Hairy Leukoplakia

Slide 1 · Hairy Leukoplakia

EBV-associated oral epithelial lesion

Clinical recognition • Morphology • Differential diagnosis

Dr Abu Suraih Sakhri

MBBS, MD (Pathology)

www.abusuraihsakhri.com

Slide 2 · Learning objectives

Recognize the characteristic site and surface appearance of oral hairy leukoplakia.

Connect EBV infection and impaired immune surveillance with epithelial changes.

Interpret hyperparakeratosis, acanthosis, balloon cells and lesional EBV detection.

Distinguish this entity from candidiasis and potentially malignant oral leukoplakia.

Slide 3 · An oral white patch is a clinical finding

Describe before naming

Then establish the cause

Document anatomical site, distribution, surface contour and removability.

Use the immune history to refine the differential.

Consider infection, reactive keratosis and dysplastic processes.

A white appearance alone does not identify the pathogen.

Scrapability may separate a surface pseudomembrane from keratosis.

A suspicious lesion may still require tissue assessment.

Slide 4 · Defining oral hairy leukoplakia

A distinctive EBV-associated epithelial lesion of the oral mucosa.

Most characteristically involves the lateral border of the tongue.

Produces a persistent white, keratotic and often corrugated plaque.

Typically occurs with immunosuppression, but is not specific to HIV.

EBV is the causal agent; Immune dysfunction is a common host context.

Slide 5 · Why the oral cavity matters

Systemic immune disorder

→

Altered host–microbe control

→

Recognizable oral lesion

Oral examination can expose evidence of otherwise unrecognized systemic disease.

Hairy leukoplakia is a named example in the systemic-disease section of Robbins.

Slide 6 · Anatomic predilection

Characteristic

Less characteristic

Lateral lingual mucosa is the classic site.

An edge-of-tongue view is essential during the examination.

The lesion may be unilateral or bilateral.

Other oral sites are possible but less typical.

A lesion confined to a different site needs a broader differential.

Do not diagnose solely from white color.

Slide 7 · Epstein–Barr virus is central

EBV is implicated by viral nucleic acids and proteins in lesional squamous cells.

The characteristic abnormality involves oral epithelial cells rather than a tumor mass.

Lesional viral detection connects the clinical plaque to a specific infection.

Slide 8 · Separate the roles of HIV and EBV

HIV or another host factor

→

Reduced immune surveillance

→

EBV-associated epithelial lesion

HIV infection can establish the permissive immunosuppressed setting.

EBV—not HIV—is the directly implicated virus in hairy leukoplakia.

Slide 9 · Immunosuppressive clinical contexts

Clinical setting

Relevant observation

Interpretive implication

HIV infection

Classic association; May accompany immune decline

Evaluate broader HIV care context

Cancer therapy

Reported setting

Review therapy-associated suppression

Organ transplantation

Immunosuppressive treatment association

Review transplant medications

Advanced age

Also encountered in older adults

Do not assume HIV infection

Slide 10 · HIV: A marker, not a diagnosis of AIDS

In a patient with HIV, hairy leukoplakia may indicate weakening immune control.

It may portend progression to AIDS.

The lesion alone does not establish an AIDS diagnosis or quantify immune function.

Its interpretation belongs with current systemic assessment.

Avoid equating “hairy leukoplakia” with “AIDS” in isolation.

Slide 11 · Cancer therapy and oral hairy leukoplakia

Therapy-related immunosuppression is a recognized setting.

A characteristic lateral-tongue lesion should not be dismissed because HIV is absent.

Review exposure and timing; Do not infer a particular drug mechanism without evidence.

Slide 12 · Transplant-associated immunosuppression

Robbins specifically includes transplant-related immunosuppression.

Clinical appearance and tissue findings remain the same diagnostic targets.

An EBV-associated lesion can emerge despite an unrelated transplant indication.

Slide 13 · Older adults and atypical host profiles

Advanced age is listed among additional immunocompromising contexts.

Rare reports describe hairy leukoplakia without overt immunodeficiency.

A normal or incomplete history should prompt assessment, not automatic exclusion.

Slide 14 · What is established—and what is not

Well supported

Do not overclaim

Lesional squamous epithelium contains EBV material.

Immunosuppression is a major clinical association.

Viral activity is prominent in superficial differentiated cells.

The specific trigger in each patient is not usually known.

The reason for the lateral-tongue predilection is not fully established.

EBV seropositivity alone is not lesion confirmation.

Slide 15 · Mechanistic sequence: Immune context to plaque

Impaired local immune control

→

EBV activity in oral keratinocytes

→

Epithelial thickening

→

White corrugated plaque

This is a teaching synthesis; It does not imply that every intermediate molecular mechanism is settled.

Slide 16 · EBV-related epithelial involvement

Surface parakeratin

Upper spinous layer

Lower spinous layer

Basal layer

Native editable schematic — not histology

Viral activity is concentrated in the more differentiated superficial epithelial compartment.

The upper spinous layer is where characteristic swollen cells are described.

Basal invasion is not required to explain the surface lesion.

Slide 17 · Gross appearance: Why it is distinctive

White confluent patches form a non-wipeable mucosal plaque.

The surface is fluffy, corrugated or “hairy” rather than smooth.

Keratotic epithelial thickening produces the distinctive raised contour.

Site + texture + non-removability is the core clinical pattern.

Slide 18 · Lateral border localization

Lateral border

Schematic — not a clinical image

Inspect both lateral surfaces of the tongue directly.

A lesion on the lateral border is more characteristic than a random oral white patch.

Distribution remains supportive—not diagnostic—evidence.

Slide 19 · White confluent mucosal patches

“White” describes the visible surface phenotype, not a microscopic diagnosis.

“Confluent” indicates that neighboring areas form a larger continuous plaque.

The surface must still be characterized by its texture and response to wiping.

Slide 20 · What does “hairy” mean?

The word refers to a fluffy, shaggy or corrugated surface texture.

It does not indicate hair follicles or true hair on oral mucosa.

Exaggerated superficial keratin contributes to the clinical contour.

Slide 21 · White appearance and keratin

The superficial epithelial compartment exhibits conspicuous keratin accumulation.

An optically pale surface is consistent with the hyperkeratotic pathology.

The visible phenotype must be interpreted together with EBV-related cytopathic changes.

Slide 22 · The non-scrapability test

A characteristic hairy-leukoplakia plaque cannot be removed by gentle scraping.

Pseudomembranous thrush usually separates, exposing an erythematous surface.

Wiping is one bedside discriminator; It is not a substitute for the entire workup.

Slide 23 · Distribution: Unilateral or bilateral

Lateral border

Schematic — not a clinical image

Lesions may affect one or both lateral borders.

Symmetry is variable and should not be treated as a required criterion.

Note any additional oral lesions separately.

Slide 24 · Symptoms may be minimal

Oral hairy leukoplakia is often asymptomatic.

An obvious lesion can be discovered incidentally during oral examination.

Symptom burden alone should not determine whether a white lesion merits assessment.

Slide 25 · Candida superinfection changes the surface

EBV-associated keratotic plaque

→

Secondary Candida colonization

→

More conspicuous “hairiness”

Candida may coexist with hairy leukoplakia; Its presence does not change EBV causation.

Interpret fungal staining together with the rest of the lesional findings.

Slide 26 · Observed clinical clues

Observation

Typical hairy leukoplakia

Diagnostic weight

Color

White

Sensitive visually, not specific

Surface

Fluffy or corrugated

Supports pattern recognition

Site

Lateral tongue

Strong distribution clue

Gentle wiping

Plaque remains

Helpful vs pseudomembranous thrush

Immune setting

Frequently immunosuppressed

Raises pretest suspicion

Slide 27 · Histology: A recognizable combination

Prominent hyperparakeratosis at the surface.

Epithelial acanthosis (expansion of squamous epithelial thickness).

Ballooned pale cells in the upper spinous layer.

EBV is demonstrable within the lesional epithelium.

Slide 28 · Orient to squamous epithelial layers

Surface parakeratin

Upper spinous layer

Lower spinous layer

Basal layer

Native editable schematic — not histology

Parakeratin forms the most superficial covering.

The spinous compartment lies beneath and contains differentiating keratinocytes.

The basal cell layer remains the deep epithelial boundary.

Distribution of the abnormal cells matters as much as their morphology.

Slide 29 · Hyperparakeratosis

Surface parakeratin

Upper spinous layer

Lower spinous layer

Basal layer

Native editable schematic — not histology

The surface keratin is conspicuously thickened.

Parakeratosis denotes retention of nuclei within the keratinized surface layer.

This is a key histologic component but not specific to EBV by itself.

Slide 30 · Acanthosis expands the epithelium

Surface parakeratin

Upper spinous layer

Lower spinous layer

Basal layer

Native editable schematic — not histology

Acanthosis denotes thickening of the prickle-cell (spinous) compartment.

It accounts for increased epithelial thickness rather than stromal tumor invasion.

Combine acanthosis with superficial cytopathic changes for pattern recognition.

Slide 31 · Ballooned keratinocytes

Surface parakeratin

Upper spinous layer

Lower spinous layer

Basal layer

Native editable schematic — not histology

Pale, swollen epithelial cells appear in the upper spinous layer.

The ballooned-cell band is an important clue to EBV-associated cytopathic change.

A ballooned cell is not in itself a virus-specific laboratory test.

Slide 32 · Why the upper spinous position matters

Surface parakeratin

Upper spinous layer

Lower spinous layer

Basal layer

Native editable schematic — not histology

The distribution places affected cells toward epithelial maturation.

It corresponds to descriptions of productive superficial EBV infection.

This relationship is more informative than identifying an isolated pale cell.

Slide 33 · Nuclear changes and HPV resemblance

Koilocyte-like superficial squamous cells may show perinuclear clearing.

Nuclear “beading” has been reported in EBV-associated lesions.

Resemblance to HPV-related koilocytosis can mislead interpretation.

Demonstration of lesional EBV resolves the viral-attribution question.

Slide 34 · Inflammation may be inconspicuous

Published histologic descriptions emphasize sparse underlying inflammation.

A dramatic inflammatory response is not required for a pronounced epithelial plaque.

Low inflammatory activity does not negate a viral etiology.

Slide 35 · Superimposed superficial Candida

Surface parakeratin

Upper spinous layer

Lower spinous layer

Basal layer

Native editable schematic — not histology

Fungal hyphae may be present in superficial keratin.

Colonization may coexist with the EBV-driven epithelial abnormality.

PAS fungal staining can demonstrate fungi but cannot establish EBV causation.

Slide 36 · Histopathology: Integrate rather than isolate

Epithelial architecture

Etiologic demonstration

Thick superficial parakeratin.

Expansion of the spinous compartment.

Band of swollen cells in the upper squamous layers.

Demonstrate EBV within epithelial lesional cells.

Investigate Candida if superficial organisms are suspected.

Interpret with site, appearance and immune status.

Slide 37 · Evidence linking EBV to the lesion

Characteristic morphology

→

EBV nucleic acid or protein in cells

→

Clinicopathologic correlation

Viral demonstration supplies stronger etiologic support than morphology alone.

Lesional epithelial localization is important to the interpretation.

Slide 38 · EBV in situ hybridization

In situ hybridization detects EBV nucleic acids in tissue sections.

EBV-encoded RNA (EBER) testing is used for confirmatory assessment.

Positive signal in lesional epithelial cells supports an EBV-associated process.

Assess staining localization together with morphology and appropriate controls.

Slide 39 · A schematic reading of EBV-positive epithelium

Surface parakeratin

Upper spinous layer

Lower spinous layer

Basal layer

Native editable schematic — not histology

Identify the signal within squamous epithelial cells—not merely on the surface.

Review the compartment distribution and staining specificity.

Slide 40 · What individual investigations answer

Investigation

What it shows

What it does not prove alone

H&E

Acanthosis, parakeratin, ballooning

EBV etiology with certainty

EBV ISH

Lesional viral nucleic acid

Clinical context without morphology

PAS fungal stain

Superficial fungal organisms

Cause of EBV lesion

Clinical examination

Site, texture, wipe response

Histologic exclusion of dysplasia

Slide 41 · Clinical recognition and confirmation

A classic presentation suggests hairy leukoplakia clinically.

Biopsy and lesional EBV assessment provide stronger diagnostic confirmation.

The threshold for tissue sampling changes if the appearance is atypical or suspicious.

Avoid labeling an unexplained high-risk white lesion on appearance alone.

Slide 42 · When a white lesion needs tissue assessment

Persistent or unusual non-removable white lesions merit differential diagnosis.

Erythema, ulceration, induration or a focal atypical area should not be ignored.

The need to exclude dysplasia or carcinoma is distinct from confirming EBV.

Slide 43 · What a defensible pathology report addresses

Descriptive findings

Etiology and modifiers

Specimen site and epithelial architecture.

Parakeratosis, acanthosis and upper-level ballooning.

Any suspicious dysplasia or atypia.

Status and epithelial distribution of EBV studies.

Presence of superficial fungi when assessed.

Clinicopathologic concordance or unresolved uncertainty.

Slide 44 · Hairy leukoplakia versus thrush

Feature

Hairy leukoplakia

Pseudomembranous thrush

Dominant cause

Epstein–Barr virus

Candida

Surface

Keratotic, corrugated plaque

Fibrinofungal pseudomembrane

Wiping

Classically not removable

Typically removable

After removal

Plaque generally persists

Erythematous mucosa exposed

Coexistence

Candida may colonize OHL

Fungal disease can occur alone

Slide 45 · Scrapability is helpful but not infallible

A non-removable plaque favors a keratotic process over classic thrush.

Some candidal disease is not pseudomembranous.

Candida may be superimposed on hairy leukoplakia.

Histology and microbiology resolve ambiguous mixed lesions.

Slide 46 · Hairy leukoplakia versus conventional leukoplakia

Feature

Oral hairy leukoplakia

Conventional leukoplakia

Basis

Named EBV-associated lesion

Unexplained white plaque after exclusion

Common site

Lateral tongue

Variable oral mucosal sites

Immune link

Often immunosuppression

Not required by definition

Cancer framing

Not ordinarily classified as OPMD

Potentially malignant clinical category

Confirmatory focus

EBV with compatible morphology

Histology to assess dysplasia

Slide 47 · The word “leukoplakia” can mislead

Conventional leukoplakia is a diagnosis of exclusion for an unexplained white plaque.

Hairy leukoplakia has an identified viral etiology and characteristic morphology.

Do not transfer premalignant risk estimates from conventional leukoplakia to OHL.

Unexpected atypia requires assessment on its own merits.

Slide 48 · Other plausible non-removable white lesions

Frictional or lichenoid patterns

Cytopathic viral patterns

Trauma-related keratosis depends on a credible local irritant.

Oral lichen planus may form reticulated, lace-like white lines.

Anatomy and morphology determine the next diagnostic step.

HPV can show koilocytosis; OHL may look koilocyte-like.

Do not assign viral etiology by cell shape alone.

EBV studies should localize to the epithelial lesion.

Slide 49 · Differential diagnosis: Reasoning matrix

Finding

Most supportive possibility

Next distinction

Scrapable white membrane

Thrush

Surface fungus and erythema

Corrugated lateral-tongue plaque

Hairy leukoplakia

EBV and epithelial morphology

Reticular white striae

Lichen planus

Clinical pattern and histology

Unexplained persistent white plaque

Conventional leukoplakia

Exclude other causes; Biopsy

Atypical ulcerated or indurated area

Potential dysplasia/carcinoma

Targeted tissue examination

Slide 50 · Practical approach to a lateral-tongue white plaque

Describe site, contour, distribution and removability.

↓

Review immunosuppressive disease and treatment exposure.

↓

Compare EBV-associated plaque with Candida and other keratoses.

↓

Sample atypical or suspicious lesions; Demonstrate EBV when confirmation is needed.

↓

Integrate pathologic findings with the clinical history.

Slide 51 · How clinical management is framed

Oral hairy leukoplakia itself is often a low-morbidity, asymptomatic lesion.

Recognition may trigger assessment of underlying immune status.

In patients with HIV, effective antiretroviral therapy is part of systemic immune care.

Clinical follow-up addresses persistence, new symptoms or altered morphology.

Slide 52 · Lesion-directed treatment is usually secondary

Mild asymptomatic lesions often need no specific local intervention.

More troublesome lesions may receive clinician-directed treatment.

An antiviral response does not replace evaluation of a suspicious white plaque.

Do not treat presumed OHL empirically when malignancy remains a concern.

Slide 53 · Case 1 — immune context

A person living with HIV has a persistent, corrugated white plaque on the lateral border of the tongue. The plaque does not wipe away.

QUESTION

Which diagnosis best links the site, texture and immune history?

Oral hairy leukoplakia is strongly suggested.

EBV is the implicated agent; Review clinical history and consider confirmation if the appearance is atypical.

Slide 54 · Case 2 — transplant recipient

A patient receiving transplant-associated immunosuppression develops a non-removable white lateral-tongue plaque. HIV infection is not reported.

QUESTION

Does absence of known HIV exclude hairy leukoplakia?

No. HIV infection is not a prerequisite.

Transplant-related immunosuppression is a recognized setting; Evaluate the lesion and clinical context.

Slide 55 · Case 3 — removable white plaque

A white creamy plaque is readily removed, exposing an erythematous mucosal surface.

QUESTION

Which diagnosis is more consistent with this wiping response?

Pseudomembranous oral candidiasis (thrush).

This contrasts with the intrinsically keratotic and non-removable plaque of hairy leukoplakia.

Slide 56 · Case 4 — atypical plaque

An older adult has a persistent irregular white lesion with a focal ulcerated or indurated region on the lateral tongue.

QUESTION

Is pattern recognition alone sufficient to declare hairy leukoplakia?

No: Exclude dysplasia or carcinoma by appropriate assessment.

A possible EBV-associated lesion must not distract from evaluation of an atypical area.

Slide 57 · Integrated interpretation

Lateral non-wipeable plaque

→

Keratosis + ballooned upper cells

→

Lesional EBV demonstration

→

Clinical correlation

The complete diagnosis uses phenotype, histologic pattern and viral evidence.

Candida may be a superimposed modifier rather than the primary explanation.

Slide 58 · Core conclusions

Oral hairy leukoplakia is an EBV-associated, often immunosuppression-linked oral lesion.

The classic lesion is a non-removable, corrugated white plaque of lateral tongue.

Hyperparakeratosis, acanthosis and ballooned upper spinous cells are key findings.

EBV localization supports confirmation; Candidiasis and conventional leukoplakia require distinction.

Slide 59 · Selected sources and image provenance

Robbins, Cotran & Kumar. Pathologic Basis of Disease. 11th ed. 2026; Ch. 16, pp. 666–667.

DermNet. Oral hairy leukoplakia pathology. 2013. dermnetnz.org/topics/oral-hairy-leukoplakia-pathology

NIDCR. HIV/AIDS & Oral Health. Reviewed 2024. nidcr.nih.gov/health-info/hiv-aids

IARC Monographs. Epstein–Barr virus: oral hairy leukoplakia. NCBI Bookshelf NBK385500.

Triantos D, et al. Clin Infect Dis. 1997;25:1392–1396. PMID: 9431384.

CDC PHIL photographs: #6059/#6061 (clinical), #6062/#6063 (H&E), public domain.

Source images were located but could not be embedded; no synthetic clinical specimens were used.