Gestational Trophoblast Disease: Classification and Staging

WHAT IS IT: 

Gestational trophoblast disease (GTD) describes a set of diseases originating in placental tissue, specifically the chorionic villi and extravillous trophoblast. GTD includes both benign and malignant conditions. Disorders within GTD are considered distinct entities and are classified as follows

Hydatidiform Mole (HM)

Partial: Karyotype 69XXX or 69XXY or 69XYY 

• Fetus usually present   
• Usually, a result of diandry (the extra haploid set is from the father) 
  • Ovum retains its maternal nucleus and is fertilized by a single sperm, with subsequent chromosome duplication, or is fertilized by two sperm 
• Less frequently, may be the result of digyny, which can occur due to  
  • Failure of one meiotic division during oogenesis leading to a diploid oocyte or 
  • Failure to extrude one polar body from the oocyte 
• Uterus small for gestation 
• Complications 
  • ~0.5% to 1% risk of progression to GTN 
  • Theca lutein cysts (rare) |Medical complications (rare) | Postmolar malignant sequelae <5% 

Complete: Karyotype 46 XX (90%) or 46 XY 

• No fetus 
• Ovum extrudes its maternal nucleus and is fertilized by either a single sperm, with subsequent chromosome duplication, or two sperm 
• Diagnosed on ultrasound as diffuse, mixed echogenic pattern 
• Uterus large for gestational age (50%) 
• Associated complications that may be present  
  • Theca lutein cysts (15-25%) | Medical complications (<25%) | ~15%–20% risk of progression to GTN

Gestational Trophoblastic Neoplasia (GTN)  

Serum HCG Plateaus or Rises Following Evacuation of the Uterus

• Invasive mole (IM) 
  • Confined to the uterus, trophoblasts invade into myometrium 
  • Edematous villi with trophoblastic proliferation 
• Gestational Choriocarcinoma (CC) 
  • Composed of both syncytiotrophoblasts and cytotrophoblasts  
  • ~50% arise after molar pregnancy | ~25% after term pregnancy | ~25% after other gestations (miscarriage or ectopic)  
• Placental site trophoblastic tumor (PSTT) 
  • Very rare 
  • Absence of villi, intermediate trophoblast proliferation 
  • Arises from intermediate trophoblast at the implantation site 
  • Much lower growth rates than choriocarcinoma 
  • Presentation after a full-term pregnancy is often delayed by months or years 
  • Resistant to chemotherapy, and therefore hysterectomy is the standard primary treatment if the tumor is confined to the uterus 
• Epithelioid trophoblastic tumor (ETT) 
  • Extremely rare  
  • May resemble squamous cell cancer of the cervix 
  • Spectrum of benign to malignant

NOTE: Medical complications include: Pregnancy-induced hypertension | Hyperthyroidism | Anemia | Hyperemesis gravidarum 

KEY POINTS: 

FIGO Anatomical Staging for malignant GTD  

• • Stage I: Disease confined to the uterus 
  • Stage II: GTN extends outside of the uterus, but is limited to the genital structures (adnexa, vagina, broad ligament) 
  • Stage III: GTN extends to the lungs, with or without known genital tract involvement 
  • Stage IV: All other metastatic sites 

FIGO Modified WHO Prognostic Scoring System as Adapted by FIGO

• Score 0 to 6
  • Low risk for resistance to single-agent chemotherapy
• Score ≥7
  • High risk for resistance to single-agent and will require combination chemotherapy

FIGO Modified WHO Prognostic Scoring System

Risk Factor	0	1	2	4
Age (years)	<40	≥40	—	—
Antecedent pregnancy	Mole	Abortion	Term	—
Interval from index pregnancy (months)	<4	4–6	7–12	>12
Pretreatment serum hCG (mIU/mL)	<10³	10³–10⁴	10⁴–10⁵	>10⁵
Largest tumor size (including uterus)	<3 cm	3–4 cm	≥5 cm	—
Site of metastases	Lung	Spleen, kidney	GI tract	Brain, liver
Number of metastases	0	1–4	5–8	>8
Prior failed chemotherapy	None	—	Single drug	≥2 drugs

Prognosis   

• Good prognosis possible even with spread to distant organs (especially if only lung metastases present) unlike most other cancer diagnoses
• Probability of cure related to the following
  • Histologic type (invasive mole or choriocarcinoma)
  • Extent of spread of the disease/largest tumor size
  • Level of serum beta-hCG
  • Duration of disease from the initial pregnancy event to start of treatment
  • Number and specific sites of metastases
  • Nature of antecedent pregnancy (no prior term pregnancy)
  • Extent of prior treatment (no prior chemotherapy)

Learn More – Primary Sources:

FIGO Guideline Update: Diagnosis and management of gestational trophoblastic disease: 2025 update

Gestational Trophoblastic Disease Treatment (PDQ®): Health Professional Version