StepWise USMLE
gynecologic pathology Β· placenta

Female Reproductive & Trophoblastic Disease

High‑yield framework for vulva, vagina, cervix, uterus, ovary & placental disorders

🫧 Vulva

  • Lichen sclerosus – epidermal thinning + dermal fibrosis β†’ pale, atrophic skin
  • Postmenopausal women; small risk of progression to squamous cell carcinoma
  • Lichen simplex chronicus – chronic scratch-itch cycle β†’ white plaques
  • Micro: squamous hyperplasia + dermal inflammation
    • HPV 6 & 11 (low oncogenic) cause condylomata acuminata and VIN (vulvar intraepithelial neoplasia)
  • HSV-2 – painless vesicles β†’ pustules β†’ painful ulcers
  • Syphilis (T. pallidum) – primary chancre: painless ulcer, heals without scarring
  • Molluscum contagiosum – DNA poxvirus; smooth papules with cytoplasmic inclusions
  • Bartholin abscess – polymicrobial; requires drainage or excision
  • Papillary hidradenoma – benign apocrine sweat gland tumor; may ulcerate, mimics carcinoma
  • Extramammary Paget – intraepidermal malignant cells (pagetoid spread); usually no underlying malignancy
  • SCC – most common vulvar malignancy; two peaks: >60 y/o (HPV-independent) & younger (HPV 16/18)
  • Melanoma – differentiate from lentigo simplex (benign)

    • πŸŒ€ Vagina

  • Vaginal adenosis – glandular epithelium in vagina; precursor to clear cell adenocarcinoma
  • DES exposure (in utero) – ↑ risk of clear cell adenocarcinoma (rare)
  • Sarcoma botryoides – embryonal rhabdomyosarcoma; infant/child <5 y/o, grapelike polypoid mass
  • Micro: cambium layer of spindle cells, desmin+ ; cross-striations rare
  • Vaginal SCC – usually HPV-related; cervical extension more common
  • Rhabdomyoma – benign skeletal muscle tumor; middle-aged women
  • Gartner duct cyst – mesonephric (Wolffian) remnant; lateral wall; associated with urinary tract anomalies
  • MRKH syndrome – congenital absence of upper vagina + uterus; primary amenorrhea
    • Vaginitis/vaginosis: diagnosis requires vaginal swab; molecular tests as indicated
  • Candidiasis – yeast/pseudohyphae; pruritus, discharge; not usually STD
  • Bacterial vaginosis – polymicrobial (Gardnerella, others); clue cells (coccobacilli-coated squamous cells); ↑ risk preterm labor, PID
  • Trichomonas – motile protozoan; often asymptomatic; β€œstrawberry cervix” not consistent

    • πŸ”¬ Cervix

  • PID – ascending infection (STD) from cervix β†’ endometritis, salpingitis, peritonitis
  • Organisms: Chlamydia, Mycoplasma, endogenous flora; broad-spectrum antibiotics
  • Fitz-Hugh-Curtis – perihepatitis; β€œviolin-string” adhesions; RUQ pleuritic pain
    • Tubal ectopic most common in ampulla; rupture β†’ acute lower abdominal pain
  • HPV – transient or persistent; persistent β†’ SIL and cancer
  • Acute cervicitis – C. trachomatis, N. gonorrhoeae, T. vaginalis, Candida, HSV-2
  • Follicular cervicitis – C. trachomatis; can cause neonatal conjunctivitis/pneumonia
    • MalignancyIncidence rankMortality rank
    Endometrial12
    Ovarian21
    Cervical33
  • Cervical carcinoma – peak 35–44 y/o; SCC most common, also adenocarcinoma, neuroendocrine
  • Risk factors: early first intercourse, multiple partners, multiparity, OCP, smoking, STDs, immunosuppression
  • HPV high-risk (16,18,31,33) – E6 (p53) + E7 (Rb)
  • CIN – at squamocolumnar junction; low-grade SIL β†’ high-grade SIL
  • Pap test for screening; colposcopy + biopsy for diagnosis
  • Endocervical polyp – common benign; columnar or squamous epithelium

    • 🧬 Uterus

  • Acute endometritis – ascending infection; associated with pregnancy/abortion
  • Chronic endometritis – PID, IUD; plasma cells in endometrium
  • Endometriosis – endometrial glands/stroma outside uterus; reproductive age
  • Sites: ovaries, ligaments, pouch of Douglas, bowel serosa, bladder, peritoneum
  • Symptoms: pelvic pain, dysmenorrhea, dyspareunia, infertility; chocolate cysts (endometrioma)
  • Adenomyosis – invagination of endometrium into myometrium β†’ menorrhagia + dysmenorrhea
  • Anovulatory bleeding – glandular/stromal breakdown in proliferative endometrium
  • Endometrial hyperplasia – benign (cystic glands) vs. EIN (crowded architecture, cytologic atypia)
  • EIN β†’ high risk for adenocarcinoma; treatment: hysterectomy or progestin + surveillance
  • Endometrial adenocarcinoma – most common gynecologic malignancy; postmenopausal bleeding
  • Risk factors: estrogen excess (early menarche, late menopause, nulliparity, obesity, chronic anovulation, estrogen-producing tumors, ERT/tamoxifen, Lynch)
  • Histologic types: endometrioid (PTEN) most common; serous (TP53)
  • Leiomyoma (fibroid) – benign smooth muscle; estrogen-dependent; common in African Americans
  • Symptoms: menorrhagia, mass, pain, infertility; whorled, white-tan cut surface
  • Malignant variants: leiomyosarcoma, carcinosarcoma (mixed malignant stromal + epithelial)

    • βšͺ Ovary

  • PCOS – androgen excess, oligo/anovulation, polycystic ovaries; elevated LH, low FSH, high testosterone
  • Presentation: oligomenorrhea, hirsutism, infertility, obesity
  • Epithelial ovarian tumors – most common; risk: nulliparity, family history, germline mutations
  • Serous: low-grade (KRAS/BRAF) vs. high-grade (TP53) – most malignant
  • Mucinous: goblet cells; CA 125 for follow-up
  • Psammoma bodies (calcifications) in well-differentiated serous
    • No routine screening test for ovarian cancer; Pap test reduces cervical cancer only
  • Teratoma (dermoid) – >95% benign; early reproductive years; all 3 germ layers; may contain hair, teeth, thyroid (struma ovarii)
  • Dysgerminoma – malignant; children/young adults; radiosensitive; similar to seminoma
  • Fibroma – most common stromal tumor; Meigs syndrome (fibroma + ascites + pleural effusion)
  • Granulosa cell tumor – estrogen-producing; Call-Exner bodies; endometrial hyperplasia/cancer risk
  • Sertoli-Leydig – androgen-producing; virilization
  • Metastatic to ovary: breast, colon, endometrial, gastric (Krukenberg – signet ring)
    • OriginAgeExamplesFrequency% Malignant
    Surface epithelial20+Serous, mucinous, endometrioid65–70%90%
    Germ cell0–25Teratoma, dysgerminoma15–20%3–5%
    Sex cord-stromaAllFibroma, granulosa, Sertoli-Leydig5–10%2–3%
    MetastasisVariableKrukenberg, etc.5%5%

    🧫 Placenta & Trophoblast

  • Complete mole – 46,XX (all paternal); no embryo; marked trophoblast proliferation; ↑↑ Ξ²-hCG
  • Partial mole – triploid 69,XXY (maternal + 2 sperm); fetus may develop briefly; focal trophoblast proliferation; ↑ Ξ²-hCG
    • FeaturePartial moleComplete mole
    PloidyTriploidDiploid (all paternal)
    Chorionic villiSome hydropicAll hydropic
    Trophoblast proliferationFocalMarked
    Fetal tissuePresentAbsent
    Invasive mole2%10%
    ChoriocarcinomaRare2%
  • Presentation: enlarged uterus, vaginal bleeding, grape-like tissue, elevated Ξ²-hCG; U/S diagnosis; curettage + Ξ²-hCG follow-up
  • Choriocarcinoma – malignant trophoblast; necrotic/hemorrhagic; 50% from complete mole; hematogenous spread (lungs, brain, liver)
  • Micro: cytotrophoblast + syncytiotrophoblast + intermediate trophoblast; chemotherapy
  • Placental site trophoblastic tumor – intermediate trophoblast; <2 years post-pregnancy; surgical (chemo-resistant)
  • Ectopic pregnancy – most common in fallopian tube; risk: PID scarring, endometriosis, ↓ tubal motility
  • Placental abruption – premature separation; risk: HTN, smoking, cocaine, older age
  • Placenta previa – overlies cervical os; risk of hemorrhage during delivery
  • Placenta accreta – implants into myometrium; hysterectomy required
  • Twin-twin transfusion – monochorionic twins with vascular anastomoses
  • Preeclampsia – new HTN + proteinuria/end-organ dysfunction after 20 wks; abnormal uteroplacental flow
  • Eclampsia = seizures; HELLP = hemolysis, elevated liver enzymes, low platelets