GESTATIONAL TROPHOBLASTIC DISEASES BY DR SHASHWAT JANI

1. Dr. Shashwat Jani.
M. S. ( Obs – Gyn )
Diploma in Advance Laparoscopy.
Consultant Assistant Professor,
Smt. N.H.L. Municipal Medical College.
Sheth V. S. General Hospital , Ahmedabad.
Mobile : +91 99099 44160.
E-mail : drshashwatjani@gmail.com

2. WHO
Classification Of GTD
• Hydatidiform mole
- Complete
- Partial
• Invasive hydatidiform mole
• Choriocarcinoma
• Placental site trophoblastic tumor
• Trophoblastic lesions, miscellaneous
Exaggerated placental site
Placental site nodule
• Unclassified trophoblastic lesions
6/5/2017
Dr Shashwat Jani.
99099 44160.
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3.  GTD = A heterogeneous group of lesions
characterized by an abnormal proliferation of
trophoblast.
 Profound differences in the
pathogenesis, morphology, and clinical behavior
of various forms of the disease.
Trophoblastic Diseases
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Dr Shashwat Jani.
99099 44160.
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4.  Hydatidiform moles (complete,
partial, and invasive) represent abnormally
formed placentas with specific genetic
abnormalities that are related to villous
trophoblast.
 Choriocarcinoma and the placental site
trophoblastic tumor are true neoplasms and
are related to previllous and extravillous
trophoblast.
6/5/2017
Dr Shashwat Jani.
99099 44160.
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5. What goes wrong ?
• Normal gestational trophoblast :
Aggressively invades endometrium
& uterine vasculature placenta.
Complex biologic & immunologic mechanisms
control relationship between fetal trophoblast &
maternal host prevent circulating trophoblast
metastases
• When GTD arises: normal regulatory mechanisms
are lost. Excessively proliferating trophoblast may
invade thru myometrium, developing rich maternal bld
supply, with tumor emboli & hematogenous spread
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Dr Shashwat Jani.
99099 44160.
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6.  They are characterized by pregnancy
associated trophoblastic proliferations.
 They range from tumor like conditions to
malignancy.
 H. mole is a common complication of
gestation (1 in 1000 to 2000).
 They can be monitored by measuring
HCG levels (to detect early recurrence and
response to Tx)
 Choriocarcinomas are highly
responsive to chemotherapy.
Trophoblastic Diseases
6/5/2017
Dr Shashwat Jani.
99099 44160.
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7. 6/5/2017
Dr Shashwat Jani.
99099 44160.
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Hydatidiform Mole (VESICULAR MOLE)
(Molar pregnancy)

8. Definition
• In latin
"hydatid" means "drop of water”
"mole" means "spot”.
• H. mole is a pregnancy
characterized by vesicular swelling of
placental villi and usually the absence of
an intact fetus.
6/5/2017
Dr Shashwat Jani.
99099 44160.
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9. Incidence
• Wide range in geographical & ethnic
variation of prevalence.
• Common in oriental countries.
• Highest in Philippines 1 : 80
• Lowest in European countries 1 : 750
• India 1 : 400 .
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Dr Shashwat Jani.
99099 44160.
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10. • Approximately 10-17% of
H. moles will result in Invasive mole.
• Approximately 2-3% of
H. Moles progress to choriocarcinoma
( most of them are curable)
Not definitely benign disease ,
has a tight relationship with GTT
6/5/2017
Dr Shashwat Jani.
99099 44160.
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11. Etiology
• Geographical distribution
• Racial factors
• Age -Early teenage pregnancies < 15yrs or
-In pregnancies of > 35yrs.
• Nutritional factors- low socio-economic status,
carotene & animal fat soluble vitamin deficiency.
• Disturbed maternal immune mechanism 
– ↑ in γ globulin level in absence of hepatic disease
– ↑ed association with AB blood group which possesses
no ABO antibody.
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Dr Shashwat Jani.
99099 44160.
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12. • H/o previous H.mole– recurrence chance 1-4%
• High parity, malnourished & Debilitated
diseases like TB.
• Cytogenic Abnormality.
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Dr Shashwat Jani.
99099 44160.
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13. Dr Shashwat Jani.
99099 44160.
Empty
ovum
Empty
ovum
46XX
46XX or
46XY
23X or Y23X
23X
Complete Mole
(46XX diploid)
Complete Mole (46XX
or 46XY, diploid)
A single sperm fertilizes
an empty ovum, with
duplication of the 23X
haploid set of
chromosomes, giving rise
to a homozygous diploid
complete mole.
Two sperms with two
independent haploid sets
of chromosomes fertilize
an empty ovum,
producing a dyspermic
complete mole with either
46XX or 46XY karyotype.
Complete Mole
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14. Hydatidiform Mole
Alterations in gene
expression profiles
Up-regulation and down-
regulation of proteins committed
to cell growth control
e.g. Up-regulation of growth
factor and cytokine mediated
pathways, and antiapoptosis
genes
Trophoblastic hyperplasia
e.g. Down-regulation of
insulin growth factor binding
proteins and tumor necrosis
factor receptor
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15. Hydatidiform Mole
• Clinical Presentation:
– Complete mole:
Vaginal
bleeding
Severe
anemia
Passage of
hydropic
villi
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Dr Shashwat Jani.
99099 44160.
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16. Usually, in
association
with,
Excessive uterine enlargement 50 %
Hyperemesis gravidarum 25 %
Preeclampsia 25%
Markedly elevated hCG 100,000
mIU/mL
Hyperthyroidism 5%
Theca lutein cysts 50 %
Clinical Presentation:
 Complete mole:
Vaginal Bleeding 95 %
Dr Shashwat Jani.
99099 44160.
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17. 6/5/2017
Dr Shashwat Jani.
99099 44160.
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18. Diagnosis
Suspicion:
Abnormal bleeding after amenorrhea
Inappropriately enlarged uterus;
Absence of fetal heart sounds or could not
feel fetal parts by palpation between 16-
20th week
Hyperemesis gravidarum
Bilateral ovarian cysts
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Dr Shashwat Jani.
99099 44160.
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19. Serum hCG monitor
An unusually high titer of hCG, especially
after the 100th day of pregnancy, help to confirm
the diagnosis of HM.
• Serum βhCG > 1,00,000 mIu/ml
• Plain X-Ray abdomen  negative fetal shadow.
• Chest X-ray  to R/O pulmonary embolism.
• CT & MRI  to detect metastasis.
6/5/2017
Dr Shashwat Jani.
99099 44160.
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20. Ultrasonography:
It is a reliable and sensitive technique
for the diagnosis of complete molar pregnancy.
Because the chorionic villi exhibit diffuse
hydatidiform swelling.
A characteristic vesicular sonographic pattern,
usually referred to as a “Snowstorm” Pattern.
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Dr Shashwat Jani.
99099 44160.
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21. Snowstorm Pattern
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Dr Shashwat Jani.
99099 44160.
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22. Differential Diagnosis
1. Threatened abortion
2. Fibroid uterus with pregnancy.
3. Ovarian tumour with pregnancy
4. Multiple pregnancy.
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Dr Shashwat Jani.
99099 44160.
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23. MANAGEMENT
Principles in management :
• Suction evacuation of uterus
(safe upto 28 wks of gestation).
• Supportive therapy – correction of anemia &
infection if any.
• Counseling for regular follow-up.
6/5/2017
Dr Shashwat Jani.
99099 44160.
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24. Evacuation & Mx of Molar Pregnancies
 Complete history & medical exam (anemia/
dehydration/ preeclampsia &/or thyrotoxicosis)
 Appropriate lab & radiologic evaluation,….stabilize
hemodynamically (preevacuation hCG, CBC, LFT, BUN,
creatinine, TFT, pelvic USG, chest x-ray)
 Based on these findings, perioperative
complications shd be anticipated …preopn.ABG, postevacuation chest
x-ray, central monitoring in ICU setting
 Suction evacuation gives the lowest incidence of
sequelae
(metal canula, medical induction, prostaglandins …NO )
6/5/2017
Dr Shashwat Jani.
99099 44160.
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25. Evacuation Technique
• Stabilize hemodynamically, address all medical
complication (antihypertensive, β blocker)
• Large bore intravenous line… central venous monitoring
• Two units blood, laparotomy tray in O.R.
• Cx grasped with single tooth tenaculum,
• NO sounding,
• Cx dilated gently to accommodate 12-14mm
cannula.
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Dr Shashwat Jani.
99099 44160.
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26. • Cannula only up to lower portion of
uterus,
• Start Oxytocin, massage fundus gently to
assist involution, rotate cannula…advance
only after involution
• Sharp curettage…both specimen separately for HPE
• Oxytocin to be cont. for 24hrs. evacuation,
...avoid fluid overload.
6/5/2017
Dr Shashwat Jani.
99099 44160.
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27. Complications of Suction evacuation.
• Injury to uterus  Perforation, infection.
• Hemorrhage.
• Shock
• Acute pulmonary insufficiency.
• Thyroid storm.
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Dr Shashwat Jani.
99099 44160.
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28. Hysterectomy (↓ risk of GTN by 5%)
Indicated in 
• Patient with age > 35 yrs
• Completed family irrespective of age.
• Uncontrolled hemorrhage/perforation during
suction evacuation.
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Dr Shashwat Jani.
99099 44160.
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29. Hysterotomy
• Rarely done.
Indicated in
• Profuse vaginal bleeding.
• Cervix unfavorable for immediate vaginal
evacuation.
• Accidental perforation of uterus during
evacuation.
6/5/2017
Dr Shashwat Jani.
99099 44160.
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30. Theca lutein cysts
• They are hormone dependent.
• Disappear spontaneously after evacuation of
the mole.
• So, they are not removed surgically unless
complication occur as torsion or rupture.
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Dr Shashwat Jani.
99099 44160.
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31. Large bilateral theca lutein cysts resembling ovarian germ cell tumors. With
resolution of the human chorionic gonadotropin(HCG) stimulation, they return to
normal-appearing ovaries.
Large bilateral theca lutein cysts resembling ovarian germ cell
tumors. With resolution of the human chorionic gonadotropin(HCG)
stimulation, they return to normal-appearing ovaries. 31

32. Partial Or Incomplete Mole
• Affection of
Chorionic Villi is
focal.
• Fetus/Amniotic sac
is present.
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Dr Shashwat Jani.
99099 44160.
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33. 23X 23X
Dyspermy
23X/23Y or
23X/23X
23Y
Partial Mole (69XXY,
or 69XXX, or 69XYY
triploid)
Partial Mole
23X
23X
23Y
69XXY
Fertilization of a normal 23X haploid ovum by two sperms,
producing a triploid partial mole with either 69XXY, 69XXX or
69XYY karyotype
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Dr Shashwat Jani.
99099 44160.
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34. Signs / Symptoms
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99099 44160.
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 Vaginal bleeding
 Absence of fetal heart tones
 Uterine enlargement and preeclampsia
is reported in only 3% of patients.
 Theca lutein cysts, hyperemesis is rare.

35. Williams Obstetrics6/5/2017
Dr Shashwat Jani.
99099 44160.
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36. USG features of Partial Mole :
 Gestational sac must be present  empty ,
amorphous echoes.
 Increase in transverse to A- P diameter of
gestational sac > 3:2 .
(90% positive predictive value).
 If fetus present, it is often growth retarded.
 Placenta is excessively large, relative to size of
uterine cavity & contain focal cystic spaces.
6/5/2017
Dr Shashwat Jani.
99099 44160.
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37. Partial Mole: Complex mass with many cystic
areas (between arrowheads) and an embryo (arrow)
in a patient with a β-HCG of 280,000 mIU/ml.

38. Management
• If fetus is not alive  termination of
pregnancy.
• If fetus is alive  woman counseled
about ↑ed risk of perinatal morbidity &
outcome of GTN. Terminate the
pregnancy.
6/5/2017
Dr Shashwat Jani.
99099 44160.
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39. Partial Mole In Twins
• Many cases have been reported of second
normal live fetus up to age of viability.
• Can continue pregnancy after explaining all
possible maternal & fetal complications.
6/5/2017
Dr Shashwat Jani.
99099 44160.
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40. Contraception during follow up
• The combined pill is started when the beta-
HCG becomes negative. Till this happens, the
condom can be used.
• If the pill is used early the beta-HCG will take
a longer time to become negative as
oestrogen stimulates the growth of
trophoplast.
6/5/2017
Dr Shashwat Jani.
99099 44160.
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41. The intrauterine device is not used because
it may lead to irregular uterine bleeding
which confuses the follow up & also
increases chances of perforation.
IUD during follow up
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Dr Shashwat Jani.
99099 44160.
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42. Follow Up
• Objective  to diagnose persistent GTT that is
considered malignant.
• If hCG  Normal within 56 days  follow up will
be for 6 months from date of uterine evacuation.
• If hCG  Not normal within 56 days  then
follow up will be for 6 months from normalization
of hCG level.
• Woman with chemotherapy should
follow up for 1 year after hCG has been normal.
6/5/2017
Dr Shashwat Jani.
99099 44160.
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43. Follow up protocol
History
Physical examination
hCG assay
Chest X-ray
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Dr Shashwat Jani.
99099 44160.
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44. • History :
–h/o irregular P/V bleeding.
–Hemoptysis
–Breathlessness
–CNS disturbance like headache, blurring of
vision, neurological deficit.
–Epigastric pain, hematuria, jaundice
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Dr Shashwat Jani.
99099 44160.
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45. Physical examination
• General examination
• P/A 
– Sub-involution of uterus,
– Palpation of mass
– Tenderness
– Hepatomegaly
• P/S  Vaginal metastasis
• P/V  Sub-involution of uterus,
Regression of theca lutein cyst .
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Dr Shashwat Jani.
99099 44160.
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46. • Quantitative serial βhCG level.
• Chest X-ray
If pre- evacuation shows metastasis 
Repeat at 4 wk interval until remission confirmed
 then 3 month interval during rest of follow-up.
If pre-evacuation chest x-ray normal 
repeated only when hCG titre plateaus or rises.
6/5/2017
Dr Shashwat Jani.
99099 44160.
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47. PROPHYLACTIC CHEMOTHERPHY
Prevent metastasis & reduce morbidity.
• 80% pts  spontaneous regression.
• Sensitive β hCG assay can identify rest that
develop malignancy.
• Chemotherapy is toxic  ↑ chance of premature
ovarian failure & menopause.
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Dr Shashwat Jani.
99099 44160.
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48. Advised in
 hCG level fails to become normal by stipulated
time (10-12 wk) or re-elevation at 4-8 wk.
Rising β hCG level after reaching normal level.
Post evacuation hemorrhage.
Follow up facilities not adequate.
Evidence of metastasis, irrespective of β hCG
level.
When malignant sequelae is higher.
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Dr Shashwat Jani.
99099 44160.
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49. •Single drug regimen
• Course is to be repeated at interval of 7 days.
• Alternatively IV Actinomycin-D
12μgm/kg x 5 days.
Methotrexate 1-1.5mg/kg IM/IV Day 1,3,5,7
Folinic Acid 0.1-0.15 mg/kg IM Day 2,4,6,8
6/5/2017
Dr Shashwat Jani.
99099 44160.
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50. RH ISOIMMUNISATION
If <12 wks gestation  50 μgm Anti-D
If >12 wks gestation  300 μgm.
In Complete Mole poor vascularisation
of chorionic villi & absence of anti-D
antigen so Anti –D prophylaxis not
required.
BUT required in partial mole.
6/5/2017
Dr Shashwat Jani.
99099 44160.
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51. Placental Site Trophoblastic Tumour
(PSTT)
• Rare
• Histological Diagnosis syncytotrophoblastic
cells are generally absent  persistent low
level of serum or urinary hCG.
• Tumor  from intermediate trophoblasts of
placental bed composed mainly of
cytotrophoblastic cells.
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Dr Shashwat Jani.
99099 44160.
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52. • C/F  Vaginal bleeding.
• Local invasion of Myometrium & Lymphatics.
• PSTT is not responsive to chemotherapy.
• Rx  Hysterectomy.
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99099 44160.
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53. Invasive mole
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99099 44160.
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54. Invasive mole
Definition:
An invasive hydatidiform mole is one in
which hydropic chorionic villi are within the
myometrium or its vascular spaces or at distant
sites, notably the vagina or lung.
“Mole that penetrates and even perforates
the uterine wall”.
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Dr Shashwat Jani.
99099 44160.
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55. Invasive mole
• Invasive hydatidiform mole is a sequela to
hydatidiform mole, complete or partial.
• The pathologic diagnosis of invasive mole
is made by establishing the presence of molar villi
growing into the myometrium and broad ligament.
• The diagnosis of an invasive mole cannot
be made on examination of curettage specimens
except when curetted fragments of myometrium
contain invasive molar villi.
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Dr Shashwat Jani.
99099 44160.
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56. Clinically identified by:
Combination of
 Abnormal uterine USG
 Persistent / rising hCG level after uterine
evacuation for mole
 Theca lutein cysts & uterine subinvolution
 Histologic verification is rarely required
 Repeat D&C contraindicated….risk of
uterine perforation, infection, life threatening
hemorrhage ..hysterectomy
6/5/2017
Dr Shashwat Jani.
99099 44160.
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57. Persistent Gestational
Trophoblastic Disease
• Definition  it is the persistence of
trophoblastic activity as evidenced by clinical,
imaging, pathological &/or hormonal study
following initial treatment.
• Post Molar GTD 
– Benign.
– Malignant.
Post Molar GTD after non-molar pregnancy is
always choriocarcinoma.
6/5/2017
Dr Shashwat Jani.
99099 44160.
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58. Incidence :
• 50% following H.Mole
• 25% following abortion or ectopic
pregnancy.
• 25% following normal delivery.
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Dr Shashwat Jani.
99099 44160.
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59. DIAGNOSIS
During post-evacuation follow-up period 
• Continued vaginal bleeding.
• Persistent Theca Lutein Cysts.
• Persistent soft & enlarged uterus.
• hCG titer either fail to become negative or
plateau or re-elevation after initial fall by 8 wk
post molar evacuation.
• Local, systemic metastasis ruled out by x-ray
chest, CT, MRI of brain, Liver etc.
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Dr Shashwat Jani.
99099 44160.
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60. FIGO Anatomic Staging of GTT
Stage I – Lesion is confined to Uterus
Stage II – Lesion spreads outside uterus but
confined to genital organs
Stage III – lesion metastatises to lungs
Stage IV – Lesion metastatise to sites such as Brain,
Liver, GIT.
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99099 44160.
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61. All stages subdivided as
• No risk factors
• One risk factor
• Two risk factors
Risks
• hCG > 1,00,000 mIu/ml
• Duration of disease > 6 mts from termination of
antecedent pregnancy.
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99099 44160.
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62. WHO prognostic scoring system of GTT as
modified by FIGO (2000)
Score
Characteristic 0 1 2 4
Age <40 ≥40 - -
Antecedent preg Mole Abortion Term -
Interval from index
pregnancy
<4
months
4-6
months
7-12 months >12 months
Pretreatment HcG <103 103- 104 104-105 >105
Largest tumor size
(including uterus)
< 3cm 3-4 cm ≥5cm -
Site of metastases Lung Spleen,
kidney
GI tract Liver, brain
Number of metastases - 1-4 5-8 >8
Previous failed
chemotherapy
- - Single drug ≥2 drugs
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99099 44160.
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63. Low risk =  6  single agent chemotherapy
High risk =  7  combination chemotherapy
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99099 44160.
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64. MAC protocol in low risk cases
Methotrexate Folinic Acid Actinomycin D Cyclophospha
mide
1-1.5mg/kg 0.1-0.15mg/kg 12mcg/kg 3mg/kg
IM/IV IM IV IV
Day 1,3,5,7 Day 2,4,6,8 Day 1-5 Day 1-5
6/5/2017
Dr Shashwat Jani.
99099 44160.
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65. EMA-CO Protocol in poor prognosis
metastatic disease
Day 1 Etoposide
Actinomycin D
Methotrexate
100 mg/m2 in 200ml saline infused over 30 min.
0.5mg IV bolus
100mg/m2 bolus followed by 200mg/m2 IV
infusion over 12 hr.
Day 2 Etoposide
Actinomycin D
Folinic Acid
100mg/m2 in 200ml saline infused over 30 min.
0.5 mg IV bolus.
15mg IM every 12 hrs x 4 doses beginning 24 hrs
after starting Methotrexate.
Day 8 Cyclophospamide
Vincristine
(Oncovin)
600mg/m2 IV in saline over 30 min.
1mg/m2 IV bolus.
Course will restart in 7-14 days if possible. 2 additional course given after hCG level is
normal. Dr Shashwat Jani.
99099 44160.
65

66. • During Chemotherapy serum hCG level checked
weekly.
• Chemotherapy should be changed if no fall in hCG titer
by atleast 25% after treatment cycle.
Place of Hysterectomy :
• Reduce trophoblastic tumour burden.
• Decrease no. of courses of chemotherapy.
• Total Hysterectomy  Ovaries usually not involved. If
involved- actively cured with post-op chemotherapy.
Radiation:
• Brain Metastasis  whole brain radiation therapy
3000cGy over 10 days.
• Liver Metastasis  whole liver radiation therapy
2000cGy over 10 days.
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Dr Shashwat Jani.
99099 44160.
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67. Prognosis
• Low risk  almost 100%
• High risk  70%.
Recurrence
• Non-metastatic GTN  2-3%
• Good prognosis metastatic disease  3-5%
• Poor prognosis disease  21%.
• Recurrence following 12 mts of normal hCG level
 < 1%.
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99099 44160.
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68. ROLE OF SURGERY
Surgery has been limited to the treatment
of :-
- Resistant cases to chemotherapy,
- Uncontrollable haemorrhage from the uterus
- Tumour perforation of the uterus
- Infected uterine tumour not responding to
antibiotics, thus delaying chemotherapy..
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99099 44160.
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69. Newer Regimen
• Newer chemotherapy agents
• Autologous bone marrow transplant
• Peripheral stem cell support
• colony stimulating factors
• Selective arterial embolisation.

70. FOLLOW-UP
• BhCG Titre wkly until 3 consecutive normal titres
• Monthly for 12 months
• 3 monthly for 1 additional year
• 6 monthly indefinitely
• Contraception for at least 1yr after remission(OCP,
Condom)
• Gynaecologic examination started 1 week post
evacuation – assess Ut size, adnexal masses, check
for metastases on the vulva, vagina, urethra, and
cervix. If no complication repeat exam 4 wkly
throughout period of surveillance.
6/5/2017
Dr Shashwat Jani.
99099 44160.
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