Skin cancer Study Guide

📖 Core Concepts Skin cancer: malignant growth of skin cells; can invade locally or metastasize. Types Basal‑cell carcinoma (BCC) – most common, low‑grade, slow‑growing, rarely metastasizes. Squamous‑cell carcinoma (SCC) – harder, scaly lesions; higher metastatic potential, especially on lips/ears or in immunosuppressed patients. Melanoma – aggressive, arises from melanocytes; responsible for 75 % of skin‑cancer deaths. UV radiation UV‑B: causes direct DNA damage → cyclobutane pyrimidine dimers. UV‑A: generates indirect damage via free radicals/ROS. ABCDE mnemonic (Melanoma warning signs): Asymmetry, Border irregularity, Color variation, Diameter > 6 mm, Evolving. Risk modifiers: light skin, early‑life UV exposure, cumulative UV dose, immunosuppression, genetic syndromes (e.g., PTCH1, BRAF mutations). Diagnosis: biopsy + histopathology; dermatoscopy improves non‑invasive detection. Treatment hierarchy: surgical excision (Mohs for BCC) → radiation/topical therapy → systemic chemo/immune‑checkpoint or targeted therapy for advanced melanoma. --- 📌 Must Remember Epidemiology: Skin cancer = 40 % of all cancers worldwide; non‑melanoma ≈ 2‑3 M cases/yr; BCC ≈ 80 % of non‑melanoma, SCC ≈ 20 %. Mortality: BCC/SCC ≈ 0.3 % overall; melanoma mortality ≈ 15‑20 %. UV‑risk pattern: Early‑life UV → BCC & melanoma; cumulative UV → SCC. Key genes: PTCH1 (Sonic hedgehog pathway) → BCC; BRAF V600E → melanoma (targeted therapy). First‑line for BCC: Mohs micrographic surgery → >95 % 5‑yr cure. Melanoma staging factors: tumor thickness (Breslow), ulceration, nodal involvement. Immune‑checkpoint drugs: ipilimumab (CTLA‑4), pembrolizumab/nivolumab (PD‑1), cemiplimab (PD‑1). Targeted melanoma drugs: BRAF inhibitors (vemurafenib, dabrafenib) + MEK inhibitor (trametinib). --- 🔄 Key Processes UV‑induced DNA damage → Carcinogenesis UV‑B → cyclobutane pyrimidine dimers → replication errors. UV‑A → ROS → oxidative DNA lesions. BCC Development PTCH1 mutation → unchecked Sonic hedgehog signaling → basal keratinocyte proliferation. Peripheral palisading & possible ulceration. SCC Development Cumulative UV → UV‑signature mutations → keratinocyte dysplasia. Basement membrane breach → dermal invasion (keratin pearls if well‑differentiated). Melanoma Progression UV‑A damage → melanocyte DNA mutations (e.g., BRAF). Uncontrolled proliferation → vertical growth phase → metastasis. Clinical Evaluation Workflow Self‑exam → note ABCDE → dermatoscopy → biopsy → histopathology → staging (for melanoma). Treatment Decision Tree Small, localized BCC/SCC → surgical excision (Mohs if cosmetically critical). Unresectable or patient‑contraindicated → radiation (BCC) / systemic chemo (SCC). Melanoma: ≤ 1 mm thickness → wide local excision; > 0.8 mm or high‑risk → sentinel node biopsy → consider adjuvant immunotherapy/targeted therapy. --- 🔍 Key Comparisons BCC vs. SCC Appearance: BCC = smooth, pearly bump; SCC = hard, scaly patch/nodule. Metastasis: BCC rare; SCC moderate, higher on lip/ear or immunosuppressed. UV pattern: BCC → early‑life exposure; SCC → cumulative exposure. Melanoma vs. Non‑melanoma Mortality: Melanoma 15‑20 % vs. <1 % for BCC/SCC. Typical location: Melanoma can arise anywhere; BCC/SCC predominate on chronically sun‑exposed sites. UV‑B vs. UV‑A Damage type: UV‑B = direct DNA dimers; UV‑A = indirect ROS damage. Cancer association: UV‑B → BCC & SCC signatures; UV‑A → melanoma driver mutations. --- ⚠️ Common Misunderstandings “Sunscreen prevents all skin cancers.” – Strong evidence for melanoma & SCC reduction; effect on BCC is still uncertain. “Only tanning beds cause melanoma.” – Sunlight accounts for >90 % of all skin‑cancer cases; tanning beds add additional risk, especially for BCC/SCC. “All dark lesions are melanoma.” – Amelanotic melanomas are pink/red; many benign lesions (seborrheic keratoses) can be dark. “A small lesion can be ignored.” – Even tiny BCCs can cause significant local destruction; early excision improves outcomes. --- 🧠 Mental Models / Intuition UV exposure timeline → “Sun‑Early = BCC/Melanoma; Sun‑All‑Life = SCC.” ABCDE as a checklist → treat any “E” (evolving) as a red flag, regardless of other criteria. “Palisading = BCC” → peripheral palisading of nuclei under the microscope is a signature pattern. “Keratin pearls = SCC” → nests of concentric keratin indicate squamous differentiation. --- 🚩 Exceptions & Edge Cases Immunosuppressed patients: SCC can metastasize even from modest lesions; lower threshold for biopsy/excision. Marjolin’s ulcer: Chronic non‑healing wound → may transform into SCC regardless of UV history. Amelanotic melanoma: Lacks pigment, often misdiagnosed; rely on evolution and ulceration rather than color. BCC in non‑sun‑exposed sites (e.g., genitalia) – may suggest genetic predisposition (e.g., Gorlin syndrome). --- 📍 When to Use Which Diagnostic tool: Dermatoscopy → first for any suspicious pigmented or keratinocytic lesion; biopsy → definitive. Surgical technique: Mohs micrographic surgery → high‑risk, cosmetically sensitive, or recurrent BCC. Conventional excision → most SCC and low‑risk BCC. Adjuvant therapy for melanoma: BRAF‑mutated → add BRAF inhibitor + MEK inhibitor. BRAF‑wildtype or high‑risk → consider PD‑1 blockade (pembrolizumab/nivolumab). Prevention: Broad‑spectrum sunscreen + protective clothing for all ages; emphasize early‑life protection for BCC/melanoma risk reduction. --- 👀 Patterns to Recognize Pearly, telangiectatic nodule → BCC. Scaly, ulcerated plaque on lip/ear → SCC. Multicolored, irregular, evolving mole → melanoma (apply ABCDE). Keratin pearls on histology → SCC; peripheral palisading → BCC. UV‑signature C→T transitions in DNA sequencing → UV‑related skin cancer. --- 🗂️ Exam Traps “Sunscreen eliminates BCC risk.” – Answer: No, evidence is uncertain. “All melanomas are pigmented.” – Answer: False; amelanotic variants exist. “Only UV‑B causes melanoma.” – Answer: Both UV‑A (indirect) and UV‑B contribute; UV‑A linked to melanoma driver mutations. “A 5‑mm mole with uniform color is benign.” – Trap: Diameter < 6 mm does not rule out melanoma if other ABCDE criteria are present. “Radiation is first‑line for all SCC.” – Wrong; surgery is primary, radiation reserved for non‑surgical candidates or adjuvant use. ---