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 that 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 1st 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 present
》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 XY
》Diffuse hydropic villi
》Diffuse trophoblastic hyperplasia
》Serum and tissue hcG markedly elevated
》No FCA
》Risk of choriocarcinoma 2%

10. 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

11. 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.

12. 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

14. 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.

15. POST EVACUATION CARE:
• Psychological support
• Anti D immunoglobulin if required
• Follow up

16. 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.

17. MALIGNANT GTDs

18. 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)

19. 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)

20. 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

21. 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

22. 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

23. Figo staging system for GTN

24. WHO prognostic scoring system for GTN
 Patients who score between 0 and 6 receive low-risk, get mono-chemotherapy.
 Patients scoring 7 or more are given high-risk, treatment (combined chemotherapy EMACO).

25. Management

26. DIAGNOSIS
• 1. Clinical features
• 2. Investigations
o Ultrasound
oSerum HCG
oCXR (snowball or cannonball appearance)
oCT chest and abdomen ,pelvis for staging.
• 3. Histological findings
oD and C
oExcision of nodule in vulva and vagina
• 4. Evidence of metastasis

27. 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

28. 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

29. Regimen for low risk
patient
Regimen for high risk
patient
Usual regimen (EMA and
CV)
1. Injection of methotrexate
(50 mg IM repeated every 48
hrs for 4 doses )
2. 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.
1. Etoposide
2. Methotrexate
3. Actinomycin-D
4. Cyclophosphamide
5. Vincristine
• Day 1
1. Etoposide 100 mg/m2
2. Actinomycin-D (0.5 mg IV )
3. Methotrexate 300 mg/m2
(IV infusion over 12 hours)
• Day 2
1. Etoposide
2. Actinomycin-D
3. Folic acid (15 mg IM every 12
hours for 4 doses)
• Day 8
1. Cyclophosphamide (600
mg/m2 infusion over
30minutes)
2. Vincristine 1mg/m2 IV 1
bolus dose

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

31. 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.

32. 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

33. 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

34. 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 ?
A. Pelvic USG
B. Maternal Karyotype
C. Serum beta HCG
D. Maternal Blood Group

35. 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

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

37. • 1-B
• 2-C
• 3- C
• 4- C
• 5- A

38. THANK YOU