Definition/General
Introduction:
Vulvar lichen sclerosus (LS) is a chronic inflammatory dermatosis of unknown etiology affecting the vulvar and perianal skin
It is characterized by epithelial atrophy and dermal sclerosis
Represents the most common non-neoplastic epithelial disorder of the vulva
Has a bimodal age distribution affecting prepubertal girls and postmenopausal women
Associated with increased risk of vulvar squamous cell carcinoma.
Origin:
Etiology remains largely unknown
Autoimmune component suggested by association with other autoimmune diseases
Genetic predisposition with familial clustering
Hormonal factors may play a role (estrogen deficiency)
Local trauma (Koebner phenomenon) may trigger lesions
Infectious agents have been investigated but not proven causative.
Classification:
Classified as primary idiopathic (most common) or secondary (drug-induced, graft-vs-host disease)
Localized (genital only) vs generalized (extragenital involvement)
Active inflammatory phase vs atrophic/sclerotic phase
May be associated with lichen planus (overlap syndrome)
Complications: scarring, dyspareunia, malignant transformation.
Epidemiology:
Bimodal distribution: prepubertal girls (peak 7-8 years) and postmenopausal women (peak 50-60 years)
Female predominance (F:M = 10:1)
Estimated prevalence 1 in 300-1000 women
Familial clustering in 12-15% cases
Associated with autoimmune diseases (thyroid, vitiligo, alopecia areata)
Malignant transformation risk 5-15%.
Clinical Features
Presentation:
Intense pruritus (cardinal symptom in 85-90%)
White, porcelain-like appearance of vulvar skin
Atrophic changes with loss of architecture
Fissuring and erosions
Purpura and ecchymoses
Introital stenosis
May extend to perianal area (figure-of-eight distribution).
Symptoms:
Severe pruritus (85-90% cases)
Burning and soreness (60-70%)
Dyspareunia (50-60%)
Dysuria
Defecation difficulties (perianal involvement)
Bleeding from fissures
Pain on touch
Sleep disturbance due to itching.
Risk Factors:
Genetic predisposition (HLA associations)
Autoimmune diseases (thyroid disorders, vitiligo)
Estrogen deficiency (postmenopausal state)
Local trauma (tight clothing, irritants)
Family history (12-15% familial)
Fair skin complexion
Northern European ancestry.
Screening:
No specific screening guidelines
Careful inspection during routine gynecological examination
High index of suspicion in at-risk populations
Biopsy confirmation recommended
Annual follow-up due to malignant potential
Photography for monitoring progression
Patient education about symptoms.
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Gross Description
Appearance:
White, porcelain-like patches with well-demarcated borders
Atrophic, wrinkled skin with cigarette paper appearance
Loss of normal architecture (labial fusion)
Fissures and erosions
Purpura and petechiae
Hyperkeratotic areas may be present.
Characteristics:
Figure-of-eight distribution around vulva and anus
Symmetric involvement
Smooth, shiny surface
Loss of elasticity
Introital narrowing
Clitoral burial in severe cases
May show secondary ulceration from scratching.
Size Location:
Variable extent from localized patches to entire vulva and perianal area
Most commonly involves labia majora and minora
Perianal extension in 50-85% cases
Clitoral hood involvement common
May extend to mons pubis and medial thighs.
Multifocality:
Confluent disease pattern typical
Skip areas may be present
Bilateral symmetric involvement characteristic
Extragenital lesions in 6-20% cases (trunk, arms, neck)
Oral involvement rare
Progressive expansion over time.
Microscopic Description
Histological Features:
Epithelial atrophy with loss of rete ridges
Hyperkeratosis and focal parakeratosis
Homogeneous, eosinophilic dermal sclerosis (hyalinization)
Chronic inflammatory infiltrate beneath sclerotic zone
Loss of elastic fibers in upper dermis
Dilated capillaries in papillary dermis.
Cellular Characteristics:
Atrophic squamous epithelium with flattened rete ridges
Basal cell vacuolization
Chronic inflammatory cells (lymphocytes, plasma cells)
Dermal fibroblasts with sclerotic collagen
Melanophages may be present
Minimal mitotic activity.
Architectural Patterns:
Three-zone pattern: hyperkeratosis, atrophic epidermis, homogeneous dermis
Loss of rete ridge pattern
Subepithelial homogenization
Chronic inflammatory band beneath sclerotic zone
Follicular plugging may be present
Absence of elastic fibers (elastin stain).
Grading Criteria:
No standard grading system
Assessment based on degree of epithelial atrophy
Extent of dermal sclerosis
Inflammatory activity
Presence of ulceration
Secondary epithelial changes
Hyperplastic changes (lichen sclerosus with hyperplasia).
Immunohistochemistry
Positive Markers:
p53 (basal layer, wild-type pattern usually)
Ki-67 (low proliferation index in basal layer)
p16 (negative or weak, patchy)
Collagen IV (basement membrane intact)
Laminin (basement membrane)
CD68 (dermal macrophages)
CD3/CD20 (inflammatory infiltrate).
Negative Markers:
High-risk HPV (ISH negative)
p16 (negative or weak in most cases)
CK17 (hyperproliferation marker, negative)
Elastic fibers (elastin stain negative in upper dermis)
Smooth muscle actin (myofibroblasts may be present).
Diagnostic Utility:
Limited utility in typical cases
p53 staining helps identify dysplastic changes
p16 negativity distinguishes from VIN
Elastic stain demonstrates loss of elastic fibers
HPV ISH confirms absence of viral etiology
Basement membrane markers show intact basement membrane.
Molecular Subtypes:
Classic lichen sclerosus: p53 wild-type, p16 negative
LS with atypia: p53 may show abnormal pattern
LS with hyperplasia: increased Ki-67
Overlap with lichen planus: interface dermatitis pattern
Secondary changes: squamous hyperplasia, dysplasia.
Molecular/Genetic
Genetic Mutations:
TP53 mutations (rare in uncomplicated LS)
CDKN2A alterations (p16 locus)
Autoimmune susceptibility genes (HLA associations)
ECM1 gene (extracellular matrix protein 1)
PTPN22 polymorphisms
IRF4 variants
Familial clustering genes under investigation.
Molecular Markers:
HLA class II associations (DQ7, DQ8, DQ9)
Cytokine dysregulation (IL-1, TNF-α, TGF-β)
Matrix metalloproteinase alterations
Collagen metabolism changes
Autoantibodies (ECM1, BP180)
Oxidative stress markers.
Prognostic Significance:
Malignant transformation risk 5-15% (to squamous cell carcinoma)
p53 mutations may precede malignant change
Chronic inflammation promotes progression
Age of onset affects prognosis
Extent of disease correlates with symptoms
Response to treatment variable.
Therapeutic Targets:
Topical corticosteroids: clobetasol propionate (first-line)
Calcineurin inhibitors: tacrolimus, pimecrolimus
Vitamin D analogues
Photodynamic therapy
Platelet-rich plasma
CO2 laser therapy
Immunomodulators under investigation.
Differential Diagnosis
Similar Entities:
Lichen planus
Morphea/localized scleroderma
Vulvar intraepithelial neoplasia
Vitiligo
Post-inflammatory hypopigmentation
Lichen simplex chronicus
Vulvar squamous cell carcinoma
Cicatricial pemphigoid.
Distinguishing Features:
LS: homogeneous dermal sclerosis, epithelial atrophy
LP: interface dermatitis, lichenoid infiltrate
Morphea: deeper sclerosis, normal epidermis
VIN: epithelial atypia, p16 positive
Vitiligo: complete depigmentation, normal histology
SCC: invasive growth, epithelial atypia
Histology essential for diagnosis.
Diagnostic Challenges:
Distinguishing LS with hyperplasia from squamous hyperplasia
LS with atypia vs differentiated VIN
Early/mild LS may lack classic features
Post-treatment changes can obscure morphology
Overlap syndromes (LS-LP)
Secondary infection altering appearance.
Rare Variants:
Bullous lichen sclerosus
Hyperkeratotic variant
Lichen sclerosus with hyperplasia
LS-lichen planus overlap
Extragenital lichen sclerosus
Guttate lichen sclerosus
Linear lichen sclerosus.
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
Vulvar biopsy from [site], measuring [size] cm
Diagnosis
Lichen sclerosus
Classification
Classification: [Primary/Secondary], activity: [Active/Chronic]
Histological Features
Shows [epithelial changes] with [dermal sclerosis] and [inflammatory pattern]
Epithelial Changes
Epithelium shows [atrophy/hyperplasia] with [keratinization pattern]
Dermal Changes
Dermis shows [homogeneous sclerosis] with [inflammatory infiltrate]
Secondary Changes
Secondary changes: [hyperplasia/atypia/ulceration/none]
Inflammatory Activity
Inflammatory activity: [mild/moderate/marked]
Special Studies
Elastic stain: [loss of elastic fibers in upper dermis/not performed]
IHC: [if performed]: [results]
[other study]: [result]
Prognostic Factors
Risk factors: extent of disease, patient age, secondary changes
Final Diagnosis
Lichen sclerosus with [secondary changes if present]