WHO Classification of CNS Tumors: A Histopathologist's Guide

const pptxgen = require("pptxgenjs");
const { execSync } = require("child_process");

// ── Fetch all histopath images ──────────────────────────────────────────────
const imageUrls = [
  "https://cdn.orris.care/cdss_images/6f73577c9233e3adefd0c9b53ef0eb6a7bcfe75d43c789bbac1b181317f8a11a.png",  // 0 astrocytoma
  "https://cdn.orris.care/cdss_images/5833f33aa53e57e77a4a03ddd2e82641b148aa2a21088a4ad06a42800b7edea0.png",  // 1 glioblastoma
  "https://cdn.orris.care/cdss_images/37f96dbc44eeb11f38631c2a3ab841d63066a0fb5f7e32f08568c6e99109eebc.png",  // 2 oligodendroglioma
  "https://cdn.orris.care/cdss_images/f62b70f2e4b792b3b8884f75603c75c22249b01994d673ad7c62f2f3133b013b.png",  // 3 pilocytic
  "https://cdn.orris.care/cdss_images/a6c268be287fee328ed484f386ad2a7a9e11578826ef3453fefd365d4648cf2a.png",  // 4 medulloblastoma
  "https://cdn.orris.care/cdss_images/597da96f78bb07db065265d59617ed66fddebe4ae5f52295253ba90ef9892f2f.png",  // 5 meningioma
];

const imgs = JSON.parse(
  execSync(
    `node /home/daytona/skills/shared/scripts/fetch_images.js ${imageUrls.map(u => `"${u}"`).join(" ")}`
  ).toString()
);

// ── Color palette ───────────────────────────────────────────────────────────
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  red:        "E05A5A",   // danger / malignant
  green:      "52B788",   // good prognosis
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// ── Build presentation ───────────────────────────────────────────────────────
const pres = new pptxgen();
pres.layout = "LAYOUT_16x9";
pres.title = "CNS Tumor Classification & Grading";
pres.author = "Orris Medical Education";

// ━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━
// SLIDE 1 — TITLE
// ━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━
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  s.addText("WHO 5th Edition (2021) | For Residents", {
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  // bottom bullets
  const topics = [
    "Gliomas (Astrocytoma · Glioblastoma · Oligodendroglioma)",
    "Pilocytic Astrocytoma · Ependymoma · Medulloblastoma",
    "Meningioma · CNS Lymphoma · Metastases",
  ];
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  s.addText("Source: Robbins & Cotran Pathologic Basis of Disease, 10e  |  WHO CNS Tumors 5th Ed, 2021", {
    x: 0.3, y: 5.36, w: 9.4, h: 0.25, fontSize: 8, color: C.mutedGray, fontFace: "Calibri",
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}

// ━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━
// SLIDE 2 — WHY CLASSIFICATION CHANGED
// ━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━
{
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  addSlideHeader(s, "Why Classification Changed: WHO 2021", "The biggest shift in CNS neuropathology in decades");

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    { title: "BEFORE (WHO 2016 & earlier)", color: C.navyLight, items: [
      "Diagnosis based mainly on H&E morphology",
      "Astrocytoma vs. Oligodendroglioma was subjective",
      'Mixed "oligoastrocytoma" category existed',
      "Grade determined histology alone",
      "Poor reproducibility between pathologists",
    ]},
    { title: "NOW (WHO 2021 — 5th Edition)", color: C.tealDark, items: [
      "Molecular markers are REQUIRED for diagnosis",
      "IDH, 1p/19q, ATRX define tumor type",
      "Oligoastrocytoma eliminated",
      "Molecular features can OVERRIDE morphology for grading",
      "Arabic numerals for grades (2, 3, 4 — not II, III, IV)",
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  s.addText("Key principle: Diagnosis = Histology + Molecular markers. Each confirms the other.", {
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// ━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━
// SLIDE 3 — OVERVIEW MAP
// ━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━
{
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  addSlideHeader(s, "CNS Tumor Categories — Overview", "Primary vs. secondary; parenchymal vs. extra-axial");

  const cats = [
    { label: "GLIOMAS", sub: "Astrocytoma · GBM · Oligodendroglioma · Ependymoma · Pilocytic", color: C.tealDark, grade: "Gr 1–4" },
    { label: "EMBRYONAL", sub: "Medulloblastoma · ATRT · Other embryonal", color: "6B3FA0", grade: "Gr 4" },
    { label: "MENINGEAL", sub: "Meningioma (Gr 1–3) · Hemangiopericytoma", color: "2E7D5E", grade: "Gr 1–3" },
    { label: "CNS LYMPHOMA", sub: "Primary DLBCL · EBV+ in immunosuppressed", color: "8B2635", grade: "Aggressive" },
    { label: "METASTASES", sub: "Lung > Breast > Melanoma > Kidney > GI", color: "5C4A1E", grade: "Variable" },
    { label: "SELLAR / NERVE", sub: "Craniopharyngioma · Schwannoma · Pituitary adenoma", color: "1A5276", grade: "Gr 1–2" },
  ];

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// ━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━
// SLIDE 4 — DIFFUSE GLIOMAS COMPARISON TABLE
// ━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━
{
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  addSlideHeader(s, "Diffuse Gliomas — Diagnostic Comparison", "Three separate entities; defined by both morphology and molecular markers");

  const rows = [
    ["Feature", "Astrocytoma, IDH-mutant", "Oligodendroglioma", "Glioblastoma, IDH-wt"],
    ["IDH status", "Mutant (IDH1/2)", "Mutant (IDH1/2)", "Wildtype"],
    ["Other key markers", "TP53 mut + ATRX loss", "1p/19q codeletion (BOTH required)", "+7/−10, TERT-mut, EGFR-amp"],
    ["WHO grades", "2, 3, 4", "2 or 3 only", "4 (by definition)"],
    ["Typical location", "Cerebral hemispheres", "Frontal / temporal lobes", "Cerebral hemispheres, BG, thalamus"],
    ["Peak age", "Young-middle adult (med. 38 yr)", "4th–5th decade", "Adults >55 yr"],
    ["Key histology", "Nuclear atypia, mitoses (Gr3), MVP+necrosis (Gr4)", "Fried-egg cells, chicken-wire vessels", "Palisading necrosis, glomeruloid MVP"],
    ["Prognosis", "Gr2 >10 yr; Gr4 ~2–4 yr", "Gr2 >10 yr (best among diffuse)", "~15 months median"],
  ];

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  s.addText("MGMT promoter methylation (GBM) predicts temozolomide sensitivity — must report in GBM. | Robbins & Cotran Table 28.5", {
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// ━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━
// SLIDE 5 — ASTROCYTOMA HISTOPATHOLOGY
// ━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━
{
  const s = darkSlide(pres);
  addSlideHeader(s, "Astrocytoma, IDH-mutant — Histopathology", "Infiltrative glioma; grading within a single entity (Grades 2–4)");

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  // right panel — grading criteria
  const grades = [
    { g: "Grade 2", items: ["Nuclear atypia (enlarged, irregular, hyperchromatic nuclei)", "Hypercellular vs. normal white matter", "GFAP+ fibrillary background", "IDH1 R132H IHC positive in ~90%"] },
    { g: "Grade 3", items: ["+ Readily detectable mitotic activity", "Increased cell density"] },
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  s.addText("Robbins, Cotran & Kumar Pathologic Basis of Disease, Fig. 28.46", {
    x: 0.3, y: 5.36, w: 9.4, h: 0.25, fontSize: 8, color: C.mutedGray, fontFace: "Calibri",
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}

// ━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━
// SLIDE 6 — GLIOBLASTOMA HISTOPATHOLOGY
// ━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━
{
  const s = darkSlide(pres);
  addSlideHeader(s, "Glioblastoma, IDH-wildtype (WHO Grade 4)", "Most common primary malignant brain tumor in adults; ~15 months median survival");

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    s.addImage({ data: imgs[1].base64, x: 0.25, y: 1.1, w: 5.6, h: 3.7 });
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  s.addText("Fig. A: Necrotic, hemorrhagic infiltrating mass\nFig. B: Serpiginous palisading necrosis; inset — microvascular proliferation (glomeruloid bodies)\n\nRobbins & Kumar Basic Pathology, Fig. 21.31", {
    x: 0.25, y: 4.85, w: 5.6, h: 0.65, fontSize: 8.5, color: C.mutedGray, fontFace: "Calibri", italic: true,
  });

  // right panel
  const features = [
    { title: "Hallmark Histologic Features", items: ["Serpiginous / pseudopalisading necrosis", "Microvascular proliferation (glomeruloid bodies)", "High cellularity + marked nuclear pleomorphism", "Brisk mitotic activity"] },
    { title: "Molecular Criteria (any 1 = Grade 4)", items: ["TERT promoter mutation", "EGFR amplification", "+7/−10 chromosome copy-number change", "IDH-wildtype (required — if IDH mut → astrocytoma)"] },
    { title: "Clinical Pearls", items: ["Ring-enhancing on MRI (leaky BBB)", '"Butterfly glioma" — crosses corpus callosum', "MGMT methylation → better TMZ response", "Median OS ~15–18 months with maximal therapy"] },
  ];

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  s.addText("Even without necrosis/MVP: IDH-wt + TERT-mut OR EGFR-amp OR +7/−10 = GBM Grade 4 by molecular criteria", {
    x: 0.3, y: 5.36, w: 9.4, h: 0.25, fontSize: 8.5, color: C.amber, bold: true, fontFace: "Calibri",
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}

// ━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━
// SLIDE 7 — OLIGODENDROGLIOMA
// ━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━
{
  const s = darkSlide(pres);
  addSlideHeader(s, "Oligodendroglioma, IDH-mutant & 1p/19q-codeleted", "Best prognosis among diffuse gliomas; defined by a DUAL molecular signature");

  if (!imgs[2].error) {
    s.addImage({ data: imgs[2].base64, x: 0.25, y: 1.1, w: 4.8, h: 4.0 });
  }
  s.addText('"Fried-egg" cells: uniform round nuclei + clear perinuclear halos\n"Chicken-wire" capillary network  |  H&E ×200\nBradley & Daroff Neurology in Clinical Practice, Fig. 72.2', {
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  });

  // right side
  const points = [
    { head: "DIAGNOSTIC CRITERIA (both required)", col: C.teal, items: ["IDH1 or IDH2 mutation", "1p/19q codeletion (chromosomal)"] },
    { head: "KEY HISTOLOGIC FEATURES", col: C.amber, items: ['"Fried-egg" appearance (formalin artifact — absent on frozen!)', '"Chicken-wire" branching capillaries', "Uniform round nuclei, bland chromatin", "Cortical involvement, microcalcifications", "Perineuronal satellitosis, mucin-rich microcysts"] },
    { head: "GRADE 3 (Anaplastic) Criteria", col: C.red, items: ["Hypercellularity + numerous mitoses", "Microvascular proliferation and/or necrosis"] },
    { head: "CLINICAL", col: C.green, items: ["5–15% of gliomas; 4th–5th decade", "Frontal > temporal lobe; gyriform calcifications on CT", "Grade 2 median OS >10 years; responds well to PCV chemo"] },
  ];

  let yy2 = 1.1;
  points.forEach(p => {
    const ht = p.items.length * 0.28 + 0.44;
    s.addShape("rect", { x: 5.35, y: yy2, w: 4.4, h: ht, fill: { color: C.navyLight }, line: { type: "none" } });
    s.addShape("rect", { x: 5.35, y: yy2, w: 4.4, h: 0.03, fill: { color: p.col }, line: { type: "none" } });
    s.addText(p.head, { x: 5.45, y: yy2 + 0.06, w: 4.2, h: 0.3, fontSize: 10, bold: true, color: p.col, fontFace: "Calibri" });
    s.addText(
      p.items.map((it, j) => ({ text: "• " + it, options: { breakLine: j < p.items.length - 1, fontSize: 9.8, color: C.lightGray, fontFace: "Calibri" } })),
      { x: 5.45, y: yy2 + 0.38, w: 4.2, h: p.items.length * 0.28 }
    );
    yy2 += ht + 0.07;
  });

  s.addShape("rect", { x: 0, y: 5.35, w: 10, h: 0.275, fill: { color: C.navyLight }, line: { type: "none" } });
  s.addText("The 'fried-egg' appearance is a fixation artifact — NOT present in intraoperative frozen sections. Don't let this trip you up!", {
    x: 0.3, y: 5.36, w: 9.4, h: 0.25, fontSize: 8.5, color: C.amber, bold: true, fontFace: "Calibri",
  });
}

// ━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━
// SLIDE 8 — PILOCYTIC ASTROCYTOMA
// ━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━
{
  const s = darkSlide(pres);
  addSlideHeader(s, "Pilocytic Astrocytoma (WHO Grade 1)", "Circumscribed glioma — NOT a diffuse glioma; excellent prognosis with surgery alone");

  if (!imgs[3].error) {
    s.addImage({ data: imgs[3].base64, x: 0.25, y: 1.1, w: 5.6, h: 3.6 });
  }
  s.addText("Fig. A: Cerebellar cyst with enhancing mural nodule  |  Fig. B: Biphasic architecture (loose + compact)  |  Fig. C: Rosenthal fibers (eosinophilic corkscrew inclusions)\nRobbins, Cotran & Kumar Pathologic Basis of Disease, Fig. 28.50", {
    x: 0.25, y: 4.75, w: 5.6, h: 0.55, fontSize: 8, color: C.mutedGray, fontFace: "Calibri", italic: true,
  });

  const cols = [
    { head: "LOCATION & AGE", col: C.teal, items: ["Children & young adults (peak <20 yr)", "Cerebellum > optic pathway > hypothalamus > brainstem", "Associated with NF1 (optic pathway gliomas)"] },
    { head: "HISTOLOGIC HALLMARKS", col: C.amber, items: ["Biphasic pattern: loose microcystic + dense compact fibrillary", "Bipolar spindle cells with 'hairlike' GFAP+ processes", "Rosenthal fibers (corkscrew eosinophilic inclusions)", "Eosinophilic granular bodies (mulberry inclusions)", "⚠ MVP & necrosis do NOT indicate high grade here!"] },
    { head: "MOLECULAR & PROGNOSIS", col: C.green, items: ["KIAA1549::BRAF fusion in >70% (diagnostic marker)", "WHO grade 1 — curable by complete resection", "10-year OS >90% in most series", "Distinct from IDH-mutant astrocytoma — different entity entirely"] },
  ];

  let yy3 = 1.1;
  cols.forEach(c => {
    const ht = c.items.length * 0.295 + 0.44;
    s.addShape("rect", { x: 6.1, y: yy3, w: 3.65, h: ht, fill: { color: C.navyLight }, line: { type: "none" } });
    s.addShape("rect", { x: 6.1, y: yy3, w: 3.65, h: 0.03, fill: { color: c.col }, line: { type: "none" } });
    s.addText(c.head, { x: 6.2, y: yy3 + 0.06, w: 3.45, h: 0.3, fontSize: 10, bold: true, color: c.col, fontFace: "Calibri" });
    s.addText(
      c.items.map((it, j) => ({ text: "• " + it, options: { breakLine: j < c.items.length - 1, fontSize: 9.5, color: C.lightGray, fontFace: "Calibri" } })),
      { x: 6.2, y: yy3 + 0.38, w: 3.45, h: c.items.length * 0.295 }
    );
    yy3 += ht + 0.07;
  });

  s.addShape("rect", { x: 0, y: 5.35, w: 10, h: 0.275, fill: { color: C.navyLight }, line: { type: "none" } });
  s.addText("MVP and necrosis in pilocytic astrocytoma do NOT upgrade it — unlike diffuse gliomas. Key distinction for residents!", {
    x: 0.3, y: 5.36, w: 9.4, h: 0.25, fontSize: 8.5, color: C.amber, bold: true, fontFace: "Calibri",
  });
}

// ━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━
// SLIDE 9 — EPENDYMOMA
// ━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━
{
  const s = darkSlide(pres);
  addSlideHeader(s, "Ependymoma — Location-Defined Classification", "WHO 2021: location + molecular subtype now part of the name");

  // 3 location boxes top row
  const locs = [
    { name: "SUPRATENTORIAL", items: ["ZFTA::RELA fusion (poor prognosis)", "YAP1 fusion (better prognosis)", "Hemispheric, may lack ventricular connection"], col: C.red },
    { name: "POSTERIOR FOSSA", items: ["PFA: H3K27me3 LOSS by IHC → poor prognosis", "PFB: H3K27me3 retained → better prognosis", "PFA: Children; PFB: Adults; floor of 4th ventricle"], col: C.amber },
    { name: "SPINAL CORD", items: ["NF2 mutation (spinal ependymoma)", "Most common CNS tumor in NF2", "MYCN-amplified: rare, poor prognosis"], col: C.green },
  ];

  locs.forEach((l, i) => {
    const x = 0.25 + i * 3.2;
    s.addShape("rect", { x, y: 1.1, w: 3.0, h: 2.1, fill: { color: C.navyLight }, line: { type: "none" } });
    s.addShape("rect", { x, y: 1.1, w: 3.0, h: 0.04, fill: { color: l.col }, line: { type: "none" } });
    s.addText(l.name, { x: x + 0.1, y: 1.16, w: 2.8, h: 0.35, fontSize: 11, bold: true, color: l.col, fontFace: "Calibri" });
    s.addText(
      l.items.map((it, j) => ({ text: "• " + it, options: { breakLine: j < l.items.length - 1, fontSize: 9.8, color: C.lightGray, fontFace: "Calibri" } })),
      { x: x + 0.1, y: 1.55, w: 2.8, h: 1.55 }
    );
  });

  // histology section
  s.addText("HISTOLOGIC FEATURES", {
    x: 0.25, y: 3.35, w: 9.5, h: 0.35, fontSize: 12, bold: true, color: C.teal, fontFace: "Calibri",
  });
  s.addShape("rect", { x: 0.25, y: 3.7, w: 9.5, h: 0.03, fill: { color: C.tealDark }, line: { type: "none" } });

  const histItems = [
    { title: "Perivascular Pseudorosettes", desc: "Most common — tumor cells radiate around blood vessels with anuclear fibrillary zones (GFAP+). NOT specific to ependymoma but classic.", col: C.teal },
    { title: "True Ependymal Rosettes / Canals", desc: "Tumor cells arranged around a central lumen. Pathognomonic but less common. Present in about one-third of cases.", col: C.amber },
    { title: "Gross", desc: "Solid, non-infiltrative masses. Well-demarcated from surrounding brain. Arise from ventricular floor or wall.", col: C.green },
  ];

  histItems.forEach((h, i) => {
    const x = 0.25 + i * 3.2;
    s.addShape("rect", { x, y: 3.78, w: 3.0, h: 1.45, fill: { color: C.navyLight }, line: { type: "none" } });
    s.addText(h.title, { x: x + 0.1, y: 3.83, w: 2.8, h: 0.32, fontSize: 10, bold: true, color: h.col, fontFace: "Calibri" });
    s.addText(h.desc, { x: x + 0.1, y: 4.18, w: 2.8, h: 1.0, fontSize: 9.5, color: C.lightGray, fontFace: "Calibri", wrap: true });
  });

  s.addShape("rect", { x: 0, y: 5.35, w: 10, h: 0.275, fill: { color: C.navyLight }, line: { type: "none" } });
  s.addText("H3K27me3 loss by IHC is highly sensitive/specific for PFA ependymoma — a practical bench-side test.", {
    x: 0.3, y: 5.36, w: 9.4, h: 0.25, fontSize: 8.5, color: C.amber, bold: true, fontFace: "Calibri",
  });
}

// ━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━
// SLIDE 10 — MEDULLOBLASTOMA
// ━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━
{
  const s = darkSlide(pres);
  addSlideHeader(s, "Medulloblastoma — Molecular & Histologic Subtypes", "Most common malignant pediatric CNS tumor; cerebellar vermis; WHO grade 4 equivalent");

  // image right
  if (!imgs[4].error) {
    s.addImage({ data: imgs[4].base64, x: 5.5, y: 1.1, w: 4.25, h: 3.5 });
  }
  s.addText("A: Cerebellar vermis mass  |  B: Classic type — dense SRBCT with Homer-Wright rosettes (arrows)\nC: Desmoplastic/nodular  |  D: Large cell/anaplastic (worst prognosis)\nRobbins, Cotran & Kumar Pathologic Basis of Disease, Fig. 28.52", {
    x: 5.5, y: 4.65, w: 4.25, h: 0.6, fontSize: 7.5, color: C.mutedGray, fontFace: "Calibri", italic: true,
  });

  // left: molecular groups
  const molGroups = [
    { name: "WNT-activated", prog: "~100% 5-yr OS", color: C.green, markers: "CTNNB1 mut, monosomy 6" },
    { name: "SHH-activated", prog: "Intermediate (TP53 mut = worse)", color: C.amber, markers: "PTCH1/SMO mut; infants + adults" },
    { name: "Group 3", prog: "20–30% 5-yr OS (worst)", color: C.red, markers: "MYC amplification; metastatic" },
    { name: "Group 4", prog: "Intermediate", color: "4A90D9", markers: "Most common; i17q; older children" },
  ];

  s.addText("MOLECULAR GROUPS (prognosis-defining)", {
    x: 0.25, y: 1.1, w: 5.0, h: 0.3, fontSize: 11, bold: true, color: C.teal, fontFace: "Calibri",
  });

  molGroups.forEach((mg, i) => {
    const y = 1.48 + i * 0.73;
    s.addShape("rect", { x: 0.25, y, w: 0.18, h: 0.6, fill: { color: mg.color }, line: { type: "none" } });
    s.addShape("rect", { x: 0.48, y, w: 4.75, h: 0.6, fill: { color: C.navyLight }, line: { type: "none" } });
    s.addText(mg.name, { x: 0.58, y: y + 0.04, w: 2.2, h: 0.28, fontSize: 11, bold: true, color: mg.color, fontFace: "Calibri" });
    s.addText("Prognosis: " + mg.prog, { x: 0.58, y: y + 0.32, w: 4.55, h: 0.22, fontSize: 9.5, color: C.mutedGray, fontFace: "Calibri" });
    s.addText(mg.markers, { x: 2.9, y: y + 0.04, w: 2.2, h: 0.28, fontSize: 9.5, color: C.lightGray, fontFace: "Calibri", italic: true });
  });

  // histologic subtypes
  s.addText("HISTOLOGIC SUBTYPES", {
    x: 0.25, y: 4.43, w: 5.0, h: 0.3, fontSize: 11, bold: true, color: C.teal, fontFace: "Calibri",
  });
  const hTypes = ["Classic: sheets of SRBCT + Homer-Wright rosettes  |  Desmoplastic/nodular: pale islands in desmoplastic stroma  |  MBEN: florid nodular (infants, excellent prognosis)  |  Large cell/anaplastic: large nuclei, nuclear molding (worst)"];
  s.addText(hTypes[0], { x: 0.25, y: 4.75, w: 5.0, h: 0.5, fontSize: 9.5, color: C.lightGray, fontFace: "Calibri", wrap: true });

  s.addShape("rect", { x: 0, y: 5.35, w: 10, h: 0.275, fill: { color: C.navyLight }, line: { type: "none" } });
  s.addText("Medulloblastoma is exquisitely radiosensitive. WNT group may be undertreated; Group 3/4 may need intensification. Molecular subtyping is now clinical standard.", {
    x: 0.3, y: 5.36, w: 9.4, h: 0.25, fontSize: 8, color: C.mutedGray, fontFace: "Calibri",
  });
}

// ━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━
// SLIDE 11 — MENINGIOMA
// ━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━
{
  const s = darkSlide(pres);
  addSlideHeader(s, "Meningioma — Grading & Histologic Subtypes", "Arise from arachnoid (meningothelial) cells; most common primary intracranial tumor overall");

  if (!imgs[5].error) {
    s.addImage({ data: imgs[5].base64, x: 0.25, y: 1.1, w: 5.2, h: 3.4 });
  }
  s.addText("Fig. A: Parasagittal lobulated dural mass compressing brain (easily separable)\nFig. B: Psammomatous meningioma — whorled cells + concentric calcified psammoma bodies\nRobbins, Cotran & Kumar Pathologic Basis of Disease, Fig. 28.53", {
    x: 0.25, y: 4.55, w: 5.2, h: 0.7, fontSize: 8, color: C.mutedGray, fontFace: "Calibri", italic: true,
  });

  const menGrades = [
    { grade: "Grade 1 (Benign) ~74%", col: C.green, items: ["Low recurrence risk; curable by resection", "Subtypes: meningothelial, fibroblastic, transitional, psammomatous, angiomatous, secretory, others", "Whorls and psammoma bodies are characteristic", "NF2 mutation most common genetic alteration"] },
    { grade: "Grade 2 (Atypical) ~25%", col: C.amber, items: ["≥4 mitoses/10 HPF OR brain invasion OR ≥3 of: hypercellularity, sheeting, macronucleoli, small cells, necrosis", "Clear cell or chordoid pattern = Grade 2 by definition", "Higher recurrence; radiation often required post-resection", "1p loss & 1q gain: emerging markers of aggressive behavior (JAMA Oncol 2025)"] },
    { grade: "Grade 3 (Anaplastic) 1–3%", col: C.red, items: ["Markedly elevated mitoses; resembles carcinoma or sarcoma", "Retains at least focal meningothelial features on IHC", "May arise de novo or from malignant progression of Grade 1/2", "Very aggressive; poor prognosis"] },
  ];

  let yy = 1.1;
  menGrades.forEach(mg => {
    const ht = mg.items.length * 0.3 + 0.44;
    s.addShape("rect", { x: 5.65, y: yy, w: 4.1, h: ht, fill: { color: C.navyLight }, line: { type: "none" } });
    s.addShape("rect", { x: 5.65, y: yy, w: 4.1, h: 0.035, fill: { color: mg.col }, line: { type: "none" } });
    s.addText(mg.grade, { x: 5.75, y: yy + 0.07, w: 3.9, h: 0.3, fontSize: 11, bold: true, color: mg.col, fontFace: "Calibri" });
    s.addText(
      mg.items.map((it, j) => ({ text: "• " + it, options: { breakLine: j < mg.items.length - 1, fontSize: 9.5, color: C.lightGray, fontFace: "Calibri" } })),
      { x: 5.75, y: yy + 0.4, w: 3.9, h: mg.items.length * 0.3 }
    );
    yy += ht + 0.07;
  });

  s.addShape("rect", { x: 0, y: 5.35, w: 10, h: 0.275, fill: { color: C.navyLight }, line: { type: "none" } });
  s.addText("Female predominance 2:1 (spinal 10:1). Multiple meningiomas → think NF2. May grow rapidly during pregnancy (progesterone receptors).", {
    x: 0.3, y: 5.36, w: 9.4, h: 0.25, fontSize: 8.5, color: C.mutedGray, fontFace: "Calibri",
  });
}

// ━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━
// SLIDE 12 — CNS LYMPHOMA & METASTASES
// ━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━
{
  const s = darkSlide(pres);
  addSlideHeader(s, "CNS Lymphoma & Metastatic Tumors", "Two critically important non-glial diagnoses — know them well");

  // two wide columns
  const col1 = [
    { head: "PRIMARY CNS LYMPHOMA", col: C.teal },
    { text: "• 2% of extranodal lymphomas; 1% of intracranial tumors" },
    { text: "• Most common CNS neoplasm in immunosuppressed (HIV, post-transplant)" },
    { text: "• Virtually always DLBCL (diffuse large B-cell lymphoma)" },
    { text: "" },
    { subhead: "HISTOLOGY", col: C.teal },
    { text: "• Angiocentric pattern — malignant cells accumulate around blood vessels" },
    { text: "• CD20+ B-cells; high proliferative index (Ki-67)" },
    { text: "• Immunosuppressed: necrosis prominent + EBV+ by EBER ISH" },
    { text: "• Immunocompetent: PDL1 gene amplification common" },
    { text: "" },
    { subhead: "IMAGING / CLINICAL", col: C.teal },
    { text: "• Multifocal, periventricular, deep subcortical" },
    { text: "• Avid FDG-PET uptake; dense/homogeneous on CT" },
    { text: "• ⚠ DO NOT biopsy if on steroids — steroids lyse lymphoma cells, causing false negative" },
  ];

  const col2 = [
    { head: "METASTATIC TUMORS", col: C.amber },
    { text: "• 25–50% of intracranial tumors in hospitalized patients" },
    { text: "• Top 5 primaries (80% combined):" },
    { text: "   1. Lung  2. Breast  3. Melanoma  4. Kidney  5. GI tract" },
    { text: "" },
    { subhead: "HISTOLOGY", col: C.amber },
    { text: "• Well-circumscribed masses at gray-white matter junction" },
    { text: "• Usually preserve primary tumor morphology (e.g., melanin in melanoma)" },
    { text: "• Ring-enhancing on MRI; marked surrounding edema" },
    { text: "• Multiple lesions in older patient = metastasis until proven otherwise" },
    { text: "" },
    { subhead: "IHC PANEL (to identify primary)", col: C.amber },
    { text: "• CK7/CK20, TTF-1, Napsin A (lung adeno), ER/PR/GATA3 (breast)" },
    { text: "• HMB-45, Melan-A, SOX10 (melanoma)" },
    { text: "• RCC, PAX8 (kidney); CDX2 (GI/colorectal)" },
  ];

  [col1, col2].forEach((col, ci) => {
    const x = ci === 0 ? 0.25 : 5.1;
    let y = 1.12;
    col.forEach(item => {
      if (item.head) {
        s.addShape("rect", { x, y, w: 4.6, h: 0.38, fill: { color: item.col === C.teal ? C.tealDark : "8B6914" }, line: { type: "none" } });
        s.addText(item.head, { x: x + 0.1, y: y + 0.05, w: 4.4, h: 0.28, fontSize: 12, bold: true, color: C.white, fontFace: "Calibri" });
        y += 0.43;
      } else if (item.subhead) {
        s.addText(item.subhead, { x: x + 0.1, y, w: 4.4, h: 0.28, fontSize: 10, bold: true, color: item.col, fontFace: "Calibri" });
        y += 0.3;
      } else if (item.text === "") {
        y += 0.12;
      } else {
        s.addText(item.text, { x: x + 0.1, y, w: 4.4, h: 0.27, fontSize: 9.8, color: C.lightGray, fontFace: "Calibri" });
        y += 0.28;
      }
    });
  });

  s.addShape("rect", { x: 0, y: 5.35, w: 10, h: 0.275, fill: { color: C.navyLight }, line: { type: "none" } });
  s.addText("Never biopsy suspected CNS lymphoma while on steroids. Always check serology for systemic primary before brain biopsy.", {
    x: 0.3, y: 5.36, w: 9.4, h: 0.25, fontSize: 8.5, color: C.amber, bold: true, fontFace: "Calibri",
  });
}

// ━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━
// SLIDE 13 — KEY MOLECULAR TESTS
// ━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━
{
  const s = darkSlide(pres);
  addSlideHeader(s, "Essential Molecular Tests for Pathologists", "WHO 2021 requires molecular workup for most CNS tumor entities");

  const tests = [
    { marker: "IDH1/2 mutation", method: "IHC (R132H) + sequencing", relevance: "Distinguishes astrocytoma/oligodendroglioma from GBM and reactive gliosis. Most important single test.", col: C.teal },
    { marker: "1p/19q codeletion", method: "FISH or NGS", relevance: "Defines oligodendroglioma (must have IDH mutation too). Both 1p AND 19q must be deleted.", col: C.teal },
    { marker: "ATRX + TP53", method: "IHC (ATRX loss + p53 overexpression)", relevance: "Supports astrocytoma lineage. Mutually exclusive with 1p/19q codeletion.", col: C.tealDark },
    { marker: "TERT promoter mutation", method: "Sequencing (hotspot C228T / C250T)", relevance: "Marks GBM (IDH-wt) and oligodendroglioma. In IDH-wt astrocytoma → upgrade to GBM.", col: C.amber },
    { marker: "EGFR amplification / +7/−10", method: "FISH / SNP array / NGS CNV", relevance: "Molecular hallmarks of GBM. Qualifies IDH-wt tumor as Grade 4 even without necrosis/MVP.", col: C.amber },
    { marker: "CDKN2A homozygous deletion", method: "FISH or NGS CNV", relevance: "Upgrades IDH-mutant astrocytoma to Grade 4, regardless of morphology.", col: C.red },
    { marker: "MGMT promoter methylation", method: "Methylation-specific PCR or pyrosequencing", relevance: "Predicts temozolomide response in GBM. Should be reported in all GBMs.", col: C.green },
    { marker: "H3K27me3 loss (IHC)", method: "IHC (H3K27me3 antibody)", relevance: "Identifies PFA ependymoma (poor prognosis). Highly sensitive and specific — practical bench test.", col: C.green },
    { marker: "KIAA1549::BRAF fusion", method: "RT-PCR or FISH or NGS RNA", relevance: "Diagnostic for pilocytic astrocytoma in >70% of cases. Guides targeted therapy (MEK/RAF inhibitors).", col: "6B3FA0" },
    { marker: "DNA methylation profiling", method: "850K array (Heidelberg classifier)", relevance: "Gold standard for difficult/ambiguous cases. Identifies >130 CNS tumor classes. Increasingly standard of care.", col: C.mutedGray },
  ];

  const colHeaders = ["MARKER", "METHOD", "CLINICAL RELEVANCE"];
  const colX = [0.25, 2.55, 4.5];
  const colW = [2.2, 1.85, 5.25];

  // header row
  colHeaders.forEach((h, ci) => {
    s.addShape("rect", { x: colX[ci], y: 1.08, w: colW[ci] - 0.05, h: 0.32, fill: { color: C.tealDark }, line: { type: "none" } });
    s.addText(h, { x: colX[ci] + 0.1, y: 1.1, w: colW[ci] - 0.2, h: 0.28, fontSize: 10, bold: true, color: C.white, fontFace: "Calibri" });
  });

  tests.forEach((t, i) => {
    const y = 1.45 + i * 0.41;
    const bg = i % 2 === 0 ? C.navyLight : C.navy;
    // row bg
    s.addShape("rect", { x: 0.25, y, w: 9.5, h: 0.38, fill: { color: bg }, line: { type: "none" } });
    // color indicator
    s.addShape("rect", { x: 0.25, y, w: 0.06, h: 0.38, fill: { color: t.col }, line: { type: "none" } });
    s.addText(t.marker, { x: colX[0] + 0.1, y: y + 0.05, w: colW[0] - 0.2, h: 0.28, fontSize: 9.5, bold: true, color: t.col, fontFace: "Calibri" });
    s.addText(t.method, { x: colX[1] + 0.1, y: y + 0.05, w: colW[1] - 0.2, h: 0.28, fontSize: 9, color: C.lightGray, fontFace: "Calibri" });
    s.addText(t.relevance, { x: colX[2] + 0.1, y: y + 0.05, w: colW[2] - 0.2, h: 0.28, fontSize: 9, color: C.lightGray, fontFace: "Calibri" });
  });

  s.addShape("rect", { x: 0, y: 5.35, w: 10, h: 0.275, fill: { color: C.navyLight }, line: { type: "none" } });
  s.addText("Horbinski et al., JAMA Oncol 2025 (PMID 39724142): Molecular testing costs <5% of total CNS tumor care costs — yet enables accurate Dx, grading, and treatment selection.", {
    x: 0.3, y: 5.36, w: 9.4, h: 0.25, fontSize: 8, color: C.mutedGray, fontFace: "Calibri",
  });
}

// ━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━
// SLIDE 14 — GRADING SUMMARY TABLE
// ━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━
{
  const s = darkSlide(pres);
  addSlideHeader(s, "CNS Tumor Grading — Quick Reference Summary", "Histologic hallmarks and molecular anchors at a glance");

  const rows = [
    ["Tumor", "Grade", "Key Histologic Hallmark", "Molecular Anchor", "Prognosis"],
    ["Pilocytic Astrocytoma", "1", "Biphasic; Rosenthal fibers; well-circumscribed", "KIAA1549::BRAF fusion", "Excellent (>90% OS)"],
    ["Astrocytoma, IDH-mutant", "2", "Nuclear atypia; fibrillary infiltrative", "IDH mut + ATRX + TP53", ">10 yr mean OS"],
    ["Astrocytoma, IDH-mutant", "3", "Grade 2 + mitoses", "IDH mut + ATRX + TP53", "~5–7 yr"],
    ["Astrocytoma, IDH-mutant", "4", "Grade 3 + MVP/necrosis OR CDKN2A HD", "IDH mut + CDKN2A HD", "~2–4 yr"],
    ["Glioblastoma, IDH-wt", "4", "Palisading necrosis + glomeruloid MVP", "IDH-wt + TERT/EGFR/+7−10", "~15 months"],
    ["Oligodendroglioma", "2", "Fried-egg + chicken-wire vessels", "IDH mut + 1p/19q codeletion", ">10 yr"],
    ["Oligodendroglioma", "3", "Grade 2 + mitoses + MVP/necrosis", "IDH mut + 1p/19q codeletion", "~3–5 yr"],
    ["Ependymoma (PFB/spinal)", "2", "Perivascular pseudorosettes", "NF2 mut (spinal); PFB", "Intermediate-good"],
    ["Ependymoma (PFA/RELA)", "2–3", "Pseudorosettes ± true rosettes", "H3K27me3 loss / ZFTA::RELA", "Poor"],
    ["Medulloblastoma (WNT)", "4 equiv.", "Sheets SRBCT + Homer-Wright rosettes", "CTNNB1 mut, monosomy 6", "~100% 5-yr OS"],
    ["Medulloblastoma (Gr3/LC-A)", "4 equiv.", "Large cells, nuclear molding", "MYC amplification", "20–30% 5-yr OS"],
    ["Meningioma", "1", "Whorls, psammoma bodies", "NF2 mut (most common)", "Curable by resection"],
    ["Meningioma (atypical)", "2", "≥4 mit/10HPF or brain invasion", "TERT mut, 1p loss emerging", "Higher recurrence"],
    ["Meningioma (anaplastic)", "3", "Sarcoma/carcinoma-like; high mitoses", "Complex genomics", "Poor"],
  ];

  const colW2 = [2.2, 0.55, 2.55, 2.3, 1.95];
  const colX2 = [0.15, 2.4, 3.0, 5.6, 7.95];
  const rh = 0.305;
  const gradeColors2 = { "1": C.green, "2": C.teal, "3": C.amber, "4": C.red, "4 equiv.": C.red, "2–3": C.amber };

  rows.forEach((row, ri) => {
    const isHeader = ri === 0;
    const y = 1.1 + ri * rh;
    const bg = isHeader ? C.tealDark : (ri % 2 === 0 ? C.navyLight : C.navy);
    s.addShape("rect", { x: 0.15, y, w: 9.75, h: rh - 0.015, fill: { color: bg }, line: { type: "none" } });
    row.forEach((cell, ci) => {
      const isGrade = ci === 1 && !isHeader;
      const gcol = isGrade ? (gradeColors2[cell] || C.teal) : null;
      if (isGrade && gcol) {
        s.addShape("rect", { x: colX2[ci], y: y + 0.03, w: colW2[ci], h: rh - 0.06, fill: { color: gcol }, line: { type: "none" }, rectRadius: 0 });
      }
      s.addText(cell, {
        x: colX2[ci] + 0.05, y: y + 0.04, w: colW2[ci] - 0.1, h: rh - 0.08,
        fontSize: isHeader ? 9.5 : 8.8,
        bold: isHeader || ci === 0,
        color: isHeader ? C.white : (ci === 0 ? C.lightGray : isGrade ? C.navy : C.lightGray),
        fontFace: "Calibri", valign: "middle", wrap: true,
      });
    });
  });
}

// ━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━
// SLIDE 15 — SUMMARY & KEY TAKE-AWAYS
// ━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━
{
  const s = darkSlide(pres);
  s.background = { color: C.navy };
  s.addShape("rect", { x: 0, y: 0, w: 0.18, h: 5.625, fill: { color: C.teal }, line: { type: "none" } });
  s.addShape("rect", { x: 0, y: 0, w: 10, h: 0.08, fill: { color: C.teal }, line: { type: "none" } });

  s.addText("KEY TAKE-AWAYS", {
    x: 0.4, y: 0.18, w: 9, h: 0.55,
    fontSize: 26, bold: true, color: C.teal, fontFace: "Calibri", charSpacing: 3,
  });
  s.addShape("rect", { x: 0.4, y: 0.8, w: 4.5, h: 0.04, fill: { color: C.amber }, line: { type: "none" } });

  const takeaways = [
    ["1", "Molecular + Morphology = Diagnosis", "H&E alone is insufficient. IDH, 1p/19q, ATRX, TERT, MGMT must be integrated for every diffuse glioma.", C.teal],
    ["2", "Grading is intratype, not spectrum", "GBM and astrocytoma are SEPARATE entities — not a continuum. IDH-wt astrocytoma = GBM grade 4 by definition.", C.amber],
    ["3", "Location defines ependymoma", "WHO 2021 renamed ependymoma subtypes by location + molecular group. H3K27me3 IHC is a practical tier-1 test.", C.green],
    ["4", "MVP/necrosis ≠ high grade in pilocytic", "Unlike diffuse gliomas, these features do NOT upgrade pilocytic astrocytoma. A critical exam distinction.", C.amber],
    ["5", "Medulloblastoma: WNT = cure; Group 3 = danger", "Molecular subtyping directly changes treatment intensity. Do not skip it.", C.red],
    ["6", "Steroids lyse lymphoma", "Never biopsy CNS DLBCL on steroids. Dense periventricular mass = think lymphoma first.", C.teal],
  ];

  takeaways.forEach((t, i) => {
    const col = Math.floor(i / 3);
    const row = i % 3;
    const x = 0.4 + col * 4.8;
    const y = 1.0 + row * 1.45;
    s.addShape("rect", { x, y, w: 4.5, h: 1.32, fill: { color: C.navyLight }, line: { type: "none" } });
    s.addShape("rect", { x, y, w: 0.05, h: 1.32, fill: { color: t[3] }, line: { type: "none" } });
    // number badge
    s.addShape("ellipse", { x: x + 0.12, y: y + 0.08, w: 0.38, h: 0.38, fill: { color: t[3] }, line: { type: "none" } });
    s.addText(t[0], { x: x + 0.12, y: y + 0.08, w: 0.38, h: 0.38, fontSize: 13, bold: true, color: C.navy, align: "center", valign: "middle", fontFace: "Calibri" });
    s.addText(t[1], { x: x + 0.6, y: y + 0.08, w: 3.8, h: 0.35, fontSize: 11, bold: true, color: C.white, fontFace: "Calibri" });
    s.addText(t[2], { x: x + 0.6, y: y + 0.46, w: 3.8, h: 0.78, fontSize: 9.8, color: C.lightGray, fontFace: "Calibri", wrap: true });
  });

  s.addShape("rect", { x: 0, y: 5.35, w: 10, h: 0.275, fill: { color: C.navyLight }, line: { type: "none" } });
  s.addText("Sources: Robbins & Cotran Pathologic Basis of Disease 10e; Robbins Basic Pathology; Bradley & Daroff Neurology; WHO CNS Tumors 5th Ed (2021); Horbinski et al. JAMA Oncol 2025", {
    x: 0.3, y: 5.36, w: 9.4, h: 0.25, fontSize: 7.5, color: C.mutedGray, fontFace: "Calibri",
  });
}

// ── Write file ──────────────────────────────────────────────────────────────
const outPath = "/home/daytona/workspace/cns-tumor-ppt/CNS_Tumor_Classification_Residents.pptx";
pres.writeFile({ fileName: outPath }).then(() => {
  console.log("DONE:", outPath);
}).catch(err => {
  console.error("ERROR:", err.message);
  process.exit(1);
});

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