nullGestational Trophoblastic Disease (GTD)Gestational Trophoblastic Disease (GTD)nullTypes of GTDTypes of GTDBenign
Hydatidiform mole/molar pregnancy (complete or incomplete)
malignant
Invasive mole
Choriocarcinoma (chorioepithelioma)
Placental site trophoblastic tumorTypes of GTDTypes of GTDThe 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)
nullPathologic and clinical classifications for gestational trophoblastic diseaseHydatidiform Mole
(molar pregnancy)Hydatidiform Mole
(molar pregnancy)Definition and Etiology 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 Definition and Etiology Definition and Etiology 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.
Definition and Etiology Definition and Etiology 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 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 > incompleteIncidence Incidence 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
Incidence Incidence 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) Not definitely benign disease ,
has a tight relationship with GTT Clinical risk factors for molar pregnancyClinical risk factors for molar pregnancyCytogenetics 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%Wrong life message , so can not develop normallyComparative Pathologic Features of Complete and Partial Hydatidiform MoleComparative Pathologic Features of Complete and Partial Hydatidiform MoleComplete hydatidiform mole demonstrating enlarged villi of various sizeComplete hydatidiform mole demonstrating enlarged villi of various sizenullHydatidiform mole: specimen from suction curettageA large amount of villi in the uterus.A large amount of villi in the uterus.nullThe microscopic appearance of hydatidiform mole:
Hyperplasia of trophobasitc cells
Hydropic swelling of all villi
Vessles are usually absentnullA sonographic findings of a molar pregnancy. The characteristic “snowstorm” pattern is evident.nullTransvaginal sonogram demonstrating the “ snow storm” appearance. nullColor Dopplor facilitates visualization of the enlarged spiral
arteriesclose proximity to the “ snow storm” appearanceColor Doppler image of a hydatidiform mole and surrounding vessels. The uterine artery is easily identified from its anatomical location.Color Doppler image of a hydatidiform mole and surrounding vessels. The uterine artery is easily identified from its anatomical location.nullnullDopplor waveform analysis demonstrates low vascular resistance(RI=0.29) in
the spiral arteries, much lower than that obtained in normal early pregnancynullnullPartial hydartidiform molenullMicroscopic image of partial molar pregnancy. Here is a partial mole in a case of triploidy. Note the scattered grape-like masses with intervening normal-appearing placental tissue. Here is a partial mole in a case of triploidy. Note the scattered grape-like masses with intervening normal-appearing placental tissue. null Large bilateral theca lutein cysts resembling ovarian germ cell tumors. With resolution of the human chorionic gonadotropin(HCG) stimulation, they return to normal-appearing ovaries.Signs and Symptoms of Complete Hydatidiform MoleSigns and Symptoms of Complete Hydatidiform MoleVaginal bleeding
Hyperemesis ( severe vomit)
Size inconsistent with gestational age( with no fetal heart beating and fetal movement)
Preeclampsia
Theca lutein ovarian cystsSigns and Symptoms of Partial Hydatidiform MoleSigns and Symptoms of Partial Hydatidiform MoleVaginal 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 moleDiagnosis of hydatidiform moleQuantitative beta-HCG
Ultrasound is the criterion standard for identifying both complete and partial molar pregnancies. The classic image is of a “snowstorm” patternDiagnosisDiagnosisThe 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 Differential diagnosis Abortion
Multiple pregnancy
Polyhydramnios
Treatment 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 contractilityTreatment Treatment Removal of the uterus (hysterectomy) : used rarely to treat hydatidiform moles if future pregnancy is no longer desired. Treatment Treatment 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 tumorHigh-risk postmolar trophoblastic tumorPre-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-upFollow-upPatients 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
Follow-upFollow-upQuantitative 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 periodInvasive moleInvasive moleDefinition 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. null Invasive mole: the tissue invades into the myometrial layer. No obvious borderline, with obvious bleeding.nullInvasive hydatidiform mole infiltrating the myometriumnullA case of invasive mole: inside the uterine cavity the typical
“snow storm” appearance can be detected, The location of
blood flow suggest an invasive mole.nullThe same patient owing to the myometrial invasion.
Reduced vascular resistance is detected in the uterine artery.nullTransvaginal color Doppler scan of a patient with invasive mole Following
uterine curettage, Persistent color signals within the myometeriunnullDoppler image of invasive molenullPower Doppler easily detects a vascular echogenic nodule within the myometrium, suggesting invasive molenullDoppler image of invasive mole. Doppler waveform
analysis depicts low vascular resistance (RI= 0.35)Common Sites for Metastatic
Gestational Trophoblastic TumorsCommon Sites for Metastatic
Gestational Trophoblastic TumorsChoriocarcinoma Choriocarcinoma Definition 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.
Definition Definition Characterized by abnormal trophoblastic hyperplasia and anaplasia , absence of chorionic villinullGross specimen of choriocarcinomanullMicroscopic image of choriocarcinomaabsence of chorionic villinullMicroscopic image of choriocarcinomanullDoppler image of choriocarcinomanullDoppler image of choriocarcinomaSymptoms and signs Symptoms and signs Bleeding
Infection
Abdominal swelling
Vaginal mass
Lung symptoms
Symptoms from other metastasesWHO Prognostic Scoring SystemWHO Prognostic Scoring System0-4 low risk, 5-7 intermediate risk, >8 high risk for death FIGO Staging System for Gestational Trophoblastic TumorsFIGO Staging System for Gestational Trophoblastic TumorsFIGO Staging System for Gestational Trophoblastic TumorsFIGO Staging System for Gestational Trophoblastic TumorsSubstages 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
nullnullIIbIIanullIIIa<3cm or locate in half lung
IIIb disease beyond IIIanullDiagnosis and evaluationDiagnosis and evaluationGestational 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 Treatment Nonmetastatic GTD
Low-Risk Metastatic GTD
High-Risk Metastatic GTDTreatment of Nonmetastatic 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.
Treatment of Nonmetastatic GTD
Treatment of Nonmetastatic GTD
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. To prevent relapse or metastasisTreatment of Low-Risk Metastatic GTD
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 remissionTreatment of High-Risk Metastatic GTD
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 DiseaseEMA-CO Chemotherapy for poor Prognostic DiseasePrognosisPrognosisCure 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 TreatmentFollow-up After Successful TreatmentQuantitative 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)Placenta Site Trophoblastic
Tumor (PSTT)Definition 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 cellsnullDignosis and treatment 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