Esophagus

A schematic of the esophagus.

Esophagus connects the pharynx to the stomach. It is afflicted by tumours on occasion. Probably the most common affliction is gastroesophageal reflux disease (GERD). Most biopsies revolve around the questions: 1. intestinal metaplasia? 2. dysplasia? and 3. cancer?

Normal esophagus

General:

• Stratified squamous non-keratinized epithelium.

Normal (esophageal) squamous epithelium:

• Should "mature" to the surface like good stratified squamous epithelium does.
  • No nuclei at luminal surface.
  • Cells should become less hyperchromatic as you go toward the lumen.
  • Mitoses should be rare and should NOT be above the basal layer.
• Inflammatory cells should be very rare.

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Nonspecific inflammation

Esophagus, Distal, Biopsy:
- Columnar epithelium with moderate chronic inflammation.
- Reactive squamous epithelium.
- NEGATIVE for intestinal metaplasia.
- NEGATIVE for dysplasia and NEGATIVE for malignancy.

Block letters

ESOPHAGUS, DISTAL, BIOPSY:
- COLUMNAR EPITHELIUM WITH MODERATE CHRONIC INFLAMMATION.
- REACTIVE SQUAMOUS EPITHELIUM.
- NEGATIVE FOR INTESTINAL METAPLASIA.
- NEGATIVE FOR DYSPLASIA AND NEGATIVE FOR MALIGNANCY.

Diagnoses

Common

• Normal.
• Metaplasia (Barrett's esophagus).
• Dysplasia.
• Adenocarcinoma.

Less common

• Squamous cell carcinoma.
• Eosinophilic esophagitis.
• Candidiasis.
• CMV esophagitis.

Tabular summary

Simplified overview

Entity	Key feature	Other features	IHC/Special	Clinical	Image
Normal	squamous epi. matures to surface	no inflammation, no atypia	-	-	Normal esophagus. (WC)
GERD	inflammation (eosinophils, lymphocytes)	elongated (epithelial) papillae, basal cell hyperplasia		incr. risk of Barrett's	c/w GERD. (WC)
Eosinophilic esophagitis	abundant eosinophils	elongated (epithelial) papillae, basal cell hyperplasia, lymphocytes		unresponsive to PPIs	Eosinophilic esophagitis. (WC/Nephron)
Barrett's type change	goblet cells	no dysplasia	Alcian blue +ve	incr. risk of adenocarcinoma	Barrett's esophagus. Alcian blue. (WC)
Dysplasia, low grade	nuclear crowding at surface	hyperchromasia, mild arch. complexity, no necrosis		incr. risk of carcinoma	LGH - intermed. mag.
Dysplasia, high grade	cribriforming and/or necrosis	nuclei often round & large, hyperchromasia		marked incr. risk of carcinoma	HGD - high mag.

Columnar dysplasia

Entity	Surface maturation	Architecture	Cytology	Other	Clinical	Image
Normal	matures	round glands	no nuclear atypia	-	-	Normal esophagus. (WC)
Barrett's esophagus	matures	round glands, normal gland density	+/-scant nuclear atypia	goblet cells	clinical diagnosis	Image
Indefinite for columnar dysplasia	minimal maturation or cannot see surface	round glands, normal gland density	mild nuclear atypia, nuclear pseudostratification, no necrosis	-	follow-up	Image
Low-grade columnar dysplasia	minimal-to-scant maturation	round glands, +/-rare budding, increased gland density	mild-to-moderate nuclear atypia, nuclear pseudostratification, no necrosis	-	follow-up	LGH - intermed. mag.
High-grade columnar dysplasia	no maturation	incr. density of irregular glands with budding and/or rare cribriforming and/or gland dilation	moderate-to-marked nuclear atypia (usu. plump round nuclei), hyperchromasia, +/-necrosis	-	EMR, surgery	HGD - high mag.
Intramucosal adenocarcinoma	no maturation	single cells or back-to-back irregular glands with budding and/or cribriforming and/or gland dilation or glands with long axis along muscularis mucosae	moderate-to-marked nuclear atypia - usu. round large nuclei, hyperchromasia, +/-necrosis	-	EMR, surgery	Adenocarcinoma - high mag.

Columnar dysplasia - another table

Feature	Indefinite for columnar dysplasia	Low-grade columnar dysplasia	High-grade columnar dysplasia	Intramucosal carcinoma (IMCa)	Utility
Depth of glands	superficial only	superficial only	superficial/deep	deep	low vs. high
Gland density	normal	near normal	increased	back-to-back	low vs. high vs. IMCa
Gland morphology	round	round	irregular/rare cribriforming	irregular/cribriform/sheeting	low vs. high vs. IMCa
Necrosis	none	none	may be present	may be present	low vs. high & IMCa
Hyperchromasia	+/-	present	present	present	indef. vs. low
Palisaded/crowded nuclei	present	present	absent/present	uncommon	low vs. high
Round nuclei + enlargement	absent	absent	present/absent	present	low vs. high
Desmoplasia	absent	absent	absent	+/- (uncommon)	high vs. IMCa
Surface involvement	present (required)	present (required)	+/-	+/-	low vs. high

Decision tree for columnar dysplasia

Odze has made an algorithm - see: Diagnostic algorithm (nih.gov).

Indications

• Pyrosis = heartburn.

Infectious esophagitis

Main article: Microorganisms

Is a relatively common problem, especially in those that live at the margins (EtOH abusers) and immunosuppressed individuals (HIV/AIDS).

Useful stains

• PAS.
• Gram stain.

Overview

• Candida - worms.
• HPV - koilocytes.
• CMV - large nuclei.
• HIV - non-specific.

Candida esophagitis

Main article: Candidiasis

• AKA esophageal candidiasis.

Gross (endoscopic)

Features:

• White patches.

DDx (endoscopic):

• Eosinophilic esophagitis.

Microscopic

Features:

• Worm-like micro-organisms - key feature.
  • Pseudohyphae (single cells).
  • Thickness ~ 1/3-1/2 of squamous cell nucleus.
  • Should be within (squamous) epithelium.
• Superficial inflammation - esp. neutrophils - important.

Notes:

• On top of epithelium does not count, i.e. it is likely an artifact.
• Bacilli and cocci may accompany the candida. They are typically ignored.

DDx:

• Acute esophagitis - no candida seen.

Image

• 

  Esophageal candidiasis. (WC)

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ESOPHAGUS, BIOPSY:
- ESOPHAGITIS WITH FUNGAL ORGANISMS CONSISTENT WITH CANDIDA.

ESOPHAGUS, BIOPSY:
- ACUTE ESOPHAGITIS WITH FUNGAL ORGANISMS CONSISTENT WITH CANDIDA.
- NEGATIVE FOR INTESTINAL METAPLASIA.
- NEGATIVE FOR DYSPLASIA.

Cytomegalovirus esophagitis

• AKA CMV esophagitis.

Microscopic

Features:

• Classically at the base of the ulcer; within endothelial cells - key point.

Note:

• Biopsying the the base of an ulcer usually just yields (non-diagnostic) necrotic debris; so, clinicians are told to biopsy the edge of the lesion. A suspected CMV infection is the exception to this rule!

Herpes esophagitis

Main article: Herpes esophagitis

Human papillomavirus esophagitis

General:

• AKA HPV esophagitis.

Microscopic

Features:

• Koilocytes:
  • Perinuclear clearing.
  • Nuclear changes.
    • Size similar (or larger) to those in the basal layer of the epithelium.
    • Nuclear enlargement should be evident on low power, i.e. 25x. [7]
    • Central location - nucleus should be smack in the middle of the cell.

Images:

• LSIL (WC).
• LSIL & endocervix (WC).

Non-neoplastic disease

The group of conditions doesn't fit neatly with the others. It is a mixture of different non-neoplastic conditions.

Gastroesophageal reflux disease

• Abbreviated GERD or GORD (gastro-oesophageal reflux disease).
• AKA reflux esophagitis.

Main article: Gastroesophageal reflux disease

Eosinophilic esophagitis

• Abbreviated EE.

Main article: Eosinophilic esophagitis

Erosive esophagitis

DDx

• Infections.
• Crohn's disease.
• Pill esophagitis.

Work-up

• GMS.
• PAS.
• IHC for HSV, CMV.

Pill esophagitis

Classic causes:

• Alendronate (Fosamax) - for osteoporosis.
• Iron - can be demonstrated with Prussian blue stain.
• Doxycycline.

Esophageal varices

Main article: Esophageal varices

Acute esophagitis

Main article: Acute esophagitis

Benign esophageal stricture

Main article: Esophageal stricture

Esophageal duplication cyst

Main article: Foregut duplication cyst

Zenker's diverticulum

Main article: Zenker's diverticulum

• AKA cricopharyngeal diverticulum, pharyngoesophageal diverticulum and hypopharyngeal diverticulum.

Radiation esophagitis

Main article: Radiation esophagitis

Preneoplastic

Barrett esophagus

Main article: Barrett esophagus

Neoplastic

Columnar dysplasia of the esophagus

• AKA esophageal columnar dysplasia, abbreviated ECD.
• AKA dysplasia in the columnar-lined esophagus.
• AKA columnar epithelial dysplasia.

Main article: Columnar dysplasia of the esophagus

Squamous dysplasia of the esophagus

• AKA esophageal squamous dysplasia.

General

• Precursor of esophageal squamous cell carcinoma.
• Common in China.
• Not very common in North America.

Microscopic

Features:

• Squamous cell nuclear atypia.
• Lack of maturation to the surface.

Note:

• Grading differences between Western pathologists and those of the east.

DDx:

• Reactive changes.
• Esophageal squamous cell carcinoma.

Images

A set of cases from Japan:

• Mild squamous dysplasia (nih.gov).
• Moderate squamous dysplasia (nih.gov).
• Severe squamous dysplasia (nih.gov).
• Carcinoma in situ (nih.gov).
• Squamous cell carcinoma of the esophagus (nih.gov).

IHC

• Ki-67 may be useful:
  • Reactive changes/normal: ~98% negative, ~2% intermediate.
  • Low-grade esophageal squamous intraepithelial neoplasia (LGESIN): ~80% intermediate, ~20% negative.
  • High-grade esophageal squamous intraepithelial neoplasia (HGESIN): ~37% intermediate, ~63% strong.

Definitions:

• Negative defined as: < 25% of epithelium +ve and staining only in lower quarter of epithelium.
• Intermediate defined: >=25% and <=50% of epithelium +ve and only in the lower half of the epithelium.
• Strong defined: >50% of epithelium +ve or upper half of epithelium.

Leiomyoma of the esophagus

Main article: Leiomyoma

General

• Benign.
• Uncommon.
  • Before the time of GISTs - this was a relatively common diagnosis.
• Like leiomyomas elswhere.

Microscopic

See: Leiomyoma.

DDx:

• Gastrointestinal stromal tumour.
• Schwannoma.

Gastrointestinal stromal tumour

Main article: Gastrointestinal stromal tumour

Cancer

General

• Proximal esophagus: squamous cell carcinoma.
• Distal esophagus: adenocarcinoma arising from Barrett's esophagus.

Risks:

• Alcohol (EtOH).
• Barrett's esophagus.
• Smoking.

Squamous cell carcinoma of the esophagus

• AKA esophageal squamous cell carcinoma, abbreviated esophageal SCC.

Main article: Squamous cell carcinoma of the esophagus

Esophageal adenocarcinoma

• AKA adenocarcinoma of the esophagus.

Main article: Esophageal adenocarcinoma

Weird stuff

• Inflammatory polyp - assoc. trauma/previous intervention.
• Giant fibrovascular polyp - loose connective tissue covered with squamous epithelium.
• Granular cell tumour.
• Squamous papilloma - koilocytes.
• Heterotopic gastric mucosa ("inlet patch") - benign appearing gastric mucosa.

Granular cell tumour

Main article: Granular cell tumour

Microscopic

Features:

• Abundant eosinophilic granular cytoplasm key feature.
  • Granules:
    • Size: 1-3 micrometers.
    • Poorly demarcated.
• Usu. bland (cytologically non-malignant) nuclei.

Images

• GCT of the esophagus (nih.gov).
• GCT - skin (WC).
• GCT - S100 (WC).

Esophagitis dissecans superficials

• AKA sloughing esophagitis.

General

• Rare & benign condition that resolves without lasting pathology.
  • Case report - chronic with strictures.
• Sloughing of large fragments of the esophageal mucosa - seen on endoscopy.

Microscopic

Features:

• Flaking of superficial squamous epithelium.
• Focal bullous separation of the layers.
• Parakeratosis.
• Variable acute or chronic inflammation.

Glycogenic acanthosis of the esophagus

Main article: Glycogenic acanthosis of the esophagus

Achalasia

Main article: Achalasia

Esophageal inlet patch

• AKA inlet patch, AKA cervical inlet patch.

General

• Benign and likely not of any significance.

Gross

• Proximal esophagus - salmon coloured lesion.

Microscopic

Features:

• Gastric mucosa.

Image:

• Esophageal inlet patch (nih.gov).

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Esophagus at 22 cm, Biopsy:
     - Gastric type mucosa with mild chronic inactive inflammation, see comment.
     - Scant unremarkable squamous epithelium.
     - NEGATIVE for intestinal metaplasia.
     - NEGATIVE for dysplasia.

Comment:
This is in keeping with an "inlet patch", also known as "heterotopic gastric mucosal patch of the proximal esophagus".

Squamous papilloma of the esophagus

Main article: Squamous papilloma of the esophagus

See also

• Stomach.
• Gastrointestinal pathology.