Molavi Chapter 6 - Esophagus

Question 1

Answer 1

Normal esophageal epithelium

Generally a squamous epithelium with a few quirks:

• Vascular pegs occasionally penetrate into the epithelium
• Occasional squiggle cells (lymphocytes) are sometimes see, so named due to their stretched-out appearance
• Salivary-like mucinous glands may occasionally be seen interrupting the epithelium
• The epithelium is underlied by a stroma that often contains numerous salivary-like mucinous glands

Question 2

Answer 2

Eosinophilic esophagitis

Characterized by proximal intraepithelial eosinophilia within the esophagus.

Mainly exists as a protein allergy-induced pediatric disease. In addition to a reactive, blue epithelium with basal cell hyperplasia, histologic features include:

• Numerous eosinophils (> 15 / HPF)
• Microabscesses of eosinophils (>4 eosinophils in a cluster)
• Evidence of eosinophil degranulation
• Eosinophil clustering at the surface of the epithelium

Question 3

Answer 3

Reflux esophagitis

Characterized by distal intraepithelial eosinophilia within the esophagus. Of note, this may not always be present and simple reactive change may be your only indicator of reflux esophagitis. The diagnosis is often descriptive, eg “reactive epithelial changes of the type seen in reflux esophagitis.”

Other features include:

• Basal cell hyperplasia (> 3 cell-deep layer)
• Elongated vascular papillae
• Balloon cell change (excess glycogen in the cytoplasm)
• Possibly co-existing with changes of Barret’s esophagus and movement of the GEJ proximally
• In long-standing reflux esophagitis, pancreatic metaplasia may be seen

Question 4

Intraepithelial neutrophils within the esophagus suggests. . .

Answer 4

. . . infection or acute injury rather than reflux

Question 5

[Insert Molavi image]

Answer 5

Candidal esophagitis

Tiny purple yeasts with pseudohyphae are seen among the squamous debris at the surface epithelium. Parakeratosis is also seen. Not well visualized in this slide, but there is often also a neutrophilic inflammatory infiltrate, however this does not need to be present to establish a diagnosis.

Yeast stains magenta on PAS, which can help highlight them amongst debris on an H and E.

Question 6

Answer 6

Pill esophagitis

In this case, clearly caused by an iron pill – you can see the iron on H and E, plus it stains on Prussian Blue. This makes it a particularly obvious case of pill esophagitis, but for many cases (NSAIDs, tetracyclines, potassium, bisphosphonates, resins) you may need your handy-dandy polarizer to visualize pill fragments.

General histologic changes include ulceration with a neutrophilic or lymphocytic infiltrate, prominent apoptosis, and sometimes eosinophilia.

Question 7

Answer 7

HSV esophagitis

HSV infects epithelial cells. Evidence of infection is often found in the context of an ulcer (often volcano-shaped) with characteristic cellular changes: multinucleation, nuclear molding,Cowdry A-type inclusions, and glassy chromatin.

Other hisotlogic features include necrosis with neutrophilic exudate, activated macrophages, and activated lymphocytes.

Question 8

Cowdry bodies

Answer 8

Types of viral intranuclear inclusions composed of nucleic acids and protein.

Cowdry A: Seen in HSV, VZV, yellow fever. Inclusions are variable, granular, and acidophilic.

Cowdry B: Seen in CMV, adenovirus, and polio. Inclusions are circumscribed, multiple, and basophilic (except polio, which is acidophilic).

Question 9

Answer 9

CMV esophagitis

CMV infects mesenchymal cells (endothelial, stromal) – it will be found at the ulcer base (often linear ulceration). Characteristic cellular changes: Cytoplasmic red-purple inclusions, giant cells, and Cowry B-type nuclear inclusions surrounded by a clear halo.

Other hisotlogic features include perivascular macrophage exudate.

Question 10

DDx for foveolar-type cells on an “esophagus” biopsy

Answer 10

• Metaplasia
• Inappropriate biopsy site
• Hiatal hernia

Question 11

Answer 11

Pancreatic metaplasia / heterotopia

Collections of pink-purple acinar cells beneath the epithelium, resembling normal pancreas, because . . . it is normal pancreas.

Pancreatic metaplasia is a common finding in long-standing reflux esophagitis.

Question 12

Answer 12

Intestinal metaplasia, aka Barret’s esophagus

Characterized by the presence of goblet cells within the esophagus.

Note that columnar metaplasia is NOT SUFFICIENT to diagnose Barret’s esophagus, goblet cells must be seen in order to correlate with risk of progression to adenocarcinoma. There must also be an endoscopically visible lesion to diagnose Barret’s, not just incidental histologic findings.

PAS/AB can help confirm the presence of mucin.

Question 13

Boxes to check to ensure the correct diagnosis if Barret’s esophagus

Answer 13

• There are goblet cells
• Apparent goblet cells are not actually foveolar cells (which also stain blue on PAS/AB)
• There is an endoscopically visisble lesion
• Biopsy was not taken from the stomach cardia accidentally (here intestinal metaplasia can also occur, but is not pre-malignant)
• If you have checked all the above and are sure that it is Barret’s, you have to go back and comment on the degree of dysplasia

Question 14

Features of dysplasia in Barret’s esophagus

Answer 14

• High N/C ratio
• Increased nuclear hyperchromatism and pleomorphism
• Loss of mucin vacuoles
• Crowding and pseudostratification
• Loss of polarity

Question 15

Answer 15

Invasive esophageal adenocarcinoma

Carcinoma can be seen invading the stroma as glands, cords, and single cells. Invasive cells may acquire a prominent nucleolus.

Question 16

Answer 16

Esophageal squamous cell carcinoma

Typical squamous cell carcinoma arising from the proximal esophagus

Risk factors include smoking and alcohol use.