Definition/General
Introduction:
Vulvar basal cell carcinoma is a rare malignant neoplasm of the vulva, accounting for 2-3% of all vulvar cancers
It arises from the basal cells of the vulvar epidermis or hair follicles
The tumor demonstrates locally invasive growth pattern with minimal metastatic potential
It shares morphological features with cutaneous basal cell carcinoma but occurs in genital skin.
Origin:
Originates from the basal layer of the stratified squamous epithelium of vulvar skin
Arises from hair follicle epithelium or sebaceous glands
Most commonly develops in hair-bearing areas of the vulva
The tumor shows continuity with surface epithelium or adnexal structures
UV radiation exposure is less relevant compared to cutaneous BCC.
Classification:
WHO classification recognizes several subtypes: Nodular basal cell carcinoma (most common)
Superficial basal cell carcinoma
Morpheaform (sclerosing) basal cell carcinoma
Infiltrative basal cell carcinoma
Micronodular basal cell carcinoma
Mixed subtypes are common
Basosquamous carcinoma (rare aggressive variant).
Epidemiology:
Peak incidence in 6th-7th decades of life
Postmenopausal women predominantly affected
Accounts for 2-3% of vulvar malignancies
Risk factors include fair skin
Chronic UV exposure
Previous radiation therapy
Immunosuppression
Genetic predisposition (basal cell nevus syndrome)
Rare before menopause.
Clinical Features
Presentation:
Slowly growing vulvar nodule (most common presentation)
Pearly or waxy appearance with telangiectatic vessels
Central ulceration with raised, rolled borders
Pigmented lesions (rare variant)
Multiple lesions possible
Asymptomatic in early stages
Location: labia majora most common.
Symptoms:
Usually asymptomatic in early stages
Vulvar itching (mild, intermittent)
Bleeding from ulcerated surface
Local irritation or discomfort
Cosmetic concerns
Secondary bacterial infection of ulcerated lesions
No systemic symptoms (unlike advanced squamous cell carcinoma).
Risk Factors:
Advanced age (>60 years)
Fair skin complexion (Fitzpatrick types I-II)
Chronic sun exposure (less relevant than cutaneous BCC)
Previous radiation therapy
Immunosuppression
Basal cell nevus syndrome (Gorlin syndrome)
Genetic mutations (PTCH1, SMO genes)
Arsenic exposure (rare).
Screening:
No specific screening recommendations
Regular gynecological examination important
Self-examination of vulvar area
Prompt evaluation of persistent vulvar lesions
Dermatological consultation for suspicious skin lesions
Biopsy of all suspicious nodules
Family history screening for Gorlin syndrome.
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Gross Description
Appearance:
Well-demarcated nodular lesion with smooth surface
Pearly or translucent appearance
Telangiectatic vessels on surface
Central depression or ulceration with rolled borders
Flesh-colored to pink coloration
Firm consistency
Size ranges from few millimeters to several centimeters.
Characteristics:
Dome-shaped or papular configuration
Smooth, shiny surface
Well-circumscribed borders
Absence of keratinization (unlike squamous cell carcinoma)
Cystic areas may be present
Pigmentation rarely seen
Secondary ulceration in larger lesions.
Size Location:
Labia majora (most common site - 80%)
Mons pubis (15%)
Labia minora (rare - 5%)
Size typically <2 cm at presentation
Single lesion in 90% cases
Multiple lesions suggest genetic syndrome
Bilateral involvement extremely rare.
Microscopic Description
Histological Features:
Basaloid cells arranged in nests, cords, and sheets
Peripheral palisading of nuclei characteristic feature
Retraction artifact around tumor nests
Central necrosis in larger nests
Mucin deposition in stroma
Lymphocytic infiltrate around tumor
Connection to surface epithelium or hair follicles.
Cellular Characteristics:
Small basophilic cells with scant cytoplasm
Oval to elongated nuclei
Hyperchromatic nuclei with fine chromatin
High nuclear-to-cytoplasmic ratio
Minimal pleomorphism
Low mitotic rate
Peripheral palisading of nuclei in tumor nests
Central cells loosely arranged.
Architectural Patterns:
Nodular type: Large nodular aggregates with peripheral palisading
Superficial type: Multifocal buds extending from epidermis
Morpheaform type: Thin strands in sclerotic stroma
Infiltrative type: Irregular cords and nests
Micronodular type: Small, well-defined nodules
Basosquamous type: Focal squamous differentiation.
Immunohistochemistry
Positive Markers:
BerEP4 (epithelial membrane antigen - highly specific)
CK5/6 (high molecular weight cytokeratins)
CK14 (basal cell marker)
p63 (nuclear positivity in basal cells)
BCL-2 (anti-apoptotic protein)
CD10 (myoepithelial marker)
Androgen receptor (variable positivity).
Negative Markers:
CK7 (negative, helps exclude adenocarcinoma)
CK20 (negative in basal cell carcinoma)
EMA (usually negative)
CEA (negative)
S-100 (negative, excludes melanoma)
Melanoma markers (Melan-A, HMB-45 negative)
High molecular weight CK (34βE12) may be positive.
Diagnostic Utility:
BerEP4 positivity highly specific for basal cell carcinoma
BCL-2 positivity helps confirm diagnosis
p63 positivity shows basal cell phenotype
CK7 negativity excludes adenocarcinoma
S-100 negativity excludes melanoma
Combination of markers confirms diagnosis
CD10 positivity in stromal cells.
Molecular/Genetic
Genetic Mutations:
PTCH1 mutations (hedgehog pathway disruption - 70%)
SMO mutations (smoothened receptor - 10%)
SUFU mutations (suppressor of fused - rare)
TP53 mutations (30-40%)
RAS mutations (uncommon)
PIK3CA mutations (rare)
CDKN2A deletions (10-15%).
Prognostic Significance:
Local recurrence risk: Higher in morpheaform and infiltrative types
Metastatic potential: Extremely rare (<1%)
Size >2 cm: Increased recurrence risk
Histological subtype: Nodular has best prognosis
Margin status: Most important prognostic factor
Perineural invasion: Rare but increases recurrence risk.
Therapeutic Targets:
Hedgehog pathway inhibitors: Vismodegib, Sonidegib for advanced cases
Topical treatments: Imiquimod for superficial lesions
Photodynamic therapy: Alternative for superficial lesions
Cryotherapy: For small, well-defined lesions
Mohs micrographic surgery: For high-risk locations
Radiation therapy: For surgically unresectable cases.
Differential Diagnosis
Similar Entities:
Vulvar squamous cell carcinoma (basaloid variant)
Sebaceous carcinoma
Merkel cell carcinoma
Metastatic small cell carcinoma
Trichoepithelioma (benign)
Adenoid cystic carcinoma
Basosquamous carcinoma.
Distinguishing Features:
Basal cell carcinoma: BerEP4 positive, peripheral palisading, retraction artifacts
Squamous cell carcinoma: Keratinization, intercellular bridges, p40 positive
Sebaceous carcinoma: Lipid vacuoles, Oil Red O positive
Merkel cell carcinoma: CK20 positive, neuroendocrine markers positive
Trichoepithelioma: Benign, no cytological atypia
Adenoid cystic carcinoma: Dual cell population, mucin pools.
Diagnostic Challenges:
Distinguishing from basaloid SCC: Lack of keratinization and intercellular bridges in BCC
Superficial BCC vs bowenoid papulosis: p16 staining and HPV testing helpful
Morpheaform BCC vs desmoplastic SCC: BerEP4 positivity in BCC
Small biopsy samples: May not show characteristic peripheral palisading
Basosquamous carcinoma: Shows features of both BCC and SCC.
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 excision specimen, measuring [X x Y x Z] cm
Diagnosis
Basal cell carcinoma, [nodular/superficial/morpheaform] subtype
Histological Subtype
[Nodular/Superficial/Morpheaform/Infiltrative/Micronodular] basal cell carcinoma
Histological Features
Tumor shows [architectural pattern] with [cellular features] and [stromal characteristics]
Size and Extent
Tumor size: [X] cm, depth of invasion: [X] mm, ulceration: [present/absent]
Surgical Margins
Margins: [involved/close/clear], closest margin: [X] mm from [location]
Perineural Invasion
Perineural invasion: [present/absent]
Immunohistochemistry
BerEP4: [positive/negative], BCL-2: [positive/negative]
p63: [positive/negative], CK5/6: [positive/negative]
CK7: [negative], S-100: [negative]
Risk Assessment
Risk category: [Low/Intermediate/High] based on [size/location/subtype/margins]
Final Diagnosis
Basal cell carcinoma of vulva, [subtype], [size] cm, margins [status]