Gestational trophoblastic disease Novak 2003 Hydatidiform Mole
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Transcript Gestational trophoblastic disease Novak 2003 Hydatidiform Mole
GESTATIONAL
TROPHOBLASTIC
DISEASE
Novak 2003
Hydatidiform Mole
Persistent Gestational
Trophoblastic Tumor
Chemotherapy
HYDATIDIFORM MOLE
Epidemiology
Complete versus partial mole
Clinical picture
Natural history
Diagnosis
Treatment
Follow up
INTRODUCTION
GTD is among the rare tumors that can be cured
even if metastasized
Types:
Complete mole
Partial mole
Placental site mole
Choriocarcinoma
Persistent GTT:
Most commonly follow molar pregnancy
May also follow: abortion, ectopic or term pregnancy
EPIDEMIOLOGY
% varies in different sites:
Japan =
2 : 1000 pregnancies
USA = 0.6 – 1.1 : 1000 pregnancies
In pathological studies:
Complete mole 1 : 945
Partial mole
1 : 695
Risk factors in complete mole:
1 – nutritional:
↓ carotene
↓ vit A
2 – Age:
> 35 years = X 2
> 40 years = X 7.5
Risk factors in partial mole:
1 - OCCP
2 - H/O irregular menstruation
COMPLETE VERSUS PARTIAL MOLE
Complete mole
Pathology:
No fetal or embryonic tissue
Villi show:
Diffuse hydropic swelling
Diffuse trophoblastic hyperplasia
Chromosome:
90% 46XX
10% 46XY
Chromosomes are entirely paternal
Mitochondria DNA is maternal in origin
1 - Absent or inactivated ovum nucleus
+ 1 haploid sperm
endoredublication
homozygous mole
2– Absent or inactivated ovum nucleus
+ 2 haploid sperms
heterozygous mole
Partial mole
Villi vary in size and show:
Focal hydropic swelling
Focal trophoblastic hyperplasia
Focal cavitation
Stromal trophoblastic inclusion
Scalloping
Fetal or embryonic tissues
Chromosomes:
Absent or inactivated ovum nucleus
+ 3 haploid sperms triploid in 90%
= 69XXX, 69XXY, 69XYY
The fetus shows triploidy stigmata:
GR
Multiple congenital anomalies as:
Syndactyly - Hydrocephalus
Complete
Fetus
absent
Karyotype
46XX(90%)
46XY
Hydropic swelling diffuse
Trophoblastic
diffuse
hyperpleasia
Scalloping
no
Stromal inclusions no
Partial
present
69XXX
(90%)
focal
focal
present
present
CLINICAL PICTURE
Complete
past
now
Vaginal bleeding
97%
84%
Anemia
50%
5%
Excessive uterine size 50%
28%
Preeclampsia
50%
1.5%
Hyperemesis
27%
8%
Hyperthyroidism
7%
0%
Trophoblastic embolism 2%
0%
Theca lutein cysts
50%
HCG > 100,000mIU/mL
Partial
74%
4%
6%
Excessive uterine size:
= ↑ trophoblastic tissue
↑ hCG
↑ preeclampsia
↑ hyperthyroidism
↑ hyperemesis gravidarum
↑ trophoblastic embolization
↑ theca lutein cyst size
Preeclampsia:
Early preeclampsia = hydatidiform mole
Hyperthyroidism:
Due to ↑ free T3, T4
C/P:
tachycardia
warm skin
tremor
Thyroid storms:
Give β–blockers before anesthesia
to avoid thyroid storms
C/P:
↑ pulse, ↑ temp, ↑ COP
+ delirium + convulsions
may HF
Trophoblastic embolization:
C/P:
dyspnea
cough
tachypnea
↑P
chest pain
asymptomatic
Chest examination diffuse rales
Chest X ray bilateral infiltrates
Causes of respiratory distress:
Trophoblastion embolization
Complications of:
• preeclampsia
• thyroid storm
• excessive fluid intake
Theca lutein ovarian cysts
Due to ovarian overstimulation by ↑ hCG
May not be felt with oversized uterus
May pressure symptoms treated
by decompression by laparoscopic or
U/S guided aspiration
If ruptured or torsion occur acute pain
laparoscope
NATURAL HISTORY
Complete mole
Invasive
= 15%
Metastatic =
4%
Risk factors:
hCG > 100,000 mIU/mL
Excessive uterine size
Theca lutein cysts = 6 cm
Low risk = 60%
3.4%
0.6% metastatic
High risk = 40%
31%
9%
Age:
> 40 years =
> 50 years =
persistent mole
persistent mole
metastatic
37%
56%
DIAGNOSIS
Complete mole
U/S vesicular pattern
Partial mole
U/S focal cystic spaces in placenta
+ ↑ transverse diameter of GS
Both together 90% +ve predictive
value
TREATMENT
I – Hystrectomy
+ aspiration of CL cyst
+ follow up as usual
2 - Suction evacuation
Preferred ttt for hydatidiform mole
Give oxytocine before anesthesia
Use 12 canula
If > 14 weeks support the fundus
+ do fundal massage
Dilatation ↑ bleeding
Suction evacuation ↓ bleeding
If RH –ve give Anti RH Ig
3 - Prophylactic chemotherapy
↓ invasive mole to 4% after 1st course
↓ “””””””””””””””””” 0% after 2nd course
Controversial : Why to expose all
patients to chemotherapy while only
20% will need it?
Useful if follow up is:
Unreliable
Unavailable
Study:
Prophylactic chemotherapy in
high risk patients ↓ persistent
mole from 47% to 14%
FOLLOW UP
1 - HCG
Average time needed to return to
normal values = 9 weeks
Measure hCG/week
3 consecutive normal results
/month 6 consecutive normal R
2 - Contraception:
OCCP or barrier methods
IUD is C/I perforation
PERSISTENT GESTATIONAL
TROPHOBLASTIC
TUMOR
Nonmetastatic disease
Placental-site TT
Metastatic D
Staging
Prognostic scoring systems
Diagnostic evaluation
Management
NONMETASTATIC DISEASE
Invasive mole = 15% after evacuation
C/P:
Irregular vaginal bleeding
Uterine subinvolution
Theca lutein cysts
↑hCG
Perforation of myometrium internal Hg
Perforation of uterine vessels vaginal Hg
Infection acute pain
purulent discharge
Histology:
After molar pregnancy
hydatidiform mole or
choriocarcinoma
After nonmolar pregnancy
choriocarcinoma
= sheets of anaplastic
cytotrophoblast and
syncytiotrophoblast
+ no villi
PLACENTAL-SITE TT
Uncommon
Variant of choriocarcinoma
Consists of intermediate trophoblast
Produce small amounts of hCG & hPL
Tends to be confined to the uterus
Metastasize late
Resistant to chemotherapy
METASTATIC DISEASE
= 4% after molar pregnancy
More often after nonmolar pregnancy
Usually associated with choriocarcinoma
Highly vascular spontaneous bleeding
Early vascular spreading
Sites:
Pulmonary
80%
Hepatic 10%
Vaginal
30% Brain
10%
Pelvic
20%
1 – Pulmonary metastases:
Symptoms:
dyspnea
cough
hemoptysis
chest pain
asymptomatic
May be acute of chronic
Chest X ray:
Snowstorm pattern
Discrete rounded densities
Pleural effusion
Pulmonary artery embolism
May be misdiagnosed as 1ry pulmonary
disease and only recognized as GTD
after thoracotomy
Pulmonary embolism may
pulmonary HTN
Early RF + intubation = bad prognosis
2 – Vaginal metastasis
highly vascular
biopsy may excessive bleeding
Symptoms:
Vaginal bleeding
Purulent discharge
Site: fornices/suburethral
3 – Hepatic metastasis
Usually in advanced cases
Symptoms:
Epigastric or upper RT ¼ pain due to
stretching subcapsular hematoma
Rupture internal Hg
4 – Brain metastasis
Usually in advanced cases
Spontaneous bleeding acute focal
neurological defects
STAGING
Stage I confined to uterus
Stage II confined to genital structures
Stage III pulmonary metastasis
Stage IV other metastasis
At any stage:
A = no risk factors
B = 1 risk factor
C = 2 risk factors
PROGNOSTIC SCORING SYSTEMS
0
1
2
4
Age
≤39
>39
Pregnancy mole
abortion term
Duration
<4m
4-6
7-12
>12
hCG
<1000 <10000 <100000 >
Largest size <3cm 3-5
>5
Site of met 0 kidney/spleen GIT/liver brain
Number
<3
1-3
4-8
>8
ABO group 0
A/O
B/AB
Chemotherapy
1
≥2
DIAGNOSTIC EVALUATION
H/O
Examination
hCG
Liver function tests
Kidney function tests
Thyroid function tests
WBCs
Platelet count
IMAGING
Chest
X-ray -- CT
Abd & pelvis U/S -- CT
Brain
MRI -- CT
If no pulmonary or vaginal metastasis
metastasis are rare
Chest CT for micrometastasis
Liver CT for abnormal LFTs
Brain CT for asymptomatic lesions
If brain CT is normalmeasure CSF hCG
If serum hCG/CSF hCG = < 60% then
there is brain metastasis
Pelvic U/S for:
Extent of uterine lesion
Localization of resistant lesions
Identifying patients who will benefit
from hystrectomy
MANAGEMENT
Stage I
Stage II & III
Stage IV
STAGE I
If the patient does not wish to
preserve fertility
Hystrectomy + Chemotherapy to:
↓ dissemination of GTD
Treat dissemination of GTD
Treat occult metastasis
↓ bleeding
↓ sepsis
If the patient wish to preserve fertility:
Low risk Single agent
High risk Combined chemotherapy
Resistant Local uterine resection
after localization of
resistant sites by U/S,
MRI, or arteriography
Placental site GTD:
- Only curative ttt for nonmetastatic
cases is hystrectomy
- Resistant to chemotherapy few
metastatic cases reported complete
remission after chemotherapy
STAGE II & III
Pulmonary metastasis
Low risk single agent 82% CR
High risk combined chemotherapy
Resistant thoracotomy after
localization of and
exclusion of other
resistant sites
Vaginal metastasis
Low risk single agent 84% CR
High risk combined chemotherapy
Resistant wide local excision
Vaginal bleeding:
Packing of the vagina
Wide local excision
Embolization of hypogastric arteries
Hystrectomy
- In metastatic disease
- to control Hg
- to control sepsis
- In extensive uterine disease
- to ↓ GTT burden
- to ↓ chemotherapy
courses
Follow up of stage I, II, III:
hCG/week
3 consecutive normal results
hCG/month
12 consecutive normal results
+ effective contraception
STAGE IV
Should be referred to specialized centers
May be unresponsive or rapidly progress
All should receive intensive combined
chemotherapy ± irradiation / surgery
Hepatic metastasis:
Resistant cases intrahepatic infusion
of chemotherapy
Hemorrhage
local excision or
arterial embolization
Brain metastasis:
All cases receive:
Whole brain irradiation by 3000
cGy in 10 fractions
Combined chemotherapy +
intrathecal MTX 86% CR
Resistant local excision
Hemorrhage craniotomy50%CR
No residual neurologic deficits
CHEMOTHERAPY
SINGLE AGENT CHEMOTHERAPY
Used in nonmetastatic and low risk mm
MTX&Act-D are used/other week X5days
1964: MTX-FA well tolerated
↓ toxicity
MTX-FA the preferred ttt for GTD
MTX-FA 88% CR
81% by single course
90% CR in stage I
68% CR in stage II
Complications:
Thrombocytopenia
1.6%
Agranulocytopenia
6%
Hepatotoxicity
14%
Resistant cases:
Choriocarcinoma
Metastasis
Initial hCG > 50,000 mIU/mL
Technique:
Measure hCG after each course
Draw a curve
Stop MTX if the curve is progressively ↓
Do not give MTX at any predetermined
or fixed interval
Give another course if:
hCG is ↑ or plateaus for > 3 weeks
hCG ↓ < 1 log at day 18 post ttt
If the response to the 1st course is
adequate give the same dose
If the response to the 1st course is
inadequate ↑ the dose to 1.5 mg/Kg
body weight/day X 4 days
Adequate response = ↓ hCG by 1 log
If the response to the 2nd & 3rd courses
is inadequate give ACT-D
If the response to ACT-D is inadequate
give combined chemotherapy
COMBINED CHEMOTHERAPY
Triple therapy ( MTX + ACT-D +
cyclophosphamide ) is inadequate in
ttt of high risk cases 50% CR only
Etoposide 95% CR in nonmetastatic
and low risk metastatic cases
1984: triple therapy + Etoposide
+ Vincristine ( EMA-CO )
83% CR in high risk patients
EMA-CO is well tolerated and is the
preferred 1ry ttt for patients with
metastasis and high risk score
76% CR when used as 1ry ttt
86% CR in brain metastasis
If resistant to EMA-CO
give EMA-EP (cisplatin) on day 8
76% CR in resistant patients
Duration of Therapy:
Give combined chemotherapy
3 consecutive normal results
Add at least 2 additional courses
to ↓ risk of relapse
SUBSEQUENT PREGNANCIES
Complete/Partial mole Persistent GTT
Term
70%
70%
PTL
7%
6%
Ectopic
1%
1%
SB
½%
11/2%
Recurrence
11/2%
1%
1st T abortion
16%
15%
2nd T abortion
1.6%
1.5%
Congenital anom
4%
2.5%
CS
16%
19%
Recurrence rate:
1 mole = 1%
2 mole = 20%
In the next pregnancy:
Do U/S < 14 weeks
Measure hCG 6 weeks after
termination/labour
Send placenta or product of
conception to pathology