Adnexal Appendage Tumors

Slide 1 · Adnexal (Appendage)

Tumors

Skin appendage differentiation, morphology and syndromic associations

Dr Abu Suraih Sakhri

MBBS, MD (Pathology)

www.abusuraihsakhri.com

Slide 2 · Learning objectives

Classify adnexal neoplasms by follicular, sebaceous, eccrine and apocrine differentiation.

Recognize the morphologic patterns emphasized.

Connect characteristic tumors with CYLD, CTNNB1, PTEN and mismatch-repair pathways.

Identify malignancy-related warnings and the differential with metastatic adenocarcinoma.

Slide 3 · Adnexal neoplasms show appendage differentiation

Definition

Tumors arising from, or differentiating toward, cutaneous appendages.

Spectrum

Hundreds of distinct entities; Clinical significance varies with context.

Biologic behavior

Most are benign, but malignant forms are documented.

The line of differentiation is the first organizing question.

Slide 4 · Four lineages organize the field

Hair follicle

Trichoepithelioma

Pilomatricoma

Sebaceous

Sebaceous adenoma

Sebaceous carcinoma

Eccrine

Poroma

Syringoma

Apocrine

Apocrine-differentiated neoplasms

Apocrine carcinoma

Slide 5 · Skin appendages: A common anatomic framework

Epidermis

Follicular unit

Sebaceous lobules

Eccrine duct / coil

Apocrine differentiation

Schematic — not histologic evidence

Slide 6 · Differentiation is not identical to anatomic origin

Observe tumor

Clinical lesion / biopsy

Characterize

Follicular, sebaceous, eccrine, apocrine features

Interpret

Type, behavior and clinical context

“arising from or showing differentiation toward” skin appendages.

Slide 7 · Most adnexal lesions are clinically nonspecific

Often present as solitary or multiple flesh-colored papules or nodules.

Surface appearance alone usually does not establish the exact lineage.

Characteristic sites may support, but do not replace, morphologic interpretation.

Multiplicity can change the clinical significance of an otherwise benign lesion.

Slide 8 · Site clues are useful—not definitive

Location / pattern

Illustrative entity

Interpretive value

Palms or soles

Eccrine poroma

Predominant distribution

Lower eyelids

Syringoma

Multiple small tan papules

Forehead / scalp

Cylindroma

Nodules may coalesce

Perinasal region

Trichoepithelioma

Multiple papules / small nodules

Apocrine-rich sites

Apocrine tumors

Especially axilla and scalp

Slide 9 · Multiplicity prompts a syndromic assessment

Multiple lesions

Age, distribution, family history

Identify tumor type

Morphologic differentiation

Look for association

CYLD, PTEN, MMR syndromes when indicated

A benign-appearing appendage tumor may serve as a marker of inherited disease.

Slide 10 · Benign and malignant categories coexist

Most appendage tumors

Malignant appendage tumors

Often benign and limited to skin.

May simulate cutaneous malignancy.

May carry syndromic significance.

Can follow an aggressive course.

Can show gland-like architecture.

May resemble a metastasis.

Slide 11 · Diagnostic reasoning must integrate three axes

Clinical

Site

Number of lesions

Family history

Architectural

Nests, lobules, ducts, primitive follicles, secretory features

Biologic

Benign or malignant

Germline association

Metastatic mimic

No single axis is adequate for the entire adnexal tumor spectrum.

Slide 12 · Keep distinct categories distinct

Appendage tumor

Common look-alike in the chapter

Key distinction

Adnexal neoplasm

Epidermal tumor

Appendage-directed differentiation

Follicular inclusion cyst

Solid appendage tumor

Cystic cavity with keratin, not merely basaloid nests

Adnexal carcinoma

Metastatic adenocarcinoma

Clinical correlation needed if gland-forming

The chapter places these categories close together; They are not interchangeable.

Slide 13 · Eccrine differentiation: The ductal concept

Epidermis

Follicular unit

Sebaceous lobules

Eccrine duct / coil

Apocrine differentiation

Schematic — not histologic evidence

Slide 14 · Eccrine poroma: Characteristic distribution

Type

An adnexal tumor with eccrine differentiation.

Favored sites

Palms and soles are predominant sites.

Diagnostic principle

Site helps suggest a lineage but does not establish it.

Slide 15 · Poroma: Use clinicomorphologic correlation

Observe

Palmar / plantar skin nodule

Consider

Eccrine poroma among possible causes

Confirm

Biopsy architecture and sweat duct differentiation

The provided Robbins excerpt does not give formal microscopic criteria for poroma.

Slide 16 · Syringoma: A recognizable clinical pattern

Morphologic lineage

Eccrine differentiation.

Usual appearance

Multiple small, tan papules.

Usual location

Near the lower eyelids.

Syrinx means “pipe” or “tube,” pointing to the ductal theme.

Slide 17 · Syringoma: Understand the ductal analogy

How to read the schematic

Tubular / duct-like differentiation

Multiple small superficial papules clinically

Exact microscopic criteria are not reproduced from this excerpt

Schematic, not photomicrograph

Slide 18 · Poroma versus syringoma: High-yield distinction

Feature

Poroma

Syringoma

Lineage

Eccrine

Eccrine

Typical site

Palms / soles

Near lower eyelids

Clinical form in excerpt

Not specifically characterized

Multiple small tan papules

Interpretive cue

Anatomic distribution

Distribution + ductal naming

Slide 19 · Cylindroma: Clinicopathologic identity

Differentiation

Apocrine or eccrine appendage differentiation.

Typical sites

Forehead and scalp.

Characteristic pattern

Basaloid nests arranged in a jigsaw-puzzle architecture.

Slide 20 · Cylindroma: Jigsaw-puzzle architecture

Morphologic architecture schematic — not a micrograph

Architectural recognition

Islands of basaloid cells

Interlocking “jigsaw” arrangement

Fibrous dermal matrix

Slide 21 · Cylindroma: Why the architecture matters

Small basaloid cells

Cellular resemblance to basal epithelial populations

Tumor islands

Discrete nests within dermis

Pattern

Islands interfit like puzzle pieces

Describe the architecture, not just the presence of basaloid cells.

Slide 22 · Multiple scalp cylindromas can become confluent

Early lesions

Multiple nodules on scalp or forehead.

Over time

Nodules may coalesce into a hat-like mass.

Traditional term

“Turban tumor” describes this growth pattern.

Slide 23 · Familial cylindromatosis is an inherited syndrome

Familial susceptibility may be inherited as an autosomal dominant trait.

Tumors may appear early in life.

Germline inactivating variants in CYLD are implicated.

Related tumors can include trichoepitheliomas and spiradenomas.

Slide 24 · CYLD restrains NF-κB signaling

CYLD

Tumor suppressor

Deubiquitinating enzyme

Normal role

Negative regulator of NF-κB activity

Loss of function

Removes a negative regulator of oncogenic signaling

This is the mechanistic relationship; Not a complete signaling pathway.

Slide 25 · CYLD-associated tumors share inherited context

Cylindroma

Characteristic basaloid jigsaw-pattern tumor.

Trichoepithelioma

Benign follicular-differentiated lesion.

Spiradenoma

An additional appendage tumor reported in some CYLD families.

Tumor combinations can be more informative than any single papule.

Slide 26 · Trichoepithelioma: Presentation and lineage

Lineage

Follicular differentiation.

Clinical clue

Perinasal papules or small nodules.

Architecture

Basaloid buds that resemble primitive hair follicles.

Slide 27 · Trichoepithelioma: Primitive follicular buds

Morphologic architecture schematic — not a micrograph

What the buds represent

Basaloid epithelial proliferation

Primitive hair follicle-like units

Follicular differentiation is the key interpretation

Slide 28 · Two basaloid lesions, different architecture

Cylindroma

Trichoepithelioma

Basaloid tumor islands.

Interlocking jigsaw configuration.

Eccrine / apocrine differentiation.

Basaloid buds.

Primitive follicular structures.

Hair-follicle differentiation.

Slide 29 · Follicular differentiation has several patterns

Entity

Follicular feature

Associated molecular / clinical clue

Trichoepithelioma

Primitive follicular buds

Can accompany CYLD-associated tumors

Pilomatricoma

Hair-matrix / anagen-type differentiation

Activating CTNNB1 variants

Trichilemmoma

Hair-related epithelial tumor

Multiplicity may indicate Cowden syndrome

Slide 30 · Pilomatricoma differentiates toward hair matrix

Tumor identity

A hair follicle-differentiated neoplasm.

Cellular pattern

Basaloid cells with hair-matrix-like maturation.

Molecular association

Activating CTNNB1 variants.

Slide 31 · Pilomatricoma: Basaloid cells to shadow cells

Morphologic architecture schematic — not a micrograph

Cellular maturation

Dark basaloid matrix-like cells

Transition toward anucleate “ghost” cells

Ghost cells indicate hair-type keratinization

Slide 32 · Ghost cells are a differentiation clue

Basaloid cells

Primitive hair-matrix-like population

Maturation

Hair-type keratinizing transition

Ghost cells

Anucleate, cell-outline-preserving elements

The Robbins figure caption specifically notes anucleate ghost cells.

Slide 33 · CTNNB1 encodes β-catenin

Gene

CTNNB1

Protein

β-catenin

Association

Activating mutation in pilomatricoma

Use precise gene/protein nomenclature: CTNNB1 ≠ β-catenin.

Slide 34 · Wnt–β-catenin signaling and hair biology

Wnt signaling

Pathway linked to hair development

β-catenin

Critical pathway mediator

Hair differentiation

Early development, growth and maintenance

CTNNB1 activation with the cell lineage of pilomatricoma.

Slide 35 · Architecture and molecular biology converge

What histology demonstrates

What molecular association suggests

Hair matrix-like basaloid cells.

Shadow / ghost cell maturation.

Follicular identity.

Activating CTNNB1 variants.

β-catenin involvement.

Biologic continuity with hair-development signaling.

Slide 36 · Sebaceous differentiation: Cellular concept

Epidermis

Follicular unit

Sebaceous lobules

Eccrine duct / coil

Apocrine differentiation

Schematic — not histologic evidence

Slide 37 · Sebaceous adenoma: Lobular architecture

Growth pattern

Lobular proliferation of sebocytes.

Periphery

An expanded basaloid population.

Center

More mature sebocytes with pale, foamy cytoplasm.

Slide 38 · Sebaceous adenoma: Lobules and maturation

Morphologic architecture schematic — not a micrograph

Read from rim to center

Peripheral basaloid cells

Maturing lipid-rich sebocytes

Frothy cytoplasm reflects lipid vesicles

Slide 39 · Foamy cytoplasm reflects lipid-rich sebocytes

Sebaceous lineage

Sebocytes undergo maturation

Lipid vesicles

Cytoplasmic lipid accumulation

Histologic appearance

Frothy / bubbly cytoplasm

The cytoplasmic appearance is a mechanistically interpretable finding.

Slide 40 · Sebaceous adenoma can be a syndrome marker

Lesion

Sebaceous adenoma

Clinical context

Association with internal malignancy in Muir–Torre syndrome

Broader linkage

Some cases are associated with Lynch syndrome / DNA mismatch repair defects

Slide 41 · Mismatch-repair defects underlie Lynch syndrome

Germline defect

DNA mismatch-repair gene

Inherited syndrome

Lynch syndrome

Cutaneous clue

A sebaceous neoplasm may raise Muir–Torre suspicion

This is a syndrome association, not a claim that every sebaceous adenoma is hereditary.

Slide 42 · Muir–Torre and Lynch: Related clinical contexts

Muir–Torre syndrome

Lynch syndrome

Sebaceous tumors are a dermatologic clue.

Association with internal malignancy.

Clinical evaluation goes beyond the skin lesion.

Heritable mismatch-repair pathway defects.

A subset of sebaceous tumor cases is associated.

Cutaneous findings may suggest inherited predisposition.

Slide 43 · When sebaceous histology changes the history

Diagnose lesion

Sebaceous differentiation on biopsy

Integrate context

Multiplicity, personal and family cancer history

Consider syndrome

Muir–Torre / Lynch assessment when appropriate

A teaching reasoning pathway; Not a formal genetic-testing guideline.

Slide 44 · Multiple trichilemmomas are associated with Cowden syndrome

Skin finding

Multiple trichilemmomas.

Germline association

Inactivating PTEN tumor-suppressor variants.

Clinical risk context

Increased risk of breast, endometrial and other malignancies.

Slide 45 · PTEN-associated lesions signal broader disease

Skin phenotype

Multiple trichilemmomas

Inherited context

Cowden syndrome / PTEN dysfunction

Clinical consequence

Consider associated cancer predisposition

The skin lesion may be small; Its inherited significance may be substantial.

Slide 46 · Three syndromic patterns not to confuse

Clinical clue

Associated gene / pathway

Named syndrome

Multiple cylindromas ± trichoepitheliomas / spiradenomas

CYLD / NF-κB regulation

Familial cylindromatosis

Multiple trichilemmomas

PTEN

Cowden syndrome

Sebaceous adenoma in appropriate clinical setting

Mismatch repair

Muir–Torre / Lynch association

Slide 47 · Apocrine differentiation has a distinct distribution

Typical sites

Regions rich in apocrine glands.

Examples

Axilla and scalp are highlighted.

Behavior

Malignant apocrine tumors are emphasized.

Slide 48 · Apocrine carcinoma: Ductal architecture

Lineage

Apocrine gland differentiation.

Histology

Ductal differentiation.

Secretory evidence

Decapitation secretion with luminal material.

Slide 49 · Decapitation secretion: An apocrine clue

Morphologic architecture schematic — not a micrograph

How to interpret

Lining cells form a ductal lumen

Apical cytoplasmic secretion enters lumen

Apocrine-type secretory differentiation

Slide 50 · Malignant apocrine tumors require caution

Most adnexal tumors overall are benign.

An unusual predominance of malignant over benign forms among apocrine tumors.

Primary eccrine and apocrine carcinomas may form gland-like structures.

Gland formation creates a differential with metastatic adenocarcinoma.

Slide 51 · Primary adnexal carcinoma versus metastasis

Primary eccrine / apocrine carcinoma

Metastatic adenocarcinoma

Cutaneous adnexal differentiation.

Gland-like architecture possible.

Anatomic and skin-pathology context essential.

Can also produce glandular structures.

May resemble a cutaneous gland-forming tumor.

History and clinicopathologic evaluation are decisive.

Slide 52 · Sebaceous carcinoma: Meibomian gland association

Anatomic origin highlighted

Meibomian glands in the eyelid.

Potential clinical behavior

Can pursue an aggressive course.

Major consequence

Systemic metastases may occur.

Slide 53 · Sebaceous adenoma and carcinoma are not equivalent

Dimension

Sebaceous adenoma

Sebaceous carcinoma

Biologic behavior

Benign appendage neoplasm

Malignant neoplasm

Source emphasis

Lobular sebocyte maturation

Eyelid / meibomian gland association

Clinical significance

Muir–Torre / Lynch clue in a subset

Potential aggressive course with metastases

Diagnostic question

Is syndrome evaluation warranted?

Is this a primary sebaceous malignancy?

Slide 54 · Histologic patterns to recognize together

Entity

Source-described architecture

Cylindroma

Basaloid islands arranged like jigsaw pieces

Trichoepithelioma

Basaloid buds resembling primitive hair follicles

Pilomatricoma

Hair-matrix-like basaloid cells and ghost cells

Sebaceous adenoma

Basaloid rim and foamy, mature sebocytes

Apocrine carcinoma

Ducts with decapitation secretion

Slide 55 · A disciplined classification pathway

Read architecture

Follicles / sebocytes / ducts / secretory cells

Assign lineage

Follicular / sebaceous / eccrine / apocrine

Assess significance

Behavior, multiplicity, syndromic or metastatic context

This is a teaching framework, not a substitute for full diagnostic criteria.

Slide 56 · Case: Multiple periocular papules

Clinical vignette

A patient has numerous small tan papules near the lower eyelids.

No features of aggression are specified in the vignette.

What lesion is favored?

Syringoma. Clinical pattern and eccrine ductal differentiation fit the source description.

Hypothetical teaching case

Slide 57 · Case: Scalp nodules coalescing

Clinical vignette

A young person develops multiple scalp and forehead nodules.

Several lesions merge; Relatives have similar nodules.

What syndrome axis?

Familial cylindromatosis; Consider CYLD-associated adnexal tumor predisposition.

Hypothetical teaching case

Slide 58 · Case: Matrix-like cells and ghost cells

Clinical vignette

A skin nodule shows basaloid cells resembling immature hair matrix.

Adjacent elements are anucleate “ghost” cells.

Most likely lesion?

Pilomatricoma. CTNNB1 / β-catenin is the source-described molecular association.

Hypothetical teaching case

Slide 59 · Case: A sebaceous adenoma with a cancer history

Clinical vignette

A skin biopsy shows a lobulated sebaceous adenoma.

The history suggests internal malignancy in family members.

What association matters?

Muir–Torre / Lynch; Consider inherited mismatch-repair context with appropriate clinical evaluation.

Hypothetical teaching case

Slide 60 · Case: A malignant eyelid tumor

Clinical vignette

A malignant epithelial lesion arises near eyelid meibomian glands.

Pathology establishes sebaceous differentiation.

Why is this consequential?

Sebaceous carcinoma can behave aggressively and produce systemic metastases.

Hypothetical teaching case

Slide 61 · Case: A dermal gland-forming carcinoma

Clinical vignette

A cutaneous malignant tumor forms gland-like structures.

The architecture suggests eccrine or apocrine differentiation.

Critical differential?

Metastatic adenocarcinoma. The source emphasizes their potential morphologic confusion.

Hypothetical teaching case

Slide 62 · Integrated tumor–morphology–syndrome map

Entity

Dominant pattern

Association / caution

Cylindroma

Basaloid jigsaw islands

CYLD-associated familial disease

Trichoepithelioma

Primitive follicular buds

May accompany CYLD-associated lesions

Pilomatricoma

Hair matrix + ghost cells

Activating CTNNB1

Sebaceous adenoma

Lobular sebocytes

Muir–Torre / Lynch association

Trichilemmoma

Follicular differentiation

PTEN / Cowden when multiple

Apocrine carcinoma

Ducts, decapitation secretion

Gland-forming metastatic mimic

Slide 63 · Central lessons of adnexal tumor pathology

Adnexal tumors are classified by appendage differentiation, not merely by surface appearance.

Architectures worth recognizing: Jigsaw islands, primitive follicular buds, ghost cells, sebocytes and secretory ducts.

Multiple or unusual tumors may be outward clues to inherited cancer predisposition.

Gland-forming cutaneous malignancies require distinction from metastatic adenocarcinoma.

Slide 64 · Primary sources and image limitations

Robbins, Cotran & Kumar. Pathologic Basis of Disease. 11th ed. (2026). Chapter 25, “The Skin,” pp. 1038–1039.

Textbook Figures 25.10–25.11: cylindroma, trichoepithelioma and diverse adnexal tumors (captions consulted).

Images in this lecture are original editable schematics. They are not representative clinical cases or H&E images.

Original chapter PDF and reuse-cleared histology images were not provided for direct figure verification.