Basal Cell Carcinoma

Skin Cancers

• Basal cell carcinoma:
  • Most common cutaneous malignancy
  • Presents as an elevated nodule with a central, ulcerated crater surrounded by dilated (telangiectatic) vessels; 'pink, pearl-like papule’
  • Classic location is the upper lip
  • Histology shows nodules of basal cells with peripheral palisading
  • Treatment is surgical excision; metastasis is rare
• Squamous cell carcinoma:
  • Malignant proliferation of squamous cells characterized by formation of keratin pearls
  • Risk factors include UVB-induced DNA damage, prolonged exposure to sunlight, albinism, xeroderma pigmentosum, immunosuppressive therapy, arsenic exposure, and chronic inflammation
  • Presents as an ulcerated, nodular mass, usually on the face (classically involving the lower lip)
  • Treatment is excision; metastasis is common
  • Actinic keratosis is a precursor lesion of squamous cell carcinoma and presents as a hyperkeratotic, scaly plaque, often on the face, back, or neck
  • Keratoacanthoma is a well-differentiated squamous cell carcinoma that develops rapidly and regresses spontaneously; presents as a cup-shaped tumor filled with keratin debris

Disorders of Pigmentation and Melanocytes

• Melanocytes:
  • Responsible for skin pigmentation
  • Present in the basal layer of the epidermis
  • Derived from the neural crest
  • Synthesize melanin in melanosomes using tyrosine as a precursor molecule
  • Pass melanosomes to keratinocytes
• Vitiligo:
  • Localized loss of skin pigmentation
  • Due to autoimmune destruction of melanocytes
• Albinism:
  • Congenital lack of pigmentation
  • Due to an enzyme defect (usually tyrosinase) that impairs melanin production
  • May involve the eyes (ocular form) or both the eyes and skin (oculocutaneous form)
  • Increased risk of squamous cell carcinoma, basal cell carcinoma, and melanoma due to reduced protection against UVB
• Freckle (Ephelis):
  • Small, tan to brown macule; darkens when exposed to sunlight
  • Due to increased number of melanosomes (melanocytes are not increased)
• Melasma:
  • Mask-like hyperpigmentation of the cheeks
  • Associated with pregnancy and oral contraceptives
• Nevus (Mole):
  • Benign neoplasm of melanocytes
  • Congenital nevus is present at birth; often associated with hair
  • Acquired nevus arises later in life
  • Characterized by a flat macule or raised papule with symmetry, sharp borders, evenly distributed color, and small diameter (< 6 mm)
  • Dysplasia may arise (dysplastic nevus), which is a precursor to melanoma
• Melanoma:
  • Malignant neoplasm of melanocytes; most common cause of death from skin cancer
  • Risk factors are based on UVB-induced DNA damage and include prolonged exposure to sunlight, albinism, and xeroderma pigmentosum
  • Presents as a mole-like growth with "ABCD" characteristics:
    • Asymmetry
    • Borders are irregular
    • Color is not uniform
    • Diameter > 6 mm
  • Characterized by two growth phases:
    • Radial growth horizontally along the epidermis and superficial dermis; low risk of metastasis
    • Vertical growth into the deep dermis; increased risk of metastasis; depth of extension (Breslow thickness) is the most important prognostic factor in predicting metastasis

Psoriasis

• Well-circumscribed, salmon-colored plaques with silvery scale, usually on extensor surfaces and the scalp; pitting of nails may also be present
• Due to excessive keratinocyte proliferation
• Possible autoimmune etiology
• Associated with HLA-C
• Lesions often arise in areas of trauma (environmental trigger)
• Histology shows:
  • Acanthosis (epidermal hyperplasia)
  • Parakeratosis (hyperkeratosis with retention of keratinocyte nuclei in the stratum corneum)
  • Collections of neutrophils in the stratum corneum (Munro microabscesses)
  • Thinning of the epidermis above elongated dermal papillae; results in bleeding when scale is picked off (Auspitz sign)
• Treatment involves corticosteroids, UV light with psoralen, or immune-modulating therapy

Lichen Planus

• Pruritic, planar, polygonal, purple papules, often with reticular white lines on their surface (Wickham striae); commonly involves wrists, elbows, and oral mucosa
• Oral involvement manifests as Wickham striae
• Histology shows inflammation of the dermal-epidermal junction with a 'saw-tooth' appearance
• Etiology is unknown; associated with chronic hepatitis C virus infection

Blistering Dermatoses

• Pemphigus Vulgaris:
  • Autoimmune destruction of desmosomes between keratinocytes
  • Due to IgG antibody against desmoglein (type II hypersensitivity)
  • Presents as skin and oral mucosa bullae:
    • Acantholysis (separation) of stratum spinosum keratinocytes (normally connected by desmosomes) results in suprabasal blisters
    • Basal layer cells remain attached to basement membrane via hemidesmosomes ('tombstone' appearance)
    • Thin-walled bullae rupture easily (Nikolsky sign), leading to shallow erosions with dried crust
    • Immunofluorescence highlights IgG surrounding keratinocytes in a 'fish net' pattern