Gestational trophoblastic disease (GTD) comprises a spectrum of abnormal proliferation of trophoblast tissue that may have a wide range of behaviors and potential for metastasis. It includes complete and partial hydatidiform moles, as well as gestational trophoblastic neoplasms such as invasive moles, choriocarcinomas, and placental site trophoblastic tumors. Diagnosis is made through beta-hCG levels and imaging, while treatment and prognosis depends on the type of GTD and presence of metastasis.

2. Outline
0 Definition
0 Pathogenesis
0 Classifications
0 Benign GTD
0 Malignant GTD

3. Definition
0 Comprises of a spectrum of abnormal proliferation of
the trophoblast which may have a wide range of
biologic behaviour and potential for metastases.
0 The spectrum includes hydatidiform moles
(complete or partial) and gestational trophoblastic
neoplasia comprising invasive moles,
choriocarcinomas, and placental-site trophoblastic
tumours (PSTT).

4. Pathogenesis
0 These tumors develop from an aberrant fertilization
event and arise from fetal tissue within the maternal
host.
0 They are composed of both syncitiotrophoblastic and
cytotrophoblastic cells (except PSTT which is derived
from intermediate trophoblastic cells).
0 First and only disseminated solid tumors that are
highly curable by chemotherapy

5. Types
Benign
1. Hydatidiform mole (complete or Incomplete/partial)
Malignant
1. Invasive or persistent mole,
2. Choriocarcinoma,
3. Placental-site trophoblastic tumour.
0 The last three are termed gestational trophoblastic
tumours (GTT); all may metastasize and are potentially
fatal if untreated.

6. 1. Hydatidiform Mole
0 Most common form
0 Results when tissue around a fertilized egg that normally would
have developed into the placenta instead develops as an
abnormal cluster of cells.
0 Thought to arise from extraembryonic trophoblasts. Studies
suggest that there’s transformation of the embryonic inner cell
mass making it lose it’s capacity to differentiate into embryonic
ectoderm and endoderm. This results in production of
extraembryonic mesoderm and molar vesicles with loose
primitive mesoderm in their villous core

7. Risk factors
0 Women <20 and >40years
0 Nulliparous
0 Low socioeconomic status
0 Diet deficient in protein, folic acid, carotene
0 Blood group A women impregnated by blood group O

8. Complete Hydatidiform Mole
0 Most common type of hydatidiform mole
0 Diffuse trophoblastic hyperplasia, hydropic swelling
of the chorionic villi, no fetal tissue or membranes
present
0 46 XX or 46 XY chromosomes completely paternal of
origin , sex chromatin postive
0 They arise when an empty ovum (w/ absent or
inactivated nucleus) is fertilized by haploid sperm
that duplicates its chromosomes or by two haploid
sperms

9. 0 Risk Factors
• Maternal age >40 years
• Vitamin A deficiency
• Smoking
• Previous molar pregnancy
0 Clinical Features
• Vaginal bleeding
• Pre-eclampsia <20 weeks GA
• Excessive uterine size for LMP
• Theca-lutein cyst > 6cm
• Hyperemesis gravidarum
• β HCG > 100 000 IU/L
• Absence of fetal heart tone
• Hyperthyroidism

10. Partial Hydatidiform Mole
0 Arising when an ovum with an active nucleus is fertilized by a
duplicated sperm or 2 haploid sperms.
0 Hydropic villi and focal trophoblastic hyperplasia are associated
with fetus / fetal parts
0 Triploid (XXY, XYY, XXX) with chromosomes complement from
both parents
0 Associated with fetus, which may be growth-restricted and/or
have multiple congenital malformations

11. Clinical Manifestation
• Typically presents similar to threatened /
spontaneous / missed miscarriage
• Vaginal bleeding
• Absence of fetal heart beat
• Theca lutein cysts

12. Comparisons
Complete Partial
Karyotype Diploid(46XX or 46XY) Triploid (69, XXX or XXY)
Fetus absent Often present
Villi Diffusely hydropic Focally hydropic
Trophoblasts Diffuse hyperplasia Mild focal hyperplasia
Implantation site
trophoblast
Diffuse atypia Focal atypia
P57, PHLDA2
immunostaining
Negative positive
Fetal RBCs absent present
Beta-hCG (mIU per
milliliter
High (>50 000) Slight elevation (>50 000)
Frequency of classical
symtoms
Common rare
Risk of GTT 20-30% <5%

13. Investigations
• Quantitative β HCG levels (will be abnormally high
for GA)
• U/S findings
If complete: No fetus (classic “snow storm” due
to swelling of villi)
If partial : molar degeneration of placenta ± fetal
anomalies, multiple echogenic regions
corresponding to hydropic villi and focal
intrauterine hemorrhage
• CXR (may show metastatic lesions)

14. Ultrasonic findings: Complete
0 Complete Hydatidiform Mole – Snow Storm
• Pattern consists of multiple hypoechoic areas
corresponding to hydropic villi (snow storm)
• A normal gestation or fetus is not presents
• Theca lutein cysts may be visualized

15. Ultrasonic Findings: Partial
0 Partial Hydatidiform Mole
• Focal areas of trophoblastic changes and fetal
tissue may be noted
• Focal cystic changes in the placenta are also a
hallmark finding

16. Management of Gestational
trophoblastic disease
0 Patient resuscitation
0 It is important to confirm whether the mole is invasive or not and
this is done by pelvic ultrasound
0 Resuscitation must include correction of fluid loss, correction of
coagulopathy and blood transfusion for severe anaemia, as well
as prescription of carbimazole and propanolol in the presence of
hyperthyroidism
0 Once it is confirmed that the mole is non-invasive,
0 Then a suction curettage can be done to evacuate the uterus of its
contents
0 A specimen of the evacuated products should be collected and
sent to the laboratory for histological evaluation
0 Oxytocin is administered in theatre and continued for 24 hours
after evacuation OR until bleeding stops

17. 0 Blood loss is usually moderate, but precautions
should be taken for the possibility of hemorrhage
requiring a transfusion.
0 When a large hydatidiform mole (>12weeks) is
evacuated by suction curettage, a laparotomy setup
should be readily available, as hysterotomy,
hysterectomy, or bilateral hypogastric artery ligation
may be necessary if perforation occurs.
0 All Rh negative patients should receive Rh immune
globulin

18. Follow-up
• The patient is advised not to conceive for 12
months and contraception may be prescribed for
those 12 months. This is done to avoid repeat of
GTD
• Serial β HCG every week until negative x3, then
monthly for 6-12 months prior to trying to
conceive
• Increase or plateau of β HCG indicated Gestational
Hydatidiform Neoplasm  Patient needs
chemotherapy

19. Gestational Trophoblastic
Tumours(Malignant)
0 Types
1. Invasive mole or persistent GTT
2. Choriocarcinoma
3. Placental-site trophoblastic tumour

20. 1. Invasive or Persistent mole
 Invasive mole is reported in 10-15 % of patients
who have had a hydatidiform mole.
 It is benign, but as the name implies, it is locally
invasive and invades the myometrium and
adjacent structures.
 It has the potential to completely penetrate the
myometrium and cause uterine rupture and lead
to haemoperitoneum.
 Metastasis is rare

21. 0 Diagnosis made by
• Rising or plateau in β- hCG

22. 2. Choriocarcinoma
0 Is reported in 2-5% of all cases of gestational
trophoblastic neoplasia
0 May be accompanied or follow any type of pregnancy
(molar, normal, miscariage)
0 Choriocarcinoma is a pure epithelial tumour
composed of syncytiotrophoblastic and
cytotrophoblastic cells
0 Highly anaplastic and vascular

23. 0 Clinical manifestation
• Often presents with symptoms from metastases
• Late vaginal bleeding in post partum period
• Enlarged uterus
• Enlarged ovaries
• Vaginal lesions

24. 3. Placental - Site
Trophoblastic Tumour
0 Rare aggressive form of gestational trophoblastic tumour
0 The tumour is usually confined to the to the uterus but
local invasion may occur into the myometrium, lymphatics
or vasculature.
0 It metastasizes late in course
0 PSTT is derived from the intermediate trophoblasts of the
placenta bed with minimal or absent syncytiotrophoblastic
tissue
0 As syncytiotrophoblastic cells are generally absent from
this tumour, minimal amounts if hCG are released
0 Production of human placental lactogen (hPL)

25. 0 May arise months or years after
• a hydatidiform mole or
• less commonly after a normal term pregnancy

26. Classification
1. Non-metastatic
• May present with abnormal bleeding
• All have rising or plateau β- hCG
• Negative metastases on staging investigations
2. Metastatic
• More common with choriocarcinoma which tends to
towards early vascular invasion and widespread
dissemination
• Signs and symptoms which are suggestive of
haematogenous spread, do not biopsy (they bleed)
 Lungs (cough, hemoptysis)
 Vagina (vaginal bleeding, blue lesions)
 Pelvis (rectal bleeding)
• Highly vascular tumour  bleeding  anemia
• All have rising or plateau β- hCG

27. Clinical manifestation
• Abnormal uterine bleeding during 1st trimester
• Nausea & Vomiting (confused with hyperemesis
gravidarum)
• Uterine size greater than expected for their GA
• Multiple theca lutein cysts causing enlargement of
one or both ovaries ( increase risk of malignancy)
• Preeclampsia
• Hyperthyroidism due to stimulation of
thyrotropin by hCG

28. Laboratory findings
• Principal characteristic of gestational
trophoblastic neoplasm is their capacity to
produce hCG
• This hormone may be detected in the serum or
urine of virtually all patients with hydatidiform
mole or malignant trophoblastic disease, its levels
correlates closely with the presence of tumour
cells.

29. Ultrasound findings
Choriocarcinoma
• Reveal an enlarged uterus with a necrotic and
haemorrhagic pattern
PSTT
• An intrauterine mass may be present

30. Diagnosis
GTN may be diagnosed when any of the following criteria are
met
1. When the plataeau of hCG levels last for four
measurements (days 1,7,14,21) over a period of three
weeks or longer.
2. When there is a rise in hCG level for three weekly
consecutive measurements (days 1, 7 and 14) or longer,
over a period of at least two weeks or more.
3. When the hCG levels remain elevated for six months or
more.
4. When there is histological diagnosis of choriocarcinoma.

31. Management of GTN
1. Scoring according to the FIGO 2000 staging system
2. Low risk patients have a score of 6 or less. High risk
7 or more
3. High risk treat with methotrexate and Dactinomycin
followed by folinic acid
4. If 7 or more chemotherapy
5. If PSTT hysterectomy

32. Staging
Modified WHO Prognostic Scoring System as Adapted by FIGOb
Scores 0 1 2 4
Age <40 ≥40 – –
Antecedent pregnancy mole abortion term –
Interval months from
index pregnancy
<4 4–6 7–12 >12
Pretreatment serum hCG
(iu/1)
<103 103–104 104–105 >105
Largest tumor size
(including uterus)
<3 3–4 cm ≥5 cm –
Site of metastases lung spleen, kidney gastrointestinal liver, brain
Number of metastases – 1–4 5–8 >8
Previous failed
chemotherapy
– – single drug ≥2 drugs

33. Investigations for staging
• History and Physical Examination
• Bloodwork: FBC, electrolytes, creatinine, β-hCG,
TSH, LFTs
• Imaging: CXR, U/S pelvis, CT abdo/pelvis, CT
brain

34. Differential Diagnosis
0 Normal pregnancy
0 Aborting pregnancy
0 Ectopic pregnancy
Complications
0 Deportation of trophoblastic tissue through the
maternal-fetal barrier to the lungs
0 Pulmonary emboli

35. References
0 Decherney., A.H., & Nathan.,L. (2007). Current
diagnosis & treatment. USA: The McGraw hill, Cenveo
publisher.
0 Hoffman., B.L., Schorge.J.O & Schaffer., J.I. (2012).
William Gynecology. USA, Texas:The McGraw hill