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- 1. Gestational Trophoblastic Disease (GTD) Ezana Wakjira MS3 May 24, 2016
- 2. Gestational Trophoblastic Disease (GTD) • GTD used to describe a Spectrum of related diseases caused by abnormal proliferation of trophoblastic tissue. • GTD encompasses: • Hydatidiform moles (80%), • Invasive moles (10-15%) • Gestational choriocarcinomas (2-5%) • Placental site trophoblastic tumors (rare) • All produce b-HCG, which is used as tumor marker and to gauge effect of treatment.
- 5. Gestational Trophoblastic Disease (GTD) - Epidemiology Incidence varies around the world - US : hydatidiform mole 1:600 TA & 1:1500 pregnancies • 20% of these will develop malignancies after evacuation of mole • Gestational choriocarcinoma 1:20-40,000 pregnancies • 50% T, 25% Molar, 25% other • Placental site trophoblastic tumor • Rare, can develop after any type of pregnancy • Decreased rate of GTD in black women • Intermediate rate in North America and Europe • High rate in Asia and Latin America • The advent of a sensitive b-hCG assay and chemotherapy has yielded almost 100% cure rate.
- 6. Risk Factors for GTD Major Risk Factors: • Extremes in age ( >35 and <20) • Prior GTD • Baseline 0.1%1%16-28% • Nulliparity (70%) – increasing parity protective Minor Risk Factors: • Diet low in beta-carotene, folic acid and animal fat • Smoking • Infertility
- 8. Complete and Partial Mole
- 9. Hydatidiform Moles • Clinical presentation • Complete mole (Sx commonly seen) • Abnormal vaginal bleeding in early pregnancy (97%) • Grape-like vesicles filling uterus (80%) • No embryo + Large for date uterine size (50%) • hCG high (>100,000) • “Snow storm” on US • Complications: HTN, hyperthyroidism, anemia, and hyperemesis gravadrum, thecal luteal cysts (15-25%), malignant sequelae 20% • Partial mole (Sx rarely seen) • Fetal part present • Missed abortion • Uterus size equal/ small date • hCG slightly elevated • Complications: malignant sequelae (5%)
- 10. Partial Mole – Swiss Cheese
- 11. Complete Mole - Snow Storm
- 12. Hydatidiform Mole Diagnosis & Treatment • Complete HM - 1st trimester characteristic Sx. + US “snow storm” • Partial HM – PE usually nl, abd. small for GA + US “Swiss Cheese appearance” • Complete and Partial HM treated similarly • D &C ± RhoGAM (for Rh-) • Chemotherapy if bHCG elevated or plateau post D&C • Repeat D & C not recommended • Hysterectomy • Decrease risk of post molar MGTD • Hysterectomy (does not decr. Risk of metastasis) • 95-100% cure rate • persistent GTD risk (15-20% complete, 5% partial)
- 13. Hydatidiform Mole follow up • Follow up: serial hCG (with in 48 hrs., weekly for 3 weeks, monthly for 6 mo.) + reliable contraception • Plateau or rise in hCG OR above normal hCG after 6 mo. indicates persistent/invasive mole • FIGO standardized hCG criteria for diagnosis of post-molar GTD: • 1. hCG level plateau of 4 values ± 10% recorded over a 3-week duration (days 1,7,14, &21) • 2. hCG level increase of ≥ 10% 3 values recorded over a 2-week duration (days 1,7, and 14) • 3. Persistence of detectable hCG for more than 6 months after molar evacuation
- 14. Malignant GTD
- 15. Invasive moles • Confined to uterus (rarely metastasize) • Almost always occur after evacuation of molar pregnancy • Neoplastic trophoblasts w/ edematous chorionic villi invading myometrium. • Clinically diagnosed • Avoid D & C to prevent uterine perforation
- 16. Gestational Carcinomas • Neoplastic Syncytiotrophoblast and cytotrophoblast elements w/out chorionic villi • Early metastasis to (vagina, lung, liver and brain) - Unknown primary site metastasis + High hCG + exclude pregnancy = GTD diagnosis • Diagnosed histologically • Tx: immediate Chemo
- 18. Placental Site Trophoblastic Tumors • Rare • Neoplastic intermediate trophoblastic cells w/out villi • Low number of synctiotrophoblsts lower level of b-hCG • Diagnosis: histological • Tx: not as sensitive to chemo, hysterectomy is treatment of choice(most are non malignant)
- 19. FIGO 2000 risk index – M GTD Classification and Staging
- 20. NIH Clinical Classification – for GTD
- 21. Malignant GTD TREATMENT • Pre-treatment lab work • Retrospective studies have shown methotrexate, dactinomycin, etoposide, 5-Flurouracil and cisplatin to be effective agents against Malignant-GTD • Weekly IM Methotrexate 30-50 mg/m^2 = 70-80% remission rate in nonmetastatic GTD (Phase II trial by Gynecology - Oncology group) • Administer chemo. until normal hCG level is reached , additional course after 1st normal hCG level • Hysterectomy may decrease amt. of chemo req’d for remission • Hysterectomy does not decr. metastasis in high risk patients. • Triple therapy w/ methotrexate, dactinomycin and chlorambucil/cylophosphamide is standard regiment • Continue chemo until hCG nl, then 2-3 additional courses • 13% recurrence rate • Follow up: serial hCG q2weeks for 3 months, then monthly until 1 year
- 22. Resouces • Blueprint : obstetrics and gynecology (2009, Callhan and Caughey) • ACOG practice bulletin: Clinical management guidelines for Obstetrician-Gynecologists. ( https://www.acog.org/- /media/List-of-Titles/PBListOfTitles.pdf) • Partial and Complete mole ultrasounds - Radiopedia.org
Editor's Notes
- Trophoblast – forms most of the placenta, aids in embryo implantation and modify uterus blood vessels in order to provide adequate blood supply to fetus - Differentiates into 2 layers (synsitiotrophoblast, cytotrophoblast and intermediate trophoblast) 6 days after fertilization
- Trophoblast – forms most of the placenta, aids in embryo implantation and modify uterus blood vessels in order to provide adequate blood supply to fetus - Differentiates into 2 layers (synsitiotrophoblast, choriotrophoblast and intermediate trophoblast) 6 days after fertilization
- Gestational choriocarcinoma 1:20-40,000 pregnancies 50% after term pregnancies 25% after molar pregnancies 25% after other types of pregnancies - Before sensitive b-hCG assay – GTD had high morbidity and mortality rate - Virtually all patients with non-metastatic GTD can be cured with single agent chemotherapy
- MAJOR RISK FACTORS: Basline risk of developing GTD is 0.1%, 1% with previous GTD, 16-28% recurrence risk with 2 or more previous GTD MINOR RISK FACTORS: - Increase GTD incidence reported in geographic location with diet low in beta-carotene, folic acid and animal fat.
- PARTIAL MOLE: normal ovum fertilized by 2 sperm at same time (69XXY) – triploid karyotype with - triploid karyotype - small for GA uterus - fetus is present (fetal heart rate may be present – most spontaneous aborted in 1st or 2nd trimester – misdiagnosed as SAB) - few and focal hydropic vili vs. complete which has diffuse hydropic villi - focal trophoblastic proliferation ( mainly cytotrophoblasts which do not producehCG thus hCG nl or slightly elevated) - “swiss-cheese” on ultrasound = anechoic space juxtaposed against chorionic vili - low malignancy potential (<5%), 0% risk of metastatic GTD COMPLETE MOLE: - empty ovum fertilized by one sperm that divides, or empty ovum fertilized by two sperm (46xx) - absent fetus, big for GA uterus, thecal leutine cysts, incr risk of postmolar maligancy - Abnormal vaginal bleeding in early pregnancy (97%) - Grape-like vesicles filling uterus (80%) - No embryo + Large for date uterine size (50%) hCG high (>100,000) “Snow storm” on US - Maligant sequelae 6-32%, 4% risk of metastatic GTD - Complications: HTN, hyperthyroidism, anemia, and hyperemesis gravidrum, thecal luteal cysts (15-25%), malignant sequelae 6-32%
- Complete mole: PE look for hypertension, tachycardia, tachypnea, hyperthroidism, early preeclampsia, absence of fetal heart sounds. Pelvic exam shows grape-like vesicles from vagina or blood in cervical os. Palpable thecal luteal cysts. Thecal leuteal cysts, hyperthyroidism d/t shared alpha subunit b/n LH, FSH, TSH and bHCG Diagnosis: usually diagnosed in 1st trimester via U.S. = snow storm
- Radiopedia.org – Swiss cheese apperance
- Ultrasound showing echogenic snow storm pattern in complete mole. Due to the swelling of chorionic villi These signs may not be seen in early molar or partial mole.
- COMPLETE MOLE DIAGNOSIS - Characteristic sx in 1st trimester such as HTN, abnormally high bHCG, hyperemesis gravidarum, enlarged uterus, no fetal heart heard, early pre-eclampia, hyperthyroidisms, anemia, - Diagnosis: usually diagnosed in 1st trimester via U.S. - Definitive diagnosis made on pathologic examination of tissue after evacuation PARTIAL MOLE DIAGNOSIS PE typically normal, abd. Small for GA, Pelvic US may show cardiac activity and congenital malformation, Intrauterine restriction. Reduced amniotic fluid Pelvic ultrasound shows Swiss-cheese appearance – anechoic spaces juxtaposed against chorionic villi TREATMENT - Pre treatment labs: CBC w/platelet determination, clotting function studies, RFT, LFT, blood type, pre-treatment hCG level, Cxr. D and C If HTN give anti-hypertensive and if hyperthyroidism (give propranolol )prior to D and C Inducing labor not recommended d/t incr. incidences of malignant sequaele Repeat D & C not recommended b/s it has not been shown to induce remission and there is increased risk of perforation and hemorrhage Prophylactic chemotherapy after evacuation – not recommended due to the potential risk of fatalities associated with it. FOLLOW UP - time to normalize for bHCG 14 WEEKS for complete mole, 8 weeks for partial mole, vs. 2-4 weeks for normal prego.
- FIGO = international federation of gynecologists and obstetricians - Measure hCG w/assay capable of detecting values <5mIU/mL
- b-hCG plateau or rising after evacuation of molar pregnancy Asymptomatic Pelvic US can show intrauterine mass invading myometrium
- Gestational choriocarcinomas (2-5%) of GTD Gestational choriocarcinoma 1:20-40,000 pregnancies 50% after term pregnancies 25% after molar pregnancies 25% after other types of pregnancies In any woman of reproductive age with metastasis from unknown primary site GTD must be considered High hCG + exclude pregnancy = GTD diagnosis - Symptoms: late post-partum bleeding, symptoms of metastatic disease (resp. distress, hemoptysis, CNS sympoms etc…)
- M-GTD mostly diagnosed w/ increasing or plateauing hCG levels. M-GTD following nonmolar pregnancies have subtle signs and sx. Making dxx difficult Hints: abnormal bleeding for >6 weeks post prego.test for new pregnancy or GTD (with hCG measurements)
- Factors to consider: Age, antecedent pregnancy, pretreatment hCG levels, site and # of metastasis, previous failed chemotherapy Low Risk = score 0-6 High risk >7 (require multiagent chemo + surgery or radiation) = survival rate is 84% - It is important to classify patients in this way b/s High risk patients have an increased risk of failure to single agent chemo, and an increased risk of death when single agent followed by multiagent regimens is used Vs. receiving initial multiagent chemo. Other systems that can be used to classify and stage MGTD are the WHO prognostic index score, and NIH clinical Classification System Several studies have found that the FIGO 2000 Risk index performed better than WHO
- - The NIH clinical classification system divides GTD patients into different categories based on Criteria.
- Pre-Tx lab work: baseline b-hcg, CBC, Rh status, Renal and Liver function test. Weekly IM Methotrexate 30-50 mg/m2 - 70-80% remission rate in nonmetastatic GTD (Phase II trial by Gynecology Oncology group) No benefit seen in increasing dose to 50mg/m2 Study concluded that methotrexate was DOC over dactinomycin when toxicity, cost and efficacy considered Monitor CBC during chemotherapy for hematologic toxicity (rare) Ensure normal Renal and Liver function before initiating methotrexate chemo. METASTATIC GTD: Recently etoposide ± cisplatin has been incorporated by some with the triple therapy Surgery may be necessary to control metastases Despite use of multiple chemo agents, and post normalization maintenance doses 13% of metastatic GTD will recur after initial remission Risk of recurrence after 1 year of remission is 1%