StepWise USMLE
preclinical · pathology

Skin & Pigment Disorders

Melanocytic lesions · Vesiculobullous · Nonmelanoma · Systemic clues

⚫ Pigmentation disorders

  • Hypopigmentation — loss of melanin
    • Vitiligo: irregular, completely depigmented patches; autoimmune etiology; no epidermal melanocytes microscopically
    • Albinism (congenital):
      • Oculocutaneous (AR): hair/skin/eyes, ↑ skin cancer risk
      • Syndromic (Chediak‑Higashi): ↑ infections, packaging defect
      • X‑linked ocular: nystagmus, iris hypopigmentation
  • Hyperpigmentation
    • Melasma: facial blotchy patches; sun, OCP, pregnancy (“mask”); may regress
    • Addison: generalized ↑ melanin (basal layer)
    • Vitiligo: no melanocytes; autoimmune association

    🟤 Melanocytic lesions & melanoma

    • Benign
      • Ephelides (freckles): ↑ melanin, normal melanocyte count
      • Solar lentigo: elongated rete ridges, discontinuous melanocytes
      • Congenital nevus: giant → ↑ melanoma risk
      • Melanocytic nevus (mole): uniform, well‑circumscribed; junctional/compound/intradermal
      • Dysplastic nevus: architectural disorder + atypia
    • Malignant melanoma
      • Risk: sunburn, fair skin, familial (p16/CDKN2A), NRAS/BRAF
      • Lesion: asymmetric, irregular borders, variegated, diameter >6mm
      • Types:
        • Lentigo maligna (face/neck, best prognosis)
        • Superficial spreading (most common, horizontal)
        • Acral lentiginous (dark skin, palms/soles/subungual)
        • Nodular (vertical, worst prognosis)
      • Staging: Breslow thickness (TNM)
      • Treatment: wide excision ± SLNB; chemo/immunotherapy for systemic
    • ⚠ Melanoma can metastasize after years of dormancy

    🧴 Benign skin growths

    • Seborrheic keratosis: coin‑shaped, “stuck‑on”; horn cysts; sign of Leser‑Trélat (paraneoplastic)
    • Verrucae (warts): HPV; verruca vulgaris most common
    • Epidermoid cyst: stratified squamous lining, keratin debris
    • Acrochordon (skin tag): pedunculated, connective tissue stalk
    • Leser‑Trélat: sudden multiple seborrheic keratoses → internal malignancy

    💧 Vesicular & bullous

    • Pemphigus vulgaris: intraepidermal; anti‑desmoglein 3; tombstone basal layer; IgG net‑like
    • Bullous pemphigoid: subepidermal; anti‑hemidesmosome (BPAG1/2); linear IgG at DEJ
    • Dermatitis herpetiformis: subepidermal; IgA anti‑gliadin; gluten‑sensitive; grouped vesicles
    • Porphyria cutanea tarda: subepidermal blisters; sun/minor trauma; thickened dermal vessels
    • Erythema multiforme: targetoid lesions; HSV/drugs; Stevens‑Johnson if extensive
    Intraepidermal → Pemphigus · Subepidermal → BP, DH, PCT

    🔴 Erythematous / papular

    • Polymorphous light eruption: pruritic macules/papules after sun exposure
    • Pityriasis rosea: herald patch → truncal eruption; viral exanthem
    • Erythema nodosum: painful shin nodules; sarcoidosis, strep
    • Psoriasis: well‑demarcated silvery plaques; Auspitz sign; acanthosis, Munro microabscesses; TNF/UV/methotrexate
    • Granuloma annulare: palisaded granulomas; usually benign

    🧴 Eczema & dry skin

    • Eczema: spongiosis (edema), pruritus
      • Acute: vesicular, erythematous; Chronic: lichenified, hyperkeratotic
    • Atopic dermatitis: filaggrin (FLG) mutation
    • Contact dermatitis: allergic (poison ivy, nickel) or phototoxic (tetracycline)
    • Ichthyosis vulgaris: AD; thickened stratum corneum, absent granulosum
    • Xerosis: elderly, EGFR inhibitors; emollients

    🔄 Systemic diseases with skin signs

    • Acanthosis nigricans: velvety hyperpigmented axillae/groin; obesity, hyperinsulinism, or paraneoplastic (GI cancer)
    • SLE: malar rash (spares nasolabial), photosensitivity, joint pain
    • ⚠ Paraneoplastic acanthosis nigricans → GI malignancy

    🧬 Nonmelanoma skin cancer

    • Squamous cell carcinoma
      • Risk: UVB, chronic ulcers, immunosuppression, xeroderma pigmentosum
      • Precursors: actinic keratosis, Bowen disease (SCC in situ)
      • Micro: keratin pearls, intercellular bridges; rare metastasis
      • Keratoacanthoma: rapidly growing, self‑limited variant
    • Basal cell carcinoma
      • Most common; face, hair‑bearing; pearly papule, telangiectasia, rodent ulcer
      • Micro: palisading basaloid nests; Hedgehog pathway mutations
      • Slow growth, locally aggressive; shave biopsy 50% recurrence
    • Vascular tumors
      • Pyogenic granuloma: capillary hemangioma, post‑trauma
      • Kaposi sarcoma: patch/plaque/nodule (HHV‑8)
      • Cutaneous angiosarcoma: elderly face, Stewart‑Treves (lymphedema), post‑RT
    • BCC rarely metastasizes, but can be locally destructive