GTDS presentation.pptx gynecology lecture

Gestational trophoblastic disease (GTD) is a group of rare diseases in which abnormal trophoblast cells grow inside the uterus after conception. In gestational trophoblastic disease (GTD), a tumor develops inside the uterus from tissue that forms after conception (the joining of sperm and egg).

1. Gestational Trophoblastic Diseases Presented By    OWAIS IRSHAD HIFIZA AIMAN HUMARA NIMRA SALEEM FATIMA BATOOL                           

2. Learning Objectives: What are GTDs? Aetiology WHO classification of GTDs Pathophysiology Clinical presentation Management

3. Gestational trophoblastic diseases Spectrum of diseases related to pregnancy t hat results due to abnormal proliferation of trophoblast. Normal functions of trophoblast : Implantation and development of extra embryonic tissue Exchange of oxygen bw mother and embryo Production of hCG Risk Factors: Maternal age Previous molar pregnancy Asian origin High parity

4. WHO Classification of GTDs Premalignant 》Hydatidiform mole * Partial mole * Complete mole Malignant * Invasive mole * Placental site trophoblastic tumor * Choriocarcinoma

5. Premalignant GTDs

6. Hydatidiform mole (molar pregnancy) It is an abnormal pregnancy characterized by fluid filled over distended chorionic villi forming grape like vesicles varying in size from few millimetres to few centimetres occupying the uterine cavity. Incidence: 1:200 – 300 births in southeast Asia 1:1000 in America and Europe Partial mole is more common than complete mole  60:40

7. Partial hydatidiform mole It develops when 2 sperm cells fertilize a normal ovum and contain foetal tissue often mixed with trophoblastic tissue. 》Foetus usually dies early in 1 st trimester 》Karyotype (triploid) 69 XXX or XXY or XYY 》Contain normal as well as hydropic villi 》Focal trophoblastic proliferation 》Serum and tissue hcG slightly raised 》FCA may be p resent 》Risk of choriocarcinoma is rare

8. Complete hydatidiform mole Develops when either 1 or 2 sperm cells fertilize an empty ovum (having no nucleus or DNA), all the genetic material comes from father’s sperm cell therefore no viable foetal tissue will be formed. 》 Karyotype 46 XX and 46 X Y 》Diffuse hydropic villi 》Diffuse trophoblastic hyperplasia 》Serum and tissue hcG markedly elevated 》No FCA 》Risk of choriocarcinoma 2 %

9. Complete mole Incomplete( partial ) mole Fertilization of EMPTY ovum with 2 sperms or 1 sperm that will divide later on Fertilization of normal ovum (haploid) with 2 sperms or 1 sperm that will divide later on No fetal components fetal components present 5-15% risk of malignancy <1% risk of malignancy Most common genetic 46 XX - followed by 46 XY Most common genetic 69 XXY - followed By 69XXX

10. Sign & symptoms Vaginal bleeding is the most common symptom. One of the differential diagnosis of bleeding in the first trimester is molar pregnancy. Patients with complete mole may have: first trimester pre- eclampsia, hyperthyroidism, hyperemesis, increased uterine size and theca- lutein cysts Patients with partial moles are diagnosed clinically as missed or incomplete abortion . Nausea and vomiting because of high Beta-HCG level.

11. Management Of Benign/Pre-malignant Trophoblastic Disease: INVESTIGATIONS: Full blood count, blood group and rhesus antibody serology Serum human chorionic gonadotrophin (hCG) [hCG levels are often > 100000 iu/l with complete hydatidiform mole (CHM) but not with partial hydatidiform mole (PHM)] Pelvic ultrasound e.g. snow storm appearance and bilateral theca luteal cyst in CHM ,focal cystic spaces within the placenta Histopathological analysis : Complete mole: Excessive trophoblastic proliferation and absence of feotal tissue. Partial mole: Presence of fetal tissue

12. TREATMENT: Surgical evacuation by suction & curettage is treatment of choice. Medical termination The administration of prostaglandin cervical preparations or oxytocin, should be avoided, because it may lead to intravascular dissemination of trophoblast by inducing uterine contractions. Single course of chemotherapy in high risk patients. If bleeding persist then , further curettage may be indicated .

13. P OST EVACUATION CARE: Psychological support Anti D immunoglobulin if required Follow up

14. FOLLOW UP Follow up to detect persistent gestational trophoblastic disease (GTD) or GTN (invasive mole, choriocarcinoma, placental site trophoblastic tumor) Measure serum B-HCG levels at 7-10 day interval. If levels fall no drug treatment needed. When levels are normal for 3 consecutive weeks, test monthly for 6 months. If normal levels for 6 consecutive months.....follow up can be discontinued Avoid pregnancy during follow up period. Oral Contraceptives may be prescibed( avoid intrauterine device) If serum b-HCG levels plateaus for more than 3 consective weeks, or rises, or if metastases detected, treat with methotraxate or for high risk patients multi-agent therapy.

15. MALIGNANT GTDs

16. Invasive Mole Commonly develop after molar pregnancy. A locally malignant tumor The villi penetrate deep into the myometrium, and may continue into the serous surface of the uterus, grow into the broad ligaments or reach the upper part of vagina. It can be distinguished from choriocarcinoma by the presence of chorionic villi. 10% of the cases of complete mole are at risk of becoming invasive mole Invasive mole Edematous chorionic villi with trophoblastic proliferation that invade into the endometrium (localised to the uterus) (most common )

17. Choriocarcinoma It is a rapidly progressive, highly malignant tumour, which originates from chorionic epithelium . May arise from any type of pregnancy. Incidence : It is a rare tumour The incidence is 1:10,000 normal pregnancies 50% cases of choriocarcinoma follow a hydatidiform mole, 20% are visible after abortion and the rest seen after a normal pregnancy . Choriocarcinoma (from normal or molar ) neoplastic syncytiotrophoblast and cytotrophoblast without chorionic villi Invade distant structures (not localised to the uterus )

18. Placental Site Trophoblastic Tumor PSTT is an uncommon tumour , localized in the uterine cavity. It arises from the placental bed. It has mostly cytotrophoblast and a very few syncytiotrophoblast elements. It produces low levels of HCG and elevated level of human placental lactogen. This tumour amongst GTDs is insensitive to chemotherapy The treatment of choice is surgery i.e. local excision or hysterectomy. Placental site trophoblastic tumor absence of villi with trophoblastic proliferation proliferation

19. Clinical Features Symptoms 1-- Vaginal bleeding 2- Vaginal discharge 3- amenorrhea 3- Other Symptoms: Symptoms may be present due to secondaries in other organs Lung- dysnea,Cough and Haemoptysis Vagina- vaginal bleeding and discharge CNS- headache,Neurological symptoms Liver- epigastric pain , jaundice

20. Signs In some patients, the following physical signs may be present Uterus : There is subinvolution of the uterus Vulva and vagina : Red dark coloured, haemorrhagic nodules Ovaries : The enlarged, bilateral, polycystic ovaries may be palpable on vaginal examination. The enlargement is due to the theca lutein cysts . Metastasis The most common sites of metastasis: Lung most common site Vagina 2nd most common Pelvis Liver Brain

21. Figo staging system for GTN

22. WHO prognostic scoring system for GTN  Patients who score between and 6 receive low- risk, get mono - chemotherapy .  Patients scoring 7 or more are given high- risk, treatment (combined chemotherapy EMACO).

23. Management

24. DIAGNOSIS 1. Clinical features 2. Investigations Ultrasound Serum HCG CXR (snowball or cannonball appearance) CT chest and abdomen ,pelvis for staging. 3. Histological findings D and C Excision of nodule in vulva and vagina 4. Evidence of metastasis

25. TREATMENT Pre- chemotherapy evaluation ; Complete physical examination Investigations : β - hCG (quantitative ) CBC (anemia, bleeding disorders) Coagulation profile screening test ; possibility of transfusion because of the bleeding. LFTs , renal function tests. because we are going to start methotrexate which is hepatotoxic and nephrotoxic, so we can’t start it in patients with impaired liver or renal function . Chest X ray Other imaging study

26. chemotherapy GTN is Sensitive to chemotherapy Single-agent chemotherapy (for treating non-metastatic disease ) Methotrexate or actinomycin D Cure rate up to 100% Combined chemotherapy for treatment of metastatic disease International Federation of Gynecology and Obstetrics (FIGO) score ≥ 7

27. Regimen for low risk patient Regimen for high risk patient Usual regimen (EMA and CV) Injection of methotrexate (50 mg IM repeated every 48 hrs for 4 doses ) Folic acid tablet ( 50 mg orally ,30 hrs after each injections) Benefits of folic acid: Reduces the toxicity of drugs. Provides opportunity of giving higher dosage. Greater chances of remission. Etoposide Methotrexate Actinomycin-D Cyclophosphamide Vincristine Day 1 Etoposide 100 mg/m2 Actinomycin-D (0.5 mg IV ) Methotrexate 300 mg/m2 (IV infusion over 12 hours) Day 2 Etoposide Actinomycin-D Folic acid (15 mg IM every 12 hours for 4 doses) • Day 8 Cyclophosphamide (600 mg/m2 infusion over 30minutes) Vincristine 1mg/m2 IV 1 bolus dose

28. SURGERY During removal of uterus, theca lutein cysts in the ovaries should not be punctured. They regress spontaneously after hysterectomy. Indications for hysterectomy Drug toxicity. Severe vaginal or intra-peritoneal hemorrhage, uterine perforation and other complications . failure of chemotherapy

29. Follow Up Goal of Therapy is to achieve REMISSION, which is 3 consecutive weekly beta- hCG titers within normal range. Once remission is achieved, monthly beta- hCG titers until negative for 12 consecutive months. Follow-up is for 1 year.

30. Q1- A 34 year old pregnant woman presents with vaginal bleeding at 12 weeks of gestation. She is troubled with excessive nausea and vomiting. The fundal height corresponds to 22 weeks. USG shows snow-storm appearance. What is most likely diagnosis ? A- partial mole B- complete mole C-choriocarcinoma D-invasive mole

31. Q2. A 22-year-old, G1PO, presents to the emergency room with 5 days of worsening nausea and vaginal bleeding. Last menstrual period (LMP) was 10 weeks ago. Pelvic examination is significant for a 14-week- sized uterus. Quantitative human chorionic gonadotropin ( hCG ) level is 120,000 units/mL, and ultrasound imaging reveals material within the endometrial canal that has a "snowstorm" appearance. There are no fetal parts seen. The patient undergoes an uncomplicated dilation and evacuation in the operating room, and the tissue is sent for genetic testing. What is the most likely genetic constitution of the specimen ? a. 69, XXX b . 69, XXY c. 46, XX d. 46, XY

32. Q3- A pregnant woman undergoes Suction and evacuation for a missed abortion and the products were sent for histopathological evaluation. 6 weeks later she comes back with the HPE report, with features consistent with molar pregnancy. She does not complain of any bleeding at present. Her pelvic examination is normal. What is the most appropriate investigation at present ? Pelvic USG Maternal Karyotype Serum beta HCG Maternal Blood Group

33. Q4- A 28-year-old, G1PO, presents to the emergency department with hemoptysis. She reports that she has had increasing cough and shortness of breath over the past 8 weeks and that she coughed up a dime-sized blood clot this morning. On review of systems, the patient endorses heavy and irregular vaginal bleeding. She says that she had a spontaneous abortion 6 months ago and that she started having increasingly irregular and heavy periods about 4 months ago. On examination, her uterus is enlarged to 12-week size. Serum [B- hCG is elevated, hemoglobin is 10 mg/ dL , and chest X-ray reveals two dense areas in her lungs, one in the right upper lobe and one in the left lower lobe. Which of the following is the most likely diagnosis ? a . Missed abortion b . Incomplete abortion c . Choriocarcinoma d . Molar pregnancy e . Ectopic pregnancy

34. Q5- Which is the most common form of GTN to develop following a molar pregnancy evacuation ? Invasive mole Choriocarcinoma Placental Site Trophoblastic Tumor Endothelial Trophoblastic Tumor

35. 1-B 2-C 3- C 4- C 5- A

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