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 (HN)

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 a 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 
  • 15% to 25% risk of developing into an invasive mole 
  • 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%) | Postmolar malignant sequelae up to 6-32%

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 (CCA) 
  • Composed of both syncytiotrophoblasts and cytotrophoblasts  
  • 50% derived from term pregnancies | 25% normal gestations | 25% hydatidiform moles  
• Placental site trophoblastic tumor (PSTT) 
  • Very rare 
  • Absence of villi, intermediate trophoblast proliferation 
  • Arising from the placental implantation site and resembles an exaggerated form of syncytial endometritis 
  • 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 the following 

• 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

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:

Epidemiology, diagnosis, and treatment of gestational trophoblastic disease: A Society of Gynecologic Oncology evidenced-based review and recommendation

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

Current FIGO staging for cancer of the vagina, fallopian tube, ovary, and gestational trophoblastic neoplasia

Understanding and management of gestational trophoblastic disease

Related ObG Topics:

Prenatal Sonographic Features and Parental Origin of Triploidy

Microarrays and Microdeletions: Key Concepts Summarized