Melanoma – Pathology (Robbins & Kumar, Basic Pathology)

from docx import Document
from docx.shared import Pt, Inches, RGBColor
from docx.enum.text import WD_ALIGN_PARAGRAPH
from docx.enum.table import WD_TABLE_ALIGNMENT
from docx.oxml.ns import qn
from docx.oxml import OxmlElement

doc = Document()

# Default styling
style = doc.styles["Normal"]
style.font.name = "Calibri"
style.font.size = Pt(11)

NAVY = RGBColor(0x1F, 0x3A, 0x5F)
DARK = RGBColor(0x33, 0x33, 0x33)

def set_heading_color(h, color=NAVY):
    for run in h.runs:
        run.font.color.rgb = color

# Title
title = doc.add_heading("Melanoma: Pathology Summary", level=0)
set_heading_color(title)
sub = doc.add_paragraph("Reference: Robbins & Kumar, Basic Pathology")
sub.runs[0].italic = True
sub.runs[0].font.size = Pt(11)
sub.alignment = WD_ALIGN_PARAGRAPH.LEFT

def add_h1(text):
    h = doc.add_heading(text, level=1)
    set_heading_color(h)
    return h

def add_h2(text):
    h = doc.add_heading(text, level=2)
    set_heading_color(h, RGBColor(0x2E, 0x5C, 0x8A))
    return h

def add_bullets(items, level=0):
    for it in items:
        p = doc.add_paragraph(it, style="List Bullet")
        if level:
            p.paragraph_format.left_indent = Inches(0.25 * (level + 1))

def add_numbered(items):
    for it in items:
        doc.add_paragraph(it, style="List Number")

# ---------------- 1. Overview ----------------
add_h1("1. Overview / Epidemiology")
doc.add_paragraph(
    "Melanoma is a malignant neoplasm arising from melanocytes. It is far less common than "
    "basal cell carcinoma or squamous cell carcinoma but carries a much higher mortality. "
    "Incidence has risen sharply in recent decades, related in part to increased UV exposure "
    "in at-risk populations and in part to improved detection of early lesions. Because of "
    "greater public awareness of early warning signs, most melanomas today are cured surgically."
)

# ---------------- 2. Pathogenesis ----------------
add_h1("2. Pathogenesis")
doc.add_paragraph(
    "As with other cutaneous malignancies, melanoma is driven mainly by UV light-induced DNA "
    "damage leading to stepwise acquisition of driver mutations."
)

add_h2("2.1 Risk Factors")
add_bullets([
    "Intense, intermittent sun exposure at an early age carries the highest risk.",
    "Highest incidence in sun-exposed skin and fair-skinned populations in high-UV locales (e.g., Australia).",
    "Hereditary predisposition in an estimated 5-10% of cases.",
    "Germline CDKN2A mutations found in up to 40% of familial melanoma cases.",
])

add_h2("2.2 CDKN2A Locus")
doc.add_paragraph(
    "CDKN2A encodes two tumor suppressors via alternate reading frames:"
)
add_bullets([
    "p16 - a cyclin-dependent kinase inhibitor that regulates the G1-S checkpoint by keeping "
    "Rb (retinoblastoma protein) in its active, growth-suppressing state.",
    "p14 - stabilizes p53 by preventing its degradation, thereby augmenting p53 tumor-suppressor activity.",
])

add_h2("2.3 Stepwise Molecular Evolution (Sun-Exposed Melanoma)")
add_numbered([
    "Initiating event: activating mutation in BRAF (most common) or RAS -> typically produces only a benign nevus.",
    "Mutations activating telomerase expression -> breaks replicative senescence; seen in atypical nevi and radial-growth-phase melanoma.",
    "Loss of CDKN2A / p16 (mutation or epigenetic silencing) -> shift from radial to invasive vertical growth phase.",
    "Additional mutations in TP53 and PTEN, plus emergence of aneuploidy/copy-number alterations -> acquisition of metastatic capacity and increased genetic heterogeneity.",
])
doc.add_paragraph(
    "Continued UV exposure throughout this evolution adds to mutational burden and drives tumor progression; "
    "UV-associated melanomas carry a high mutation burden, some of which generate neoantigens."
)

add_h2("2.4 Alternative Pathways (Non-UV Driven)")
add_bullets([
    "Acral and mucosal melanomas (non-sun-exposed sites): often initiated by gain-of-function mutation "
    "in the KIT receptor tyrosine kinase gene.",
    "Uveal (ocular) melanoma: distinct driver mutations, most notably mutually exclusive activating "
    "mutations in GNAQ or GNA11 (GTP-binding proteins).",
])

# ---------------- 3. Growth Phases ----------------
add_h1("3. Growth Phases")
add_h2("3.1 Radial Growth Phase")
doc.add_paragraph(
    "Lateral, intraepidermal expansion of melanocytes along the dermoepidermal junction "
    "(lentiginous hyperplasia / junctional nevus progressing to early melanoma). Malignant cells spread "
    "as poorly formed nests or single cells at all levels of the epidermis (\"pagetoid spread\"). "
    "Cells in this phase lack the capacity to invade or metastasize, and this stage may persist for a "
    "prolonged period."
)
add_h2("3.2 Vertical Growth Phase")
doc.add_paragraph(
    "Tumor grows downward into the dermis as an expansile mass lacking cellular maturation. Clinically "
    "heralded by the appearance of a nodule within a previously flat lesion. This transition correlates "
    "with the emergence of metastatic potential and is a key prognostic turning point."
)

# ---------------- 4. Morphology ----------------
add_h1("4. Morphology")
add_h2("4.1 Gross Appearance")
add_bullets([
    "Striking variation in pigmentation: shades of black, brown, red, dark blue, and gray.",
    "Irregular, often \"notched\" borders.",
    "Macular areas indicate radial (superficial) growth; elevated/nodular areas indicate vertical "
    "(dermal invasive) growth.",
])

add_h2("4.2 Microscopic Features")
add_bullets([
    "Malignant melanocytes form poorly formed nests or single cells at all epidermal levels (pagetoid spread) "
    "and expansile dermal nodules, corresponding to radial and vertical growth phases respectively.",
    "Superficial spreading melanoma is often accompanied by a brisk lymphocytic infiltrate, possibly "
    "reflecting host immune response to tumor antigens.",
    "Melanoma cells are considerably larger than nevus cells.",
    "Nuclei are large with irregular contours, chromatin clumped at the nuclear membrane periphery, and "
    "prominent \"cherry-red\" eosinophilic nucleoli.",
    "Atypical mitotic figures may be seen.",
    "Immunohistochemistry (e.g., HMB-45, S-100, Melan-A) helps confirm melanocytic origin and identify "
    "metastatic deposits, including micrometastases in sentinel lymph nodes.",
])

# ---------------- 5. Clinical Features ----------------
add_h1("5. Clinical Features")
doc.add_paragraph(
    "Melanoma most often arises in the skin but may also occur in oral and anogenital mucosa, the "
    "esophagus, the meninges, and the eye. Incidence of cutaneous melanoma is inversely related to the "
    "degree of skin pigmentation; however, melanoma does occur in darker-skinned individuals, most "
    "commonly as acral melanoma (sole, palm, or nail bed). Cutaneous melanoma is usually asymptomatic; "
    "pruritus may be an early symptom."
)

add_h2("5.1 Clinical Warning Signs")
add_numbered([
    "Rapid enlargement of a preexisting nevus",
    "Itching or pain in a lesion",
    "Development of a new pigmented lesion during adult life",
    "Irregularity of the borders of a pigmented lesion",
    "Variegation of color within a pigmented lesion",
])
doc.add_paragraph(
    "(These correspond clinically to the widely used ABCDE criteria: Asymmetry, Border irregularity, "
    "Color variation, Diameter >6 mm, Evolution/change.)"
)

add_h2("5.2 Precursor Lesion: Dysplastic Nevus")
add_bullets([
    "Larger than most acquired nevi (often >5 mm), may number in the hundreds; flat macules to slightly "
    "raised plaques with a \"pebbly\" surface and variegated pigmentation.",
    "Microscopically: compound nevi with architectural and cytologic atypia; enlarged nevus-cell nests with "
    "abnormal fusion (\"bridging\"); lentiginous hyperplasia of basal melanocytes; irregular/angulated, "
    "hyperchromatic nuclei; sparse dermal lymphocytic infiltrate; melanin pigment incontinence with dermal "
    "macrophages; linear fibrosis around epidermal nests.",
    "Familial dysplastic nevus syndrome carries a lifetime melanoma risk approaching 100%.",
    "In sporadic cases, risk is increased mainly in individuals with 10 or more dysplastic nevi.",
    "Most melanomas arise de novo rather than from a pre-existing nevus; dysplastic nevi are best regarded "
    "as markers of melanoma risk rather than obligate precursors.",
])

# ---------------- 6. Prognosis ----------------
add_h1("6. Prognosis")
doc.add_paragraph(
    "Tumor (Breslow) thickness is the single most important prognostic determinant in cutaneous "
    "melanoma: increasing thickness correlates strongly with worse biologic behavior and higher metastatic "
    "risk. Combined with other histologic variables (e.g., growth phase, mitotic rate, ulceration, "
    "lymphocytic response), accurate prognostication and staging are possible."
)

# ---------------- 7. Quick Recall Table ----------------
add_h1("7. Quick Recall Table")
table = doc.add_table(rows=1, cols=2)
table.style = "Light Grid Accent 1"
table.alignment = WD_TABLE_ALIGNMENT.CENTER
hdr = table.rows[0].cells
hdr[0].text = "Feature"
hdr[1].text = "Key Point"
for cell in hdr:
    for p in cell.paragraphs:
        for r in p.runs:
            r.bold = True

rows = [
    ("Cell of origin", "Melanocyte"),
    ("Main cause", "UV-induced DNA damage (cumulative mutational burden)"),
    ("Familial gene", "CDKN2A (p16/p14) germline mutation - ~40% of familial cases"),
    ("Initiating mutation", "BRAF (most common) or RAS"),
    ("Senescence bypass", "Telomerase-activating mutations"),
    ("Radial -> Vertical trigger", "Loss of CDKN2A/p16"),
    ("Metastatic competence", "TP53 and PTEN mutations + aneuploidy"),
    ("Acral/mucosal driver", "KIT gain-of-function mutation"),
    ("Uveal melanoma driver", "GNAQ or GNA11 mutation (mutually exclusive)"),
    ("Radial growth phase", "Intraepidermal, pagetoid spread; non-metastatic"),
    ("Vertical growth phase", "Dermal invasion, nodular; metastatic potential begins"),
    ("Key histologic clue", "Large cells, irregular nuclei, peripheral chromatin clumping, cherry-red nucleoli"),
    ("IHC markers", "HMB-45, S-100, Melan-A"),
    ("Best prognostic factor", "Breslow (tumor) thickness"),
    ("Precursor marker lesion", "Dysplastic nevus (marker of risk, not obligate precursor)"),
]
for feat, pt in rows:
    row_cells = table.add_row().cells
    row_cells[0].text = feat
    row_cells[1].text = pt

for row in table.rows:
    for cell in row.cells:
        cell.width = Inches(3.25)

# Footer / citation note
doc.add_paragraph()
note = doc.add_paragraph()
note_run = note.add_run(
    "Source: Robbins & Kumar, Basic Pathology - Melanoma, pp. 893-896 (10th ed.). "
    "Compiled as a study reference summary; consult the full textbook chapter for figures "
    "(Fig. 22.20-22.22) and complete discussion."
)
note_run.italic = True
note_run.font.size = Pt(9)
note_run.font.color.rgb = RGBColor(0x66, 0x66, 0x66)

doc.save("/tmp/workspace/melanoma-pathology/output/Melanoma_Pathology_Summary.docx")
print("saved")