15-gestational Trophoplastic Diseases

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, nonmolar 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

Loss of Maternal Genetic material

23x

23 x

Duplication of haploid sperm

23 23 x x

23 x

4-8%: 46xx : Dispermy

23 x

Two paternal genetic contribution

23 x

23x

23 x

23 x

Loss of Maternal Genetic material

PARTIAL HYDATIDIFORM MOLE

23x

23x 23x

23x

23x 23x

69xxx: Triploid Conceptus

Partial mole is l less frequently followed by malignant sequele than complete mole

Maternal genetic contribution is retained Two paternal genetic contribution

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 2436 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

Age

<39

>39

•<4:low-risk

Antecedent pregnancy

H.M

abortion

Term

•5-7:Midlle

Interval (months)

4

4-6

7-12

•>8:High risk

hCG level

10³

10³-10*

10*-10**

ABO group(♀,♂)

O×A A×O

B AB

Largest tumor

3-5

>5cm

Spleen,kidney 1-4

GI,liver 4-8

>8

Single drug

2 or more

If Score:

Site No. of metastases Prior chemotherapy

2

4

>10**

Chemotherapy Strategy: Group

Regime

Side -effect

Others

Low-risk

Methotrexate Ca folinate

Alopecia, oral ulceration, photosensitivity, myelosuppression

75% will be cured 20% need to change drug 5% intolerant to Rx

Middle-risk

Etoposide Actinomycin D

As above Drug resistance

96% complete response 4% relapse

High-risk

EMA/CO Etoposide Methotrexate Actinomycin D Cyclophosphamon covine

93% complete remission (no prior chemo…) 76% (those had prior chemo)

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.

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