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GESTATIONAL TROPHOBLASTIC NEOPLASIA (GTN). 1. Hydatidiform mole 2. Invasive mole 3. Choriocarcinoma 4. Placental site trophoblastic tumour. Incidence of molar pregnancy: 1/1000 – 1/1500 pregnancies Higher incidence in Asian women Highest risk: age <20 or >40 years
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GESTATIONAL TROPHOBLASTIC NEOPLASIA(GTN) • 1. Hydatidiform mole • 2. Invasive mole • 3. Choriocarcinoma • 4. Placental site trophoblastic tumour
Incidence of molar pregnancy: 1/1000 – 1/1500 pregnancies Higher incidence in Asian women Highest risk: age <20 or >40 years Placenta contains trophoblastic cells: cytotrophoblast syncytiotrophoblast – produces HCG (human chorionic gonadotropin) intermediate trophoblast – produces HPL (human placental lactogen) HCG: indicates presence of syncytiotrophoblast elevated in normal or abnormal pregnancy, including GTN used as a “marker” in follow-up and treatment of GTN
1. Hydatidiform mole – based on error at time of fertilization 2 different syndromes a) Complete mole: “empty egg” + N sperm 23 chromosomes duplicates 46XX but all are paternal chromosomes (or: “empty egg” + sperm X + sperm Y 46XY) There are no maternal chromosomes in the Empty egg. It gets fertilized by a normal sperm. It will duplicate to form 46 XX. Do get formation of placenta, Don’t Get a fetus. Can also get an empty egg fertilized by 2 sperm)
Presentation: • uterine bleeding between 6 and 16th week (95%) • uterus large for dates (50%) • - pre-eclampsia and hyperemesis (25%) • bilateral theca-lutein cysts (15%) benign • HCG higher than expected for dates • hyperthyroidism (rare) – due to high HCG (has an alpha and beta subunit. The alpha subunit is the same as TSH, FSH, etc…can mimic hyperthyroidism) • Diagnosis: • U/S – “snowstorm pattern”. Tissue with cysts. No fetus or embryo • Treatment: • D&C – “grape-like vesicles”. Cure in >80% (Must empty the uterus) • (residual tissue in the uterus or in myometrium – the immune system gets rid of it…. But in 20%, the immune system will not get rid of it, called invasive mole and require chemotherapy) • Pathology: • widespread trophoblastic hyperplasia • hydropic swelling of villi; no vasculature • no embryo or fetus
Partial mole • maternal 23X + 2 sperm (or diploid sperm) • triploid (69XXY) • Excess paternal over maternal chromosomes 2:1 • (usually doesn’t survive past 2nd trimester, because of the excess of • Paternal chromosomes will get an abnormal placenta) • Presentation: • - usually present as missed or incomplete abortion • - HCG less elevated than in complete mole • - fewer patients have theca-lutein cysts • - fewer patients have uterus large for dates • - fetal heart tones may be present because fetus is developing here
Diagnosis: • U/S – missed abortion or non-viable pregnancy • Treatment: • D&C • Pathology: • focal trophoblastic hyperplasia and villous swelling can have areas of normal placenta in between the areas of abnormal • scalloping of villous outline • fetus/embryo present or vasculature present • Partial mole: “dilute” or “bland” version of complete mole • < 5% develop invasive mole and require • chemotherapy.
2. Invasive mole Molar tissue may penetrate deep into uterine wall. Penetration of venous vasculature draining uterus and adnexa results in pulmonary embolization of hydatidiform vesicles and trophoblast. Gets into blood stream and can metastasize. Therefore women who have undergone D&C, may present with metastasis to: lung (most common) vagina cervix vulva broad ligament Persistence of trophoblast beyond uterine cavity: *focus of prolonged HCG secretion – DIAGNOSIS OF INVASIVE MOLE BASED ON RISING HCG LEVELS AFTER EVACUATION OF A HYDATIDIFORM MOLE. We know the immune system isnt clearing the tissue . Watch HCG and if they are still going up, we know there is trophoblast and that our immune system is not clearing it.
SURVEILLANCE AFTER D&C FOR HYDATIDIFORM MOLE: • 2002 SOGC Clinical Practice Guidelines: • (Society of Obstetricians and Gynecologists of Canada) • Serum HCG weekly until negative x 3, then monthly x 6 months. • Regular pelvic exam. • Contraception x 6 months (preferably BCP). • HCG should steadily decline to neg. (may take 12-16 weeks) • If HCG rises or plateaus – invasive mole • Plateau of HCG – HCG done weekly; values not declining over 3 weeks. Need to • Drop more than 10% per week If HCG goes up, sometimes don’t know if it is mole or pregnancy. This can cause Problems. Need to keep testing HCG. HCGs go down slower after a hyatidiform Mole than after pregnancy. US to tell takes 6 weeks. Therefore we don’t want the Women getting pregnant. Don’t want 6 weeks to treat if it is molar
2. Invasive mole (continued) • ~ 5 – 15% of patients with hydatidiform mole will require treatment • for invasive mole. • Higher risk for invasive mole: • uterus large for dates (>20 week size) • bilateral theca-lutein cysts • patient’s age >40 years • post-evacuation uterine bleeding • This is not considered cancer, it is just abnormal placental tissue. • Diagnosis: • Plateau or rise of HCG values done weekly • Treatment: • Chemotherapy – methotrexate or actinomycin-D
GTN requiring treatment with chemotherapy: • Invasive mole – plateau or rise in weekly HCG values following • evacuation of a hydatidiform mole. • 2. Choriocarcinoma – malignant form of GTN • Investigations prior to chemotherapy: • CBC, creatinine, liver function tests • CT scan brain, thorax, liver • Can then classify GTN as non-metastatic or metastatic and plan • treatment.
Clinical classification of GTN • Non-metastatic GTN methotrexate/actimomycin-100% cure • Metastatic GTN • A. Good prognosis • 1. Pretherapy HCG <40,000 • 2. Short duration: <4 months methotrexate and/or • 3. No brain or liver mets actinomycin-D • 4. No prior chemotherapy • 5. No antecedent term pregnancy • B. Poor prognosis • 1. Pretherapy HCG >40,000 • 2. Long duration: > 4 months • since last pregnancy multi-agent chemo • 3. Brain or liver mets (choriocarcinoma) surgery • 4. Prior chemotherapy radiation • 5. Antecedent term pregnancy
Case #1 23 yo G1P0 Presented at 8 weeks gestational age with vaginal spotting Pelvic exam: uterus 14 week size Ultrasound: Hydatidiform mole Pre-op HCG: 206,000 mIU/ml Chest X-ray: neg. Bloodwork normal Dilatation and curettage Path: complete hydatidiform mole Started on birth control pill Followed with weekly HCGs – fell to negative Followed for 6 months – HCG remained negative
Case #2 30 yo G1P0 4 year history of infertility – endometriosis Presented at 8 weeks gestation with vaginal spotting Pelvic exam: uterus 6-8 week size Ultrasound: nonviable pregnancy, no fetal heart Dx: missed abortion Dilatation and curettage Path: partial hydatidiform mole Post-op HCG: 670 mIU/ml Chest X-ray: neg. Started on birth control pill Followed with weekly HCGs – fell to negative 5 weeks after D&C Followed for 6 months
Case #3 26 yo G2P1 Presented at 12 weeks gestation with vaginal spotting, nausea and vomiting Pelvic exam: uterus 16 weeks size, no fetal heart heard Ultrasound: Hydatidiform mole Pre-op HCG: 103,348 mIU/ml Chest X-ray: neg. Bloodwork: neg. Dilatation and curettage Path: complete hydatidiform mole Started on birth control pill Followed with weekly HCG
Case #3 (continued) Rise of HCG Chest X-ray: neg Renal function tests, liver function tests: normal CT scan brain, thorax, abdomen: neg Dx: non-metastatic GTN Methotrexate Followed for 1 year, and asked to avoid pregnancy for 1 year On birth control pill
Case #4 19 yo G1P0 Presented at 10 weeks gestation with vaginal spotting Pelvic exam: uterus 14 week size Ultrasound: Hydatidiform mole. Bilateral theca lutein cysts (5-6 cm) Pre-op HCG: 900,000 mIU/ml Chest x-ray: neg. Bloodwork: neg. Dilatation and curettage Path: complete hydatidiform mole Started on birth control pill Followed with weekly HCG After 4 weeks, plateau of HCG: 16,789 14,976 14,550
Case #4 (continued) Chest X-ray: lung mets CT brain, abdomen: neg CT thorax: lung mets Liver function tests, renal function tests: normal Dx: metastatic GTN, good prognosis Methotrexate Actinomycin-D Followed for 1 year
3. Choriocarcinoma Incidence: 1/40,000 pregnancies Highly malignant – arises from trophoblast of any type of gestation: Normal pregnancy 50% Hydatidiform mole 25% Abortion/ectopic 25% If GTN diagnosed after normal pregnancy – choriocarcinoma Complete hydatidiform mole – risk of choriocarcinoma 2-3% Biphasic proliferation of cyto- and syncytiotrophoblast Chorionic villi not present Tumour cells invade venous vasculature, therefore large number of patients (66%) present with hematogenous metastasis: lung (most common) brain liver vagina, kidney, gi tract, lymph nodes, skin
Presentation: • abnormal uterine bleeding • hemorrhage from mets (lung, brain, liver) • Diagnosis: • clinical suspicion – HCG • can’t rely on D&C or other “biopsies” to give a histologic diagnosis • ( a tissue report of “hemorrhage and necrosis” is common) • biopsy of metastases may cause significant bleeding because it is very vascular • metastatic survey • Treatment: • multi-agent chemotherapy
Case #5 33 yo G2P2 Spontaneous vaginal delivery. No complications. Four weeks postpartum: heavy vaginal bleeding with clots. Ultrasound : retained placental tissue. Dilatation and curettage. Path: choriocarcinoma. HCG: 392,807 (very high) CT scan brain, thorax, abdomen: lung metastasis. Cisplatin, Etoposide, Methotrexate, Actinomycin-D
Case #6 19 yo G3P2 Presented to hospital with shortness of breath Normal vaginal delivery 9 months prior to admission Therapeutic abortion 2 months prior to admission Chest X-ray: multiple large nodules Anemic Ultrasound abdomen: large liver lesions Path report from abortion: no products of conception – she wasn’t newly pregnant HCG: 1,000,000 mIU/ml Dx: choriocarcinoma Respiratory arrest Rupture of liver metastases during CPR Died of hemorrhage from metastases
Survivals with treatment: Non-metastatic GTN 100% Metastatic GTN 90% Choriocarcinoma 81% Choriocarcinoma with mets 71% Most common cause of death: Hemorrhage from mets Pulmonary insufficiency With one molar pregnancy, risk of second molar pregnancy increased: goes from 1/1000 to 1/100 1 – 2% Therefore, good chance of subsequent normal pregnancy despite treatment for GTN.
4. Placental site trophoblastic tumour RARE Composed predominately of intermediate trophoblast (IT); no villi IT produces HPL (human placental lactogen) and low levels of HCG PSTT – generally benign and self-limited, but can be highly aggressive and malignant. Usually present as missed abortion. DDx: placental site reaction of normal pregnancy (IT plays key role in implantation and development of uteroplacental circulation) Treatment: D&C may be curative Total abdominal hysterectomy Poor response to chemo – reserve for recurrences or mets