const pptxgen = require("pptxgenjs");

// Fetch images helper
const { execSync } = require("child_process");

function fetchImages(urls) {
  try {
    const result = execSync(
      `node /home/daytona/skills/shared/scripts/fetch_images.js ${urls.map(u => `"${u}"`).join(" ")}`,
      { timeout: 60000 }
    ).toString();
    return JSON.parse(result);
  } catch (e) {
    console.log("Image fetch error:", e.message);
    return urls.map(u => ({ url: u, base64: null, error: e.message }));
  }
}

// ── Color Palette ──────────────────────────────────────────────
const DARK_BG   = "0D1B2A";   // deep navy
const MID_BG    = "1B2A3B";   // slightly lighter navy
const ACCENT1   = "E63946";   // vivid red (cancer/alert)
const ACCENT2   = "F4A261";   // warm amber
const ACCENT3   = "2EC4B6";   // teal
const WHITE     = "FFFFFF";
const LIGHT_TXT = "D9E2EC";
const GREY_TXT  = "A8B2BD";
const LIGHT_BG  = "F0F4F8";
const CARD_BG   = "152030";

let pres = new pptxgen();
pres.layout = "LAYOUT_WIDE"; // 13.3 × 7.5 inches
pres.title = "Melanoma: Metastasis & Nevus vs Melanoma";
pres.author = "Medical Education";

// ═══════════════════════════════════════════════════
// HELPER: add a gradient-style title bar
// ═══════════════════════════════════════════════════
function addSlideHeader(slide, title, subtitle, bgColor = DARK_BG) {
  slide.addShape(pres.ShapeType.rect, {
    x: 0, y: 0, w: 13.3, h: 7.5, fill: { color: bgColor }
  });
  // decorative top stripe
  slide.addShape(pres.ShapeType.rect, {
    x: 0, y: 0, w: 13.3, h: 0.08, fill: { color: ACCENT1 }
  });
}

function addTitleSlide(slide, mainTitle, subtitle) {
  // Full dark background
  slide.addShape(pres.ShapeType.rect, {
    x: 0, y: 0, w: 13.3, h: 7.5, fill: { color: DARK_BG }
  });
  // Red accent bar left
  slide.addShape(pres.ShapeType.rect, {
    x: 0, y: 0, w: 0.15, h: 7.5, fill: { color: ACCENT1 }
  });
  // Bottom accent
  slide.addShape(pres.ShapeType.rect, {
    x: 0, y: 7.0, w: 13.3, h: 0.5, fill: { color: ACCENT1 }
  });
  slide.addText(mainTitle, {
    x: 0.6, y: 1.8, w: 12, h: 1.6, fontSize: 48, bold: true,
    color: WHITE, align: "center", fontFace: "Calibri"
  });
  slide.addText(subtitle, {
    x: 0.6, y: 3.6, w: 12, h: 0.8, fontSize: 22,
    color: ACCENT2, align: "center", fontFace: "Calibri"
  });
  slide.addText("Source: Robbins Pathology | Fitzpatrick's Dermatology | Dermatology 2-Vol Set", {
    x: 0.6, y: 6.8, w: 12, h: 0.4, fontSize: 11,
    color: GREY_TXT, align: "center"
  });
}

function addSectionDivider(slide, sectionNumber, sectionTitle, color = ACCENT1) {
  slide.addShape(pres.ShapeType.rect, {
    x: 0, y: 0, w: 13.3, h: 7.5, fill: { color: MID_BG }
  });
  slide.addShape(pres.ShapeType.rect, {
    x: 0, y: 3.2, w: 13.3, h: 0.1, fill: { color: color }
  });
  slide.addText(`Section ${sectionNumber}`, {
    x: 1, y: 2.0, w: 11.3, h: 0.7, fontSize: 20,
    color: color, align: "center", bold: true
  });
  slide.addText(sectionTitle, {
    x: 1, y: 2.8, w: 11.3, h: 1.2, fontSize: 42,
    color: WHITE, align: "center", bold: true
  });
}

function addContentSlideHeader(slide, title) {
  slide.addShape(pres.ShapeType.rect, {
    x: 0, y: 0, w: 13.3, h: 7.5, fill: { color: DARK_BG }
  });
  slide.addShape(pres.ShapeType.rect, {
    x: 0, y: 0, w: 13.3, h: 0.06, fill: { color: ACCENT1 }
  });
  slide.addShape(pres.ShapeType.rect, {
    x: 0, y: 0.06, w: 13.3, h: 1.04, fill: { color: CARD_BG }
  });
  slide.addText(title, {
    x: 0.3, y: 0.1, w: 12.7, h: 0.9, fontSize: 28, bold: true,
    color: WHITE, align: "left", fontFace: "Calibri", margin: 0
  });
}

// ═══════════════════════════════════════════════════
// SLIDE 1 — Title
// ═══════════════════════════════════════════════════
{
  let s = pres.addSlide();
  addTitleSlide(
    s,
    "Melanoma:\nMetastasis & Nevus vs Melanoma",
    "Pathology | Dermoscopy | Staging | Molecular Basis"
  );
}

// ═══════════════════════════════════════════════════
// SLIDE 2 — Agenda / Overview
// ═══════════════════════════════════════════════════
{
  let s = pres.addSlide();
  addContentSlideHeader(s, "📋  What We'll Cover");

  const items = [
    { num: "01", label: "What is Melanoma?", color: ACCENT1 },
    { num: "02", label: "Nevus vs Melanoma — ABCDE & Histology", color: ACCENT2 },
    { num: "03", label: "Radial & Vertical Growth Phases", color: ACCENT3 },
    { num: "04", label: "Metastasis: Pathways & Mechanisms", color: "A29BFE" },
    { num: "05", label: "Staging (TNM) & Sites of Spread", color: ACCENT1 },
    { num: "06", label: "Molecular Drivers & Targeted Therapy", color: ACCENT2 },
    { num: "07", label: "Key Takeaways", color: ACCENT3 },
  ];

  items.forEach((item, i) => {
    const col = i < 4 ? 0 : 1;
    const row = i < 4 ? i : i - 4;
    const x = col === 0 ? 0.4 : 7.0;
    const y = 1.35 + row * 1.45;

    // Number badge
    s.addShape(pres.ShapeType.roundRect, {
      x: x, y: y, w: 0.7, h: 0.7,
      fill: { color: item.color }, line: { color: item.color }
    });
    s.addText(item.num, {
      x: x, y: y, w: 0.7, h: 0.7, fontSize: 18, bold: true,
      color: WHITE, align: "center", valign: "middle"
    });
    s.addText(item.label, {
      x: x + 0.85, y: y + 0.05, w: 5.8, h: 0.6, fontSize: 18,
      color: LIGHT_TXT, align: "left", valign: "middle"
    });
  });
}

// ═══════════════════════════════════════════════════
// SLIDE 3 — Section divider: What is Melanoma?
// ═══════════════════════════════════════════════════
{
  let s = pres.addSlide();
  addSectionDivider(s, "01", "What Is Melanoma?", ACCENT1);
  s.addText("The skin's most deadly cancer — arising from melanocytes", {
    x: 1, y: 4.5, w: 11.3, h: 0.7, fontSize: 18,
    color: GREY_TXT, align: "center", italic: true
  });
}

// ═══════════════════════════════════════════════════
// SLIDE 4 — What is Melanoma?
// ═══════════════════════════════════════════════════
{
  let s = pres.addSlide();
  addContentSlideHeader(s, "🎯  Melanoma — The Basics");

  // Left panel facts
  const facts = [
    { icon: "🔬", head: "Origin", body: "Malignant transformation of melanocytes — pigment-producing cells in the basal epidermis" },
    { icon: "☀️", head: "Main Risk Factor", body: "UV radiation from sunlight; especially severe sunburns in early life" },
    { icon: "💀", head: "Lethality", body: "Most lethal skin cancer — 5-yr survival drops to <10% at Stage IV" },
    { icon: "📈", head: "Epidemiology", body: "~40-50% carry BRAF mutations; 15-20% have RAS mutations" },
  ];

  facts.forEach((f, i) => {
    const y = 1.3 + i * 1.5;
    s.addShape(pres.ShapeType.roundRect, {
      x: 0.3, y: y, w: 6.0, h: 1.25,
      fill: { color: CARD_BG }, line: { color: "2A3F55" }
    });
    s.addText(f.icon + " " + f.head, {
      x: 0.5, y: y + 0.1, w: 5.6, h: 0.4, fontSize: 15, bold: true,
      color: ACCENT2, align: "left"
    });
    s.addText(f.body, {
      x: 0.5, y: y + 0.5, w: 5.7, h: 0.6, fontSize: 13,
      color: LIGHT_TXT, align: "left"
    });
  });

  // Right panel — risk factors visual
  s.addShape(pres.ShapeType.roundRect, {
    x: 6.8, y: 1.3, w: 6.2, h: 5.8,
    fill: { color: CARD_BG }, line: { color: ACCENT1 }
  });
  s.addText("⚠️  Risk Factors", {
    x: 7.0, y: 1.4, w: 5.8, h: 0.5, fontSize: 18, bold: true,
    color: ACCENT1, align: "center"
  });
  const risks = [
    "Fair skin, light hair & eyes",
    "History of sunburns / UV exposure",
    "Personal/family history of melanoma",
    "Large number of moles (>50)",
    "Dysplastic nevi (atypical moles)",
    "Immunosuppression",
    "CDKN2A / BRAF germline mutations",
    "Xeroderma pigmentosum",
  ];
  risks.forEach((r, i) => {
    s.addShape(pres.ShapeType.ellipse, {
      x: 7.1, y: 2.05 + i * 0.65, w: 0.18, h: 0.18,
      fill: { color: ACCENT1 }
    });
    s.addText(r, {
      x: 7.4, y: 2.0 + i * 0.65, w: 5.4, h: 0.55, fontSize: 14,
      color: LIGHT_TXT, align: "left"
    });
  });
}

// ═══════════════════════════════════════════════════
// SLIDE 5 — Section divider: Nevus vs Melanoma
// ═══════════════════════════════════════════════════
{
  let s = pres.addSlide();
  addSectionDivider(s, "02", "Nevus vs Melanoma", ACCENT2);
  s.addText("ABCDE criteria | Histology | Molecular differences", {
    x: 1, y: 4.5, w: 11.3, h: 0.7, fontSize: 18,
    color: GREY_TXT, align: "center", italic: true
  });
}

// ═══════════════════════════════════════════════════
// SLIDE 6 — ABCDE comparison (visual table)
// ═══════════════════════════════════════════════════
{
  let s = pres.addSlide();
  addContentSlideHeader(s, "🔍  The ABCDE Rule — Mole vs Melanoma");

  const rows = [
    { letter: "A", label: "Asymmetry", nevus: "Symmetrical — both halves match", mel: "Asymmetrical — halves differ in shape & color", color: ACCENT1 },
    { letter: "B", label: "Border", nevus: "Smooth, well-defined, regular", mel: "Irregular, ragged, notched or blurred", color: ACCENT2 },
    { letter: "C", label: "Color", nevus: "Uniform tan or brown", mel: "Multiple shades: black, brown, red, grey, white zones", color: ACCENT3 },
    { letter: "D", label: "Diameter", nevus: "Usually < 6 mm", mel: "Often > 6 mm; growing lesion is suspicious", color: "A29BFE" },
    { letter: "E", label: "Evolution", nevus: "Stable — no change over time", mel: "CHANGING in size, shape, color; may itch/bleed", color: "FF6B6B" },
  ];

  // Header row
  s.addShape(pres.ShapeType.rect, { x: 0.3, y: 1.2, w: 1.2, h: 0.55, fill: { color: "0F2030" } });
  s.addShape(pres.ShapeType.rect, { x: 1.55, y: 1.2, w: 2.0, h: 0.55, fill: { color: "0F2030" } });
  s.addShape(pres.ShapeType.rect, { x: 3.6, y: 1.2, w: 4.5, h: 0.55, fill: { color: "203A4F" } });
  s.addShape(pres.ShapeType.rect, { x: 8.15, y: 1.2, w: 4.85, h: 0.55, fill: { color: "3A1020" } });
  s.addText("Letter", { x: 0.3, y: 1.2, w: 1.2, h: 0.55, fontSize: 13, bold: true, color: GREY_TXT, align: "center", valign: "middle" });
  s.addText("Feature", { x: 1.55, y: 1.2, w: 2.0, h: 0.55, fontSize: 13, bold: true, color: GREY_TXT, align: "center", valign: "middle" });
  s.addText("✅  Benign Nevus", { x: 3.6, y: 1.2, w: 4.5, h: 0.55, fontSize: 13, bold: true, color: ACCENT3, align: "center", valign: "middle" });
  s.addText("🚨  Melanoma", { x: 8.15, y: 1.2, w: 4.85, h: 0.55, fontSize: 13, bold: true, color: ACCENT1, align: "center", valign: "middle" });

  rows.forEach((row, i) => {
    const y = 1.8 + i * 1.12;
    const bg = i % 2 === 0 ? CARD_BG : "121F2C";

    s.addShape(pres.ShapeType.rect, { x: 0.3, y, w: 1.2, h: 1.0, fill: { color: row.color } });
    s.addText(row.letter, { x: 0.3, y, w: 1.2, h: 1.0, fontSize: 36, bold: true, color: WHITE, align: "center", valign: "middle" });

    s.addShape(pres.ShapeType.rect, { x: 1.55, y, w: 2.0, h: 1.0, fill: { color: bg } });
    s.addText(row.label, { x: 1.55, y, w: 2.0, h: 1.0, fontSize: 16, bold: true, color: row.color, align: "center", valign: "middle" });

    s.addShape(pres.ShapeType.rect, { x: 3.6, y, w: 4.5, h: 1.0, fill: { color: bg } });
    s.addText(row.nevus, { x: 3.7, y: y + 0.15, w: 4.3, h: 0.7, fontSize: 13, color: LIGHT_TXT, align: "left", valign: "middle" });

    s.addShape(pres.ShapeType.rect, { x: 8.15, y, w: 4.85, h: 1.0, fill: { color: bg } });
    s.addText(row.mel, { x: 8.25, y: y + 0.15, w: 4.65, h: 0.7, fontSize: 13, color: LIGHT_TXT, align: "left", valign: "middle" });
  });
}

// ═══════════════════════════════════════════════════
// SLIDE 7 — Histology comparison
// ═══════════════════════════════════════════════════
{
  let s = pres.addSlide();
  addContentSlideHeader(s, "🔬  Histology: Nevus vs Melanoma");

  // NEVUS panel
  s.addShape(pres.ShapeType.roundRect, { x: 0.3, y: 1.25, w: 6.2, h: 5.9, fill: { color: CARD_BG }, line: { color: ACCENT3 } });
  s.addText("✅  Benign Nevus", { x: 0.4, y: 1.35, w: 6.0, h: 0.55, fontSize: 19, bold: true, color: ACCENT3, align: "center" });

  const nevusPoints = [
    "Small, uniform, round melanocytes",
    "Nests equidistant along DEJ",
    "Maturation with depth ('neurotization')",
    "Deeper cells lose pigment & become spindle-shaped",
    "No mitotic figures",
    "BRAF or RAS mutation — but senescence maintained by p16",
    "Smooth, well-circumscribed borders",
  ];
  nevusPoints.forEach((p, i) => {
    s.addShape(pres.ShapeType.ellipse, { x: 0.55, y: 2.1 + i * 0.72, w: 0.18, h: 0.18, fill: { color: ACCENT3 } });
    s.addText(p, { x: 0.85, y: 2.05 + i * 0.72, w: 5.5, h: 0.6, fontSize: 13.5, color: LIGHT_TXT });
  });

  // MELANOMA panel
  s.addShape(pres.ShapeType.roundRect, { x: 6.8, y: 1.25, w: 6.2, h: 5.9, fill: { color: CARD_BG }, line: { color: ACCENT1 } });
  s.addText("🚨  Melanoma", { x: 6.9, y: 1.35, w: 6.0, h: 0.55, fontSize: 19, bold: true, color: ACCENT1, align: "center" });

  const melPoints = [
    "Large cells with pleomorphic nuclei",
    "Chromatin clumped at nuclear membrane",
    "Prominent eosinophilic (red) nucleoli",
    "Irregular, asymmetric nests — varying size",
    "Pagetoid scatter above DEJ",
    "Mitotic figures present (esp. in VGP)",
    "NO maturation with depth",
    "Necrotic melanocytes may be seen",
  ];
  melPoints.forEach((p, i) => {
    s.addShape(pres.ShapeType.ellipse, { x: 7.0, y: 2.1 + i * 0.63, w: 0.18, h: 0.18, fill: { color: ACCENT1 } });
    s.addText(p, { x: 7.3, y: 2.05 + i * 0.63, w: 5.5, h: 0.55, fontSize: 13, color: LIGHT_TXT });
  });
}

// ═══════════════════════════════════════════════════
// SLIDE 8 — Radial vs Vertical Growth Phase
// ═══════════════════════════════════════════════════
{
  let s = pres.addSlide();
  addContentSlideHeader(s, "📐  Growth Phases: Radial → Vertical");

  // Diagram area
  // Epidermis layer
  s.addShape(pres.ShapeType.rect, { x: 0.4, y: 1.5, w: 12.5, h: 0.25, fill: { color: "F4A261" } });
  s.addText("Epidermis", { x: 0.4, y: 1.5, w: 2.0, h: 0.25, fontSize: 10, bold: true, color: DARK_BG, align: "center", valign: "middle" });

  // Dermis layer
  s.addShape(pres.ShapeType.rect, { x: 0.4, y: 1.75, w: 12.5, h: 2.0, fill: { color: "1E3A4C" } });
  s.addText("Dermis", { x: 0.4, y: 2.5, w: 1.3, h: 0.4, fontSize: 10, bold: true, color: ACCENT2 });

  // Fat layer
  s.addShape(pres.ShapeType.rect, { x: 0.4, y: 3.75, w: 12.5, h: 0.8, fill: { color: "0A2030" } });
  s.addText("Subcutaneous fat", { x: 0.4, y: 3.85, w: 2.8, h: 0.4, fontSize: 10, bold: true, color: GREY_TXT });

  // NORMAL NEVUS
  s.addShape(pres.ShapeType.ellipse, { x: 0.7, y: 1.35, w: 0.8, h: 0.45, fill: { color: "8B6914" } });
  s.addText("Nevus\n(normal)", { x: 0.7, y: 0.85, w: 0.9, h: 0.55, fontSize: 10, color: ACCENT2, align: "center" });

  // RGP melanoma (horizontal spread)
  s.addShape(pres.ShapeType.rect, { x: 2.5, y: 1.3, w: 3.2, h: 0.45, fill: { color: ACCENT1 } });
  s.addText("Radial Growth Phase", { x: 2.5, y: 0.75, w: 3.2, h: 0.5, fontSize: 11, bold: true, color: ACCENT1, align: "center" });
  s.addText("Spreads horizontally within epidermis\nNo metastatic potential (yet)", {
    x: 2.5, y: 4.65, w: 3.2, h: 0.9, fontSize: 11, color: LIGHT_TXT, align: "center"
  });
  // Arrow
  s.addShape(pres.ShapeType.rect, { x: 3.9, y: 1.6, w: 0.08, h: 0.25, fill: { color: ACCENT1 } });

  // VGP melanoma (vertical spread)
  s.addShape(pres.ShapeType.rect, { x: 7.0, y: 1.3, w: 1.2, h: 0.45, fill: { color: ACCENT1 } });
  s.addShape(pres.ShapeType.rect, { x: 7.3, y: 1.75, w: 0.6, h: 1.8, fill: { color: "C0392B" } });
  s.addText("Vertical Growth Phase", { x: 6.6, y: 0.75, w: 2.2, h: 0.5, fontSize: 11, bold: true, color: "C0392B", align: "center" });
  s.addText("Invades dermis — nodule forms\nMetastatic potential EMERGES", {
    x: 6.5, y: 4.65, w: 2.5, h: 0.9, fontSize: 11, color: LIGHT_TXT, align: "center"
  });

  // Advanced invasion
  s.addShape(pres.ShapeType.rect, { x: 10.2, y: 1.3, w: 1.4, h: 0.45, fill: { color: ACCENT1 } });
  s.addShape(pres.ShapeType.rect, { x: 10.6, y: 1.75, w: 0.7, h: 2.5, fill: { color: "8E1414" } });
  s.addText("Deep Invasion", { x: 10.0, y: 0.75, w: 2.0, h: 0.5, fontSize: 11, bold: true, color: "FF4444", align: "center" });
  s.addText("Extends to fat\nLymph/blood vessel invasion\nSTAGE III / IV", {
    x: 9.9, y: 4.65, w: 2.4, h: 0.9, fontSize: 11, color: LIGHT_TXT, align: "center"
  });

  // Arrows between stages
  s.addShape(pres.ShapeType.rect, { x: 5.85, y: 1.5, w: 0.8, h: 0.12, fill: { color: ACCENT2 } });
  s.addText("→", { x: 5.85, y: 1.4, w: 0.8, h: 0.3, fontSize: 14, color: ACCENT2, align: "center" });
  s.addShape(pres.ShapeType.rect, { x: 8.7, y: 1.5, w: 0.8, h: 0.12, fill: { color: ACCENT2 } });
  s.addText("→", { x: 8.7, y: 1.4, w: 0.8, h: 0.3, fontSize: 14, color: ACCENT2, align: "center" });
}

// ═══════════════════════════════════════════════════
// SLIDE 9 — Section divider: Metastasis
// ═══════════════════════════════════════════════════
{
  let s = pres.addSlide();
  addSectionDivider(s, "03", "Metastasis of Melanoma", ACCENT1);
  s.addText("Pathways • Sites • Mechanisms • Prognosis", {
    x: 1, y: 4.5, w: 11.3, h: 0.7, fontSize: 18,
    color: GREY_TXT, align: "center", italic: true
  });
}

// ═══════════════════════════════════════════════════
// SLIDE 10 — Metastatic Pathways
// ═══════════════════════════════════════════════════
{
  let s = pres.addSlide();
  addContentSlideHeader(s, "🛣️  Routes of Metastatic Spread");

  const pathways = [
    {
      title: "1. Lymphatic Spread",
      icon: "🫀",
      color: ACCENT3,
      points: [
        "Most common initial route",
        "Primary tumor → afferent lymphatics → regional LN",
        "CCR7 & CCR10 receptors guide lymph node homing",
        "SLNB detects occult nodal spread",
        "Sentinel node = first draining lymph node",
        "15-20% of melanomas >1mm show nodal spread",
      ]
    },
    {
      title: "2. Hematogenous Spread",
      icon: "🩸",
      color: ACCENT1,
      points: [
        "Via blood vessels — especially in VGP",
        "Tumor cells invade dermal vessels",
        "Circulating melanoma cells seed distant organs",
        "CXCR4 receptor drives lung/distant metastasis",
        "CCR9 implicated in small bowel metastasis",
        "IL-8 acts as autocrine growth + migration factor",
      ]
    },
    {
      title: "3. Direct / In-Transit",
      icon: "🔗",
      color: ACCENT2,
      points: [
        "Satellite: melanoma focus within 2 cm of primary",
        "In-transit: lymphatic metastasis >2 cm from primary",
        "Microsatellite: microscopic foci adjacent to primary",
        "All three = Stage III (N category) disease",
        "Appear as nodules, papules or plaques on skin",
      ]
    },
  ];

  pathways.forEach((pw, i) => {
    const x = 0.3 + i * 4.35;
    s.addShape(pres.ShapeType.roundRect, { x, y: 1.25, w: 4.15, h: 5.9, fill: { color: CARD_BG }, line: { color: pw.color } });
    // Color header bar
    s.addShape(pres.ShapeType.roundRect, { x, y: 1.25, w: 4.15, h: 0.85, fill: { color: pw.color } });
    s.addText(pw.icon + " " + pw.title, { x: x + 0.1, y: 1.3, w: 3.95, h: 0.75, fontSize: 15, bold: true, color: WHITE, align: "center", valign: "middle" });

    pw.points.forEach((p, j) => {
      s.addShape(pres.ShapeType.ellipse, { x: x + 0.2, y: 2.3 + j * 0.75, w: 0.15, h: 0.15, fill: { color: pw.color } });
      s.addText(p, { x: x + 0.45, y: 2.2 + j * 0.75, w: 3.6, h: 0.65, fontSize: 12.5, color: LIGHT_TXT });
    });
  });
}

// ═══════════════════════════════════════════════════
// SLIDE 11 — Sites of Metastasis (Body Map)
// ═══════════════════════════════════════════════════
{
  let s = pres.addSlide();
  addContentSlideHeader(s, "🗺️  Where Does Melanoma Spread?");

  // Body silhouette (simplified with shapes)
  // Head
  s.addShape(pres.ShapeType.ellipse, { x: 5.9, y: 1.2, w: 1.5, h: 1.5, fill: { color: "2A3F55" }, line: { color: ACCENT2 } });
  s.addText("🧠", { x: 5.9, y: 1.3, w: 1.5, h: 1.0, fontSize: 28, align: "center" });
  // Neck
  s.addShape(pres.ShapeType.rect, { x: 6.3, y: 2.7, w: 0.7, h: 0.5, fill: { color: "2A3F55" } });
  // Torso
  s.addShape(pres.ShapeType.rect, { x: 5.7, y: 3.2, w: 1.9, h: 2.2, fill: { color: "2A3F55" }, line: { color: ACCENT2 } });
  // Lung/liver icons inside torso
  s.addText("🫁  🫀", { x: 5.7, y: 3.35, w: 1.9, h: 0.7, fontSize: 18, align: "center" });
  s.addText("🩺", { x: 5.7, y: 4.0, w: 1.9, h: 0.7, fontSize: 22, align: "center" });
  // Arms
  s.addShape(pres.ShapeType.rect, { x: 4.7, y: 3.2, w: 0.85, h: 1.5, fill: { color: "2A3F55" } });
  s.addShape(pres.ShapeType.rect, { x: 7.75, y: 3.2, w: 0.85, h: 1.5, fill: { color: "2A3F55" } });
  // Legs
  s.addShape(pres.ShapeType.rect, { x: 5.75, y: 5.4, w: 0.8, h: 1.8, fill: { color: "2A3F55" } });
  s.addShape(pres.ShapeType.rect, { x: 6.75, y: 5.4, w: 0.8, h: 1.8, fill: { color: "2A3F55" } });

  // Annotation callouts
  const callouts = [
    { x: 0.3, y: 1.4, label: "🧠 Brain", pct: "15-30%", color: "A29BFE", desc: "Seizures, headache, focal neurology; detected on MRI" },
    { x: 0.3, y: 2.9, label: "🫁 Lung", pct: "18-36%", color: ACCENT3, desc: "Most common distant site; chest X-ray / CT" },
    { x: 0.3, y: 4.4, label: "🫀 Liver", pct: "14-20%", color: ACCENT2, desc: "#1 site for uveal melanoma; US / MRI surveillance" },
    { x: 9.0, y: 1.4, label: "🦴 Bone", pct: "6-7%", color: "FF6B6B", desc: "Lytic lesions; pain and fractures" },
    { x: 9.0, y: 2.9, label: "🧫 Skin/LN", pct: "~70%", color: ACCENT1, desc: "Most common = Stage III; in-transit / satellite" },
    { x: 9.0, y: 4.4, label: "🩺 GI Tract", pct: "Rare", color: ACCENT2, desc: "Small bowel via CCR9; obstruction, bleeding" },
  ];

  callouts.forEach(c => {
    s.addShape(pres.ShapeType.roundRect, { x: c.x, y: c.y, w: 4.0, h: 1.2, fill: { color: CARD_BG }, line: { color: c.color } });
    s.addText(c.label, { x: c.x + 0.1, y: c.y + 0.08, w: 2.0, h: 0.45, fontSize: 15, bold: true, color: c.color });
    s.addText(c.pct + " of cases", { x: c.x + 2.1, y: c.y + 0.08, w: 1.8, h: 0.45, fontSize: 14, bold: true, color: WHITE, align: "right" });
    s.addText(c.desc, { x: c.x + 0.1, y: c.y + 0.55, w: 3.8, h: 0.55, fontSize: 11.5, color: GREY_TXT });
  });
}

// ═══════════════════════════════════════════════════
// SLIDE 12 — TNM Staging
// ═══════════════════════════════════════════════════
{
  let s = pres.addSlide();
  addContentSlideHeader(s, "📊  TNM Staging & Survival");

  const stages = [
    { stage: "Stage I", tnm: "T1-T2a, N0, M0", desc: "Thin, no ulceration, localized", survival: "≥80%", color: ACCENT3, w: 2.5, bar: 10.0 },
    { stage: "Stage II", tnm: "T2b-T4, N0, M0", desc: "Thick / ulcerated, localized", survival: "60-80%", color: ACCENT2, w: 2.0, bar: 8.0 },
    { stage: "Stage III", tnm: "N1-N3, M0", desc: "Regional nodes / in-transit mets", survival: "10-60%", color: "FF6B6B", w: 1.5, bar: 5.5 },
    { stage: "Stage IV", tnm: "M1 — any T, N", desc: "Distant metastases", survival: "<10%", color: ACCENT1, w: 0.8, bar: 2.5 },
  ];

  stages.forEach((st, i) => {
    const y = 1.3 + i * 1.48;
    // Stage badge
    s.addShape(pres.ShapeType.roundRect, { x: 0.3, y, w: 1.5, h: 1.2, fill: { color: st.color } });
    s.addText(st.stage, { x: 0.3, y, w: 1.5, h: 1.2, fontSize: 17, bold: true, color: WHITE, align: "center", valign: "middle" });
    // TNM
    s.addText(st.tnm, { x: 1.95, y: y + 0.05, w: 3.5, h: 0.5, fontSize: 14, bold: true, color: st.color });
    s.addText(st.desc, { x: 1.95, y: y + 0.55, w: 3.5, h: 0.5, fontSize: 12.5, color: LIGHT_TXT });
    // Survival bar
    s.addShape(pres.ShapeType.rect, { x: 5.7, y: y + 0.3, w: 6.5, h: 0.5, fill: { color: CARD_BG } });
    s.addShape(pres.ShapeType.rect, { x: 5.7, y: y + 0.3, w: st.bar * 0.65, h: 0.5, fill: { color: st.color } });
    s.addText(st.survival + " 5-yr survival", { x: 12.2, y: y + 0.3, w: 1.0, h: 0.5, fontSize: 12, bold: true, color: st.color, align: "left" });
  });

  // Footnote about depth
  s.addShape(pres.ShapeType.roundRect, { x: 0.3, y: 7.0, w: 13.0, h: 0.38, fill: { color: CARD_BG }, line: { color: "2A3F55" } });
  s.addText("T category = Breslow thickness (mm) + ulceration status  |  N = regional nodes / in-transit  |  M = distant metastases", {
    x: 0.5, y: 7.03, w: 12.8, h: 0.33, fontSize: 11, color: GREY_TXT, align: "center"
  });
}

// ═══════════════════════════════════════════════════
// SLIDE 13 — Chemokine Receptors & Molecular Basis
// ═══════════════════════════════════════════════════
{
  let s = pres.addSlide();
  addContentSlideHeader(s, "🧬  Molecular Drivers of Metastasis");

  // Left: Chemokine receptor roles
  s.addShape(pres.ShapeType.roundRect, { x: 0.3, y: 1.3, w: 6.2, h: 5.9, fill: { color: CARD_BG }, line: { color: ACCENT2 } });
  s.addText("🔗  Chemokine Receptors", { x: 0.4, y: 1.4, w: 6.0, h: 0.5, fontSize: 18, bold: true, color: ACCENT2, align: "center" });

  const chemokines = [
    { receptor: "CCR10", role: "Survival in primary tumor & skin mets" },
    { receptor: "CCR7", role: "Lymph node metastasis — migration to LN" },
    { receptor: "CXCR4", role: "Primary tumor + distant organs (lungs)" },
    { receptor: "CCR9", role: "Small bowel metastasis" },
    { receptor: "IL-8", role: "Autocrine growth + attracts cells to primary tumor" },
    { receptor: "CCR2 / MCP-1", role: "Recruits tumor-supporting macrophages" },
  ];

  chemokines.forEach((c, i) => {
    s.addShape(pres.ShapeType.roundRect, { x: 0.5, y: 2.05 + i * 0.85, w: 5.8, h: 0.72, fill: { color: "0F2030" }, line: { color: "1C3E55" } });
    s.addText(c.receptor, { x: 0.6, y: 2.1 + i * 0.85, w: 1.5, h: 0.62, fontSize: 14, bold: true, color: ACCENT2, valign: "middle" });
    s.addText("→ " + c.role, { x: 2.2, y: 2.1 + i * 0.85, w: 4.0, h: 0.62, fontSize: 13, color: LIGHT_TXT, valign: "middle" });
  });

  // Right: Mutation panel
  s.addShape(pres.ShapeType.roundRect, { x: 6.8, y: 1.3, w: 6.2, h: 5.9, fill: { color: CARD_BG }, line: { color: ACCENT1 } });
  s.addText("🧬  Key Mutations in Melanoma", { x: 6.9, y: 1.4, w: 6.0, h: 0.5, fontSize: 18, bold: true, color: ACCENT1, align: "center" });

  const mutations = [
    { gene: "BRAF V600E", pct: "40-50%", effect: "Activates RAS-MAPK pathway → proliferation", therapy: "Vemurafenib, Dabrafenib" },
    { gene: "RAS (NRAS)", pct: "15-20%", effect: "Upstream activator of BRAF and PI3K", therapy: "MEK inhibitors" },
    { gene: "CDKN2A", pct: "~40% familial", effect: "Loss of p16/ARF → cell cycle escape", therapy: "CDK4/6 inhibitors" },
    { gene: "PTEN loss", pct: "~20%", effect: "PI3K/AKT pathway hyperactivation", therapy: "PI3K inhibitors" },
    { gene: "KIT", pct: "Acral/mucosal", effect: "Receptor tyrosine kinase activation", therapy: "Imatinib, Nilotinib" },
    { gene: "TERT promoter", pct: "Common", effect: "Telomerase reactivation → immortality", therapy: "Under investigation" },
  ];

  mutations.forEach((m, i) => {
    const y = 2.05 + i * 0.85;
    s.addShape(pres.ShapeType.roundRect, { x: 7.0, y, w: 5.8, h: 0.72, fill: { color: "0F2030" }, line: { color: "3A1020" } });
    s.addText(m.gene, { x: 7.1, y: y + 0.05, w: 1.6, h: 0.3, fontSize: 13, bold: true, color: ACCENT1 });
    s.addText(m.pct, { x: 8.75, y: y + 0.05, w: 1.0, h: 0.3, fontSize: 11, color: ACCENT2 });
    s.addText(m.effect, { x: 7.1, y: y + 0.35, w: 4.0, h: 0.3, fontSize: 11, color: LIGHT_TXT });
    s.addText("💊 " + m.therapy, { x: 10.75, y: y + 0.3, w: 1.9, h: 0.35, fontSize: 10, color: ACCENT3, align: "right" });
  });
}

// ═══════════════════════════════════════════════════
// SLIDE 14 — Nevus vs Melanoma Types (Visual Gallery)
// ═══════════════════════════════════════════════════
{
  let s = pres.addSlide();
  addContentSlideHeader(s, "🖼️  Types of Melanoma vs Nevi");

  // Types of melanoma
  const melTypes = [
    { name: "Superficial\nSpreading", pct: "70%", color: ACCENT1, desc: "Most common; sun-exposed skin; RGP dominant" },
    { name: "Nodular\nMelanoma", pct: "15-30%", color: "C0392B", desc: "VGP only; fastest growing; worst prognosis" },
    { name: "Lentigo Maligna\nMelanoma", pct: "4-10%", color: ACCENT2, desc: "Elderly, face; indolent RGP for decades" },
    { name: "Acral Lentiginous", pct: "5%", color: ACCENT3, desc: "Palms, soles, subungual; common in dark skin; KIT mutation" },
  ];

  s.addText("Types of Melanoma", { x: 0.3, y: 1.25, w: 7.0, h: 0.45, fontSize: 16, bold: true, color: WHITE });

  melTypes.forEach((mt, i) => {
    const x = 0.3 + i * 3.3;
    s.addShape(pres.ShapeType.roundRect, { x, y: 1.75, w: 3.1, h: 2.9, fill: { color: CARD_BG }, line: { color: mt.color } });
    s.addShape(pres.ShapeType.roundRect, { x, y: 1.75, w: 3.1, h: 0.75, fill: { color: mt.color } });
    s.addText(mt.name, { x, y: 1.8, w: 3.1, h: 0.65, fontSize: 14, bold: true, color: WHITE, align: "center", valign: "middle" });
    s.addText(mt.pct + " of cases", { x, y: 2.6, w: 3.1, h: 0.4, fontSize: 13, bold: true, color: mt.color, align: "center" });
    s.addText(mt.desc, { x: x + 0.15, y: 3.1, w: 2.8, h: 1.4, fontSize: 12, color: LIGHT_TXT, align: "center" });
  });

  // Nevi types
  const neviTypes = [
    { name: "Junctional Nevus", color: ACCENT3, desc: "Flat macule; nests at DEJ" },
    { name: "Compound Nevus", color: ACCENT2, desc: "Slightly raised; nests in epidermis & dermis" },
    { name: "Intradermal Nevus", color: "A29BFE", desc: "Dome-shaped papule; only dermis" },
    { name: "Dysplastic Nevus", color: "FF6B6B", desc: "Atypical; melanoma risk marker" },
  ];

  s.addText("Types of Nevi (Moles)", { x: 0.3, y: 4.75, w: 7.0, h: 0.45, fontSize: 16, bold: true, color: WHITE });

  neviTypes.forEach((n, i) => {
    const x = 0.3 + i * 3.3;
    s.addShape(pres.ShapeType.roundRect, { x, y: 5.25, w: 3.1, h: 1.9, fill: { color: CARD_BG }, line: { color: n.color } });
    s.addText(n.name, { x, y: 5.3, w: 3.1, h: 0.5, fontSize: 14, bold: true, color: n.color, align: "center" });
    s.addText(n.desc, { x: x + 0.1, y: 5.85, w: 2.9, h: 1.1, fontSize: 12.5, color: LIGHT_TXT, align: "center" });
  });

  // Right panel — warning signs
  s.addShape(pres.ShapeType.roundRect, { x: 9.5, y: 1.25, w: 3.5, h: 5.9, fill: { color: CARD_BG }, line: { color: ACCENT1 } });
  s.addShape(pres.ShapeType.roundRect, { x: 9.5, y: 1.25, w: 3.5, h: 0.7, fill: { color: ACCENT1 } });
  s.addText("⚠️ Ugly Duckling Sign", { x: 9.5, y: 1.3, w: 3.5, h: 0.6, fontSize: 14, bold: true, color: WHITE, align: "center", valign: "middle" });
  s.addText([
    { text: "A lesion that looks different from all the other moles on the patient — the 'odd one out' — deserves immediate evaluation regardless of ABCDE features.\n\n", options: { breakLine: false } },
    { text: "Also watch for:", options: { bold: true, color: ACCENT2, breakLine: true } },
    { text: "• Lesion that bleeds spontaneously\n• Persistent itch or pain\n• Rapid change in any feature\n• Amelanotic (pink) nodules\n• EFG rule: Elevated, Firm, Growing", options: { breakLine: false } }
  ], {
    x: 9.6, y: 2.05, w: 3.3, h: 5.0, fontSize: 12, color: LIGHT_TXT, valign: "top"
  });
}

// ═══════════════════════════════════════════════════
// SLIDE 15 — Key Takeaways
// ═══════════════════════════════════════════════════
{
  let s = pres.addSlide();
  addSectionDivider(s, "Final", "Key Takeaways", ACCENT3);
  s.addText("Everything you need to remember", {
    x: 1, y: 4.5, w: 11.3, h: 0.7, fontSize: 18,
    color: GREY_TXT, align: "center", italic: true
  });
}

{
  let s = pres.addSlide();
  addContentSlideHeader(s, "✅  Key Takeaways");

  const takeaways = [
    { icon: "🔬", text: "Nevus = benign melanocyte proliferation; BRAF/RAS mutant but senescence kept intact by p16" },
    { icon: "🚨", text: "Melanoma = malignant; ABCDE criteria (Asymmetry, Border, Color, Diameter, Evolution) guide detection" },
    { icon: "📐", text: "Radial growth phase lacks metastatic potential; Vertical growth phase = invasion & metastasis risk" },
    { icon: "🛣️", text: "Metastasis occurs via lymphatics (CCR7/CCR10), blood (CXCR4), or direct extension (satellite/in-transit)" },
    { icon: "🗺️", text: "Top metastatic sites: Skin/LN (Stage III, ~70%), Lung, Liver, Brain, Bone" },
    { icon: "🧬", text: "BRAF V600E in 40-50% — targetable with vemurafenib/dabrafenib + trametinib (MEK inhibitor)" },
    { icon: "📊", text: "Breslow thickness + ulceration = most important prognostic factors; Stage IV <10% 5-yr survival" },
    { icon: "💊", text: "PD-1 checkpoint inhibitors (pembrolizumab, nivolumab) dramatically improve Stage III/IV outcomes" },
  ];

  takeaways.forEach((t, i) => {
    const col = i < 4 ? 0 : 1;
    const row = i < 4 ? i : i - 4;
    const x = col === 0 ? 0.3 : 6.9;
    const y = 1.3 + row * 1.5;

    s.addShape(pres.ShapeType.roundRect, { x, y, w: 6.3, h: 1.3, fill: { color: CARD_BG }, line: { color: "2A3F55" } });
    s.addText(t.icon, { x: x + 0.15, y, w: 0.7, h: 1.3, fontSize: 24, align: "center", valign: "middle" });
    s.addText(t.text, { x: x + 0.95, y: y + 0.2, w: 5.2, h: 0.9, fontSize: 13, color: LIGHT_TXT, valign: "middle" });
  });
}

// ═══════════════════════════════════════════════════
// OUTPUT
// ═══════════════════════════════════════════════════
pres.writeFile({ fileName: "/home/daytona/workspace/melanoma-ppt/Melanoma_Metastasis_Nevus.pptx" })
  .then(() => console.log("✅ Presentation saved successfully!"))
  .catch(err => console.error("Error:", err));

<!DOCTYPE html>
<html lang="en">
<head>
<meta charset="UTF-8">
<meta name="viewport" content="width=device-width, initial-scale=1.0">
<title>Melanoma: Metastasis & Nevus vs Melanoma</title>
<style>
  * { margin: 0; padding: 0; box-sizing: border-box; }
  body { background: #000; font-family: 'Segoe UI', Calibri, Arial, sans-serif; overflow: hidden; }

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  .hint { position: fixed; top: 12px; right: 18px; color: #555; font-size: 12px; z-index: 999; }

  /* ── Colors ── */
  :root {
    --dark: #0D1B2A; --mid: #1B2A3B; --card: #152030;
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    --white: #FFFFFF; --light: #D9E2EC; --grey: #A8B2BD;
    --purple: #A29BFE;
  }

  /* ── SLIDE 1: Title ── */
  #s1 { background: var(--dark); justify-content: center; align-items: center; }
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  #s1 .src { position: absolute; bottom: 15px; color: rgba(255,255,255,0.6); font-size: 12px; z-index:2; }

  /* ── SLIDE 2: Agenda ── */
  #s2 { background: var(--dark); }
  .slide-header { background: var(--card); padding: 14px 28px; border-top: 5px solid var(--red); }
  .slide-header h2 { color: #fff; font-size: clamp(18px,2.5vw,30px); }
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  /* ── Basics Slide ── */
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  .fact-list { display: flex; flex-direction: column; gap: 10px; flex: 1; }
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  .risk-panel { background: var(--card); border-radius: 12px; padding: 16px 18px; border: 2px solid var(--red); flex: 1; }
  .risk-panel h3 { color: var(--red); font-size: clamp(14px,1.6vw,19px); margin-bottom: 12px; text-align: center; }
  .risk-item { display: flex; align-items: flex-start; gap: 8px; margin-bottom: 8px; }
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  .risk-item span { color: var(--light); font-size: clamp(11px,1.2vw,14px); }

  /* ── ABCDE Slide ── */
  #s6 { background: var(--dark); flex-direction: column; }
  .abcde-table { padding: 10px 22px; flex: 1; display: flex; flex-direction: column; gap: 5px; }
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  /* ── TNM Staging ── */
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</style>
</head>
<body>

<div class="hint">← → Arrow keys or click buttons</div>

<!-- ══════════════════════════════════════════════════ -->
<!-- SLIDE 1 — Title -->
<!-- ══════════════════════════════════════════════════ -->
<div class="slide active" id="s1">
  <div class="left-bar"></div>
  <div class="bottom-bar"></div>
  <h1>Melanoma:<br>Metastasis &amp; Nevus vs Melanoma</h1>
  <p class="sub">Pathology &nbsp;|&nbsp; Dermoscopy &nbsp;|&nbsp; Staging &nbsp;|&nbsp; Molecular Basis</p>
  <p class="src">Source: Robbins Pathology · Fitzpatrick's Dermatology · Dermatology 2-Vol Set (Elsevier)</p>
</div>

<!-- ══════════════════════════════════════════════════ -->
<!-- SLIDE 2 — Agenda -->
<!-- ══════════════════════════════════════════════════ -->
<div class="slide" id="s2">
  <div class="slide-header"><h2>📋 What We'll Cover</h2></div>
  <div class="agenda-grid">
    <div class="agenda-item"><div class="agenda-num" style="background:var(--red)">01</div><div class="agenda-label">What is Melanoma?</div></div>
    <div class="agenda-item"><div class="agenda-num" style="background:var(--amber)">02</div><div class="agenda-label">Nevus vs Melanoma — ABCDE &amp; Histology</div></div>
    <div class="agenda-item"><div class="agenda-num" style="background:var(--teal)">03</div><div class="agenda-label">Radial &amp; Vertical Growth Phases</div></div>
    <div class="agenda-item"><div class="agenda-num" style="background:var(--purple)">04</div><div class="agenda-label">Metastasis: Pathways &amp; Mechanisms</div></div>
    <div class="agenda-item"><div class="agenda-num" style="background:var(--red)">05</div><div class="agenda-label">Staging (TNM) &amp; Sites of Spread</div></div>
    <div class="agenda-item"><div class="agenda-num" style="background:var(--amber)">06</div><div class="agenda-label">Molecular Drivers &amp; Targeted Therapy</div></div>
    <div class="agenda-item"><div class="agenda-num" style="background:var(--teal)">07</div><div class="agenda-label">Types of Melanoma &amp; Nevi</div></div>
    <div class="agenda-item"><div class="agenda-num" style="background:#FF6B6B">08</div><div class="agenda-label">Key Takeaways</div></div>
  </div>
</div>

<!-- ══════════════════════════════════════════════════ -->
<!-- SLIDE 3 — Section: What is Melanoma -->
<!-- ══════════════════════════════════════════════════ -->
<div class="slide section-div" id="s3">
  <div class="sec-num" style="color:var(--red)">SECTION 01</div>
  <div class="divider-line" style="background:var(--red)"></div>
  <h2>What Is Melanoma?</h2>
  <p class="sec-sub">The skin's most deadly cancer — arising from melanocytes</p>
</div>

<!-- ══════════════════════════════════════════════════ -->
<!-- SLIDE 4 — Melanoma Basics -->
<!-- ══════════════════════════════════════════════════ -->
<div class="slide" id="s4" style="flex-direction:column;background:var(--dark)">
  <div class="slide-header"><h2>🎯 Melanoma — The Basics</h2></div>
  <div class="two-col">
    <div class="fact-list">
      <div class="fact-card"><div class="fh">🔬 Origin</div><div class="fb">Malignant transformation of melanocytes — pigment-producing cells in the basal epidermis at the dermoepidermal junction</div></div>
      <div class="fact-card"><div class="fh">☀️ Main Risk Factor</div><div class="fb">UV radiation from sunlight; periodic severe sunburns especially early in life are the most critical risk factor</div></div>
      <div class="fact-card"><div class="fh">💀 Lethality</div><div class="fb">Most lethal skin cancer — 5-year survival drops to &lt;10% at Stage IV. Tumor metastasis is the #1 cause of mortality</div></div>
      <div class="fact-card"><div class="fh">📈 Molecular Epidemiology</div><div class="fb">40–50% carry BRAF V600E mutations; 15–20% have RAS mutations; CDKN2A mutated in ~40% of familial cases</div></div>
    </div>
    <div class="risk-panel">
      <h3>⚠️ Risk Factors</h3>
      <div class="risk-item"><div class="risk-dot"></div><span>Fair skin, light hair &amp; eyes</span></div>
      <div class="risk-item"><div class="risk-dot"></div><span>History of sunburns / UV exposure</span></div>
      <div class="risk-item"><div class="risk-dot"></div><span>Personal or family history of melanoma</span></div>
      <div class="risk-item"><div class="risk-dot"></div><span>Large number of moles (&gt;50)</span></div>
      <div class="risk-item"><div class="risk-dot"></div><span>Dysplastic nevi (atypical moles)</span></div>
      <div class="risk-item"><div class="risk-dot"></div><span>Immunosuppression</span></div>
      <div class="risk-item"><div class="risk-dot"></div><span>CDKN2A / BRAF germline mutations</span></div>
      <div class="risk-item"><div class="risk-dot"></div><span>Xeroderma pigmentosum</span></div>
      <div class="risk-item"><div class="risk-dot"></div><span>Estrogen — receptors implicated in progression</span></div>
    </div>
  </div>
</div>

<!-- ══════════════════════════════════════════════════ -->
<!-- SLIDE 5 — Section: Nevus vs Melanoma -->
<!-- ══════════════════════════════════════════════════ -->
<div class="slide section-div" id="s5">
  <div class="sec-num" style="color:var(--amber)">SECTION 02</div>
  <div class="divider-line" style="background:var(--amber)"></div>
  <h2>Nevus vs Melanoma</h2>
  <p class="sec-sub">ABCDE criteria &nbsp;|&nbsp; Histology &nbsp;|&nbsp; Molecular differences</p>
</div>

<!-- ══════════════════════════════════════════════════ -->
<!-- SLIDE 6 — ABCDE -->
<!-- ══════════════════════════════════════════════════ -->
<div class="slide" id="s6">
  <div class="slide-header"><h2>🔍 The ABCDE Rule — Mole vs Melanoma</h2></div>
  <div class="abcde-table">
    <div class="abcde-header">
      <div style="color:var(--grey)">Letter</div>
      <div style="color:var(--grey)">Feature</div>
      <div style="background:#0e2a1a;color:var(--teal)">✅ Benign Nevus</div>
      <div style="background:#2a0e0e;color:var(--red)">🚨 Melanoma</div>
    </div>
    <div class="abcde-row">
      <div class="abcde-letter" style="background:var(--red)">A</div>
      <div class="abcde-feature" style="background:var(--card);color:var(--red)">Asymmetry</div>
      <div class="abcde-cell">Symmetrical — both halves match in shape and colour</div>
      <div class="abcde-cell">Asymmetrical — two halves differ markedly in shape and/or colour</div>
    </div>
    <div class="abcde-row">
      <div class="abcde-letter" style="background:var(--amber)">B</div>
      <div class="abcde-feature" style="background:var(--card);color:var(--amber)">Border</div>
      <div class="abcde-cell">Smooth, well-defined, regular rounded edges</div>
      <div class="abcde-cell">Irregular, ragged, notched or blurred borders</div>
    </div>
    <div class="abcde-row">
      <div class="abcde-letter" style="background:var(--teal)">C</div>
      <div class="abcde-feature" style="background:var(--card);color:var(--teal)">Color</div>
      <div class="abcde-cell">Uniform tan or brown pigmentation throughout</div>
      <div class="abcde-cell">Multiple shades: black, brown, red, grey, white zones — &gt;2 colours</div>
    </div>
    <div class="abcde-row">
      <div class="abcde-letter" style="background:var(--purple)">D</div>
      <div class="abcde-feature" style="background:var(--card);color:var(--purple)">Diameter</div>
      <div class="abcde-cell">Usually &lt; 6 mm (size of a pencil eraser)</div>
      <div class="abcde-cell">Often &gt; 6 mm; any growing lesion is suspicious</div>
    </div>
    <div class="abcde-row">
      <div class="abcde-letter" style="background:#FF6B6B">E</div>
      <div class="abcde-feature" style="background:var(--card);color:#FF6B6B">Evolution</div>
      <div class="abcde-cell">Stable — no change in size, shape or colour over years</div>
      <div class="abcde-cell">CHANGING in size, shape, colour; may itch, bleed or crust</div>
    </div>
  </div>
</div>

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<!-- SLIDE 7 — Histology -->
<!-- ══════════════════════════════════════════════════ -->
<div class="slide" id="s7">
  <div class="slide-header"><h2>🔬 Histology: Nevus vs Melanoma</h2></div>
  <div class="histo-cols">
    <div class="histo-panel" style="border:2px solid var(--teal)">
      <h3 style="color:var(--teal)">✅ Benign Nevus</h3>
      <div class="histo-item"><div class="histo-dot" style="background:var(--teal)"></div><span>Small, uniform, round melanocytes with regular nuclei</span></div>
      <div class="histo-item"><div class="histo-dot" style="background:var(--teal)"></div><span>Nests equidistant along the dermoepidermal junction (DEJ)</span></div>
      <div class="histo-item"><div class="histo-dot" style="background:var(--teal)"></div><span><strong style="color:var(--teal)">Maturation with depth</strong> — "neurotization": cells become smaller &amp; spindle-shaped</span></div>
      <div class="histo-item"><div class="histo-dot" style="background:var(--teal)"></div><span>Deeper cells lose pigment (progressive loss of tyrosinase activity)</span></div>
      <div class="histo-item"><div class="histo-dot" style="background:var(--teal)"></div><span>No mitotic figures in deeper layers</span></div>
      <div class="histo-item"><div class="histo-dot" style="background:var(--teal)"></div><span>BRAF/RAS mutant but senescence maintained by <strong style="color:var(--teal)">p16 (CDKN2A)</strong></span></div>
      <div class="histo-item"><div class="histo-dot" style="background:var(--teal)"></div><span>Smooth, well-circumscribed borders; symmetric silhouette</span></div>
      <div class="histo-item"><div class="histo-dot" style="background:var(--teal)"></div><span>Types: Junctional → Compound → Intradermal (progression)</span></div>
    </div>
    <div class="histo-panel" style="border:2px solid var(--red)">
      <h3 style="color:var(--red)">🚨 Melanoma</h3>
      <div class="histo-item"><div class="histo-dot" style="background:var(--red)"></div><span>Large cells with <strong style="color:var(--red)">pleomorphic nuclei</strong> — irregular contours</span></div>
      <div class="histo-item"><div class="histo-dot" style="background:var(--red)"></div><span>Chromatin clumped at <strong style="color:var(--red)">nuclear membrane periphery</strong></span></div>
      <div class="histo-item"><div class="histo-dot" style="background:var(--red)"></div><span>Prominent <strong style="color:var(--red)">eosinophilic (red) nucleoli</strong></span></div>
      <div class="histo-item"><div class="histo-dot" style="background:var(--red)"></div><span>Irregular, asymmetric nests — varying size &amp; shape; some confluent</span></div>
      <div class="histo-item"><div class="histo-dot" style="background:var(--red)"></div><span><strong style="color:var(--red)">Pagetoid scatter</strong> — solitary cells above DEJ into upper epidermis</span></div>
      <div class="histo-item"><div class="histo-dot" style="background:var(--red)"></div><span>Mitotic figures present (especially in Vertical Growth Phase)</span></div>
      <div class="histo-item"><div class="histo-dot" style="background:var(--red)"></div><span><strong style="color:var(--red)">NO maturation</strong> with depth — cells remain large throughout</span></div>
      <div class="histo-item"><div class="histo-dot" style="background:var(--red)"></div><span>Necrotic melanocytes may be seen; lymphovascular invasion in VGP</span></div>
    </div>
  </div>
</div>

<!-- ══════════════════════════════════════════════════ -->
<!-- SLIDE 8 — Growth Phases -->
<!-- ══════════════════════════════════════════════════ -->
<div class="slide" id="s8">
  <div class="slide-header"><h2>📐 Growth Phases: Radial → Vertical</h2></div>
  <div class="growth-diagram">
    <div class="skin-layers">
      <div class="layer-epi">── Epidermis / DEJ ──</div>
      <div class="layer-derm" style="display:flex;align-items:center;padding:0 20px;color:#A8B2BD;font-size:13px;">── Dermis ──</div>
      <div class="layer-fat">── Subcutaneous Fat ──</div>
    </div>
    <div class="growth-phases">
      <div class="phase-card" style="border-top:3px solid var(--teal)">
        <div class="phase-icon">🟤</div>
        <h4 style="color:var(--teal)">Normal Nevus</h4>
        <p>Confined to DEJ. Benign melanocytes with oncogene-induced senescence. No invasion.</p>
      </div>
      <div class="phase-card" style="border-top:3px solid var(--amber)">
        <div class="phase-icon">↔️</div>
        <h4 style="color:var(--amber)">Radial Growth Phase (RGP)</h4>
        <p>Centrifugal spread within epidermis. May invade papillary dermis as single cells. <strong style="color:var(--amber)">No metastatic potential.</strong> Includes: SSM, Lentigo Maligna, Acral LM.</p>
      </div>
      <div class="phase-card" style="border-top:3px solid var(--red)">
        <div class="phase-icon">⬇️</div>
        <h4 style="color:var(--red)">Vertical Growth Phase (VGP)</h4>
        <p>Dermal nodule forms — larger nests invade downward. <strong style="color:var(--red)">Metastatic potential EMERGES.</strong> Subclone with migratory capacity selected.</p>
      </div>
      <div class="phase-card" style="border-top:3px solid #8E1414">
        <div class="phase-icon">🩸</div>
        <h4 style="color:#FF4444">Deep Invasion</h4>
        <p>Extends into reticular dermis &amp; fat. Lymphovascular invasion. <strong style="color:#FF4444">Stage III/IV disease.</strong> Breslow thickness &gt;4 mm (T4).</p>
      </div>
    </div>
  </div>
</div>

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<!-- SLIDE 9 — Section: Metastasis -->
<!-- ══════════════════════════════════════════════════ -->
<div class="slide section-div" id="s9">
  <div class="sec-num" style="color:var(--red)">SECTION 03</div>
  <div class="divider-line" style="background:var(--red)"></div>
  <h2>Metastasis of Melanoma</h2>
  <p class="sec-sub">Pathways &nbsp;•&nbsp; Sites &nbsp;•&nbsp; Mechanisms &nbsp;•&nbsp; Prognosis</p>
</div>

<!-- ══════════════════════════════════════════════════ -->
<!-- SLIDE 10 — Pathways -->
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<div class="slide" id="s10">
  <div class="slide-header"><h2>🛣️ Routes of Metastatic Spread</h2></div>
  <div class="pathway-grid">
    <div class="pathway-card" style="border-top:4px solid var(--teal)">
      <div class="pathway-header" style="background:var(--teal)"><span>🫀 1. Lymphatic Spread</span></div>
      <div class="pathway-body">
        <div class="pathway-item"><span style="color:var(--teal)">●</span><span>Most common initial route of spread</span></div>
        <div class="pathway-item"><span style="color:var(--teal)">●</span><span>Primary tumor → afferent lymphatics → regional lymph nodes</span></div>
        <div class="pathway-item"><span style="color:var(--teal)">●</span><span>CCR7 &amp; CCR10 receptors guide lymph node homing</span></div>
        <div class="pathway-item"><span style="color:var(--teal)">●</span><span>SLNB detects occult nodal spread (15–20% positive for &gt;1mm tumors)</span></div>
        <div class="pathway-item"><span style="color:var(--teal)">●</span><span>Nodal metastasis = most powerful negative prognostic factor</span></div>
      </div>
    </div>
    <div class="pathway-card" style="border-top:4px solid var(--red)">
      <div class="pathway-header" style="background:var(--red)"><span>🩸 2. Hematogenous Spread</span></div>
      <div class="pathway-body">
        <div class="pathway-item"><span style="color:var(--red)">●</span><span>Via blood vessels — primarily in Vertical Growth Phase</span></div>
        <div class="pathway-item"><span style="color:var(--red)">●</span><span>Tumor cells invade dermal vessels → circulating melanoma cells</span></div>
        <div class="pathway-item"><span style="color:var(--red)">●</span><span>CXCR4 receptor drives spread to lungs &amp; distant organs</span></div>
        <div class="pathway-item"><span style="color:var(--red)">●</span><span>CCR9 implicated in small bowel metastasis</span></div>
        <div class="pathway-item"><span style="color:var(--red)">●</span><span>IL-8 acts as autocrine growth factor + attracts cells to primary tumor</span></div>
        <div class="pathway-item"><span style="color:var(--red)">●</span><span>Macrophages (via MCP-1/CCR2) promote invasion &amp; metastasis</span></div>
      </div>
    </div>
    <div class="pathway-card" style="border-top:4px solid var(--amber)">
      <div class="pathway-header" style="background:var(--amber)"><span>🔗 3. Direct / In-Transit</span></div>
      <div class="pathway-body">
        <div class="pathway-item"><span style="color:var(--amber)">●</span><span><strong style="color:var(--amber)">Microsatellite:</strong> microscopic foci adjacent to / deep to primary</span></div>
        <div class="pathway-item"><span style="color:var(--amber)">●</span><span><strong style="color:var(--amber)">Satellite:</strong> clinically evident focus within 2 cm of primary, discontinuous</span></div>
        <div class="pathway-item"><span style="color:var(--amber)">●</span><span><strong style="color:var(--amber)">In-transit:</strong> lymphatic metastasis &gt;2 cm from primary tumor</span></div>
        <div class="pathway-item"><span style="color:var(--amber)">●</span><span>All three = <strong style="color:var(--amber)">Stage III (N category)</strong> disease</span></div>
        <div class="pathway-item"><span style="color:var(--amber)">●</span><span>Appear as brown/black or pink papules, plaques on skin surface</span></div>
      </div>
    </div>
  </div>
</div>

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<!-- SLIDE 11 — Sites -->
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<div class="slide" id="s11">
  <div class="slide-header"><h2>🗺️ Where Does Melanoma Spread?</h2></div>
  <div class="body-map-layout">
    <div class="body-figure">
      <div style="font-size:80px;line-height:1">🧍</div>
      <div style="color:var(--grey);font-size:12px;text-align:center;margin-top:8px;">Melanoma disseminates<br>via lymphatics &amp; blood</div>
    </div>
    <div class="sites-grid">
      <div class="site-card" style="border-color:var(--purple)">
        <div class="site-name" style="color:var(--purple)">🧠 Brain <span class="site-pct" style="color:var(--purple)">15–30%</span></div>
        <div class="site-desc">Seizures, headache, focal neurology; detected on MRI. Necrosis, perilesional edema &amp; hemorrhage are features.</div>
      </div>
      <div class="site-card" style="border-color:var(--teal)">
        <div class="site-name" style="color:var(--teal)">🫁 Lung <span class="site-pct" style="color:var(--teal)">18–36%</span></div>
        <div class="site-desc">Most common distant site via CXCR4 signalling. Detected on CT chest. Presents as pulmonary nodules.</div>
      </div>
      <div class="site-card" style="border-color:var(--amber)">
        <div class="site-name" style="color:var(--amber)">🫀 Liver <span class="site-pct" style="color:var(--amber)">14–20%</span></div>
        <div class="site-desc">#1 site for uveal (ocular) melanoma metastasis. Detected by US/MRI surveillance. Poor prognosis when involved.</div>
      </div>
      <div class="site-card" style="border-color:#FF6B6B">
        <div class="site-name" style="color:#FF6B6B">🦴 Bone <span class="site-pct" style="color:#FF6B6B">6–7%</span></div>
        <div class="site-desc">Lytic lesions causing pain and pathological fractures. Detected on bone scan / PET-CT.</div>
      </div>
      <div class="site-card" style="border-color:var(--red)">
        <div class="site-name" style="color:var(--red)">🔴 Skin / LN <span class="site-pct" style="color:var(--red)">~70%</span></div>
        <div class="site-desc">Most common = Stage III. In-transit, satellite metastases on skin surface. Palpable nodal disease.</div>
      </div>
      <div class="site-card" style="border-color:var(--amber)">
        <div class="site-name" style="color:var(--amber)">🩺 GI Tract <span class="site-pct" style="color:var(--amber)">Rare</span></div>
        <div class="site-desc">Small bowel via CCR9 signalling. Presents with obstruction, bleeding, intussusception.</div>
      </div>
    </div>
  </div>
</div>

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<!-- SLIDE 12 — TNM Staging -->
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<div class="slide" id="s12">
  <div class="slide-header"><h2>📊 TNM Staging &amp; Survival (AJCC)</h2></div>
  <div class="staging-list">
    <div class="stage-row">
      <div class="stage-badge" style="background:var(--teal)">Stage I</div>
      <div><div class="stage-tnm" style="color:var(--teal)">T1–T2a, N0, M0</div><div class="stage-desc">Thin, no ulceration, completely localized</div></div>
      <div class="survival-bar-wrap"><div class="bar-bg"><div class="bar-fill" style="width:90%;background:var(--teal)"></div></div></div>
      <div class="bar-label" style="color:var(--teal)">≥80% 5-yr survival</div>
    </div>
    <div class="stage-row">
      <div class="stage-badge" style="background:var(--amber)">Stage II</div>
      <div><div class="stage-tnm" style="color:var(--amber)">T2b–T4, N0, M0</div><div class="stage-desc">Thick and/or ulcerated, still localized</div></div>
      <div class="survival-bar-wrap"><div class="bar-bg"><div class="bar-fill" style="width:70%;background:var(--amber)"></div></div></div>
      <div class="bar-label" style="color:var(--amber)">60–80% 5-yr survival</div>
    </div>
    <div class="stage-row">
      <div class="stage-badge" style="background:#FF6B6B">Stage III</div>
      <div><div class="stage-tnm" style="color:#FF6B6B">N1–N3, M0</div><div class="stage-desc">Regional nodes / in-transit / satellite metastases</div></div>
      <div class="survival-bar-wrap"><div class="bar-bg"><div class="bar-fill" style="width:35%;background:#FF6B6B"></div></div></div>
      <div class="bar-label" style="color:#FF6B6B">10–60% 5-yr survival</div>
    </div>
    <div class="stage-row">
      <div class="stage-badge" style="background:var(--red)">Stage IV</div>
      <div><div class="stage-tnm" style="color:var(--red)">M1 — any T, any N</div><div class="stage-desc">Distant metastases (brain, lung, liver, bone...)</div></div>
      <div class="survival-bar-wrap"><div class="bar-bg"><div class="bar-fill" style="width:10%;background:var(--red)"></div></div></div>
      <div class="bar-label" style="color:var(--red)">&lt;10% 5-yr survival</div>
    </div>
  </div>
  <div class="staging-note">T = Breslow thickness (mm) + ulceration &nbsp;|&nbsp; N = regional nodes / in-transit &nbsp;|&nbsp; M = distant metastases &nbsp;|&nbsp; Key: ulceration upgrades T stage from 'a' to 'b'</div>
</div>

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<!-- SLIDE 13 — Molecular -->
<!-- ══════════════════════════════════════════════════ -->
<div class="slide" id="s13">
  <div class="slide-header"><h2>🧬 Molecular Drivers of Metastasis</h2></div>
  <div class="mol-cols">
    <div class="mol-panel" style="border:2px solid var(--amber)">
      <h3 style="color:var(--amber)">🔗 Chemokine Receptors</h3>
      <div class="mol-item"><span class="mol-key" style="color:var(--amber)">CCR10</span><span class="mol-val">Survival of primary tumor cells &amp; skin metastases</span></div>
      <div class="mol-item"><span class="mol-key" style="color:var(--amber)">CCR7</span><span class="mol-val">Lymph node homing — migration toward lymphatics</span></div>
      <div class="mol-item"><span class="mol-key" style="color:var(--amber)">CXCR4</span><span class="mol-val">Primary tumor development + distant organs (lungs)</span></div>
      <div class="mol-item"><span class="mol-key" style="color:var(--amber)">CCR9</span><span class="mol-val">Small bowel metastasis — gut-specific homing</span></div>
      <div class="mol-item"><span class="mol-key" style="color:var(--amber)">IL-8</span><span class="mol-val">Autocrine growth + attracts cells; detected with metastatic dissemination</span></div>
      <div class="mol-item"><span class="mol-key" style="color:var(--amber)">CCR2 / MCP-1</span><span class="mol-val">Recruits macrophages that promote invasion &amp; suppress immune clearance</span></div>
    </div>
    <div class="mol-panel" style="border:2px solid var(--red)">
      <h3 style="color:var(--red)">🧬 Key Mutations &amp; Therapies</h3>
      <div class="mol-item">
        <span class="mol-key" style="color:var(--red)">BRAF V600E</span>
        <span class="mol-val">40–50% | Activates RAS-MAPK → proliferation &nbsp;<strong style="color:var(--teal)">→ Vemurafenib, Dabrafenib</strong></span>
      </div>
      <div class="mol-item">
        <span class="mol-key" style="color:var(--red)">NRAS</span>
        <span class="mol-val">15–20% | Upstream activator of BRAF &amp; PI3K &nbsp;<strong style="color:var(--teal)">→ MEK inhibitors</strong></span>
      </div>
      <div class="mol-item">
        <span class="mol-key" style="color:var(--red)">CDKN2A loss</span>
        <span class="mol-val">~40% familial | Loss of p16/ARF → cell cycle escape, senescence override</span>
      </div>
      <div class="mol-item">
        <span class="mol-key" style="color:var(--red)">PTEN loss</span>
        <span class="mol-val">~20% | Uncontrolled PI3K/AKT pathway activation &amp; survival</span>
      </div>
      <div class="mol-item">
        <span class="mol-key" style="color:var(--red)">KIT</span>
        <span class="mol-val">Acral/mucosal melanoma | RTK activation &nbsp;<strong style="color:var(--teal)">→ Imatinib, Nilotinib</strong></span>
      </div>
      <div class="mol-item">
        <span class="mol-key" style="color:var(--red)">TERT promoter</span>
        <span class="mol-val">Common | Reactivates telomerase → immortality / escape from senescence</span>
      </div>
    </div>
  </div>
</div>

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<!-- SLIDE 14 — Types -->
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<div class="slide" id="s14">
  <div class="slide-header"><h2>🖼️ Types of Melanoma &amp; Nevi</h2></div>
  <div style="display:flex;gap:16px;padding:12px 20px;flex:1;overflow:hidden">
    <div style="flex:1;display:flex;flex-direction:column;gap:8px">
      <div style="color:#fff;font-size:clamp(13px,1.5vw,17px);font-weight:bold;margin-bottom:2px">Types of Melanoma</div>
      <div style="display:grid;grid-template-columns:1fr 1fr;gap:8px">
        <div class="type-card"><div class="type-card-header" style="background:var(--red)">Superficial Spreading</div><div class="type-card-body"><div class="type-pct" style="color:var(--red)">70% of cases</div><div class="type-desc">Most common; sun-exposed skin; radial growth phase dominant; irregular pigmentation</div></div></div>
        <div class="type-card"><div class="type-card-header" style="background:#8E1414">Nodular Melanoma</div><div class="type-card-body"><div class="type-pct" style="color:#FF4444">15–30% of cases</div><div class="type-desc">VGP only from the start; fastest growing; worst prognosis; often amelanotic (pink)</div></div></div>
        <div class="type-card"><div class="type-card-header" style="background:var(--amber)">Lentigo Maligna</div><div class="type-card-body"><div class="type-pct" style="color:var(--amber)">4–10% of cases</div><div class="type-desc">Elderly; face/sun-damaged skin; indolent RGP for decades before invasion</div></div></div>
        <div class="type-card"><div class="type-card-header" style="background:var(--teal)">Acral Lentiginous</div><div class="type-card-body"><div class="type-pct" style="color:var(--teal)">~5% (more in dark skin)</div><div class="type-desc">Palms, soles, subungual; most common type in darker-skinned people; KIT mutation common</div></div></div>
      </div>
      <div style="color:#fff;font-size:clamp(13px,1.5vw,17px);font-weight:bold;margin-top:4px">Types of Nevi</div>
      <div style="display:grid;grid-template-columns:1fr 1fr 1fr 1fr;gap:8px">
        <div class="type-card" style="border:1px solid var(--teal)"><div class="type-card-body"><div class="type-pct" style="color:var(--teal)">Junctional</div><div class="type-desc">Flat macule; nests at DEJ only</div></div></div>
        <div class="type-card" style="border:1px solid var(--amber)"><div class="type-card-body"><div class="type-pct" style="color:var(--amber)">Compound</div><div class="type-desc">Slightly raised; nests in epidermis &amp; dermis</div></div></div>
        <div class="type-card" style="border:1px solid var(--purple)"><div class="type-card-body"><div class="type-pct" style="color:var(--purple)">Intradermal</div><div class="type-desc">Dome-shaped; dermis only; mature cells</div></div></div>
        <div class="type-card" style="border:1px solid #FF6B6B"><div class="type-card-body"><div class="type-pct" style="color:#FF6B6B">Dysplastic</div><div class="type-desc">Atypical mole; melanoma risk marker</div></div></div>
      </div>
    </div>
    <div style="width:260px;flex-shrink:0">
      <div class="ugly-box" style="height:calc(100% - 8px)">
        <h4>⚠️ Ugly Duckling Sign</h4>
        <p>A lesion that looks <strong>different from all other moles</strong> on the patient — the "odd one out" — deserves immediate evaluation regardless of ABCDE features.<br><br>
        <strong style="color:var(--amber)">Also watch for (EFG rule):</strong><br>
        • <strong>E</strong>levated above skin surface<br>
        • <strong>F</strong>irm to touch<br>
        • <strong>G</strong>rowing rapidly<br><br>
        Other red flags:<br>
        • Spontaneous bleeding<br>
        • Persistent itch or pain<br>
        • Amelanotic (pink) nodules<br>
        • Subungual (nail) pigmentation</p>
      </div>
    </div>
  </div>
</div>

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<!-- SLIDE 15 — Section: Takeaways -->
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<div class="slide section-div" id="s15">
  <div class="sec-num" style="color:var(--teal)">FINAL</div>
  <div class="divider-line" style="background:var(--teal)"></div>
  <h2>Key Takeaways</h2>
  <p class="sec-sub">Everything you need to remember</p>
</div>

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<!-- SLIDE 16 — Takeaways -->
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<div class="slide" id="s16">
  <div class="slide-header"><h2>✅ Key Takeaways</h2></div>
  <div class="takeaway-grid">
    <div class="takeaway-card" style="border-color:var(--teal)"><div class="takeaway-icon">🔬</div><div class="takeaway-text"><strong style="color:var(--teal)">Nevus</strong> = benign melanocyte proliferation; BRAF/RAS mutant but senescence kept intact by p16 — rarely transforms to melanoma</div></div>
    <div class="takeaway-card" style="border-color:var(--red)"><div class="takeaway-icon">🚨</div><div class="takeaway-text"><strong style="color:var(--red)">Melanoma</strong> = malignant; use <strong>ABCDE</strong> (Asymmetry, Border, Color, Diameter, Evolution) and EFG rule for nodular melanoma</div></div>
    <div class="takeaway-card" style="border-color:var(--amber)"><div class="takeaway-icon">📐</div><div class="takeaway-text"><strong style="color:var(--amber)">Radial growth phase</strong> lacks metastatic potential; <strong style="color:var(--red)">Vertical growth phase</strong> = invasion, nodule formation &amp; metastasis risk</div></div>
    <div class="takeaway-card" style="border-color:var(--purple)"><div class="takeaway-icon">🛣️</div><div class="takeaway-text">Metastasis via <strong style="color:var(--teal)">lymphatics</strong> (CCR7/CCR10), <strong style="color:var(--red)">blood</strong> (CXCR4), or <strong style="color:var(--amber)">direct</strong> (satellite/in-transit). ~70% Stage III = locoregional</div></div>
    <div class="takeaway-card" style="border-color:#FF6B6B"><div class="takeaway-icon">🗺️</div><div class="takeaway-text">Top metastatic sites: <strong>Skin/LN</strong> (Stage III), <strong>Lung</strong> (18–36%), <strong>Liver</strong> (14–20%, #1 in uveal melanoma), <strong>Brain</strong> (15–30%)</div></div>
    <div class="takeaway-card" style="border-color:var(--red)"><div class="takeaway-icon">🧬</div><div class="takeaway-text"><strong style="color:var(--red)">BRAF V600E</strong> in 40–50% — targetable with vemurafenib + trametinib. <strong>KIT</strong> in acral/mucosal → imatinib</div></div>
    <div class="takeaway-card" style="border-color:var(--amber)"><div class="takeaway-icon">📊</div><div class="takeaway-text"><strong style="color:var(--amber)">Breslow thickness + ulceration</strong> = key prognostic factors. Stage I ≥80% vs Stage IV &lt;10% 5-year survival</div></div>
    <div class="takeaway-card" style="border-color:var(--teal)"><div class="takeaway-icon">💊</div><div class="takeaway-text"><strong style="color:var(--teal)">PD-1 checkpoint inhibitors</strong> (pembrolizumab, nivolumab) dramatically improve Stage III/IV outcomes — melanoma is highly immunogenic</div></div>
  </div>
</div>

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