Seborrheic Keratosis

Slide 1 · Seborrheic keratosis

Epidermal neoplasm: pathogenesis, morphology and diagnostic interpretation

Dr Abu Suraih Sakhri

MBBS, MD (Pathology)

www.abusuraihsakhri.com

Slide 2 · Learning outcomes

Distinguish benign epidermal keratinocytic lesions from melanocytic lesions.

Explain the proposed role of activating FGFR3 mutations.

Recognize macroscopic and microscopic features of seborrheic keratosis.

Relate keratin-filled structures to dermoscopic appearances.

Identify diagnostic mimics and interpret eruptive lesions cautiously.

Slide 3 · Epithelial rather than melanocytic

Seborrheic keratosis is an epidermal keratinocytic tumor.

Pigmentation reflects melanin within proliferating basaloid cells.

Dark coloration alone does not establish melanocytic origin.

Cell of origin

Epidermal

Keratinocyte

Melanocyte

Seborrheic keratosis

Melanocytic nevus

Original editable schematic; Not a clinical or histologic specimen

Slide 4 · Why a brown lesion can mislead

Both keratinocytic and melanocytic lesions may be pigmented.

Clinical appearance must be interpreted with surface texture and architecture.

An atypical lesion cannot be declared benign on color alone.

Keratinocyte tumor can contain melanin

Original editable schematic; Not a clinical or histologic specimen

Slide 5 · Definition and biological behavior

A common benign epidermal tumor of keratinocytes.

Usually presents as a discrete plaque or papule on the skin surface.

Growth is typically exophytic and well circumscribed.

Clinical significance is primarily recognition and exclusion of mimics.

Slide 6 · Typical age distribution

Most frequently encountered in middle-aged and older individuals.

Age supports but does not establish the diagnosis.

A new pigmented lesion still requires appropriate morphologic assessment.

Middle-aged

And older adults

Original editable schematic; Not a clinical or histologic specimen

Slide 7 · Usual anatomical distribution

Lesions are especially common on the trunk.

Head and neck may be affected.

Extremities also develop seborrheic keratoses.

Site is contextual evidence, not a definitive criterion.

Trunk → head / neck

→ extremities

Original editable schematic; Not a clinical or histologic specimen

Slide 8 · Single versus multiple lesions

Seborrheic keratoses may be solitary or numerous.

A group of clinically similar plaques can be reassuring but not diagnostic.

Evaluate a morphologically different or changing lesion independently.

Slide 9 · The “stuck-on” clinical impression

A sharply bordered plaque seems attached to the skin surface.

Exophytic architecture provides a histologic correlate.

The impression is a useful clue, not a stand-alone rule-out test for melanoma.

Raised, sharply edged epidermal plaque

Original editable schematic; Not a clinical or histologic specimen

Slide 10 · Shape, contour and borders

Classic lesions are round to oval.

They are generally well demarcated from adjacent skin.

Surface relief can be flat or elevated.

Irregular clinical lesions warrant greater diagnostic caution.

Well-circumscribed clinical outline

Original editable schematic; Not a clinical or histologic specimen

Slide 11 · Waxy, velvety or granular surface

The lesion surface may appear waxy.

Velvety or granular texture is characteristic.

Abundant surface keratin helps explain the texture.

Textured, keratinizing upper surface

Original editable schematic; Not a clinical or histologic specimen

Slide 12 · A broad spectrum of coloration

Typical colors span tan to dark brown.

Variable melanin is present in basaloid tumor cells.

Pigmented seborrheic keratosis can resemble melanocytic lesions.

Variable pigment intensity

Original editable schematic; Not a clinical or histologic specimen

Slide 13 · Dimensions and morphology

Diameter ranges from millimeters to several centimeters.

A larger lesion can remain benign; Size alone does not define malignancy.

Assess the full pattern: Contour, pigment, surface and trajectory.

Slide 14 · Keratin-filled surface ostia

Hand-lens inspection may reveal round, pore-like openings.

Ostia are packed with keratin.

These openings support epidermal keratinization as the source of the surface pattern.

Schematic: Keratin-filled surface pores

Original editable schematic; Not a clinical or histologic specimen

Slide 15 · An integrated bedside description

A circumscribed, tan–brown, waxy plaque with a granular “stuck-on” surface and keratin-filled openings.

This combination is typical of seborrheic keratosis, but atypical lesions require further assessment.

Slide 16 · Dermatosis papulosa nigra

A recognized presentation related to seborrheic keratosis.

Appears as multiple small, dark brown to black facial papules.

Its occurrence in darker-skinned individuals.

Multiple small pigmented papules

Original editable schematic; Not a clinical or histologic specimen

Slide 17 · Why dermatosis papulosa nigra matters

Pigment intensity must be assessed relative to skin phototype.

The combination of numerous small facial lesions forms a recognizable phenotype.

Recognition prevents assuming that every dark facial papule is melanocytic.

Slide 18 · Classical plaque versus DPN

Typical seborrheic keratosis

Dermatosis papulosa nigra

Often trunk; other sites possible

Typically facial distribution

Tan to dark-brown waxy plaque

Small dark-brown to black papules

May be solitary or multiple

Often multiple

Shared benign epidermal lineage

Related clinicopathologic phenotype

Slide 19 · FGFR3 is a receptor tyrosine kinase

Fibroblast growth factor receptor 3 (FGFR3) is a surface signaling receptor.

Activating FGFR3 mutations in many sporadic lesions.

The mutation is implicated in lesion growth rather than used as a routine diagnostic requirement.

FGFR3

Increased growth signaling

Original editable schematic; Not a clinical or histologic specimen

Slide 20 · An activating mutation changes signaling

Activating FGFR3 mutation

Genetic alteration

Increased receptor signaling

Pathway activation

Keratinocyte proliferation

Benign epidermal growth

Causal schematic based on textbook statements; Molecular intermediates are not specified.

Slide 21 · What FGFR3 does—and does not—show

Supported inference

Not established by FGFR3 alone

A growth-promoting driver in many SKs

A required mutation in every SK

A plausible mechanism of epidermal expansion

Malignant behavior

A molecular link with some acanthosis disorders

An indication for molecular testing in routine SK

Slide 22 · Morphology is central to diagnosis

The characteristic lesion is defined by architecture and differentiation.

Histologic recognition does not depend on routine molecular analysis.

Atypical pigmented lesions are evaluated by clinicopathologic correlation.

Slide 23 · From an epidermal clone to a plaque

Expansion of basaloid cells

Epidermal component

Outward / exophytic growth

Raised plaque

Keratinization and pigmentation

Characteristic surface

Causal schematic based on textbook statements; Molecular intermediates are not specified.

Slide 24 · Exophytic growth: Directional concept

The dominant growth is outward from the epidermal plane.

The lesion projects above adjacent skin.

Schematic represents architecture, not a diagnostic photomicrograph.

Exophytic projection

SCHEMATIC — not H&E

Slide 25 · A sharply circumscribed interface

Tumor is relatively well defined versus neighboring epidermis.

Circumscription underlies the visible plaque-like border.

Infiltrative/destructive growth should prompt reassessment.

Sharp lesion–epidermis interface

SCHEMATIC — not H&E

Slide 26 · The basaloid epithelial population

Sheets of small cells resemble basal epidermal keratinocytes.

Uniform basaloid appearance is part of the classic phenotype.

Interpret basaloid cytology within the overall epidermal architecture.

Basaloid cells

Basaloid epithelial expansion

SCHEMATIC — not H&E

Slide 27 · Pigmentation arises in basaloid cells

Variable melanin occurs within the proliferating basaloid cells.

This contributes to tan, brown or black coloration.

Melanin does not convert the lesion into a melanocytic neoplasm.

Melanin in basaloid cells

SCHEMATIC — not H&E

Slide 28 · Hyperkeratosis at the surface

A thickened keratin layer overlies the epidermal growth.

Surface keratin contributes to a rough, waxy or granular appearance.

Keratin may also accumulate within epithelial pockets.

Surface hyperkeratosis

SCHEMATIC — not H&E

Slide 29 · Horn cysts are keratin-filled spaces

Intraepidermal round spaces are packed with keratin.

They are characteristic of the lesion.

The lining is part of the epidermal epithelial proliferation.

Intraepidermal horn cysts

SCHEMATIC — not H&E

Slide 30 · Invagination cysts communicate with the surface

Surface epidermis may fold inward into the tumor.

Keratin accumulates in the invaginated space.

On section these appear as pseudohorn / invagination cysts.

Surface-connected invagination

SCHEMATIC — not H&E

Slide 31 · Horn cyst versus pseudohorn cyst

True horn cyst

Pseudohorn / invagination cyst

Closed keratin-containing intraepidermal space

Keratin-containing invagination

No direct surface continuity in the section

Connection to surface may be demonstrable

May correspond to white-yellow dermoscopic dots

May correspond to dark comedo-like openings

Slide 32 · Where the horn structures form

Horn cysts lie within basaloid epidermal proliferation.

Pseudohorn cysts are surface-connected invaginations.

Distribution and size vary across a lesion.

Two keratin-filled architectures

SCHEMATIC — not H&E

Slide 33 · A low-power histologic checklist

Exophytic and sharply demarcated epidermal proliferation.

Small basaloid cells within the expanded epidermis.

Surface hyperkeratosis.

Keratin-filled horn cysts and surface invaginations.

Variable melanin pigmentation.

Slide 34 · From low power to high power

Low power

Outline + exophytic architecture

Intermediate power

Basaloid epithelial sheets + keratin pools

High power

Keratin cysts + cellular differentiation

Causal schematic based on textbook statements; Molecular intermediates are not specified.

Slide 35 · Irritation changes the histologic picture

An irritated lesion may become inflamed.

Reactive squamous differentiation can become more prominent.

Interpret changes alongside residual classic seborrheic keratosis architecture.

Slide 36 · Squamous eddies in irritated lesions

Whirling foci of squamous differentiation can develop.

The pattern to eddy currents.

Squamous eddies should not be equated automatically with invasion.

Squamous eddy pattern

SCHEMATIC — not H&E

Slide 37 · Inflammation can obscure recognition

Clinical erythema or irritation may alter the usual waxy appearance.

Histologic squamous maturation may dominate a portion of the section.

Sampling and morphology determine whether an alternative diagnosis must be excluded.

Atypical pattern ≠

Benign diagnosis

Original editable schematic; Not a clinical or histologic specimen

Slide 38 · Clinical finding and histologic counterpart

Clinical / dermoscopic observation

Principal morphologic correlate

Stuck-on, raised border

Exophytic sharply demarcated lesion

Waxy, granular surface

Hyperkeratosis and surface relief

Brown to black pigmentation

Melanin in basaloid cells

Keratin plugs / openings

Invagination / pseudohorn cysts

White–yellow cyst-like structures

Intraepidermal keratin-filled cysts

Slide 39 · Dermoscopy: Comedo-like openings

Dark round or irregular crypts are common clues.

These correlate with keratin-filled surface connections.

They are supportive, not pathognomonic.

Schematic: Keratin-filled surface pores

Original editable schematic; Not a clinical or histologic specimen

Slide 40 · Dermoscopy: Milia-like cysts

White or yellow clods may reflect intraepidermal keratin.

Histologic horn cysts explain this appearance.

The finding alone cannot exclude melanoma or other tumors.

Schematic: Keratin-filled intraepidermal spaces

Original editable schematic; Not a clinical or histologic specimen

Slide 41 · Dermoscopy: Fissures and ridges

Fissures separate raised ridges of the epidermal surface.

A cerebriform pattern may result.

These observations complement the clinical stuck-on appearance.

Schematic: Fissures alternating with ridges

Original editable schematic; Not a clinical or histologic specimen

Slide 42 · Why dermoscopic clues are not absolute

Seborrheic keratosis can show asymmetry and multiple colors.

Melanoma and basal cell carcinoma occasionally share isolated SK-like structures.

Discordant evolution or atypical findings warrant definitive evaluation.

Slide 43 · Differential: Pigmented melanoma

Favored seborrheic keratosis

Findings that require melanoma assessment

Waxy, surface-keratin pattern

Changing shape, color or size

Well-defined exophytic lesion

Irregular contour and variegated pigmentation

Horn / pseudohorn cyst morphology

Melanocytic atypia or malignant architecture on histology

Slide 44 · Differential: Actinic keratosis

Seborrheic keratosis

Actinic keratosis

Common waxy plaque; variable sites

Rough sandpaper lesion at sun-exposed sites

Basaloid cells and horn cysts

Basal keratinocyte cytologic atypia

Benign epidermal neoplasm

May progress toward squamous cell carcinoma

Slide 45 · Differential: Pigmented basal cell carcinoma

Seborrheic keratosis

Basal cell carcinoma

Surface-based, keratinizing basaloid proliferation

Locally invasive carcinoma

Keratin-filled cysts favor SK

Dermal tumor nests with characteristic BCC architecture

No characteristic invasive growth

Hedgehog signaling pathway is implicated

Slide 46 · Differential: Acanthosis nigricans

Seborrheic keratosis

Acanthosis nigricans

Discrete plaques / papules

Diffuse velvety thickening, especially flexures

Horn cysts and basaloid growth

Undulating epidermis + enlarged dermal papillae

May be sporadic with FGFR3 mutation

Often associated with metabolic/endocrine disorders

Slide 47 · A practical differential framework

Ask first whether the lesion is an epidermal plaque, a melanocytic lesion, or invasive tumor.

Seek supporting keratinization features without over-relying on them.

Use histology when the clinical–dermoscopic pattern is atypical.

Clinical

Morphology

Dermoscopy

Pattern

Histology

When indicated

Original editable schematic; Not a clinical or histologic specimen

Slide 48 · When histologic assessment becomes important

Unusual pigmentation, shape or surface morphology.

Changes that are not typical of established benign lesions.

Concern for melanoma, basal cell carcinoma or squamous neoplasia.

Clinical findings inconsistent with a straightforward diagnosis.

Slide 49 · Leser–Trélat: Abrupt eruption of lesions

A sudden appearance of numerous seborrheic keratoses has been described as the Leser–Trélat sign.

An association with internal malignancy.

The historical paraneoplastic interpretation remains debated.

Conceptual: Abrupt multiplicity

Original editable schematic; Not a clinical or histologic specimen

Slide 50 · Proposed growth-factor mechanism

Some internal carcinomas

Reported context

Proposed tumor-derived TGF-α

Hypothesis—not established universally

Keratinocyte growth stimulation

Possible eruptive SKs

Proposed mechanism: The TGF-α link is hypothetical, not universal.

Slide 51 · The cancer association is not deterministic

Gastrointestinal carcinomas among associated tumors.

Seborrheic keratoses are independently common in older adults.

Coincidence and selection bias complicate causal interpretation.

An abrupt eruption is a clinical cue, not a cancer diagnosis.

Slide 52 · Leser–Trélat and diagnostic restraint

Obtain a careful history and examination when lesions erupt abruptly.

Assess accompanying systemic or cutaneous findings in context.

Avoid representing TGF-α mediation as proven for all cases.

Atypical pattern ≠

Benign diagnosis

Original editable schematic; Not a clinical or histologic specimen

Slide 53 · Acanthosis nigricans in the same context

Presents as thickened, hyperpigmented, velvety flexural skin.

Many cases associate with obesity, insulin resistance or endocrine causes.

A minority occur as a paraneoplastic phenomenon.

Flexural skin:

Neck, axillae, groin

Original editable schematic; Not a clinical or histologic specimen

Slide 54 · Histology of acanthosis nigricans

Acanthosis nigricans

Seborrheic keratosis

Papillary undulation forming peaks and valleys

Exophytic sharply defined epidermal tumor

Hyperkeratosis ± epidermal hyperplasia

Basaloid expansion + horn cysts

Basal pigmentation without melanocytic hyperplasia

Variable melanin in basaloid cells

Slide 55 · A shared receptor does not mean one disease

FGFR3 activation is described in many sporadic seborrheic keratoses.

Familial acanthosis nigricans may involve germline FGFR3 mutations.

Differing phenotypes are not fully explained.

Tissue architecture and clinical setting remain essential.

Slide 56 · Case 1: A waxy trunk plaque

Constructed teaching vignette

A 68-year-old has a long-standing oval, sharply bordered brown plaque on the back. The surface appears waxy, granular and “stuck on.”

Diagnostic question

Which clinical features most favor seborrheic keratosis?

Interpretation

Combination of well-defined raised plaque, waxy/granular surface and keratin-related surface openings; Inspect for atypical features.

Slide 57 · Case 2: The epidermal biopsy pattern

Constructed teaching vignette

Biopsy shows an exophytic circumscribed proliferation of small basaloid epithelial cells, hyperkeratosis, and multiple keratin-filled cysts.

Diagnostic question

Which structures carry the most diagnostic weight?

Interpretation

Horn cysts and surface-connected keratin invaginations within a characteristic basaloid, exophytic proliferation.

Slide 58 · Case 3: Numerous dark facial papules

Constructed teaching vignette

An older adult with deeply pigmented skin has many small dark-brown to black facial papules of similar morphology.

Diagnostic question

Which seborrheic keratosis phenotype should be considered?

Interpretation

Dermatosis papulosa nigra. Evaluate lesions that differ from the common pattern on their own merits.

Slide 59 · Case 4: A change that breaks the pattern

Constructed teaching vignette

A patient with several stable waxy plaques develops one lesion with a distinctly changing outline and heterogeneous pigmentation.

Diagnostic question

Should the new lesion be assumed to be another seborrheic keratosis?

Interpretation

No. Pigmented malignancy remains a differential; Clinical examination, dermoscopy and biopsy when indicated are appropriate.

Slide 60 · Case 5: Sudden widespread eruption

Constructed teaching vignette

A patient reports rapid appearance of many clinically similar keratoses over a short interval.

Diagnostic question

How should the potential Leser–Trélat association be communicated?

Interpretation

An eruptive pattern has been reported with internal tumors, but the causal association is debated; Clinical context guides evaluation.

Slide 61 · Synthesis: Diagnostic reasoning

SK is a benign epidermal tumor whose macroscopic “stuck-on” morphology mirrors an exophytic basaloid proliferation with surface keratinization and horn cysts.

Recognize classic morphology, but do not use one benign feature to dismiss an atypical lesion.

Slide 62 · References and image policy

Robbins, Cotran & Kumar. Pathologic Basis of Disease. 11th ed. 2026. Chapter 25, pp. 1036–1037 and adjacent skin-lesion sections.

DermNet. Dermoscopy of seborrhoeic keratosis; Sign of Leser–Trélat.

Minagawa A. Dermoscopy–pathology relationship in seborrheic keratosis. J Dermatol. 2017;44:518–524. doi:10.1111/1346-8138.13657

All histologic/clinical-looking drawings in this lecture are original editable schematics—not patient photographs or tissue micrographs.