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GESTATIONAL TROPHOBLASTIC TUMORS
GESTATIONAL TROPHOBLASTIC Disease (GTD) (GTT)
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Learning Objective At the end of this session, I would like you to be able to: Have an idea about GTT Diagnose GTT Know how to manage GTT Know how to monitor GTT
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Abnormalities of trophoblasts
It is a diverse group of tumors 80%- 90% benign. Abnormalities of trophoblasts Resulting from abnormal events occurring at or shortly after fertilization GTT follow normal or abnormal pregnancy Contains paternal genes
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Types: Benign Hydatidiform mole 80%-90% Malignant Invasive mole
Persistent trophoblastic tumor Choriocarcinoma Placental site tumors (Rare)
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Unique about GTT Cure almost 100% Sensitive marker- secreted by all types Allow: Accurate assessment Follow-up
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Epidemiology: Varies More in far east Diet More in extreme of reproductive ages Risk of having another mole is 1- 3%
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Hydatidiform mole: Results from abnormal events occur at or shortly after fertilization, ? Abnormal gametogensis Types: Histoligically Cytogenically Complete mole Partial mole
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Genetic composition Complete (diploid karyotype &paternal in origin
• Chromosomes = 46 xx • Both xx, are paternally derived Fertilization of abnormal egg- no nucleus Haploid sperm 23x empty egg sperm duplicate 46xx diploid(>90%) < 20% empty ovum fertilized by 2 sperm resulting in 46xy % progress to Gestational Trophoblastic Tumor
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Partial mole Chromosomes, triploid 69 xxy (80%) Minority triploid 69 xxx 20%(dispermic) Maternal& paternal genes Often present with fetal tissue Fetus may be abnormal Rarely reach term 5% progress to persistent gestational trophoblastic tumor
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Hydatidiform mole: Confined to the uterine cavity
Occasionally trophoblastic-Embolic to lungs Partial mole • some hydropic villi. • other villi normal. • less hyperplasia of trophoblast. • some fetal vessels or fetal Rbc. Complete mole • all villi hydropic oedematous •all trophoblast are hyperplasia • absence of fetal blood vessels Greater risk of becoming malignant
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Hydatidiform mole: Symptoms: • majority >90% have irregular vaginal bleeding 1st, 2nd trimester (does not indicate a problem) • bleeding is painless • may expel vesicles • 1/3 excessive nausea/ vomiting, Why?? hyperemesis gravidarum 25% • pre-eclampsia occurs Early <24 weeks gestation 3-12% What other conditions in pregnancy, when PET occurs early??? •hyperthyroidism 2- 10%, test before surgery Theca luteal cysts, bilateral
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Signs: Pale complexion Tachycardia sign of thyrotoxicosis Tachypnea- sign of pulmonary Embolism Uterus: Enlarged 50% Theca luteal cyst, 10-15% Secondary post partum bleeding (PPH) Persistent bleeding , should always think GTT/GTD What should you do??
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Partial Mole More common May be undetected
May not appear abnormal on Ultrasound (USS) USS ordered for ?? Histopathology of Retained product of conception (RPOC) partial or complete.
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SNOWSTORM APPEARANCE OF MOLAR PREGNANCY
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Requirement for chemotherapy
H mole may not regress spontaneously and require chemotherapy, more common with?? 10-17% of H. mole result in invasive mole 3% of mole progress to choriocarcinoma
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Diagnosis: High index of suspicious from clinical data
Quantatative beta-hCG Ultrasound shows _______ appearance Differential diagnosis: ________________ Chest x-ray ??
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Laboratory investigations:
Full blood count? Blood group – Rh________? Coagulation profile? Liver function test Renal function test base line? Chest film
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Treatment: Pre-requisites ____________ Surgery
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Blood cross match in theatre
Syntocinon infusion Dilation – suction evacuation Complication ___________? Hysterectomy: When _________? _________?
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Complication: Uterine perforation Uterine haemorrhage
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Monitoring: Follow-up Serum- β human chronic gonadotrophin
What happens to βhCG ? Initially Post evacuation – immediate 6-8 weeks post evacuation Follow-up Weekly βhCG, until 3 consecutive normal values Monthly βhCG , until 6 months Contraception?? History of molar pregnancy, Postpartum check βhCG at delivery, 6 and 10 weeks Repeat H> mole occur in 1-3 %, have greater risk of invasive or choriocarcinoma
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Chemotherapy: Prophylactic not justified >79% spontaneous remission
When does chemotherapy is indicated in hydatidiform mole?
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Invasive mole: Villi penetrate myometrium
5 – 10 % preceded by hydatidiform mole βhCG persistently high after evacuation of hydatidiform mole Locally invasive Rarely metastases to: Vagina Lung Brain
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Placental site trophoblast tumor
Extremely rare Occur after non-molar pregnancy Sheets of cytotrophoblasts only When melastasis occur – fatal βhCG levels are relatively low Relatively chemotherapy-resistant Surgery has been the main stay of treatment
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Choriocarcinoma: Metastastatic Non-metastatatic Histopathology:
Invade uterine wall Metastasis Sheet of cytotrophoblast and synchiotriphoblast No identifiable villi
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Choriocarcinoma: 50% of choriocarcinoma have preceding hydatidiform mole 50% of choriocarcinoma follow: Ectopic Abortion Normal pregnancy • Trophoblast after normal pregnancy almost always choriocarcioma
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Choriocarcinoma Subdivided into: Good Poor prognosis
Low risk and high risk Depending on: Site Size of metastasis Clinical variables
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Good Prognostic Factor:
Initial βhCG < 40,000 miu/L Therapy started within 4 months of antecedent pregnancy Metastasis only to lung or pelvis No prior chemotherapy.
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Poor Prognostic Factor :
βhCG > 40,000 miu/L (initial) Therapy > 4 months from the pregnancy Metastasis to brain or liver failed response to a single agent of chemotherapy Choriocarcinoma following full term pregnancy.
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FIGO Staging for GTT Description Stage
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Chemotherapy Methotrexate Etoposide Actinomycin D Cyclophosphomide
Oncovin Folinic acid IM
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Further Reading www.hmole-chorio.org.uk www.swot.org.uk
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Questions time Molar pregnancy Never include a fetus
Commonly present with vaginal bleeding in early pregnancy If complete contains only paternal genes HCG levels will lower than normal in early pregnancy May result in a need for chemotherapy
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GTT There is a decreased incidence with increasing age
It gives typical USS appearance It is monitored post evacuation by urinary oestriol It can be treated with trimthoprate
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Following a diagnosis of a molar pregnancy
Serum hCG level should fall to within normal range in the first 4 weeks Pregnancy should be avoided by inserting IUCD Hysterectomy reduces the necessity for hCG monitoring
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Clinical case scenario
Mrs. F is a 22 years old ward clerk. She is 8 weeks pregnant, and is complaining of severe nausea and vomiting, the uterus is compatible with 14 weeks. What is the differential diagnosis??
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