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Gestational trophoblastic diseases
1. GESTATIONAL TROPHOBLASTIC
DISEASES
Prof. M.C.Bansal
MBBS,MS,MICOG,FICOG
Professor OBGY
Ex-Principal & Controller
Jhalawar Medical College & Hospital
Mahatma Gandhi Medical College, Jaipur.
2. HYDATIDIFORM MOLE
• Epidemiology:
▫ Incidence of GTD vary dramatically in different regions of the
world- incidence in Japan (2 per 1000 pregnancies) is about
3 times higher than in Europe or North America(0.6 to 1.1 per
1000 pregnancies)
▫ Incidence of partial mole (about 1 per 695 pregnancies) is 3
times higher than complete mole (about 1 per 1945
pregnancies)
• Risk factors of complete molar pregnancy:
▫ Low dietary intake of carotene
▫ Vitamin A deficiency
▫ Higher maternal age(35 yrs)
• Risk factor for partial mole:
▫ It has been associated with use of OCPs and history of
irregular menstruation.
▫ Not associated with dietary factors or maternal age
3. Types: (on the basis of gross morphology,
histopathology and karyotype)
• Complete mole
• Partial mole
Features Complete Mole Partial Mole
Fetal or embryonic tissue Absent Present
Hydatidiform swelling of Diffuse Focal
chorionic villi
Trophoblastic hyperplasia Diffuse Focal
Scalloping of chorionic villi Absent Present
Trophoblastic stromal inclusions Abse nt Present
Karyotype 46XX (90%); 46 XY Triploid
4. COMPLETE H. MOLE
• Complete H. Moles exhibit
characterstic swelling and
trophoblastic hyperplasia.
• Karyotype: 46XX (90% cases);
46XY(10%)
• Molar chromosomes- entirely
paternal in origin, although
mitochondrial DNA is maternal.
Complete moles arise from an
ovum that has been fertilized by a
haploid sperm, which then
duplicates its own chromosomes.
Ovum nucleus may be either
absent or inactivated.
5.
6. PARTIAL H. Mole
• Characterized by:
1. Chorionic villi of varying size with focal
hydatidiform swelling, cavitation and
trophoblastic hyperplasia.
2. Marked villous scalloping
3. Prominent stromal trophoblastic
inclusions
4. Identifiable fetal or embryonic tissues.
• Karyotype: triploid, the extra haploid set
is derived from father.
• When a fetus is present with partial
mole, it generally exhibits stigmata of
triploidy: growth retardation, multiple
congenital malformations- syndactyly,
hydrocephaly
7.
8.
9. Clinical features of complete mole:
A. Vaginal Bleeding: most common symptom (84%
patients)- may cause anaemia.
B. Excessive uterine size relative to gestational age: one
of the classic symptoms (28% patients). Endometrial
cavity may be expanded by both chorionic tissue and
retained blood. Is generally asociated with markedly
elevated hCG levels.
C. Preeclampsia: develops almost exclusively in
patients with excessive uterine size and markedly
elevated hCG levels.
D. Hyperemesis gravidarum: 8% patients, particularly
those with excessive uterine size and markedly
elevated hCG levels
10. E. Hyperthyroidism: rare these days. Anaesthesia or surgery may
precipitate thyroid storm.
• if hyperthyroidism is suspected, beta-adrenergic blocking
agents shud be given before induction of anaesthesia for molar
evacuation.
• Hyperthyroidism develops almost exclusively in patients with
very high hCG levels as hCG is thyroid stimulator in women
with GTD.
F. Respiratory distress due to trophoblastic embolization: occurs
rarely these days.
G. Theca leutin ovarian cysts: prominent cysts(>=6cm diameter)
develop in about half of patients with complete mole.
• Result from ovarian hyperstimulation by high serum hCG
levels.
• Regress spontaneously 2-4 mths after molar evacuation.
11. Clinical features of Partial H. Mole:
• Have signs and symptoms of incomplete of missed
abortion. Diagnosis is made after histological review of
tissue obtained by curettage.
• Vaginal bleeding is main symptom.
• Excessive uterine enlargement and pre eclampsia
occur rarely.
12. NATURAL HISTORY:
A. COMPLETE MOLE: after molar evacuation:
Local uterine invasion(15%)
Metastasis(4%)
High risk factors for postmolar tumor:
hCG levels> 100,000 mIU/ml
Excessive uterine enlargement
Theca leutin cysts 6cm in diameter
Older patients are also at increased risk.
B. PARTIAL H.MOLE: persistent tumor usually non-
metastatic develops in 2-4% cases. Chemotherapy is
required to achieve remission.
13. DIAGNOSIS:
USG-
• sensitive and reliable
method for complete
mole- characteristic
vesicular pattern even in
1st trimester.
• In partial molar
pregnancy-focal cystic
spaces in placental
tissues and increase in
transverse diameter of
gestational sac is seen.
14. Treatment:
• Pt should be evaluated carefully for presence of associated
medical complications.
• Most appropriate method of evacuation:
1. Hysterectomy: if patient desires surgical sterilization-
hysterectomy with mole in situ. Ovaries may be preserved
even in the presence of prominent theca leutin
cysts.hysterectomy doesn’t prevent metastasis, so patients
still require followup assessment of hCG levels.
2. Suction curettage: preferred method of evacuation regardless
of uterine size, for patients who desire fertility. Steps:
oxytocin infusion started before induction of anaesthesia.2.
cervical dilatation. 3. suction curettage. 4. blunt curettage.
• Trophoblastic cells express RhD factor, Rh neg patients
should receive Rh immunoglobulin at the time of evacuation.
15. Prophylactic chemotherapy:
• Prevents metastasis and local uterine invasion.
• It is particularly useful in management of high risk
complete molar pregnancy, esp. when hCG
assessments for follow-up are unavailable or
unreliable
16. Follow-up:
1. hCG: weekly -hCG levels until normal for 3
consecutive weeks, followed by monthly estimations
until normal for 6 consecutive months.
2. Contraception: patients are encouraged to use
effective contraception during entire hCG follow up
interval. IUCDs ar not used until patient achieves
normal hCG levels because of potential risk of
perforation. OCPs or barrier methods are used if
patient doesn’t desire surgical sterilization.
18. PERSISTENT GESTATIONAL
TROPHOBLASTIC TUMOR
A. NONMETASTATIC DISEASE: locally invasive GTT
develops in about 15% patients after evacuation of
complete mole and infrequently after other gestations.
Symptoms:
1. Irregular vaginal bleeding
2. Theca leutin cysts
3. Uterine subinvolution or assymetric enlargement
4. Persistently elevated serum hCG levels.
After molar evacuation, persistent GTT may exhibit the
histological features of either H. Mole or
choriocarcinoma.
After a non molar pregnancy, persistent GTT always has the
histological pattern of choriocarcinoma
19. B. PLACENTAL SITE TROPHOBLATIC
TUMOR:
• Placental-site trophoblastic tumor is an uncommon
but important variant of choriocarcinoma that consists
predominently of intermediate trophoblas. Relative to
their masses, these produce small amout of hCG and
hPL.
• They tend to remain confined to uterus, metastasizing
late in their course.
• These are relatively insensitive to chemotherapy.
20. C. METASTATIC DISEASE:
• Metastatic GTT occurs in 4% patients after evacuation
of complete mole, but it is seen more often when GTT
develops after nonmolar pregnancies.
• It has tendency towards early vascular invasion and
widespread dissemination.
• Most common sites are:
• PULMONARY(80%)- alveolar or snowstorm
appearence, discrete rounded opacities’canon-
appearence’, pleural effusion, embolic pattern.
respiratory symptoms and sonographic findings may
be dramatic, can be confused with primary pulmonary
disease.
21. Contn..
• VAGINAL(30%): suburethral, highly vascular
and may bleed vigorously when biopsied.
• HEPATIC(10%): painful enlargement,
intraperitoneal hemorrhage may occur.
• CNS(10%): may develop focal neurological
deficits.
22. Staging (FIGO)
• Staging 1-persistently elevated hCG&
tumorconfined to uterine carpus
• Stage2- metastesis to vagina,pelvis or both
• Stage3-Pulmonary metastesis with or without
uterine,vaginal,pelvic involment
• Stage4-advanced desease and Brain,kidneys
GIT, liver involment
23.
24. Prognostic Scoring system (WHO)
• Predicts potential for resistance to
chemotherapy.
• When score is >7- high risk case- requires
intensive chemotherapy for remission.
• Stage1 disease have low risk score while stage 4
disease have high risk score.
26. DIAGNOSTIC EVALUATION:
• Patients with persistent GTT should be carefully
evaluated before starting treatment:
1. Complete history and physical examination
2. Measurement of serum hCG value
3. Hepatic, renal and thyroid function tests
4. Determination of baseline TLC and platelet
counts.
27. Metastatic workup:
• Includes:
• Xray chest and CT scan
• USG and CT scan abdomen and pelvis
• CT or MRI scan of head
• hCG levels can be measured in CSF to exclude cerebral
involvement if CT brain is normal.
• Ratio of plasma to CSF hCG has to be lower than 60 in
presence of cerebral metastasis.
• Pelvic USG- useful in detecting extensive trophoblastic
uterine involvement and may also add in identifying
sites of resistent uterine tumors.
29. Management contn..
• Stage-1: If pt does not wish to preserve fertility ,
• Hysterectomy with Adjuvant single agent
chemotherapy------
• 1. To reduce dissamination of tumor cells
• 2.To mantain cytotoxic levelof drug inblood
circulation---to kill circulating cancer cells
• 3.To treat occult metastesis if any present.
Hysterectomy can also be done in all pts with stage1
placental site Trophpblastic tumor
Sngle drugChemotherapy alone is recomonded to stage1
pt who wants to presrve fertility.in resistant cases
,combination therapy should be administated.
30. Management of stageII and III
• Low risk patients with vaginal and pelvic metastasis
respond well(80%) to single agent therapy but high
risk cases are are treated with primary intensive
combination chemotherapy, bleeding from vaginal
metastasis may be controleed by packing or wide
local excision.
• Pt with pulmonary metastis—Primary intensive
combine chemotherapy.
• To control genital bleeding and sepsis----
Hysterectomymay be needed.
31. Follow up of stage1 2 3
• It should be done by:-
1. Weekly hCG measurement until they are
normal for 3 consecutive weeks
2. Monthly- for hCG measurement until they are
normal for 12 consecutive months
3. Effective contraception during the entire
interval of hrmonal follow up.
32. Management of stage 4
• Should be treated with intensive combination
chemotherapy and and surgery.
• Hepatic metastasis- hepatic artery infusion of
chemothapy may induce complte remission in
selected cases.
• Cerebral metastasis: whole brain
irradiation(3000cGy) in 10 fractions may be
instituated promptly. Crainotomy may be required
to provide acute decompression or to control
bleeding.
33. Follow up of stage 4
1. Weekly determination of hCG levels until they
are normal for 3 consecutive weeks
2. Monthly determination of hCG until they are
normal for 24 consecutive months.
3. These patients require gonadotropin follow up
because of high risk of recurrence.
34. CHEMOTHERAPY:
• Single-agent treatment: with either Actinomycin D or MTX have
achieved comparable and excellent remission rates in both non
metastatic and low risk metastatic GTT. Mtx 5mg with folinic acid x
3-5 days orally for 5-6 weeks is safe and effective.
▫ serum hCG level is measured weekly after each course of chemotherapy.
▫ After first treatment:
1. further chemotherapy is withheld as long as hCG level is falling
progressively.
2. Additional single agent chemotherapy is not administered at any
predetermined or fixed interval.
▫ Second course:
If hCG level plateaus for more than 3 consecutive weeks or begins to
raose again.
If hCG level doesn’t decline by 1 log within 18 days after completion of
first treatment.
▫ If response to first treatment is inadequate, dose of MTX is increased
from 1mg/kg per day to 1.5mg /kg per day for eack of the 4 treatment
days.
35. Combination Chemotherapy:
• Triple therapy: with MTX, Act-D and cyclophosphamide is in
• Duration of therapy: patients who require combination
chemotherapy must be treated intensively to attain remission.
It should be given as often as toxicity permits until patient
achieves 3 consecutive normal hCG levels. After normal hCG
levels are attained , atleast 2 additional courses of
chemotherapy
• adequate as an initial treatment in patients with metastasis and a high-risk prognostic score.
• are administered to reduce the risk of relapse.
37. Subsequent pregnancies:
A. Pregnancies after H. Mole:
increased risk of having a molar gestation in
subsequent conceptions. Risk: 1%
1. Pelvic USG during 1st trimester to confirm normal
gestational development
2. hCG measurement 6 weeks after completion of pregnancy
to exclude trophoblastic neoplasia.
B. Pregnancies after persistent GTT: patients who are
treated successfully with chemotherapy can expect
normal reproduction in future. The frequency of
congenital malformations is also not increased.