AFTER MID
TOTAL LEC: 22
Gynaecology
Dr. Wasan
Lec 22 - Gestational trophoblastic disease
DR. WASAN - LEC 2
Gestational trophoblastic disease
It is defined as proliferation abnormalities originating from
trophoblast of the placenta.
Classification:
Benign (molar pregnancy)
Malignant (Invasive mole, choriocarcinoma)
Hydatidiform Mole
Abnormal proliferation of placental trophoblastic cells, tends to
invade the myometrium (villi) more than normal placental tissue.
There are two types:
1) COMPLETE MOLE: without fetus
The problem starts at time of conception when an empty oocyte
(genetic material absent or inactivated) is fertilized by a normal haploid
sperm (23X) which will duplicate itself to complete (46XX) after meiosis
OR
Less commonly (4%), an empty oocyte is fertilized by a dispermic
process (two sperms) resulting in 46(XX or XY)
So the Karyotype is: 46XX, 46XY (PURELY PATERNAL)
Morphology: Numerous oedematous vesicles appear as a bunch of
small clear grapes, with no fetal tissue.
2) PARTIAL MOLE:
Here a Normal ovum (23X) is fertilized by 2 sperm or one sperm
that has failed to undergo meiosis & carries a paternal load of XY, both
resulting in triploidy 69XXY (70%) OR 69XYY,69XXX in (27%).
Fetal & placental tissue is present. Pregnancy is complicated by
hypertension and IUGR.
Histopathology: Marked oedematous & swollen villi with
disappearance of the villous blood vessels & proliferation of trophoblastic
lining villi with fetal tissue in partial mole only.
Epidemiology of molar pregnancy:
Geographical: is more common in Asian than western women
Diet & socioeconomic status: deficiency of protein diet, iron, and
folic acid lead to vascular agenesis. Vitamin A & carotene
deficiency cause increase incidence of molar pregnancy.
Maternal age: it is higher in women older than 40 years &
primigravida (14-16) years old
Blood group: greatest risk with maternal blood group B or AB
Previous molar pregnancy: recurrence 0.5-2%
Clinical presentation of Hydatidiform Mole:
The exaggerated signs & symptoms of molar pregnancy occur due to
the proliferative activity of the trophoblastic tissue.
1. Vaginal bleeding & anemia: occurs in 90% of cases may be
considered initially threatened abortion. anemia occurs due to
bleeding (iron deficiency), while folic acid deficiency develops as a
result of poor intake due to nausea & vomiting or increase folate
requirement due to the rapid proliferation of trophoblastic tissue.
2. Hyperemsis gravidarum: (25%) related to high level of HCG.
3. Pre- eclampsia : before 24 weeks.
4. Thyroid dysfunction (2%): molar pregnancy is associated with
increase thyroxine (alpha subunit of HCG is identical to TSH which
stimulate thyroid gland.
5. Embolism (trophoblastic tissue escapes from uterus through venous
outflow), large emboli may block the pulmonary vessels leading to
pulmonary embolism. while small emboli block vessels and invade
the lung parenchyma (lung metastasis).
6. DIC: emboli of trophoblast tissue release thromboplastin to
circulation & stimulate fibrin & platelet deposition (coagulation
failure).
Abdominal Examination:
1. Uterine enlargement (large for date uterus in 50%), doughy in
consistency, does not contract, no detectable FH, and No palpable
fetal parts (complete mole).
2. Prolonged high level of HCG leads to stimulation of ovaries causing
bilateral ovarian cyst (Theca lutean cyst) in 25 - 60% of patients
which regress after evacuation of mole (does not need surgical
interference).
Diagnosis:
o U/S: it shows snowstorm appearance from many echoes of
vesicular tissue.
o QUANTITATIVE measurement of serum HCG
Treatment:
Aim: elimination of all trophoblastic tissue
o Preparation prior to evacuation:
CBP, Coagulation screen, electrolyte check (correct anemia,
electrolyte imbalance)
Chest x ray: should be done at time of evacuation of uterus to
exclude lung metastasis (we can find cannon ball appearance,
solitary lesion, or pulmonary hypertension).
o Evacuation:
(SUCTION curettage), vacuum aspiration using –ve pressure
between -60 to -70 cmHg, and send for histopathology.
Uterine stimulants like PGE2 and Oxytocin
Hysterectomy: if age of patient is more than 40 years & has
completed her family.
Follow up:
o
Serial quantitative HCG: 48 hours after evacuation, then every 1
week. complete elimination occurs after 8-10 weeks. If 3 consecutive
readings are normal do monthly HCG for 6 months for partial mole &
for 1 year for complete mole.
o
Monthly pelvic examination: to rule out any vaginal or vulval
metastasis, check the size of uterus and detect the presence of ovarian
cyst and its size.
o
Secondary curettage: in case of incomplete uterus evacuation
o
Contraception: for at least 1 year, Barrier method is best. medroxy
progesterone injections and low dose estrogen OCP (estradiol =30
micro gram) can also be used.
IUCD is not advisable because it increases bleeding & may perforate
the uterus.
o
Chemotherapy: Indications:
1. Raised HCG level 6 months after evacuation.
2. HCG plateau in 3 consecutive serum sample.
3. HCG level is more than 20.000 IU after 4 weeks of evacuation.
4. Rising HCG in 2 consecutive serum samples.
5. Heavy vaginal, GIT or intraperitoneal bleeding.
6. Pulmonary, vulval or vaginal metastasis unless HCG level is
falling.
7. Brain, liver, GIT or lung metastasis more than 2 cm on CXR.
8. Histological evidence of choriocarcinoma.
Complications of molar pregnancy:
Immediate: massive bleeding, sepsis, severe pre-eclampsia.
Remote: metastasis & malignancy (20% of complete mole and 4%
of partial mole progress to persistent gestational trophoblastic
disease)
Persistent gestational trophoblastic tumor
NON Metastatic ( invasive mole) 15%
Metastatic (distant) 5% after molar pregnancy.
Incidence & Epidemiology:
Geographical: is more common in Asia.
Age: is more common in older women.
Parity: is more common in high parity.
Socioeconomic: is more common in low class.
Antecedent pregnancy: molar pregnancy 50% - 75% of cases, Normal
term pregnancy 25%, abortion 25%.
All are within an interval of 2-5 years.
Maternal blood group: is high in women with blood group A, and low in
woman blood group O.
Clinical features:
1.
Vaginal bleeding, vaginal nodule or abdominal swelling.
2.
Amenorrhea due to producing HCG FROM DISTANT tumor metastasis.
3.
Pulmonary metastasis (dyspnea, haemoptysis).
Diagnosis:
o Quantitative HCG: HCG is normal 48 hours after term pregnancy, 2
weeks after abortion, 8-10 wk after molar pregnancy.
So persistent increase in HCG level means PGTT.
o CXR to exclude metastasis to lung.
o Imaging technique (MRI, CT scan, U/S TO abdomen & pelvis).
o MRI to brain to exclude CNS metastasis.
Staging of persistent GTT:
Number of factors influence on the prognosis of PGTT:
1. Level of HCG: if it is high (before treatment), so if it is more than
100.000 IU means worse prognosis.
2. Metastasis:
site: the prognosis is worse if it involves the Brain (because
chemotherapy cannot cross blood brain barrier) and Liver because
the chemotherapy is rapidly detoxified in liver.
Number of metastasic lesions: more number means poor
prognosis.
Size of largest mass: large mass means poor prognosis.
3. Antecedent pregnancy: worst prognosis after normal term pregnancy
and better prognosis after abortion & best after molar pregnancy.
4. Pregnancy/ treatment interval: the longer the interval between
pregnancy & starting chemotherapy the worse the prognosis. Interval
more than 4 months indicates (poor prognosis).
5. Previous unsuccessful chemotherapy: associated with poor prognosis
due to
Drug resistance (impermeability of chemotherapy agents to tumor
mass because of scarring & fibrosis).
Accumulating drug toxicity.
6. Age more than 40 years ( poor prognosis).
7. High Parity is of poor prognosis
Each of above prognostic factor is given score ranging from 0-4
3
2
1
0
score
More than 40
Less than 40
Age
term
abortion
mole
Antecedent
pregnancy
Brain, liver
GIT
Spleen, kidney
lung
Site of
metastasis
More than 8
5-8
1- 4
Number of
metastasis
الجدول غير مطلوب
According to this score, the patient is considered as
Low risk patient (score less than or equal 6) OR
High risk patient ( score more than or equal 7).
Treatment:
1) Chemotherapy
Low risk patients (survival rate is 100%)
Methotrexate (is the drug of choice) because of its Simplicity & low
toxicity (available antidote).
Before giving chemotherapy: we should send patient for full
Investigations CBC (WBC, PLT, Hb), LFT, RFT ,CXR.
It is given parentally IM/ IV
Excreted in urine, contraindicated in renal failure.
Methotrexate is given in alternative days with folinic acid
During period of therapy, we should monitor HCG (2times/wk), WBC/
daily ( if less than 1000 stop MTX), PLT/ daily ( if less than 50.000 stop
MTX)
Toxicity of Methotrexate
Mylosuppression ( thrombo - cytopnea, granulocytopnea)
Mucus membrane inflammation( stomatitis, conjuctivitis, vaginitis)
Skin rash
Nephrotoxicity
Heptotoxicity
Course of Methotrexate
After 8 days course of chemotherapy, 1 week of rest is given & then
start 2
nd
course of treatment
We need 2-4 courses to reach undetected level of HCG
2-3 extra courses of treatment is needed (because Approximately
100.000 of trophoblastic cells may escape & are undetected by HCG).
Actinomycin (I.M for 5 days)
High risk patient/ EMA/CO chemotherapy
Day1 (etoposide, methotrexate, actinomycin)
Day2 (etoposide , folinic acid, actinomycin)
2
nd
wk (Day8) vincristine / cyclophosphamide
2) Surgical treatment: indicated in:
o Uterine perforation by invasive mole
o Uncontrolled uterine bleeding
o Drug resistance focus (HCG is high instead of chemotherapy or focal
lesion increase or plateau in size)
o Age is more than 40 years & has completed her family
3)
Follow up
Aim: to detect remission or relapse
Monthly HCG in first year. Then yearly in the next 5 years.