from reportlab.lib.pagesizes import A4
from reportlab.lib import colors
from reportlab.lib.styles import getSampleStyleSheet, ParagraphStyle
from reportlab.lib.units import cm
from reportlab.platypus import (SimpleDocTemplate, Paragraph, Spacer, Table,
                                 TableStyle, HRFlowable)
from reportlab.lib.enums import TA_CENTER, TA_LEFT

OUTPUT = "/home/daytona/workspace/aml-revision/AML_Classification_Summary.pdf"

doc = SimpleDocTemplate(
    OUTPUT,
    pagesize=A4,
    rightMargin=1.8*cm, leftMargin=1.8*cm,
    topMargin=1.8*cm, bottomMargin=1.8*cm
)

# ── Colours ──────────────────────────────────────────────────────────────────
DARK_BLUE   = colors.HexColor("#1A3A5C")
MED_BLUE    = colors.HexColor("#2E6DA4")
LIGHT_BLUE  = colors.HexColor("#D6E8F7")
ACCENT_RED  = colors.HexColor("#C0392B")
ACCENT_GRN  = colors.HexColor("#1E8449")
ACCENT_ORG  = colors.HexColor("#D35400")
LIGHT_GREY  = colors.HexColor("#F4F6F7")
MID_GREY    = colors.HexColor("#BDC3C7")
WHITE       = colors.white
YELLOW_BG   = colors.HexColor("#FFF9C4")
YELLOW_BDR  = colors.HexColor("#F9A825")

styles = getSampleStyleSheet()

def S(name, **kw):
    return ParagraphStyle(name, **kw)

title_style = S("Title2",
    fontSize=22, textColor=WHITE, alignment=TA_CENTER,
    fontName="Helvetica-Bold", spaceAfter=4)

subtitle_style = S("Sub2",
    fontSize=11, textColor=LIGHT_BLUE, alignment=TA_CENTER,
    fontName="Helvetica", spaceAfter=2)

source_style = S("Src",
    fontSize=8, textColor=MID_GREY, alignment=TA_CENTER,
    fontName="Helvetica-Oblique")

sec_header = S("SecH",
    fontSize=13, textColor=WHITE, fontName="Helvetica-Bold",
    alignment=TA_LEFT, spaceAfter=2, spaceBefore=8)

body = S("Body2",
    fontSize=9.5, textColor=colors.HexColor("#2C3E50"),
    fontName="Helvetica", spaceAfter=3, leading=14)

bold_body = S("BoldBody",
    fontSize=9.5, textColor=DARK_BLUE,
    fontName="Helvetica-Bold", spaceAfter=2)

note_style = S("Note",
    fontSize=9, textColor=colors.HexColor("#5D4037"),
    fontName="Helvetica-Oblique", spaceAfter=2, leading=13)

bullet_style = S("Bullet",
    fontSize=9.5, textColor=colors.HexColor("#2C3E50"),
    fontName="Helvetica", leftIndent=14, spaceAfter=2, leading=13)


def section_header(text, bg=MED_BLUE):
    data = [[Paragraph(text, sec_header)]]
    t = Table(data, colWidths=[17.4*cm])
    t.setStyle(TableStyle([
        ("BACKGROUND", (0,0), (-1,-1), bg),
        ("TOPPADDING",    (0,0), (-1,-1), 6),
        ("BOTTOMPADDING", (0,0), (-1,-1), 6),
        ("LEFTPADDING",   (0,0), (-1,-1), 10),
        ("ROUNDEDCORNERS", [4]),
    ]))
    return t


story = []

# ── TITLE BANNER ─────────────────────────────────────────────────────────────
banner_data = [[
    Paragraph("AML Classification", title_style),
    Paragraph("Quick Revision Summary", subtitle_style),
    Paragraph("Source: Robbins, Cotran & Kumar – Pathologic Basis of Disease", source_style),
]]
# Stack vertically in one cell using a nested table approach
title_content = [
    [Paragraph("AML Classification", title_style)],
    [Paragraph("Quick Revision Summary", subtitle_style)],
    [Paragraph("Source: Robbins, Cotran & Kumar – Pathologic Basis of Disease", source_style)],
]
banner = Table(title_content, colWidths=[17.4*cm])
banner.setStyle(TableStyle([
    ("BACKGROUND",    (0,0), (-1,-1), DARK_BLUE),
    ("TOPPADDING",    (0,0), (-1,-1), 8),
    ("BOTTOMPADDING", (0,0), (-1,-1), 8),
    ("LEFTPADDING",   (0,0), (-1,-1), 12),
    ("RIGHTPADDING",  (0,0), (-1,-1), 12),
    ("ROUNDEDCORNERS", [6]),
]))
story.append(banner)
story.append(Spacer(1, 10))

# ── DEFINITION BOX ───────────────────────────────────────────────────────────
story.append(section_header("📌  Definition"))
story.append(Spacer(1, 4))
story.append(Paragraph(
    "AML is a <b>tumor of hematopoietic progenitors</b> caused by acquired oncogenic mutations "
    "that <b>impede differentiation</b>, leading to accumulation of immature myeloid blasts in the marrow. "
    "Replacement of marrow → failure → <b>Anemia, Thrombocytopenia, Neutropenia</b>.",
    body))
story.append(Paragraph(
    "Incidence peaks after age <b>60 years</b>. Diagnosis requires <b>&gt;20% blasts</b> in bone marrow.",
    body))
story.append(Spacer(1, 6))

# ── WHO CLASSIFICATION TABLE ─────────────────────────────────────────────────
story.append(section_header("🔬  WHO Classification (Table 13.10, Robbins)"))
story.append(Spacer(1, 5))

# Header row
hdr = [
    Paragraph("<b>Subtype</b>", S("th", fontSize=9, textColor=WHITE, fontName="Helvetica-Bold", alignment=TA_CENTER)),
    Paragraph("<b>Translocation / Mutation</b>", S("th2", fontSize=9, textColor=WHITE, fontName="Helvetica-Bold", alignment=TA_CENTER)),
    Paragraph("<b>Prognosis</b>", S("th3", fontSize=9, textColor=WHITE, fontName="Helvetica-Bold", alignment=TA_CENTER)),
    Paragraph("<b>Key Feature</b>", S("th4", fontSize=9, textColor=WHITE, fontName="Helvetica-Bold", alignment=TA_CENTER)),
]

def P(t, clr=colors.HexColor("#2C3E50"), bold=False):
    fn = "Helvetica-Bold" if bold else "Helvetica"
    return Paragraph(t, S("td", fontSize=8.5, textColor=clr, fontName=fn, leading=12))

def prog(text, color):
    return Paragraph(f"<b>{text}</b>", S("pg", fontSize=8.5, textColor=color, fontName="Helvetica-Bold", alignment=TA_CENTER))

CAT1_ROWS = [
    # subtype, mutation, prognosis, key feature
    ["AML with RUNX1::RUNX1T1",       "t(8;21)",     "Favorable",      "Auer rods easily found; abnormal cytoplasmic granules"],
    ["AML with CBFB::MYH11",          "inv(16)",      "Favorable",      "Myelocytic + monocytic diff.; abnormal eosinophils"],
    ["APL – PML::RARA\n(Acute Promyelocytic)", "t(15;17)",   "VERY Favorable", "Bundles of Auer rods; HIGH DIC risk → treat with ATRA"],
    ["AML with KMT2A rearrangement",  "t(11q23)",    "Poor",           "Monocytic differentiation"],
    ["AML with mutated NPM1",         "NPM1 mut",    "Favorable",      "Detected by DNA sequencing"],
    ["AML, myelodysplasia-related",   "del(5q)/del(7q)", "Poor",       "SRSF2, SF3B1, ASXL1 mutations"],
]

PROG_COLOR = {
    "Favorable":      ACCENT_GRN,
    "VERY Favorable": colors.HexColor("#0D6E3A"),
    "Poor":           ACCENT_RED,
    "Intermediate":   ACCENT_ORG,
}

cat1_label = [
    [Paragraph("<b>CATEGORY I – AML with Specific Genetic Aberrations</b>",
               S("cl", fontSize=9, textColor=WHITE, fontName="Helvetica-Bold")),
     "", "", ""]
]

rows = [hdr]
for r in CAT1_ROWS:
    rows.append([
        P(r[0], DARK_BLUE, bold=True),
        P(r[1], MED_BLUE, bold=True),
        prog(r[2], PROG_COLOR.get(r[2], ACCENT_ORG)),
        P(r[3]),
    ])

# Category II
CAT2_ROWS = [
    ["Minimally differentiated",   "—",  "Intermediate", "MPO negative; diagnosed by flow cytometry"],
    ["Without maturation",         "—",  "Intermediate", ">3% blasts MPO positive"],
    ["With maturation",            "—",  "Intermediate", "Full range of myelocytic maturation"],
    ["Myelomonocytic",             "—",  "Intermediate", "Myeloid + monocytic differentiation"],
    ["Monocytic",                  "—",  "Intermediate", "Nonspecific esterase positive; monoblasts"],
    ["Erythroid",                  "—",  "Intermediate", ">50% dysplastic erythroid precursors"],
    ["Megakaryocytic",             "—",  "Intermediate", "Most common AML in Down syndrome; marrow fibrosis"],
]

cat2_label = [[
    Paragraph("<b>CATEGORY II – AML Defined by Differentiation (all Intermediate prognosis)</b>",
              S("cl2", fontSize=9, textColor=WHITE, fontName="Helvetica-Bold")),
    "", "", ""
]]

rows += cat2_label
rows += [[
    P(r[0], DARK_BLUE, bold=True),
    P(r[1], MED_BLUE),
    prog(r[2], PROG_COLOR.get(r[2], ACCENT_ORG)),
    P(r[3]),
] for r in CAT2_ROWS]

col_w = [4.5*cm, 3.2*cm, 2.5*cm, 7.2*cm]
tbl = Table(rows, colWidths=col_w, repeatRows=1)

n_cat1 = len(CAT1_ROWS)
n_cat2 = len(CAT2_ROWS)
total_rows = 1 + n_cat1 + 1 + n_cat2  # hdr + cat1 + cat2_label + cat2

cat2_label_row = 1 + n_cat1  # 0-indexed: row 7

tbl_style = TableStyle([
    # Header
    ("BACKGROUND",    (0,0),  (-1,0),  MED_BLUE),
    ("TEXTCOLOR",     (0,0),  (-1,0),  WHITE),
    ("ALIGN",         (0,0),  (-1,-1), "LEFT"),
    ("VALIGN",        (0,0),  (-1,-1), "MIDDLE"),
    ("TOPPADDING",    (0,0),  (-1,-1), 5),
    ("BOTTOMPADDING", (0,0),  (-1,-1), 5),
    ("LEFTPADDING",   (0,0),  (-1,-1), 6),
    ("RIGHTPADDING",  (0,0),  (-1,-1), 6),
    ("GRID",          (0,0),  (-1,-1), 0.4, MID_GREY),
    # Cat 1 rows alternating
    *[("BACKGROUND", (0, i), (-1, i), LIGHT_BLUE if i % 2 == 0 else WHITE)
      for i in range(1, cat2_label_row)],
    # Cat 2 label span
    ("BACKGROUND",    (0, cat2_label_row), (-1, cat2_label_row), DARK_BLUE),
    ("SPAN",          (0, cat2_label_row), (-1, cat2_label_row)),
    # Cat 2 rows alternating
    *[("BACKGROUND", (0, i), (-1, i), LIGHT_GREY if i % 2 == 0 else WHITE)
      for i in range(cat2_label_row+1, total_rows)],
    ("FONTNAME",      (0,0),  (-1,0),  "Helvetica-Bold"),
    ("ROWBACKGROUNDS", (0, 1), (-1, cat2_label_row-1), [LIGHT_BLUE, WHITE]),
])
tbl.setStyle(tbl_style)
story.append(tbl)
story.append(Spacer(1, 8))

# ── PATHOGENESIS FLOW ────────────────────────────────────────────────────────
story.append(section_header("⚡  Pathogenesis – 4 Mutation Categories"))
story.append(Spacer(1, 4))

path_data = [
    ["1. Transcription Factor Mutations",
     "t(8;21) → RUNX1 disrupted\ninv(16) → CBFB disrupted\nt(15;17) → PML-RARα fusion\n→ Block myeloid differentiation"],
    ["2. Epigenetic Regulator Mutations",
     "IDH1/IDH2 mutations\nDNMT3A mutations\n→ Abnormal epigenetic patterns"],
    ["3. Signal Transduction Mutations",
     "FLT3 – most common mutation in AML\n→ Drives survival & proliferation\n→ Poor prognosis"],
    ["4. Tumor Suppressor Loss",
     "TP53 mutations\n→ No DNA damage response\n→ Worst prognosis"],
]

path_rows = []
for cat, detail in path_data:
    path_rows.append([
        Paragraph(f"<b>{cat}</b>", S("pc", fontSize=9, textColor=DARK_BLUE, fontName="Helvetica-Bold", leading=13)),
        Paragraph(detail.replace("\n", "<br/>"),
                  S("pd", fontSize=9, textColor=colors.HexColor("#2C3E50"), fontName="Helvetica", leading=13)),
    ])

path_tbl = Table(path_rows, colWidths=[5.5*cm, 11.9*cm])
path_tbl.setStyle(TableStyle([
    ("BACKGROUND",    (0,0), (0,-1), LIGHT_BLUE),
    ("BACKGROUND",    (1,0), (1,-1), WHITE),
    *[("BACKGROUND",  (1,i), (1,i),  LIGHT_GREY) for i in range(0, 4, 2)],
    ("VALIGN",        (0,0), (-1,-1), "TOP"),
    ("TOPPADDING",    (0,0), (-1,-1), 6),
    ("BOTTOMPADDING", (0,0), (-1,-1), 6),
    ("LEFTPADDING",   (0,0), (-1,-1), 8),
    ("GRID",          (0,0), (-1,-1), 0.4, MID_GREY),
]))
story.append(path_tbl)
story.append(Spacer(1, 8))

# ── APL STAR BOX ─────────────────────────────────────────────────────────────
story.append(section_header("⭐  APL – Highest Yield Exam Subtype", bg=colors.HexColor("#7B241C")))
story.append(Spacer(1, 4))

apl_rows = [
    ["Translocation",  "t(15;17) → PML::RARα fusion protein"],
    ["Mechanism",      "Fusion protein blocks myeloid differentiation at promyelocyte stage"],
    ["Morphology",     "Promyelocytes with BUNDLES of Auer rods (faggot cells)"],
    ["Complication",   "HIGH risk of DIC (release of granule contents)"],
    ["Treatment",      "ATRA (All-Trans Retinoic Acid) → forces differentiation → cures APL"],
    ["Prognosis",      "VERY FAVORABLE with ATRA treatment"],
]

apl_tbl = Table(
    [[Paragraph(f"<b>{k}</b>", S("ak", fontSize=9, textColor=colors.HexColor("#7B241C"), fontName="Helvetica-Bold")),
      Paragraph(v, S("av", fontSize=9, textColor=DARK_BLUE, fontName="Helvetica", leading=13))]
     for k, v in apl_rows],
    colWidths=[3.5*cm, 13.9*cm]
)
apl_tbl.setStyle(TableStyle([
    ("BACKGROUND",    (0,0), (0,-1), colors.HexColor("#FDECEA")),
    ("BACKGROUND",    (1,0), (1,-1), WHITE),
    *[("BACKGROUND",  (1,i), (1,i),  YELLOW_BG) for i in range(0, 6, 2)],
    ("VALIGN",        (0,0), (-1,-1), "MIDDLE"),
    ("TOPPADDING",    (0,0), (-1,-1), 5),
    ("BOTTOMPADDING", (0,0), (-1,-1), 5),
    ("LEFTPADDING",   (0,0), (-1,-1), 8),
    ("GRID",          (0,0), (-1,-1), 0.4, MID_GREY),
]))
story.append(apl_tbl)
story.append(Spacer(1, 8))

# ── MORPHOLOGY ────────────────────────────────────────────────────────────────
story.append(section_header("🔍  Key Morphology Points"))
story.append(Spacer(1, 4))

morph_items = [
    "<b>Blasts &gt;20%</b> in bone marrow → diagnostic threshold for AML",
    "<b>Auer rods</b> = pink needle-like cytoplasmic inclusions in myeloblasts → <b>pathognomonic for AML</b>",
    "Bundles of Auer rods = <b>'faggot cells'</b> → specific to APL (M3)",
    "Proliferation centers = NOT seen in AML (seen in CLL/SLL)",
    "Peripheral blood smear: leukocytosis with circulating blasts",
]
for item in morph_items:
    story.append(Paragraph(f"• {item}", bullet_style))

story.append(Spacer(1, 8))

# ── PROGNOSIS QUICK GUIDE ─────────────────────────────────────────────────────
story.append(section_header("📊  Prognosis Quick Guide"))
story.append(Spacer(1, 4))

prog_data = [
    [Paragraph("<b>VERY FAVORABLE</b>", S("pv", fontSize=9, textColor=colors.HexColor("#0D6E3A"), fontName="Helvetica-Bold")),
     Paragraph("t(15;17) APL → ATRA treatment → near cure", body)],
    [Paragraph("<b>FAVORABLE</b>", S("pf", fontSize=9, textColor=ACCENT_GRN, fontName="Helvetica-Bold")),
     Paragraph("t(8;21), inv(16), NPM1 mutation", body)],
    [Paragraph("<b>INTERMEDIATE</b>", S("pi", fontSize=9, textColor=ACCENT_ORG, fontName="Helvetica-Bold")),
     Paragraph("AML defined by differentiation (Category II)", body)],
    [Paragraph("<b>POOR</b>", S("pp", fontSize=9, textColor=ACCENT_RED, fontName="Helvetica-Bold")),
     Paragraph("t(11q23)/KMT2A rearrangement, myelodysplasia-related, FLT3 mutation", body)],
    [Paragraph("<b>WORST</b>", S("pw", fontSize=9, textColor=colors.HexColor("#7B241C"), fontName="Helvetica-Bold")),
     Paragraph("del(17p) / TP53 mutation → chemo resistant", body)],
]
prog_tbl = Table(prog_data, colWidths=[3.8*cm, 13.6*cm])
prog_tbl.setStyle(TableStyle([
    ("VALIGN",        (0,0), (-1,-1), "MIDDLE"),
    ("TOPPADDING",    (0,0), (-1,-1), 5),
    ("BOTTOMPADDING", (0,0), (-1,-1), 5),
    ("LEFTPADDING",   (0,0), (-1,-1), 8),
    ("GRID",          (0,0), (-1,-1), 0.4, MID_GREY),
    *[("BACKGROUND",  (0,i), (-1,i), LIGHT_GREY if i%2==0 else WHITE) for i in range(5)],
]))
story.append(prog_tbl)
story.append(Spacer(1, 8))

# ── MEMORY TRICKS ─────────────────────────────────────────────────────────────
story.append(section_header("💡  Memory Tricks"))
story.append(Spacer(1, 4))

tricks = [
    "<b>t(15;17)</b> = <b>15 + 17 = 32</b> → Remember: APL is treatable with <b>ATRA</b> → very favorable",
    "<b>Auer rods</b> = AML's signature; <b>bundles of Auer rods</b> = APL specifically",
    "<b>FLT3</b> = most common mutation overall in AML → Poor prognosis (targeted by midostaurin)",
    "<b>inv(16)</b> = look for abnormal <b>eosinophils</b> in the marrow",
    "<b>Down syndrome + AML</b> → always think <b>Megakaryocytic</b> subtype",
    "<b>DIC + leukemia</b> → always think <b>APL (M3)</b> first",
]
for trick in tricks:
    story.append(Paragraph(f"✦  {trick}", bullet_style))

story.append(Spacer(1, 6))

# ── FOOTER ────────────────────────────────────────────────────────────────────
story.append(HRFlowable(width="100%", thickness=0.5, color=MID_GREY))
story.append(Spacer(1, 3))
story.append(Paragraph(
    "Robbins, Cotran &amp; Kumar – Pathologic Basis of Disease | Table 13.10 | Quick Revision by Orris",
    S("ft", fontSize=7.5, textColor=MID_GREY, fontName="Helvetica-Oblique", alignment=TA_CENTER)
))

# ── BUILD ─────────────────────────────────────────────────────────────────────
doc.build(story)
print(f"PDF saved to: {OUTPUT}")