Gestational Trophoblastic Diseases (GTD) Definition Spectrum of abnormalities of trophoblasts associated with pregnancy Secrete hCG (human chorionic

gonadotrophins) Can be cured with preservation of reproductive function (even malignant) Epidemiology Poor nutrition y Socioeconomic y Dietary intake of carotin, folic acid Maternal age <20y/o, >40 y/o (due to defective fertilization)

Hydatidiform Mole Complete Contains no fetal tissue 46, XX (90%) | 46, XY (10%) Paternal chromosome fertilize empty egg Duplication of paternal chromosome (adrogenesis) Grape like tissues packing up uterine cavity No fetus Uterine enlargement larger than expected for gestational age Caused by excessive trophoblastic growth, retained blood Pre-eclampsia Severe hyperemesis gravidarum -hCG > 100,000 mIU/mL Ultrasound Snowstorm pattern (represent hydropic chorionic villi) Intrauterine mass contain many small cysts Histology Edematous placental villi Hyperplasia of trophoblasts No fetal blood vessels Homozygous (80%) Heterozygous (20%) Two identical paternal chromosome All chromosomes are paternal origin Derived from duplication of paternal (due to dispermy) Male/ female haploid chromosomes Always female (46YY never observed) Partial Fetal tissue is often present Both maternal, paternal origin (69,XXX)| (69,XXY) Mechanisms y Haploid egg being fertilized by 2 sperms y Abnormal diploid sperm fertilize the haploid egg Smaller vesicles in uterus May have abnormal fetus Uterus may correspond to date Do not have same clinical features as those with complete mole Signs, symptoms consistent with an incomplete, missed abortion y Vaginal bleeding y Absence of fetal heart tones -hCG < 100,000 mIU/mL Morphology Fetal tissue present Chorionic villi contain vessels with fetal RBC (within mesenchyme of villi) Hydropic (edematous) villi Trophoblastic proliferation present (but minimal) Villous scalloping Trophoblastic inclusions (within mesenchyme of villi)

True (hydatidiform) mole Enlarged uterus Thinned out (uterine muscle) Inside packed with molar tissue No invasion on wall of uterus Grape-like Clinical Features Abnormal vaginal bleeding in early pregnancy Lower abdominal pain y Toxaemia (before 24w of gestation) y Hyperemesis gravidarum y Uterus large for date y Enlargement of ovary (Theca lutein ovarian cyst) y Absent of fetal heart tones, fetal parts y Expulsion of swollen villi y Trophoblastic embolization (RDs)

Partial mole Villi Normal placental tissue

Clinical Features Signs, symptoms of incomplete, missed abortion Diagnosis by histologic review of curettings

Prognosis Uterine invasion (15% of patient of complete mole) Metastasis (4% of complete mole) Persistent tumour (4% of partial mole) Follow Up Monitored for potential development of malignant sequalae (by serial determination of -hCG) Risk of GTT with Large uterus HCG level Lutein cyst History of molar pregnancy Age > 40y/o HCG follow up is weekly until ve results (then monthly up to 1 year) Pelvic examination every 2 weeks until normal (then every 3 months) Oral contraceptive for 1 year Placental Site Trophoblastic Tumour Rare Consists of groups of mononucleated, multinucleated trophoblastic cell Cells are human placental lactogen (HPL) +ve > than HCG Present with chronic vaginal bleeding after delivery Hysterectomy (treatment) Invasive Mole Hydatidiform mole invade uterine myometrium Metastasize to extrauterine tissues Biologic behaviour Invasive mole villus may invade myometrium, blood vessels Spread locally Invade myometrium Penetrate uterine wall Spread to broad ligament, abdominal cavity Clinical Manifestations Irregular vaginal bleeding Uterine subinvolution Theca lutein cysts does not disappear after emptying uterus Abdominal pain Metastatic focus manifestation

Gestational Choriocarcinoma Highly malignant tumour Metastasize (through blood circulation) Damage tissues, organs Cause bleeding, severe necrosis 50% gestational choriocarcinoma result from hydatidiform mole (generally occurs over 1 year after emptying mole) y cases after molar pregnancy y cases after normal pregnancy y cases after abortion, ectopic pregnancy Common metastatic site Lung (most common) Vagina Brain Liver Clinical Manifestations Vaginal bleeding Pain Uterine enlargement Mass Pathology Gross Large mass in uterus Diameter 2-10cm Massive necrosis Hemorrhagic Cancer embolus y Paarauterine veins y Ovarian Luteinizing cyst (formed in ovaries) Histology Cytotrophoblastic, syntrophoblastic cells invade myometrium, vessels Severe necrosis, hemorrhage Few viable cancer cells

FIGO Classification Stage Details I Confined to corpus II Metastasis outside uterus to vagina, pelvic structure III Metastasis on lungs IV Distant metastasis Management Chemotherapy Surgery Differential Diagnosis of Bleeding in Early Pregnancy Abortion (different type) Ectopic pregnancy Molar pregnancy Partial mole Choriocarcinoma Blood diseases Local causes

Ectopic Pregnancy Ectopic Pregnancy Pregnancy outside uterus Commonest site ovary

Risk Factors Pelvic inflammatory disease (PID) Endometriosis History of prior ectopic pregnancy History of tubal surgery, conception after tubal ligation Clinical Features Pregnancy symptoms Depending on site RIF, LIF Emergency Acute tenderness Shock (if ruptures)