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
Feature Complete Mole Partial Mole
Karyotype Usually diploid 46XX Usually triploidy 69XXX most common.
Villi All villi hydropin; no normal adjacent villi Normal adjacent villi may be present
vessels present they contain no fetal blood cells blood cells
Fetal tissue None present Usually present
Trophoblast Hyperplasia usually present to variable degrees Hyperplasia mild and focal
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
Invasive mole
Definition
This term is applied to a molar pregnancy in which molar villi grow into the myometrium or its blood vessels, and may extend into the broad ligament and metastasize to the lungs, the vagina or the vulva.
Common Sites for Metastatic
Gestational Trophoblastic Tumors
Site Per cent
Lung 60-95
Vagina 40-50
Vulva/cervix 10-15
Brain 5-15
Liver 5-15
Kidney 0-5
Spleen 0-5
Gastrointestinal 0-5
Choriocarcinoma
Definition
A malignant form of GTD which can develop from a hydatidiform mole or from placental trophoblast cells associated with a healthy fetus ,an abortion or an ectopic pregnancy.
Characterized by abnormal trophoblastic hyperplasia and anaplasia , absence of chorionic villi
Symptoms and signs
• Bleeding
• Infection
• Abdominal swelling
• Vaginal mass
• Lung symptoms
• Symptoms from other metastases
FIGO Staging System for Gestational Trophoblastic Tumors
Stage Description
Ⅰ Limited to uterine corpus
Ⅱ Extends to the adnexae, outside the uterus, but limited to the genital structures
Ⅲ Extends to the lungs with or without genital tract
Ⅳ All other metastatic sites
Substages assigned for each stage as follows:
A: No risk factors present
B: One risk factor
C: Both risk factors
Risk factors used to assign substages:
1. Pretherapy serum hCG > 100,000 mlU/ml
2. Duration of disease >6 months
Diagnosis and evaluation
Gestational trophoblastic tumor is diagnosed by rising hCG following evacuation of a molar pregnancy or any pregnancy event
Once the diagnosis established the further examinations should be done to determine the extent of disease ( X-ray, CT, MRI)
Treatment
Nonmetastatic GTD
Low-Risk Metastatic GTD
High-Risk Metastatic GTD
Treatment of Nonmetastatic GTD
Hysterectomy is advisable as initial treatment in patients with nonmetastatic GTD who no longer wish to preserve fertility
This choice can reduce the number of course and shorter duration of chemotherapy.
Adjusted single-agent chemotherapy at the time of operation is indicated to eradicate any occult metastases and reduce tumor dissemination.
Single-agent chemotherapy is the treatment of choice for patients wishing to preserve their fertility.
Methotrexate(MTX) and Actinomycin-D are generally chemotherapy agents
Treatment is continued until three consecutive normal hCG levels have been obtained and two courses have been given after the first normal hCG level.
Treatment of Low-Risk Metastatic GTD
Single-agent chemotherapy with MTX or actinomycin-D is the treatment for patients in this category
If resistance to sequential single-agent chemotherapy develops, combination chemotherapy would be taken
Approximately 10-15% of patients treated with single-agent chemotherapy will require combination chemotherapy with or without surgery to achieve remission
Treatment of High-Risk Metastatic GTD
Multiagent chemotherapy with or without adjuvant radiotherapy or surgery should be the initial treatment for patients with high-rist metastatic GTD
EMA-CO regimen formula is good choice for high-rist metastatic GTD
Adjusted surgeries such as removing foci of chemotherapy-resistant disease, controlling hemorrhage may be the one of treatment regimen
EMA-CO Chemotherapy for poor Prognostic Disease
Etoposide(VP-16) 100mg/M2 IV daily×2 days (over 30-45 minutes)
Methotrexate 100mg/M2 IV losding dose, then 200mg/M2 over 12 hours day 1
Actinomycin D 0.5mg IV daily×2 days
Folinic acid 15mg IM or p.o. q 12 hours×4 starting 24 hours after starting methotrexate
Cyclophosphamide 600mg/M2 IV on day8
Oncovin (vincristine) 1mg/M2 IV on day8
(Repeat every 15 days as toxicity permits)
Prognosis
Cure rates should approach 100% in nonmetastatic and low-risk metastatic GTD
Intensive multimodality therapy has resulted in cure rates of 80-90% in patients with high-risk metastatic GTD
Follow-up After Successful Treatment
Quantitative serum hCG levels should be obtained monthly for 6 months, every two months for remainder of the first year, every 3 months during the second year
Contraception should be maintained for at least 1 year after the completion of chemotherapy. Condom is the choice.
Placenta Site Trophoblastic
Tumor (PSTT)
Definition
Placenta Site Trophoblastic Tumor is an extremely rare tumor that arised from the placental implantation site
Tumor cells infiltrate the myometrium and grow between smooth-muscle cells
Dignosis and treatment
Surum hCG levels are relatively low compared to those seen with choriocarcinoma.
Several reports have noted a benign behavior of this disease. They are relatively chemotherapy-resistant, and deaths from metastasis have occurred.
Surgery has been the mainstay of treatment
