Definition/General
Introduction:
Basal cell carcinoma (BCC) is the most common skin malignancy worldwide
It constitutes 70-80% of all skin cancers
It arises from the basal layer of epidermis or hair follicles
It demonstrates slow growth with local invasive behavior
It rarely metastasizes (<1% of cases).
Origin:
Originates from pluripotent cells in the basal layer of epidermis
Also arises from hair follicle bulge region
The neoplastic transformation involves loss of tumor suppressor function
It primarily affects sun-exposed areas
It shows strong association with UV radiation exposure.
Classification:
WHO classification recognizes multiple subtypes
Nodular BCC (60-70% of cases)
Superficial BCC (15-25%)
Micronodular BCC (5-10%)
Infiltrative BCC (5-10%)
Morpheaform/sclerosing BCC (1-2%)
Basosquamous carcinoma (mixed type)
Adenoid BCC (cribriform pattern).
Epidemiology:
Peak incidence in 6th-7th decades
Male predominance in head and neck lesions
Equal gender distribution in trunk lesions
Risk factors include fair skin
Chronic UV exposure
Family history
Gorlin syndrome
Immunosuppression
Previous radiation therapy
Indian population shows lower incidence but increasing trends in urban areas.
Clinical Features
Presentation:
Pearly papule or nodule with telangiectasia (most common)
Rolled borders with central depression
Translucent appearance
May show ulceration (rodent ulcer)
Non-healing sore that bleeds easily
Superficial lesions appear as scaly patches
Morpheaform type presents as scar-like induration.
Symptoms:
Usually asymptomatic
Occasional bleeding (60-70%)
Itching (30-40%)
Crusting and scaling
Slow growth over months to years
Pain is uncommon unless infected
Patients often report non-healing wound.
Risk Factors:
Age >50 years
Fair skin (Fitzpatrick types I-II)
Chronic sun exposure
History of sunburns in childhood
Family history of skin cancer
Gorlin syndrome (NBCCS)
Previous radiation therapy
Immunosuppression
Arsenic exposure
Chronic scarring or burns.
Screening:
Clinical skin examination by dermatologist
Dermoscopy for suspicious lesions
Annual screening for high-risk patients
Biopsy of suspicious lesions
Patient education on self-examination
Sun protection counseling.
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Gross Description
Appearance:
Well-circumscribed to ill-defined lesions
Pearly or waxy surface appearance
Size varies from few millimeters to several centimeters
Rolled borders with central depression or ulceration
Cut surface shows grayish-white solid tissue.
Characteristics:
Firm consistency with smooth or lobulated surface
May show black pigmentation (pigmented variant)
Telangiectatic vessels on surface
Central ulceration with raised pearly margins
Cut surface shows homogeneous appearance.
Size Location:
Variable size (2mm to >5cm)
Most commonly on head and neck (80%)
Nose most frequent site (30%)
Eyelids, ears, lips are high-risk locations
Trunk and extremities less common
Sun-exposed areas predominantly affected.
Multifocality:
Multifocal disease in 20-30% cases
Multiple primary tumors may occur
Gorlin syndrome patients show numerous lesions
Superficial type often shows multifocality
Recurrent lesions may show more aggressive behavior.
Microscopic Description
Histological Features:
Nests and islands of basaloid cells in dermis
Cells show peripheral palisading
Large hyperchromatic nuclei with scant cytoplasm
Increased nuclear-cytoplasmic ratio
Connection to surface epithelium often present
Clefting artifact between tumor and stroma.
Cellular Characteristics:
Uniform basaloid cells with oval nuclei
Peripheral palisading of nuclei
Scant basophilic cytoplasm
High nuclear-cytoplasmic ratio
Minimal pleomorphism
Mitotic activity present but not prominent
Apoptotic bodies may be seen.
Architectural Patterns:
Nodular pattern (well-circumscribed nests)
Superficial pattern (buds from epidermis)
Micronodular pattern (small uniform nests)
Infiltrative pattern (jagged borders)
Morpheaform pattern (sclerotic stroma)
Adenoid pattern (cribriform appearance).
Grading Criteria:
Low-grade: Nodular and superficial types
Intermediate-grade: Micronodular type
High-grade: Infiltrative and morpheaform types
Basosquamous: Mixed features with squamous differentiation
Grading based on growth pattern and stromal response.
Immunohistochemistry
Positive Markers:
BerEP4 (95-100% positive)
CK5/6 (90-95%)
p63 (nuclear, 90-95%)
CK14 (85-90%)
Bcl-2 (70-80%)
CK17 (70-80%)
CD10 (stromal myofibroblasts)
Androgen receptor (80-85%).
Negative Markers:
CK20 (consistently negative)
CEA (negative)
EMA (negative)
CK7 (usually negative)
TTF-1 (negative)
Help distinguish from Merkel cell carcinoma
Help distinguish from metastatic carcinoma.
Diagnostic Utility:
BerEP4 most specific marker
p63 confirms squamous/basal differentiation
Bcl-2 helpful in superficial lesions
Useful in small biopsies
Essential for basosquamous carcinoma diagnosis
Helpful in morpheaform variants.
Molecular Subtypes:
Sonic hedgehog pathway activation (90% cases)
PTCH1 mutations (70-80%)
SMO mutations (10-20%)
TP53 mutations (40-60%)
PIK3CA mutations (15-20%)
TERT promoter mutations (60-70%).
Molecular/Genetic
Genetic Mutations:
PTCH1 mutations (70-80%)
TP53 mutations (40-60%)
SMO mutations (10-20%)
SUFU mutations (rare)
PIK3CA mutations (15-20%)
TERT promoter mutations (60-70%)
MYC amplification (aggressive variants).
Molecular Markers:
Sonic hedgehog pathway activation (hallmark)
GLI1/GLI2 transcription factor activation
Cyclin D1 overexpression
p53 protein accumulation
Bcl-2 overexpression
Beta-catenin altered expression.
Prognostic Significance:
PTCH1 mutations indicate sporadic cases
Multiple mutations suggest Gorlin syndrome
TP53 mutations associated with aggressive behavior
PIK3CA mutations correlate with larger size
Sonic hedgehog activation predicts response to targeted therapy.
Therapeutic Targets:
Vismodegib (SMO antagonist)
Sonidegib (SMO antagonist)
Patidegib (topical SMO inhibitor)
Itraconazole (hedgehog pathway inhibitor)
LEQ506 (SMO antagonist)
Combination therapy for resistant cases.
Differential Diagnosis
Similar Entities:
Squamous cell carcinoma (keratinization, intercellular bridges)
Sebaceous carcinoma (foamy cytoplasm, Oil Red O positive)
Merkel cell carcinoma (CK20+, neuroendocrine markers)
Trichoepithelioma (benign, multiple lesions)
Adenoid cystic carcinoma (cribriform pattern, perineural invasion).
Distinguishing Features:
BCC: Peripheral palisading
BCC: BerEP4 positive
BCC: Connection to surface epithelium
SCC: Intercellular bridges
SCC: Keratinization present
Sebaceous carcinoma: Foamy cytoplasm
Merkel cell: CK20 positive
Trichoepithelioma: Benign behavior.
Diagnostic Challenges:
Distinguishing infiltrative BCC from morpheaform type
Separating basosquamous carcinoma from SCC
Small biopsy samples may be non-representative
Crush artifact obscuring morphology
Distinguishing from adnexal tumors
Immunohistochemistry essential in difficult cases.
Rare Variants:
Fibroepithelioma of Pinkus (fenestrating BCC)
Granular cell BCC (granular cytoplasm)
Clear cell BCC (clear cell change)
Pigmented BCC (melanin deposition)
Pleomorphic BCC (giant cells)
Adamantinoid BCC (follicular differentiation).
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
Skin excision from [site], measuring [X x Y x Z] cm
Diagnosis
Basal Cell Carcinoma
Histological Subtype
Subtype: [nodular/superficial/micronodular/infiltrative/morpheaform/mixed]
Microscopic Features
Shows nests of basaloid cells with peripheral palisading and [specific pattern features]
Margins
Margins: [involved/uninvolved], closest margin [X] mm [specify margin]
Depth of Invasion
Maximum depth of invasion: [X] mm
Ulceration
Ulceration: [present/absent]
Perineural Invasion
Perineural invasion: [present/absent/not identified]
Special Studies
IHC: [BerEP4/p63/other]: [result]
[other study if performed]: [result]
Risk Assessment
Risk: [low/intermediate/high] based on subtype, size, location, and margins
Final Diagnosis
Basal Cell Carcinoma, [subtype], [risk level]