Non-melanocytic skin tumors

Non-melanocytic skin tumors = all types of skin tumors that are not melanoma.

1. Benign + Pre-Malignant Epithelial Lesions

Derive from stem cells in epidermis + hair follicles; most do not undergo malignant transformation.

A) Seborrheic Keratosis (Benign)

• Most commonly occurs on the trunk in middle-aged + older people.
• FGFR3 mutation (fibroblast GF receptor 3) → stimulates epidermal proliferation.
• Warty, raised, round lesions.
• Dark brown color (melanin in cells).
• Hyperkeratosis on surface + keratin-filled cysts (“horn cysts”) inside tumor mass.
• Usually “stuck-on” appearance clinically.
• Removed only if inflamed or mimics melanoma; otherwise just cosmetic.
• Leser-Trélat sign: sudden appearance of multiple seborrheic keratoses → paraneoplastic, suggests internal GI adenocarcinoma.

B) Sebaceous Adenoma (Benign)

• Rare; occurs on head + neck of older people.
• Flesh-colored papules.
• Marker for internal malignancy (most often colon carcinoma) — part of Muir-Torre syndrome / HNPCC (DNA mismatch repair protein defect, MSH2/MLH1).
• Histology: lobular proliferations of sebocytes of sebaceous glands.
• Basal layer (normally 2 layers thick) is expanded.
• Benign + self-limited.

C) Actinic Keratosis (Pre-Malignant)

• Skin dysplasia from chronic sun exposure with hyperkeratosis (actinic = sun-related).
• p53 mutation suggestive of UV-light injury.
• Precursor of squamous cell carcinoma.

Morphology

• Solar elastosis (thickened basophilic elastic fibers in dermis).
• Parakeratosis, atypia of keratinocytes.
• Inflammation; basal cell hyperplasia + atypia.

Clinical Features

• Sites: sun-exposed areas (face, arms, dorsum of hands, ears).
• Lesions < 1 cm, red-brown, with rough sandpaper consistency.
• Cutaneous keratin horns can grow.
• Treatment: local cryotherapy (superficial freezing); 5-fluorouracil, imiquimod.

2. Malignant Epidermal Tumors

A) Squamous Cell Carcinoma (SCC)

• Tumor arising on sun-exposed sites in older people.
• 2nd most common skin cancer (after BCC).
• Causes: sun exposure (#1), industrial carcinogens (arsenic, tar), chronic ulcers, old burn scars (Marjolin ulcer), ionizing radiation.

Pathogenesis

• UV light → unrepaired DNA damage → p53 mutation.
• UV → transient immunosuppression by impairing antigen presentation by Langerhans cells.
• Immunosuppression (organ transplant) = major risk factor.

Morphology

• SCC in situ (Bowen disease): atypical cells in epidermis with nuclear crowding + disorganization; breaks through BM → invasive.
• Invasive form: variable morphology; presence of keratinization (keratin pearls), intercellular bridges.

Clinical Features

• In situ lesions: sharply defined, red scaling plaques; may arise from prior actinic keratoses (behave less aggressively).
• Invasive lesions: nodules that may ulcerate.
• Metastasis likelihood relates to degree of invasion + thickness.
• Mucosal SCC (oral, pulmonary, esophageal) is more aggressive.
• Tx: surgical excision ± Mohs.

B) Basal Cell Carcinoma (BCC)

• Most common human cancer.
• Slow-growing; rarely metastasizes.
• Sites: chronic sun-exposed areas in lightly pigmented people.
• Risk ↑ with immunosuppression + UV (DNA damage).
• Genetic: PTCH1 mutation (hedgehog signaling); Gorlin syndrome (nevoid BCC syndrome) = multiple BCCs + medulloblastoma + jaw cysts.

Morphology

• Pearly papules with prominent dilated blood vessels (telangiectasia).
• Some tumors have melanin pigment → resembles nevi/melanomas.
• Histology: cells resemble normal epidermal basal cells; 2 growth patterns:
  • Multifocal/superficial growth from epidermis.
  • Nodular lesions growing downward into dermis.
• Classic: palisading nuclei at periphery of tumor nests, retraction artifact.

Clinical Features

• Advanced lesions: central ulceration (rodent ulcer).
• Neglected lesions: bone or facial sinus infiltration.
• Treatment: local excision; vismodegib (hedgehog inhibitor) for advanced.

3. Comparison Table

Tumor	Type	Key features
Seborrheic keratosis	Benign	Trunk; “stuck-on” warty lesions + horn cysts; FGFR3; Leser-Trélat = GI adenocarcinoma
Sebaceous adenoma	Benign	Head/neck; Muir-Torre syndrome → colon carcinoma
Actinic keratosis	Pre-malignant	Sun-exposed; sandpaper; p53; → SCC; cryotherapy
Squamous cell carcinoma	Malignant	Sun-exposed; keratin pearls; Marjolin ulcer; p53; mucosal more aggressive
Basal cell carcinoma	Malignant	#1 human cancer; pearly papule + telangiectasia + rodent ulcer; palisading nuclei; PTCH1; Gorlin syndrome

💡 High-yield: Seborrheic keratosis = benign, trunk, “stuck-on” + horn cysts, FGFR3; Leser-Trélat sign → GI adenocarcinoma. Sebaceous adenoma = head/neck; Muir-Torre → colon Ca (HNPCC/MMR defect). Actinic keratosis = pre-malignant, sandpaper texture, sun-exposed, p53 mutation → SCC. SCC = keratin pearls, sun + immunosuppression + Marjolin ulcer; p53; mucosal more aggressive. BCC = #1 human cancer; pearly papule + telangiectasia + rodent ulcer; palisading nuclei; PTCH1 (hedgehog); Gorlin syndrome (multiple BCC + medulloblastoma + jaw cysts); rarely mets; Tx vismodegib.