3. Definition
• Gestational trophoblastic disease constitutes a
diverse group of lesions that includes abnormally
formed placentas (hydatidiform moles), benign
nonneoplastic lesions, and gestational
trophoblastic neoplasms
5. Epidemiology
• Gestational trophoblastic disease (GTD) varies
widely among various populations, As high as 1 in 120
pregnancies in some areas of Asia and South America
• The incidence of hydatidiform moles is greater in women
older than 40 years and is also increased inthose younger
than 20 years.
• Patients who have had prior GTD are more at risk of
having a second GTD after subsequent pregnancies.
Other risk factors include: a diet low in vitamin A, lower
socioeconomic status and blood group A and women
married to group 0 men
6. Hydatidiform Mole
• Abnormal pregnancy characterised histologically
by aberrant changes within placenta
• Chorionic villi: trophoblast proliferation and
stromal edema
• Categorised as Partial and complete mole
9. Transverse sonographic view of a uterus with a complete
hydatidiform mole. The classic “snowstorm” appearance
is created by the multiple placental vesicles. The mole
completely fills this uterine cavity
Source: Williams Gynaecology 3rd edition
11. Low-magnification photomicrograph shows generalized
edema and cistern formation (black asterisks) within
avascular villi. Haphazard trophoblastic hyperplasia is
marked by a yellow asterisk on the right.
Source: Williams Obstetrics 24th edition
12. • Clinical Presentation:
Uterus size enlarged in excess of gestational age
Bleeding Per Vaginum
Anemia
Hyperemesis Gravidarum
Pre-Eclampsia
Theca-Lutein Cysts
Hyperthyroidism
Source:Berek and Novak’s Gynaecology 15th edition
13. Transvaginal sonogram of multiple theca-lutein
cysts within one ovary of a woman with a complete
molar pregnancy. Bilateral, multiple simple cysts are
characteristic findings
14. Partial Hydatidiform Mole
• Trophoblastic proliferation and villous edema
are focal
• May contain fetal tissue and amnion
• Signs and symptoms of incomplete or missed
abortion
• Triploid Karyotype (69,XXX; 69XXY; 69XYY)
composed of one maternal and two paternal
haploid sets of chromosomes
18. Ancillary echniques:
• Immunohistochemical staining for p57
expression and molecular genoyping
• p57K1P2 is a nuclear protein which is paternally
imprinted and maternally expressed, complete
moles do not pick up this stain
• Molecular genotyping determines the parental
source of polymorphic genes
Williams Gynaecology 3rd Edition
19. Treatment
• Suction curettage: preferred method of
evacuation regardless of uterine size.
(American College of Obstetricians and Gynecologists, 2014;
Tidy, 2000)
• Hysterectomy: rare
patient wishes surgical sterilization
approaching menopause.
• Theca-lutein ovarian cysts: unusual, tend to
regress after molar evacuation
may be aspirated.
20. Prophylactic Chemotherapy
• Prophylactic chemotherapy should not be routinely
used.
• Indication:
Histological evidence of choriocarcinoma
Evidence of metastasis in brain, liver, GIT or
radiologic opacities >2 cm on CXR.
Pulmonary, vulval or vaginal mets
Heavy vaginal/intraperitoneal haemorrhage.
Rising hCG or persistantly elevated after evacuation.
Serum hCG > 20,000 IU/l after 4 weeks of
evacuation.
• MTX with folinic acid > Actinomycin D
(Recent advances in OBS/GYN 24 )
21. • Things to Remember:
- Evaluation of associated medical complications:
Thyroid storm from untreated hyperthyroidism,
respiratory insufficiency from trophoblastic emboli.
- Blood products should be available.
- Prostanoids to avoid: can induce uterine
contractions and increase the risk of trophoblastic
embolization to the pulmonary vasculature. Can
be started after anesthesia.
- Rh immune globulin is given to nonsensitized Rh
D-negative women.
22. Postmolar Surveillance
Serial quantitative serum β-hCG levels: Every weekly till
they become undetectable for 3 consecutive weeks.
Followed by monthly evaluations for 6 months. (Berek
and Novak’s 15th edition)
OR
monthly titers until the level is undetectable or 12
months. Patients with high-risk disease are followed for
24 months due to the greater risk o late relapse.
(williams gynecology 3rd edition)
• Contraception:
COC, Medroxyprogesterone acetate.
Till β-hCG titer < 5 mIU/mL
23. GESTATIONAL TROPHOBLASTIC
NEOPLASIA
• Non metastatic disease: 15% after evacuation of
complete mole and 4-6 % after partial mole.
• Metastatic disease: 4% after evacuation of
complete mole. More common when GTN occurs
after non molar pregnancy.
• Symptoms:
irregular vaginal bleeding
theca lutein cysts
Uterine subinvolution
Persistently elevated serum hCG levels.
24. GESTATIONAL TROPHOBLASTIC NEOPLASIA….
• Investigations: serum/ urine hCG, CXR, pelvic
doppler USG, Lumbar puncture for CSF: Serum
hCG ratio.
• Histology: After molar evacuation; histologic
features of hydatidiform mole or
choriocarcinoma. After nonmolar pregnancy,
resembles choriocarcinoma.
25. GESTATIONAL TROPHOBLASTIC NEOPLASIA….
FIGO Anatomic Staging of GTN ( 2009)
I Disease confined to the uterus
II GTN extends outside of the uterus but is
limited to the genital structures (adnexa, vagina,
broad ligament)
III GTN extends to the lungs, with or without
known genital tract involvement
IV All other metastatic sites.
26. GESTATIONAL TROPHOBLASTIC NEOPLASIA:
Histological classification
1. Invasive Mole: excessive trophoblastic
overgrowth and invasion into myometrium,
sometimes peritoneum, adjacent parametrium
or vaginal vault.
Locally invasive.
Originate from a complete or a partial hydatidiform
mole.
27. 2. Gestational
Choriocarcinoma
- Extremely malignant tumor.
- Contains sheets of
anaplastic trophoblast and
prominent hemorrhage,
necrosis, and vascular
invasion.
- Villous structures
characteristically absent.
- Tends to develop early
blood-borne systemic
metastases
- Mortality rates range from
10 to 15 percent.
28. 3. Placental-site Trophoblastic Tumor:
- Rare
- Intermediate trophoblasts at the placental site.
- Develops most commonly following a term
gestation.
- Irregular bleeding months or years after the
antecedent pregnancy.
- Diagnosis: endometrial sampling.
- Infiltrates within the uterus, disseminates late.
- Metastases often spread to the lungs, liver, or
vagina.
- Relative insensitivity to chemotherapy
- Hysterectomy is the primary treatment of
nonmetastatic
PSTT.
- Metastatic PSTT: poorer prognosis.
29. • Epithelioid Trophoblastic Tumor
Develops from neoplastic transformation of
chorionic-type intermediate trophoblasts.
Microscopically, this tumor resembles PSTT but
the cells are smaller and display less nuclear
Pleomorphism.
Grossly, epithelioid trophoblastic tumor grows
in a nodular fashion rather than the infiltrative
pattern.
Chemoresistance
Hysterectomy
31. GESTATIONAL TROPHOBLASTIC NEOPLASIA….
Modified WHO Prognostic Scoring System
FIGO 2009
Low risk: WHO score of 0 to 6;
high risk: WHO score of ≥ 7; multimodal therapy
needed including chemotherapy, surgery and
radiation.
33. Hydatidiform mole
Evacuation
Serial hCG monitoring resolution, 6 months hCG
f/up
GTN
FIGO scoring
Low risk High risk
Single agent chemo combination chemo
serial hCG
Relapse/resistance Resolution
Secondline chemo Lifelong hCG f/up
With or without
Surgical debulking.
34. Low risk treatment regimen
• Methotrexate 50 mg IM every 48 hrs interval total 4
doses with Folinic acid 15 mg orally 30 hrs after each
injection of MTX. Cycle repeated every 14 days.
Excellent therapeutic outcome with minimal systemic
toxicity.
• Actinomycin D 1.25 mg/m2 IV biweekly.
(Berek and Novak’s 15th edition)
35. Low risk treatment regimen
• hCG level measured weekly after each course of
chemo.
• After first treatment, further chemo is withheld
as long as hCG level is falling progressively.
Indication for second course chemo:
hCG level plateaus for more than 3 consecutive
weeks.
If hCG level does not decline by 1 log within 18
days after completion of first treatment.
• If second course fails then patient is considered
resistant to MTX and Actinomycin D is added.
36. High risk treatment regimen
(Berek and Novak’s 15th edition)
1. EMA-CO: (Etoposide, MTX, Acctinomycin D,
Cyclophosphamide, Vincristine):
▫ complete remission in 95% cases with non metastatic
and low risk metastatic GTN.
▫ 83% in metastatic and high risk score.
2. EMA-EP: (etoposide and cisplatin with
etoposide, methotrexate, and dactinomycin):
remission was seen in 76% of patients who were
resistant to EMA-CO.
37. Management of refractory GTN
(Berek and Novak’s 15th edition)
• When patients are resistant to all standard
chemotherapy.
• PVB (cisplatin, vinblastine, bleomycin)
• TE/TP (paclitaxel, cisplatin, etoposide)
• ( floxuridine) FUDR containing regimens.
• 5 FU with ActD
38. Management of residual post-
treatment mass (Recent advances in OB/GYN 24)
• In increased uterine vascular malformation: no
inervention unless bleeding occurs. Uterine
artery embolization; most effective and fertility
preserving.
• Residual brain mass: excision or stereotactic
radiotherapy.
• Residual mass at other sites: no intervention.
f/up with β hCG
39. Phantom β hCG
• Persistent mild elevations of serum β-hCG when
in reality no true β-hCG molecule or trophoblastic
disease is present.
• Heterophilic antibodies in the serum that
interfere with the β-hCG immunoassay and
cause a false-positive result.
Q. How to differentiate ?
a. UPT
b. Serial dilution of serum sample of β hCG.
