Gestational Trophoblastic Disease

GTD Basics - Trophoblast Trouble

• Definition: Gestational Trophoblastic Disease (GTD): spectrum of proliferative disorders from placental trophoblast.
• Spectrum & Classification:
  • Benign (Molar Pregnancies):
    • Hydatidiform Mole: Complete (CM), Partial (PM)
  • Malignant (Gestational Trophoblastic Neoplasia - GTN):
    • Invasive Mole
    • Choriocarcinoma
    • Placental Site Trophoblastic Tumor (PSTT)
    • Epithelioid Trophoblastic Tumor (ETT)
• Epidemiology:
  • Incidence: ↑ in Asian countries (India: ~1/350-400 pregnancies).
  • Age extremes: <20 yrs, >40 yrs.
• Risk Factors:
  • Prior GTD (strongest)
  • Advanced Maternal Age (AMA >35 yrs)
  • Advanced Paternal Age (APA >45 yrs)
  • History of infertility, prior spontaneous abortions
  • Diet: ↓ carotene/Vitamin A, ↓ animal fat.

⭐ The risk of a repeat molar pregnancy is ~1-2%; after two molar pregnancies, risk ↑ to 15-20%.

Molar Pregnancy - Grape Expectations

📌 Complete Mole: Chromosomes Completely Paternal, Can't grow fetus, Crazy hCG levels.

Hydatidiform moles are characterized by abnormal trophoblastic proliferation. Key differences distinguish complete and partial moles:

⭐ p57kip2 immunostaining: Negative in complete moles (no maternal DNA to express p57), positive in partial moles (maternal DNA present).

Malignant GTD (GTN) - When Moles Go Rogue

Gestational Trophoblastic Neoplasia (GTN) encompasses malignant forms of GTD:

• Invasive Mole
  • Myometrial invasion by hydropic villi.
  • Persistent ↑ hCG post-evacuation.
  • Metastases (lungs, vagina); often regresses.
• Choriocarcinoma
  • Pure epithelial malignancy (cytotrophoblasts & syncytiotrophoblasts); NO villi.
  • Extensive necrosis; early hematogenous spread (lungs, brain, liver, kidney, vagina).
  • Highly chemosensitive.
  • Follows mole, abortion, ectopic, or term pregnancy.

  ⭐ Choriocarcinoma is the GTN most likely to metastasize to the brain.

• Placental Site Trophoblastic Tumor (PSTT)
  • Neoplasm of intermediate trophoblasts at implantation site.
  • Produces hPL, low hCG levels.
  • Relatively chemoresistant; presents with amenorrhea/irregular bleeding.
• Epithelioid Trophoblastic Tumor (ETT)
  • Rare; from chorionic-type intermediate trophoblasts.
  • Often discrete nodule; indolent or aggressive.

Diagnosis, Staging & Management - Charting the Course

• Diagnosis (Post-Molar GTN Criteria):
  • hCG plateau (4 values, ±10%) >3 wks
  • hCG ↑ (≥10%, 3 values) >2 wks
  • hCG persists 6 months post-evac
  • Histology (Choriocarcinoma/PSTT/ETT) or Metastases
• FIGO Anatomical Staging (2000):
  • I: Confined to uterus
  • II: Extends to genital structures (outside uterus)
  • III: Lung metastases
  • IV: Other distant metastases (e.g., brain, liver)
• WHO Prognostic Scoring System: 📌 'A PALM SSite Chemo' (Age, Pregnancy antecedent, Interval from index pregnancy, pre-treatment hCG Level, Largest tumor size, Metastases site/number, Site of mets, Previous Chemo).
  • Score: ≤6 = Low-risk
  • Score: ≥7 = High-risk

  ⭐ The WHO prognostic scoring system is crucial for stratifying GTN patients into low-risk and high-risk groups, guiding chemotherapy selection.

• Management & Follow-up Flow:

• Key Management Points: Suction evacuation for molar pregnancy. Hysterectomy for chemoresistance or PSTT/ETT. Brain/Liver metastases may require specific therapy (e.g., radiotherapy, intrathecal chemo).
• Follow-up: Serial hCG monitoring (weekly until normal for 3 consecutive weeks, then monthly for 6-12 months). Effective contraception during follow-up period.

High‑Yield Points - ⚡ Biggest Takeaways

• Complete mole: 46,XX (all paternal), "snowstorm" USG, very high β-hCG, ↑ malignancy risk (choriocarcinoma).
• Partial mole: Triploid (e.g., 69,XXY), often has fetal parts, lower β-hCG, ↓ malignancy risk.
• Choriocarcinoma: Most aggressive GTD, early hematogenous spread (commonly lungs, vagina); treat with chemotherapy.
• Serial β-hCG monitoring: Crucial for diagnosis, assessing treatment response, and detecting persistent GTD/GTN.
• Suction evacuation is the standard primary treatment for molar pregnancies.
• Gestational Trophoblastic Neoplasia (GTN) requires chemotherapy; FIGO staging guides management decisions for GTN.