Chemical and Infectious Esophagitis

Slide 1 · Chemical and Infectious

Esophagitis

Etiology · tissue injury · diagnostic morphology

Clinical pathology teaching lecture

Dr Abu Suraih Sakhri

MBBS, MD (Pathology)

www.abusuraihsakhri.com

Slide 2 · Learning objectives

Identify principal chemical, iatrogenic, and infectious causes of esophageal mucosal injury.

Correlate ulcer patterns and biopsy findings with Candida, HSV, and CMV.

Recognize the distinctive vascular and epithelial changes of irradiation injury and GVHD.

Use clinicopathologic context to distinguish these disorders from reflux injury.

Slide 3 · The shared target is squamous mucosa

Common tissue compartment

Stratified squamous epithelium of the esophagus

Exposure to luminal irritants

Injury from therapy or immune disease

Direct microbial infection

Slide 4 · Etiology determines the tissue response

Insult

Chemical, drug, infection or immune injury

Target

Squamous epithelium, vessels or stromal cells

Response

Inflammation, necrosis, inclusion or apoptosis

Expression

Pain, ulceration and complications

The dominant histologic clue depends on the causal process.

Slide 5 · Major classes of esophagitis in this topic

Direct chemical

Corrosive agents, alcohol, heat and smoking

Localized medication

Pills that lodge and dissolve

Treatment-related / immune

Chemotherapy, irradiation and graft-versus-host disease

Infectious

Viruses, Candida and other pathogenic organisms

Slide 6 · Odynophagia is a central symptom

Odynophagia means pain on swallowing.

Chemical and infectious esophagitis may produce acute or persistent discomfort.

Symptoms alone do not establish the etiology or severity of tissue injury.

Slide 7 · Clinical consequences span a broad spectrum

Pain

Mucosal irritation

Hemorrhage

Damaged mucosal vessels

Stricture

Luminal narrowing after injury

Perforation

Loss of wall integrity

Slide 8 · Recognize severe disease

Potentially serious complications

Hemorrhage · stricture · perforation

These appear in severe cases.

A mild symptomatic course is also possible.

Histologic and clinical severity can differ.

Slide 9 · Irritants capable of chemical injury

Ingested agents

Alcohol, corrosive acids and alkalis

Physical exposure

Excessively hot liquids

Tobacco exposure

Heavy smoking

Consumer products

Household cleaners and related corrosives

Slide 10 · How corrosive injury occurs

Exposure setting

Accidental ingestion

Intentional ingestion

Cleaning products or other corrosives

Possible tissue outcome

Acute mucosal damage

Extensive necrosis in severe injury

Subsequent hemorrhage, stricture or perforation

Slide 11 · Conceptual sequence of caustic injury

Corrosive contact

Acid, alkali or detergent exposure

Acute damage

Direct injury to squamous mucosa

Tissue loss

Necrosis may dominate

Clinical effect

Pain; Serious complications if extensive

A causal schematic; The book does not prescribe a single uniform histologic pattern for all agents.

Slide 12 · Chemical necrosis can dominate the lesion

Lumen

Squamous epithelium

Lamina propria / deeper tissue

Loss of epithelium

Ulceration exposes underlying tissue; Etiologic features must be sought in the residual tissue and ulcer bed.

Teaching schematic—not a histologic specimen

Slide 13 · A histologic caution in corrosive injury

Do not require abundant neutrophils

Acute necrosis may occur with few or no neutrophils

Described after lye ingestion

Also described with acids

Also described with detergents

Slide 14 · Necrosis and inflammation are distinct observations

Evidence of tissue death

Necrotic epithelium or wall tissue

Loss of viable mucosal integrity

Can be prominent in acute caustic injury

Evidence of inflammatory response

Dense neutrophils commonly occur

They are not uniformly present

Absence does not exclude severe chemical injury

Slide 15 · Why a retained pill can cause injury

Medication

A pill is swallowed

Retention

Pill lodges in esophagus

Dissolution

Local drug contact persists

Result

Focal mucosal irritation or injury

This is the defining sequence of pill-induced esophagitis in the source.

Slide 16 · Pill-induced esophagitis: Anatomic clue

Predisposing local feature

Preexisting esophageal stricture

Pill-induced lesions often arise at sites of a stricture.

The retained material creates a localized exposure.

Evaluate the causal role of an underlying luminal narrowing.

Slide 17 · Caustic versus pill-related esophagitis

Dimension

Corrosive exposure

Pill retention

Typical circumstance

Ingestion of acid, alkali or cleaner

Medication lodges and dissolves

Injury distribution

Depends on direct mucosal contact

Localized to retention site

Named morphologic point

Necrosis may lack neutrophils

Often at preexisting strictures

Severity

May be severe

Described as often less severe

Slide 18 · Iatrogenic and systemic noninfectious causes

Cytotoxic therapy

Chemotherapy-associated mucosal injury

Radiotherapy

Vascular injury contributes to mucosal damage

Immune-mediated

Graft-versus-host disease

Other systemic disease

Desquamative disorders and rare Crohn involvement

Slide 19 · Radiation injury is partly vascular

Radiotherapy

Irradiation of esophageal tissue

Vessel response

Intimal proliferation

Vascular effect

Luminal narrowing

Secondary effect

Contributes to mucosal injury

Slide 20 · A vascular mechanism of radiation esophagitis

Radiation-associated injury to submucosal and mural vessels

Before injury

Patent lumen

After irradiation

Narrowed lumen

Intimal proliferation → luminal narrowing → contributes to mucosal damage

Slide 21 · What radiation-damaged vessels show

Intimal proliferation develops within submucosal and mural vessels.

The vascular lumen becomes narrowed.

Esophageal mucosal injury is partly secondary to this vascular damage.

The book explicitly relates this pattern to irradiation injury in other tissues.

Slide 22 · Do not equate all iatrogenic mechanisms

Cytotoxic chemotherapy

Identified by Robbins as a cause of injury

The assigned passage does not give a defining microscopic pattern

Review treatment history alongside the biopsy

Radiation therapy

Intimal thickening is specifically described

Submucosal and mural vessel lumina narrow

Vascular injury helps explain mucosal damage

Slide 23 · GVHD: A different mode of injury

Setting

Graft-versus-host disease

Epithelial event

Basal cell apoptosis

Tissue changes

Mucosal atrophy and submucosal fibrosis

Pattern

Little significant acute inflammation

Slide 24 · Esophageal GVHD: Microscopic triad

Structure

Described change

Interpretive value

Basal epithelial layer

Apoptosis

Epithelial injury clue

Mucosa

Atrophy

Reduced epithelial thickness

Submucosa

Fibrosis

Chronic tissue remodeling

Acute inflammatory cells

Not prominent

Distinctive relative to purulent lesions

Slide 25 · Why GVHD can be missed as infection

Clinical context

GVHD is a recognized noninfectious cause

Dominant cell lesion

Basal epithelial apoptosis

Structural effects

Mucosal atrophy and submucosal fibrosis

Negative pattern

Significant acute inflammation is not required

Slide 26 · Uncommon associated inflammatory disorders

Desquamative skin disorders

Bullous pemphigoid

Epidermolysis bullosa

Esophageal morphology resembles lesions at other sites

Crohn disease

Esophageal involvement is rare

Appearance parallels disease elsewhere

Requires clinicopathologic correlation

Slide 27 · Noninfectious injury: Distinguishing clues

Entity

Source-described mechanism or clue

Corrosive esophagitis

Contact injury and possible necrosis without neutrophils

Pill-induced esophagitis

Pill lodged and dissolved; often a preexisting stricture

Radiation injury

Vascular intimal proliferation; narrowed lumina

GVHD

Basal apoptosis, atrophy, submucosal fibrosis

Desquamative / Crohn involvement

Morphology mirrors lesions at other body sites

Slide 28 · Host status changes the infection differential

Otherwise healthy individuals

HSV is the most frequent infection identified in this group

A viral cause remains plausible despite immunocompetence

Do not presume all esophageal infection implies immunosuppression

Debilitated or immunosuppressed patients

Infections are more frequent

HSV, CMV and fungal organisms are recognized

Host context helps prioritize morphology

Slide 29 · Infectious agents identified by Robbins

Viral

Herpes simplex virus and cytomegalovirus

Common fungal

Candida species

Other fungal

Mucormycosis and aspergillosis

Bacterial

Pathogenic bacteria may invade damaged mucosa

Slide 30 · The dominant fungal cause

Among esophageal fungal infections

Candidiasis is the most common

Gray-white pseudomembranes

Fungal hyphae and inflammatory cells

Risk increased in compromised hosts

Slide 31 · Microbes in ulcers: Colonizer or pathogen?

Incidental organisms

Oral bacteria may occur in ulcer beds

Their presence alone need not establish causation

Context and tissue damage matter

Invasive pathogens

Pathogenic fungi or bacteria may invade

Invasion can produce mucosal necrosis

A true invasive process is mechanistically different

Slide 32 · Infection may be primary or superimposed

Preexisting injury

An ulcer may already be present

Microbial entry

Organisms occupy the damaged site

Possible invasion

Pathogens breach tissue

Consequences

Further necrosis or inflammation

Slide 33 · The role of pathogenic bacteria and fungi

Infection by bacteria or fungi may initiate injury or complicate a preexisting ulcer.

Nonpathogenic oral bacteria are frequent in ulcer beds.

True invasive pathogenic bacteria and fungi can produce necrosis.

The source attributes roughly one tenth of infectious cases to pathogenic bacteria and fungi as a group.

Slide 34 · Candida: Characteristic endoscopic appearance

Macroscopic hallmark

Adherent gray-white pseudomembranes

Adherent to esophageal mucosa

May form a conspicuous surface coating

Link the gross appearance to its composition

Slide 35 · What forms a candidal pseudomembrane

Lumen

Squamous epithelium

Lamina propria / deeper tissue

Adherent surface material

Gray-white pseudomembrane containing fungal hyphae and inflammatory cells

Teaching schematic—not a histologic specimen

Slide 36 · Microscopic substrate of pseudomembranes

Densely matted fungal hyphae form the structural component.

Inflammatory cells intermingle with the fungal material.

The pseudomembrane covers the esophageal mucosal surface.

This appearance contrasts with discrete viral ulcers.

Slide 37 · Fungal inflammation versus viral ulceration

Candida pattern

Adherent gray-white surface pseudomembrane

Hyphae mixed with inflammatory cells

Fungal invasion may cause necrosis

Viral pattern

Discrete punched-out ulcers

Virus-specific changes in host cells

Cell identity separates HSV from CMV

Slide 38 · Less frequent esophageal fungi

Mucormycosis among uncommon infectious causes.

Aspergillosis can also involve the esophagus.

The assigned excerpt does not provide organism-specific endoscopic or microscopic criteria for either mold.

Do not substitute Candida morphology for all fungal etiologies.

Slide 39 · The viral pattern begins with a discrete ulcer

Lumen

Squamous epithelium

Lamina propria / deeper tissue

Loss of epithelium

Ulceration exposes underlying tissue; Etiologic features must be sought in the residual tissue and ulcer bed.

Teaching schematic—not a histologic specimen

Slide 40 · Viral infection: A gross pattern clue

Endoscopic / gross morphology

Discrete “punched-out” ulcers

The pattern raises suspicion for viral etiology.

Herpes viruses can produce punched-out ulcers.

Interpret morphology with biopsy cellular changes.

Slide 41 · HSV esophagitis: Clinical context

HSV is the most frequent named infectious cause in otherwise healthy individuals.

HSV also occurs in debilitated or immunosuppressed patients.

Its characteristic histologic target is the squamous epithelium at ulcer edges.

Slide 42 · HSV morphology: From ulcer to cell

Ulcer

Discrete punched-out lesion

Edge epithelium

Degenerating squamous cells

Cytopathy

Often multinucleated

Viral clue

Intranuclear inclusions

Slide 43 · HSV inclusions occur in squamous epithelial cells

Degenerating squamous epithelial cell at ulcer margin

Multinucleation

Intranuclear viral inclusions

Cellular site: Squamous epithelium

Simplified schematic—not a microscopy image

Slide 44 · Where the HSV diagnostic clue resides

Location is as important as appearance

Ulcer margin squamous cells

Degeneration of epithelial cells

Multinucleation may be present

Nuclear viral inclusions

Slide 45 · HSV biopsy interpretation: Source-based logic

Examine viable squamous epithelial tissue bordering the ulcer.

Look for degenerating, sometimes multinucleated cells.

Identify intranuclear inclusions consistent with herpesvirus effect.

Viral immunohistochemistry can support the morphologic diagnosis.

Slide 46 · CMV esophagitis: Host and lesion

CMV is among the important pathogens in immunosuppressed or debilitated patients.

Its ulcers as shallower than herpetic punched-out ulcers.

The diagnostic cellular changes involve capillary endothelium and stromal cells.

Slide 47 · CMV morphology: Trace the host cell

Ulcer

Relatively shallow ulceration

Cell compartment

Endothelial and stromal cells

Cytopathy

Nuclear and cytoplasmic inclusions

Ancillary tool

CMV-specific immunostain

Slide 48 · CMV inclusions occur in endothelial and stromal cells

Capillary endothelial / stromal cell in an ulcer

Nuclear inclusion

Cytoplasmic inclusions

Cellular site: Endothelium / stroma

Simplified schematic—not a microscopy image

Slide 49 · HSV and CMV: Localization of infected cells

HSV

Degenerating squamous epithelium

Changes at ulcer margins

Usually intranuclear inclusions

Multinucleated cells may be seen

CMV

Capillary endothelial cells

Ulcer stromal cells

Nuclear plus cytoplasmic inclusions

Ulcers described as shallower

Slide 50 · A diagnostic matrix for the viral causes

Characteristic

HSV

CMV

Gross ulcer

Discrete / punched-out

Shallower ulceration

Primary cells described

Squamous epithelium

Endothelial and stromal

Cell location

Ulcer margins

Ulcer-associated stroma/vessels

Inclusional pattern

Nuclear; multinucleation often

Nuclear and cytoplasmic

Ancillary method

Virus-specific IHC

Virus-specific IHC

Slide 51 · Viral immunohistochemistry

When morphology suggests HSV or CMV

Virus-specific antigen stains are useful adjuncts

The diagnosis begins with tissue pattern.

Immunostains add antigen specificity.

Use results in the context of the observed cellular lesion.

Slide 52 · Do not overinterpret ulcer shape

A punched-out ulcer suggests a viral cause; It is not a stand-alone organism identification.

HSV and CMV differ principally by their infected cell populations and inclusion patterns.

Ancillary virus-specific IHC can clarify difficult morphology.

Slide 53 · Rapid morphologic pattern recognition

Adherent white surface material

Consider candidal pseudomembrane

Viral ulcer + squamous inclusions

Favor HSV-associated changes

Viral ulcer + endothelial/stromal inclusions

Favor CMV-associated changes

Basal apoptosis with little acute inflammation

Consider GVHD

Slide 54 · Neutrophils: A useful but nonspecific clue

Setting

Source-described inflammatory pattern

Most chemical/infectious injury

Often dense neutrophilic infiltrates

Severe acute caustic necrosis

Neutrophils may be absent

Esophageal GVHD

No significant acute inflammatory infiltrate

GERD (adjacent section)

Neutrophils less common than eosinophils

Slide 55 · Chemical or infectious injury versus reflux

This topic

Specific exposure or immunosuppressive context

Chemical injury may be necrotizing

Fungal pseudomembranes or virus-specific inclusions

Reflux esophagitis (adjacent topic)

Distal gastric reflux is the driver

Basal zone hyperplasia / papillary elongation

Eosinophils may enter squamous epithelium

Slide 56 · GVHD versus infectious ulceration

GVHD

Basal epithelial apoptosis

Atrophy with submucosal fibrosis

Little significant acute inflammation

Infectious injury

Pathogen or viral cytopathic changes

Neutrophils often present

Fungal invasion or viral inclusions identify cause

Slide 57 · An editable reasoning pathway for a biopsy

Describe injury

Ulcer, pseudomembrane, apoptosis or necrosis

Locate clue

Epithelium versus vessels/stroma

Review context

Exposure, therapy, GVHD or immune status

Refine diagnosis

Use appropriate pathogen-specific IHC if indicated

Slide 58 · Case application: Corrosive ingestion

Hypothetical teaching vignette

After ingestion of an alkaline household product, a patient develops marked odynophagia. Biopsy from a damaged region shows extensive mucosal necrosis with very few neutrophils.

Which source-based principle prevents a diagnostic error?

A. Few neutrophils exclude serious injury.

B. Acute caustic necrosis may lack neutrophils.

C. Ulceration proves CMV infection.

Slide 59 · Case interpretation: Caustic necrosis

Correct interpretation

Marked necrosis can occur without neutrophilic infiltration

Exposure provides etiologic context.

Neutrophil abundance is not a severity scale.

Correlate with risk of stricture or perforation.

Slide 60 · Case application: Viral ulcer

Hypothetical teaching vignette

An immunosuppressed patient has esophageal ulceration. Biopsy shows enlarged infected endothelial and stromal cells containing nuclear and cytoplasmic inclusions.

Which etiologic pattern is described?

A. CMV esophagitis

B. HSV esophagitis

C. Pill-induced esophagitis

Slide 61 · Case interpretation: Infected cell type

Most consistent etiology

Cytomegalovirus (CMV)

Endothelial and stromal inclusions are the key distinction.

Nuclear and cytoplasmic inclusions are described.

Virus-specific IHC is a useful confirmatory adjunct.

Slide 62 · Case application: Adherent surface plaques

Hypothetical teaching vignette

A debilitated patient has painful swallowing and adherent gray-white esophageal plaques. Histology shows a dense surface mat of fungal hyphae and inflammatory cells.

Which morphology is most characteristic?

A. Candidal pseudomembrane

B. GVHD-associated apoptosis

C. Radiation-induced vasculopathy

Slide 63 · Case interpretation: Candidiasis

Most consistent pattern

Candidal esophagitis

A pseudomembrane links gross and microscopic findings.

Hyphae and inflammatory cells form the surface coating.

Candida is the most common fungal cause named in the source.

Slide 64 · Case application: Post-treatment injury

Hypothetical teaching vignette

An esophageal biopsy after irradiation demonstrates proliferation of vascular intima and narrowing of blood vessel lumina.

What mechanism contributes to the mucosal injury?

A. Radiation-associated vascular damage

B. HSV replication in squamous epithelial cells

C. Pseudomembranous fungal infection

Slide 65 · Case interpretation: Irradiation

Mechanism highlighted

Vascular compromise contributes to mucosal injury

Changes involve submucosal and mural vessels.

The lumina become narrowed by intimal proliferation.

The source emphasizes a partly secondary mucosal effect.

Slide 66 · Five high-yield pattern–etiology links

Corrosive agent

Necrosis may be severe with absent neutrophils

Retained pill

Look for a preexisting stricture

Radiotherapy

Intimal proliferation and luminal narrowing

Candida

Adherent hyphal pseudomembrane

HSV vs CMV

Squamous inclusions vs endothelial/stromal inclusions

Slide 67 · Consolidated clinicopathologic principles

History of exposure or therapy narrows the noninfectious differential.

Host immune status alters the likelihood of infectious causes.

Gross ulcer pattern is a clue, not a complete etiologic diagnosis.

Cellular localization and inclusion pattern are critical in viral esophagitis.

Ancillary IHC supports, rather than replaces, morphologic assessment.

Slide 68 · Primary reference

Robbins, Cotran & Kumar: Pathologic Basis of Disease

11th edition (2026)

Chapter 17: The Gastrointestinal Tract

Chemical and Infectious Esophagitis, pp. 689–690

Adjacent reflux text consulted only for diagnostic differentiation.