Definition/General
Introduction:
Cutaneous adnexal tumors are diverse group of benign and malignant neoplasms
They show differentiation toward hair follicles, sebaceous glands, or sweat glands
They constitute 1-2% of all skin tumors
They demonstrate complex classification based on differentiation
They range from benign to highly malignant.
Origin:
Arise from pluripotent cells of pilosebaceous unit
Show differentiation toward specific adnexal structures
May originate from hair follicle stem cells
Can arise from eccrine or apocrine gland precursors
Involve dermis and subcutis
Show varying degrees of structural organization.
Classification:
WHO classifies into four main categories
Tumors with follicular differentiation (trichoepithelioma, pilomatrixoma)
Tumors with sebaceous differentiation (sebaceous adenoma, carcinoma)
Tumors with eccrine differentiation (eccrine poroma, carcinoma)
Tumors with apocrine differentiation (hidradenoma, carcinoma)
Mixed differentiation tumors.
Epidemiology:
Wide age range from children to elderly
Equal gender distribution for most types
Some show genetic predisposition
Geographic variation in certain types
Gorlin syndrome associated with multiple trichoepitheliomas
Indian population shows similar patterns with regional variations.
Clinical Features
Presentation:
Papules or nodules of variable size
Skin-colored to yellow (sebaceous types)
Cystic lesions (some follicular types)
Multiple lesions (genetic syndromes)
Facial distribution common
Slow growth pattern typical.
Symptoms:
Usually asymptomatic
Cosmetic concerns (facial lesions)
Occasional tenderness
Discharge (cystic types)
Bleeding (traumatized lesions)
Patients report slowly growing lumps
Family history (genetic cases).
Risk Factors:
Genetic syndromes (Gorlin, Muir-Torre)
Family history
Advanced age
Sun exposure (some types)
Immunosuppression
Previous radiation
Most cases are sporadic.
Screening:
Complete skin examination
Family history assessment
Genetic counseling (multiple lesions)
Biopsy of suspicious lesions
Dermoscopy for characterization
Associated syndrome evaluation.
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Gross Description
Appearance:
Variable morphology based on subtype
Papules to large nodules
Skin-colored to yellow
Cystic or solid consistency
Smooth or lobulated surface
Well-circumscribed margins typical.
Characteristics:
Size varies from few mm to several cm
Follicular tumors: skin-colored, firm
Sebaceous tumors: yellow, soft
Eccrine tumors: translucent, firm
Apocrine tumors: nodular, variable color
Cut surface shows specific features.
Size Location:
Size ranges from 2mm to 5cm
Face most common location (60%)
Scalp (follicular types)
Axilla (apocrine types)
Palms/soles (eccrine types)
Trunk and extremities less common.
Multifocality:
Multiple lesions in genetic syndromes
Gorlin syndrome: numerous trichoepitheliomas
Muir-Torre syndrome: multiple sebaceous tumors
Familial clustering
Bilateral distribution (syndrome cases)
Age-related multiplicity.
Microscopic Description
Histological Features:
Follicular differentiation: keratin cysts, peripheral palisading
Sebaceous differentiation: foamy cells, lipid vacuoles
Eccrine differentiation: ductular structures, clear cells
Apocrine differentiation: decapitation secretion, eosinophilic cytoplasm
Mixed patterns possible.
Cellular Characteristics:
Basaloid cells (follicular)
Sebaceous cells with foamy cytoplasm
Clear cells (eccrine)
Oncocytic cells (apocrine)
Variable nuclear morphology
Differentiation markers helpful
Architecture-specific patterns.
Architectural Patterns:
Nodular or cystic growth patterns
Connection to epidermis (some types)
Ductular formation (glandular types)
Solid nests vs cystic spaces
Stromal reaction variable
Calcification (pilomatrixoma).
Grading Criteria:
Benign: Well-differentiated architecture
Malignant: Loss of differentiation, pleomorphism
Mitotic activity assessment
Necrosis in malignant types
Infiltrative growth pattern
Vascular invasion (malignant).
Immunohistochemistry
Positive Markers:
Follicular markers: CK5/6, p63, CK14
Sebaceous markers: Adipophilin, AR
Eccrine markers: CEA, EMA, CK7
Apocrine markers: GCDFP-15, CK5/6
Myoepithelial markers: p63, SMA
Proliferation markers: Ki-67.
Negative Markers:
Variable based on type
Melanoma markers (usually negative)
Neuroendocrine markers (usually negative)
Muscle markers (except myoepithelial)
Vascular markers (negative)
Specific patterns for differential diagnosis.
Diagnostic Utility:
Differentiation marker panels essential
CK5/6 for follicular differentiation
Adipophilin for sebaceous differentiation
GCDFP-15 for apocrine differentiation
p63 for myoepithelial cells
Useful in challenging cases.
Molecular Subtypes:
PTCH1 mutations (Gorlin syndrome)
MSH2/MLH1 mutations (Muir-Torre)
CYLD mutations (cylindromatosis)
TP53 mutations (malignant types)
PIK3CA mutations (some types)
Wnt pathway alterations.
Molecular/Genetic
Genetic Mutations:
PTCH1 mutations (basal cell nevus syndrome)
MSH2/MLH1/MSH6 mutations (Muir-Torre syndrome)
CYLD mutations (cylindromatosis)
TP53 mutations (malignant transformation)
CTNNB1 mutations (pilomatrixoma)
PIK3CA mutations (subset).
Molecular Markers:
Beta-catenin (pilomatrixoma)
MSH2/MLH1 loss (Muir-Torre)
p53 accumulation (malignant types)
Cyclin D1 overexpression
EGFR expression
Hedgehog pathway activation.
Prognostic Significance:
Syndrome association indicates genetic predisposition
Multiple lesions suggest genetic syndrome
Malignant transformation rare but possible
Size and location affect prognosis
Completeness of excision important.
Therapeutic Targets:
Surgical excision (primary treatment)
Mohs surgery (cosmetically sensitive areas)
Hedgehog pathway inhibitors (vismodegib)
Targeted therapy based on mutations
Radiation therapy (selected cases)
Topical therapies (investigational).
Differential Diagnosis
Similar Entities:
Basal cell carcinoma (follicular differentiation)
Seborrheic keratosis (papillomatous types)
Metastatic adenocarcinoma (glandular types)
Primary cutaneous adenocarcinoma
Eccrine carcinoma vs benign eccrine tumors
Pilomatrixoma vs other cystic lesions.
Distinguishing Features:
Adnexal tumors: Specific differentiation markers
BCC: Peripheral palisading, BerEP4 positive
SK: Horn pseudocysts
Metastatic carcinoma: Clinical history, organ-specific markers
Primary carcinoma: High-grade cytology.
Diagnostic Challenges:
Overlapping morphology between subtypes
Mixed differentiation patterns
Poor differentiation in malignant cases
Small biopsy specimens
Immunohistochemistry panels essential
Clinical correlation important.
Rare Variants:
Syringocystadenoma papilliferum
Chondroid syringoma
Spiradenocylindroma
Microcystic adnexal carcinoma
Adenoid cystic carcinoma
Hidradenocarcinoma
Sebaceous lymphadenocarcinoma.
Sample Pathology Report
Template Format
Sample Pathology Report
Complete Report: This is an example of how the final pathology report should be structured for this condition.
Specimen Information
Excision from [site], measuring [X x Y x Z] cm
Diagnosis
[Specific adnexal tumor name]
Tumor Classification
Type: [follicular/sebaceous/eccrine/apocrine/mixed] differentiation
Biological Behavior
Behavior: [benign/malignant/borderline]
Microscopic Features
Shows [specific architectural pattern] with [differentiation features]
Size and Extent
Size: [X] cm; Extent: [dermal/subcutaneous/deeper]
Margins
Margins: [involved/uninvolved], closest margin [X] mm
Special Studies
IHC: [specific markers]: [results]; [other studies]: [results]
Syndrome Association
Clinical correlation recommended for [genetic syndrome evaluation if applicable]
Final Diagnosis
[Specific adnexal tumor], [behavior], [size] cm