Gestational Trophoblastic Disease (GTD)

Types of GTD
Benign
•    Hydatidiform mole/molar pregnancy (complete or incomplete)
malignant
•    Invasive mole 
•    Choriocarcinoma (chorioepithelioma)
•    Placental site trophoblastic tumor

    The term Gestational Trophoblastic Tumors  has been applied the latter three conditions
    Arise from the trophoblastic elements
    Retain the invasive tendencies of the normal placenta or  metastasis
    Keep secretion of the human chorionic gonadotropin (hCG).

Hydatidiform Mole

 (molar pregnancy)

Definition and Etiology 
     Hydatidiform mole is a pregnancy characterized by vesicular swelling of placental villi and usually the absence of an intact fetus.
     The etiology of hydatidiform mole remains unclear, but it appears to be due to abnormal gametogenesis and fertilization 
    In a ‘complete mole’ the mass of tissue is completely made up of abnormal cells 
    There is no fetus and nothing can be found at the time of the first scan. 

    In a ‘partial mole’, the mass may contain both these abnormal cells and often a fetus that has severe defects. 
    In this case the fetus will be consumed ( destroyed) by the growing abnormal mass very quickly.  (shrink)

Incidence 

•    1 out of 1500-2000 pregnancies in the U.S. and Europe
•    1 out of 500-600 (another report 1%) pregnancies in  some Asian countries. 
•    Complete > incomplete
    Repeat hydatidiform moles occure in 0.5-2.6% of patients, and these patiens have a subsequent greater risk of developing invasive mole or choriocarcinoma
    There is an increased risk of molar pregnancy for women over the age 40
    Approximately 10-17% of hydatidiform moles will result in invasive mole
    Approximately 2-3% of hydatidiform moles progress to choriocarcinoma ( most of them are curable) 

Clinical risk factors for molar pregnancy

• Age (extremes of reproductive years)
                  <15
                  >40
• Reproductive history
                  prior hydatidiform mole
                  prior spontaneous abortion
• Diet
                  Vitamin A deficiency
• Birthplace 
                  Outside North America( occasionally has this disease).

Cytogenetics 

• Complete molar pregnancy 
  Chromosomes are paternal , diploid
      46,XX in 90% cases
      46,XY in a small part
• Partial molar pregnancy 
  Chromosomes are paternal and maternal, triploid. 
      69,XXY   80%
      69,XXX or 69,XYY  10-20%

Comparative Pathologic Features of Complete and Partial Hydatidiform Mole

Signs and Symptoms of Complete Hydatidiform Mole

• Vaginal bleeding
• Hyperemesis ( severe vomit)
• Size inconsistent with gestational age( with no fetal heart beating and fetal movement)
• Preeclampsia
• Theca lutein ovarian cysts

Signs and Symptoms of Partial Hydatidiform Mole

• Vaginal bleeding
• Absence of fetal heart tones
• Uterine enlargement and preeclampsia is reported in only 3% of patients.
• Theca lutein cysts, hyperemesis is rare.

Diagnosis of hydatidiform mole

Quantitative beta-HCG
Ultrasound is the criterion standard for identifying both complete and partial molar pregnancies. The classic image is of a “snowstorm” pattern
    The most common symptom of a mole is vaginal bleeding during the first trimester 
    however very often no signs of a problem appear and the mole can only be diagnosed by use of ultrasound scanning. (rutting check)
    Occasionally, a uterus that is too large for the stage of the pregnancy can be an indication.   
    NOTE:  Vaginal bleeding does not always indicate a problem!


Differential diagnosis 
•    Abortion
•    Multiple pregnancy 
•    Polyhydramnios

Treatment 

 Suction dilation and curettage :to remove benign hydatidiform moles
   When the diagnosis of hydatidiform mole is established, the molar pregnancy should be evacuated. 
    An oxytocic agent should be infused intravenously  after the start of evacuation and continued for several hours to enhance uterine contractility
•    
•    Removal of the uterus (hysterectomy) : used rarely to treat hydatidiform moles if future pregnancy is no longer desired.  

Chemotherapy with a single-agent drug
     Prophylactic (for prevention) chemotherapy at the time of or immediately following molar evacuation may be considered for the high-risk patients( to prevent spread of disease )



High-risk postmolar trophoblastic tumor
    Pre-evacuation uterine size larger than expected for gestational duration
    Bilateral ovarian enlargement (> 9 cm theca lutein cysts) 
    Age greater than 40 years
    Very high hCG levels(>100,000 m IU/ml)
    Medical complications of molar pregnancy such as toxemia, hyperthyrodism and trophoblastic embolization (villi come out of placenta )
     repeat hydatidiform mole 


Follow-up
    Patients with hudatidiform mole are curative over 80% by treatment of evacuation. 
    The follow-up after evacuation is key necessary 
    uterine involution, ovarian cyst regression and cessation of bleeding
    Quantitative serum hCG levels should be obtained every 1-2 weeks until negative for three consecutive determinations, 
    Followed by every 3 months for 1 years. 
    Contraception should be practiced during this follow-up period