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GESTATIONAL TROPHOPLASTIC

DISEASES
G.T.D:
1-Hydatidiform Mole (V.M): Complete and partial
2-Invasive Mole
3-Placental site trophoplastic tumor
4-Gestational choriocarcinoma
PATHOLOGY

•Complete hydatidiform Mole:


-Trophoblastic hyperplasia (Both cytotrophoblast, syncytial)
-Hydropic changes of villi
-No fetus

•Partial hydatidiform Mole:


-Focal trophoblastic hyperplasia (usually only syncytial)
-hydropic changes of villi
-There is embryo which usually die early
•Invasive Mole (chorioadenoma destruens):

-Invading the myometrium ( complete or partial)


-Does not progress to choriocarcinoma
-It may metastasize but does not progress like true cancer.
-It may regress spontaneously
-distinguished from choriocarcinoma by the presence of
chorionic villi.
Gestational Choriocarcinoma:

-Carcinoma arising from trophoblastic epithelium both cyto and


syncytio elements.
-Can follow conception give rise to live birth, stillbirth,
abortion, ectopic or hydatidiform mole.
-lack of villous structures distinguish choriocarcinoma from
invasive mole
->50% of choriocarcinoma are preceded by hydatidiform
mole.
-25% after abortion , 22.5% after delivery ( even 5 yrs, most serious).
-Principal risk is uterine perforation or severe uterine bleeding
•Placental site trophoblastic tumor:
-Composed mainly of cytotrophoblastic cells
-relatively low hCG
-less common than invasive mole and
choriocarcinoma
-Complete surgical excision is preferred as the tumor
is not chemo sensitive as choriocarcinoma
-Produce abundant amount of human placental
lactogen (HPL)
-Slow growth and may present years after term, non-
molar abortion or complete H.M
Usually no distant metastases
GESTATIONAL TROPHOBLASTIC TUMORS:
1-Invasive Mole
2-Choriocarcinoma
3-Placental site tumor
EPIDEMIOLOGY:

-Overall incidence: 1-10 per 1000 ( in U.K: 1 in 1000)


-less frequent in blacks
-Racial differences: higher incidence of hydatidiform mole in Asia
-Age: hydatidiform mole is more common : 40-45 (3xfolds),45-49
(26xfols), >50(400xfolds), below 15 (6Xfolds)
-previous hydatidiform mole increase risk 20-fold
-Partial mole is less frequent than complete H.M
-3% of H.M will finally develop choriocarcinoma
-Blood group: AB , B
GENETICS

Complete hydatidiform mole :


Maternal nucleus lost with sperm duplication of haploid sperm
or two different sperms( fertilization of empty egg)

Partial hydatidiform mole :


one maternal and two paternal chromosome sets
COMPETE HYDATIDIFORM MOLE

> 90%: 46xx: single sperm 4-8%: 46xx : Dispermy

Loss of 23 23
23x 23
Maternal x 23x x
Genetic x
material

Loss of
Two paternal 23 23
23 Maternal
genetic x x
x Genetic
contribution
material

23 23
Duplication x x
of haploid
sperm
PARTIAL HYDATIDIFORM MOLE

23x
23x
23x

23x 23x Maternal genetic contribution is retained


Two paternal genetic contribution
23x

69xxx: Triploid Conceptus

Partial mole is l less frequently followed by malignant


sequele than complete mole
Presentation of VM
-Amenorrhea
-Bleeding
-Brownish discharge
-Complications (esp. HG)
-Pain (comp. ovarian cyst, expulsion)
PRESENTATION:

Choriocarcinoma:
-Choriocarcinoma is 1500 times more common after a molar
pregnancy than after a term delivery
-It is usually suspected after molar pregnancy if hCG failed
normalized after 6 months of evacuation.
-Choriocarcinoma and placental site tumor are the only G.T.T
originating from a term delivery or a non-molar pregnancy.
-Majority of choriocarcinoma present within a year of an
apparently normal pregnancy or non-molar abortion. However,
the presentation may be delayed for several years.
-Vaginal bleeding, bloodstained discharge, abdominal pain..
-Extra uterine and ovarian masses are frequent.
-In about 30%, the presenting features are non-gynecological:
pulmonary, cerebral, and hepatic (dyspnea,haemoptysis…..
Complications of GTD
-Hyperemesis gravidarum
-Thyrotoxicosis
-DIC
-AF EMBOLISM
-Local He
-Invasive Mole: perforation
-Choriocarcinoma:2-5%
-complication of cyst (TRH)
INVESTIGATION:

-hCG estimation: secreted by syncytiotrophoblasts


-Ultrasound: snowstorm appearance, ±fetus, theca-lutein cysts
-Chest x-ray
-CBC (anaemia) ,coag. profile
-T3,T4
hCG
-Polypeptide excreted in the urine with a half-life of 24-
36 hours
-Measurement is using RIA with sensitivity 1 i.u/l in
serum and 20 i.u/l in the urine
-hCG assay does not discriminate between G.T.D and
normal pregnancy though very high levels may lead to
suspicion.
-Significance of hCG measurement:
a) indication of tumor volume b) determine prognosis
c) monitoring the treatment (detection of drug resistance, treatment
period till hCG undetectable)
Ultrasound:

-Snow storm appearance , not entirely specific.


-Theca lutein cysts
-Hepatic, renal metastases
Others:

-C.T, MRI: Pulmonary, intraperitoneal and


cerebral metastases
MANAGEMENT:

-Suction evacuation of hydatidiform mole


-Hysterectomy: old age , GMP
-Factors increasing the risk of persistent trophoblastic disease:
a) uterine size > date
b) Bilateral cystic ovarian enlargement
c) Pre-evacuation serum hCG> 100,000 i.u/l
d) Methods of evacuation (medical induction,
hysterectomy….)
e) Age: more than 40 years
Follow-up

-: measurement of hCG
* every 2 weeks till limit of detection
then *monthly during first year
then *3-monthly during second year
and after all further pregnancy (bec. Risk of recurrence and risk
of choriocarcinoma arising even following normal pregnancy)
-Further pregnancy should not be attempted till hCG is normal for at
least 6 months
Indications for chemotherapy of G.T.T:

hCG monitoring:
-Rising hCG after evacuation
-hCG is not falling (plateau) 4 months after evacuation
-hCG > 20,000 mIU/L
Metastases:
-pulmonary, vulval or vaginal metastasis
-Any other metastases
Presentation:
-Heavy vaginal bleeding or intraperitoneal bleeding
Histopathological diagnosis of choriocarcinoma
Prognostic Factors:
Prognostic factor 0 1 2 4

Age <39 >39


If Score:
Antecedent H.M abortion Term
•<4:low-risk pregnancy

•5-7:Midlle Interval (months) 4 4-6 7-12

•>8:High risk hCG level 10³ 10³-10* 10*-10** >10**

ABO group(♀,♂) O×A B


A×O AB
Largest tumor 3-5 >5cm

Site Spleen,kidney GI,liver >8


No. of metastases 1-4 4-8

Prior Single drug 2 or more


chemotherapy
Chemotherapy Strategy:
Group Regime Side -effect Others

Low-risk Methotrexate Alopecia, 75% will be cured


Ca folinate oral ulceration, 20% need to change drug
photosensitivity, 5% intolerant to Rx
myelosuppression
Middle-risk Etoposide As above 96% complete response
Actinomycin D Drug resistance 4% relapse

High-risk EMA/CO 93% complete remission


Etoposide (no prior chemo…)
Methotrexate 76% (those had prior
Actinomycin D chemo)
Cyclophosphamon
covine
SURVIVAL:

-100% in low-risk group


-98% in medium-risk group
-93% in high-risk group with no prior chemtherapy
74% in high-risk group with prior chemotherapy
FOLLOW-UP :

-For H.M for 2 years


-For persistant trophoblastic diseases for life
-Patients usually advised to avoid pregnancy for a year after
completion of chemotherapy.
THANK YOU