia from early adenocarcinoma in Barrett's esophagus.Gastroenterology. 1993 Jul;105(1):40-50.

Following treatment in Barrett's esophagus the biopsy shows squamous re-epithelization. The histopathologist plays an important role in identifying  hidden foci of glandular mucosa under surface squamous epithelium (deep biopsy is advised in these cases).

Note:   It is often difficult to make a confident diagnosis: 1) if the esophageal biopsy is crushed 2) if the biopsy is tangentially cut and 3) in the presence of inflammation and regenerative changes.