Molar pregnancy

1. Gesta&onal Trophoblas&c Disease
Dr Sai Lakshmi Daayana
MBBS, MRCOG, MD (University of Manchester, UK)
RCOG approved Sub-specialty training in Gynaecological Oncology (UK)
Consultant in Gynaecological Oncology
Apollo InsEtutes of Cancer, Jubilee Hills, Hyderabad

2. GestationaltrophoblasticDisease
n Molar pregnancy
-Complete hydaEdiIorm mole
-Incomplete hydaEdiIorm mole
n Choriocarcinoma
n Placental-site trophoblas&c tumor

3. MolarPregnancy
• Completemole
-Fertilizationanemptyeggby
onesperm.
-Allplacentalvillaswollen.
-Fetus,cord,amniotic
membraneareabsent.
-Paternalchromosomesonly.46
XX.
-diploidy
• Incompletemole
-fertilizationofaneggbytwo
sperms
-someplacentalvillaswollen
- Fetus,cord,amniotic
membranearepresent
- Paternalandmaternal
69XXY
-Triploid

6. MolarPregnancy
• Incidenceandepidemiology:
-InUSA1:1000
-InAsia8:1000
• Riskfactorsformolarpregnancy:
-Extremeofage
-Lowersocioeconomicstatus
-Raceandethnicorigin
-Blackshavelowerincidence

7. MolarPregnancy
• Symptomsandsignsofmolarpregnancy
-Abnormalbleedinginearlypregnancy
-Lowerabdominalpain
-Toxemiabefore24weeksofgestation
-hyperemesisgravidarum

8. MolarPregnancy
-Uteruslargefordates
-Nofetalheartrate
-Enlargementoftheovaries
-Hyperthyroidism
-Expulsionofswollenvilli

9. MolarPregnancy
• Diagnosis:
-Ultrasoundshowssnowstorm-likeappearance,nofetus,
thecaluteincyst
-BetahCGinnormalpregnancythelevelisatitpeakat
around14weeks(100,000mIU/ml)

10. TORONTO,CANADA,1998,SANT.JOS.HOS.

12. Management
• Oncethediagnosisismadeevacuationofthe
uterusshouldbedonebutpriortothat:
hCGpreevacuation.
Chestx-ray.
Correct:anemia,toxemia,hyperthyroidism,
pulmonarycompromise.

13. Followup
n HCG weekly unEl normal for two values then
monthly for one year.
n Repeat x- ray if HCG rises or plateau.
n ContracepEon for one year.
n Pelvic examinaEon every 3 weeks for 3
months.

15. Followup
• Initiatechemotherapyif:
-HCGlevelisincreasingorplateaus
-Metastasisdiseaseispresent
-HCGlevelisstillelevatedafter6monthsof
evacuation
-HCGstartstoriseafterbeingundetectable

16. Gesta&onal Trophoblas&c Neoplasia
(GTN)
• Persistent/Invasive Mole
• Choriocarcinoma
• Placental-Site Trophoblas&c Tumor (PSTT)
** Malignant

17. FICOClassificationSystemofGTT
I.Confinedtocorpusuteri
II.Metastasestovaginaorpelvicorgans
III.Metastasestolungs
IV.Distantmetastases

18. Risk Factors for GTN AIer Mole
• Preevacua&on uterine size greater than
gesta&onl age or larger than 20 weeks
gesta&on
• Theca-lutein cysts larger than 6 cm
• Age > 40 years
• Serum hCG levels > 100,000 mIU/mL
• Previous hyda&diform mole

19. Invasive Mole
• Myometrial invasion by hyda&diform mole
• Formerly known as chorioadenoma destruens
• 1 in 15,000 pregnancies
• 10-17% of hyda&diform moles will progress to
invasive moles

20. Persistent Mole
Defini&on of persistent molar disease and need for
chemotherapy (at least one of the following):
– B-hCG plateau for ≥ 4 values for ≥ 3 weeks
– B-hCG increase of ≥ 10% for ≥ 3 values for ≥ 2
weeks
– B-hCG persistence 6 months aIer molar
evacua&on
– Histopathologic diagnosis of choriocarcinoma
– Presence of metasta&c disease

21. Choriocarcinoma
• Most aggressive type of GTN
• Abnormal trophoblas&c hyperplasia
• Absence of chorionic villi
• Direct invasion of myometrium
• Most oIen develops from a complete
hyda&diform mole
• Vascular spread to distant sites:
– Lungs
– Brain
– Liver
– Pelvis and vagina
– Spleen, intes&nes, and kidney

22. Choriocarcinoma
• May come from any type of pregnancy
- 25% follow abor&on or tubal pregnancy
- 25% with term gesta&on
- 50% from hyda&diform moles
• 2-3% of moles progress to choriocarcinoma
• Incidence 1 in 40,000 pregnancies
– Rarely,choriocarcinomascandevelopinotherpartsofthe
bodyinbothmenandwomen.Thesearenotrelatedto
pregnancyasovariesandtesticles
• Nongestationalchoriocarcinomatendstobeless
responsivetochemotherapyandhasalessfavorable
prognosisthanthegestationalvariant

23. Placental-Site Trophoblas&c Tumor (PSTT)
• Originate from intermediate cytotrophoblast
cells
• Secrete human placental lactogen (hPL)
• B-hCG oIen normal
• Less vascular invasion, necrosis and
hemorrhage than choriocarcinoma
• Lympha&c spread
• Arise months to years aIer term pregnancy
but can occur aIer spontaneous abor&on or
molar pregnancy

24. Placental-Site Trophoblas&c Tumor (PSTT)
• Most common symptom is vaginal bleeding
• Tend to:
- Remain in uterus
- Disseminate late
- Produce low levels of B-hCG compared to
other GTN
- Be resistant to chemotherapy (treat with
surgery)

25. Signs & Symptoms GTN
• Con&nued uterine bleeding, uterine
perfora&on, enlarged irregular uterus,
persistent bilateral ovarian enlargement
• From metasta&c lesions: abdominal pain,
hemoptysis, melena, increased intracranial
pressure (headaches, seizures, hemiplegia),
dyspnea, cough, chest pain

26. Diagnosis of GTN
• Increase or plateau in B-hCG aIer molar
pregnancy
• Pathologic diagnosis by D&C or biopsy of
metasta&c lesions
• WARNING: biopsy of metasta&c lesions can
result in massive hemorrhage
• Metasta&c workup: CXR (or CT chest), CT
abdomen/pelvis +/- CT/MR of brain

27. Classifica&on & Staging of GTD
• FIGO Staging
– Describes anatomic distribu&on of disease
• World Health Organiza&on (WHO) Scoring
Index
– Describes prognosis

28. FIGO Staging
Stage Descrip&on
I Disease confined to the uterus
II Disease extends outside the uterus but
limited to genital structures (adnexa,
vagina, and broad ligament)
III Disease extends to the lungs with or
without genital tract involvement
IV Disease involves any other metasta&c sites

29. Therapy for GTN
• Single agent therapy for nonmetasta&c (stage
I) or low-risk metasta&c (stage II and III) with
score <7 à survival rates ~ 100%
• Combina&on chemotherapy +/- radia&on
and/or surgery for high-risk metasta&c
disease with score ≥7

30. Therapy: Nonmetasta&c GTN
• Single-agent with either methotrexate or
dac&nomycin
• Chemotherapy con&nued un&l hCG values normal
and then 2-3 cycles beyond
• Change to alterna&ve single-agent for hCG plateaus
above normal or toxici&es
• If significant eleva&on of hCG or new metastases,
switch to mul&agent
• 85-90% cured with ini&al regimen, <5% will require
hysterectomy for cure

31. Therapy: Low-risk Metasta&c GTN
• Low-risk metasta&c disease can be treated
with single-agent therapy with 5-day
regimens
• Cure rates ~100% but 30-50% will be develop
resistance to first agent
• If resistance to sequen&al single-agent
chemotherapy (5-10% of pa&ents), switch to
mul&agent chemotherapy

32. Therapy: High-risk Metasta&c GTN
• Stage IV
• Stage II/III with score > 7
• Disease refractory to single-agent chemotherapy
Combina&on Chemotherapy:
• EMACO:
– Day 1: Etoposide, Methotrexate and Dac&nomycin
– Day 8: Cyclophosphamide and Vincris&ne
(Oncovorin)
– Repeat q2 weeks un&l remission
– Con&nue for at least 2-3 cycles beyond first normal
hCG
• MAC (Methotrexate, Dac&nomycin, Cyclophosphamide)
• EMA/EP – EMA + Etoposide and Cispla&n

33. Metasta&c Gesta&onal Trophoblas&c Tumors
• Surgery
– It is indicated for tumor resistant to
chemotherapy and single metastases persisEng
despite chemotherapy.
• RT
– RT, in combinaEon with chemotherapy, is clearly
indicated for the primary management of paEents
with brain metastases.

34. PSTT Therapy
• Hysterectomy
• Chemotherapy for metasta&c disease or
nonmetasta&c disease with poor prognosis:
- Interval from index pregnancy > 2 years
- Deep myometrial invasion
- Tumor necrosis
- Mito&c count > 6 per 10 high-power fields
• Survival rates:
– ~100% for nonmetasta&c disease
– 50-60% for metasta&c disease

35. Follow-up Care
• AIer comple&on of chemotherapy, follow
serial hCG every 2 weeks for three months,
then monthly for one year
• Physical examina&ons every 6-12 months and
imaging as indicated

36. Reproduc&ve Performance
• Most women resume normal ovarian
func&on
• Women who undergo chemotherapy are
advised not to conceive for one year aIer
comple&on of treatment
• No increase risk of s&llbirths, abor&ons,
congenital anomalies, prematurity, or major
obstetric complica&ons

37. False Posi&ve Serum hCG
• Phantom hCG syndrome/ phantom
choriocarcinoma
• 3-4% of healthy individuals have human-an&mouse
an&bodies that can mimic hCG immunoreac&vity
• To verify:
– Urine hCG should be nega&ve
– Should not show parallel decrease with serial dilu&ons
– Test at na&onal B-hCG reference lab

38. Summary
• Hyda&diform mole is a benign condi&on, 80%
cured with suc&on D&C
• Malignant GTN:
– Persistent or invasive mole
– Choriocarcinoma
– PSTT
• WHO score > 7 represents high-risk disease
• GTN very sensi&ve to chemotherapy