Tanga regional refferal hospital Thursday clinical presentationDEPARTMENT:obs/ gynTOPIC: Gestational trophoblastic diseasesPRESENTER: Dr.Hamisi Mkindi,MD FACILITATOR: Dr.Joseph Mberesero,MD,Mmed Obs/Gyn

CONTENTS

1. Introduction2. Classification3. Epidemiology4. Risk factors5. Pathogenesis6. Clinical features7. Work up8. Treatment9. Follow up

Introduction Dfn Gestational trophoblastic disease is a spectrum of

interrelated disease processes originating from the placenta.

GTD is a spectrum of tumours with a wide range of biologic behaviour and potential for metastases

They are characterised by an abnormally high amount of HcG levels in the blood

Modified WHO Classification

1. Molar lesionsa. Hydatidiform mole

• complete• partial

b. Invasive mole (Chorioadenoma destruens)

2. Nonmolar lesionsa. Choriocarcinomab. Placental site trophoblastic tumor

EPIDEMIOLOGYHydatidiform moles The most common GTDs Incidence:

Varies worldwide from 1:125 deliveries in Mexico and Taiwan to 1:1500 in USA

Common in under 20 and above 40 women 10% to 17% of cases, can progress to become an

invasive mole or persistent GTDs.

EPIDEMIOLOGY

Choriocarcinoma A malignant form of GTDs Incidence:

More common in many Asian and African countries, where it affects up to 1 pregnancy in 2,500.

1% to 3% of hydatidiform moles progress to become choriocarcinoma.

50% develop from moles. 25% follows abortions, tubal pregnancy 25% follows normal term pregnancy.

RISK FACTORS• Age.

– The incidence of molar pregnancy highest in women aged 15 years or younger, and those aged 45 years or older. In the latter group, the relative frequency of the lesion is at least 10 times greater than that at ages 20 to 40 years

• Previous Mole– Women with molar pregnancies are at increased risk of

developing either a complete or a partial mole in a future pregnancy

Diet In women whose diets are deficient in protein,

folic acid, animal fat and carotene Genetic factors

There is an increased association with the AB blood group which possesses no ABO antibodies

Other risk factors are alcoholism, smoking and the use of contraceptives

PATHOGENESIS Complete mole Partial mole Invasive mole Choriocarcinoma

+

+

Complete Mole: Pathogenesis

Two sperm(XX or XY)

Duplication of Sperm DNA

X sperm

46 XXor46 XY

Empty egg

or

+

+

Partial Mole: Pathogenesis

One diploid sperm

Two haploid sperm

or

23Y

23X 23X

23X46XY

69XXY or69XXX

Differences btn complete vs partial mole: pathologic features and behavior

Feature Complete mole Partial mole1. Karyotype2. Embryo/fetus

3. Hydropic swelling

46,XX(46,XY)Absent

Marked, cisterns present,all villi involved

TriploidPresent

Less pronounced, focalCisterns less prominen

4. Trophoblastic proliferation

Variable, may be marked

Focal, minimal

5. Behavior 10-30% develop GTN 0.5-4%

Invasive mole

Hydatidiform mole in which hydropic villi invade the myometrium or blood vessels or more rarely, are deported to extrauterine sites.

Lack the tendency to widespread metastasize Can regress spontaneously unlike

choriocarcinoma Can be distiguished from choriocarcinoma by the

presence of villi

Choriocarcinoma

Highly malignant epithelial tumor. Arises from the trophoblast of any type of

gestational event, most often hydatidiform mole.

Consists of dimorphic (trophoblasts and syncytiotrophoblasts) without chorionic villi

Rapid proliferation with vessel invasion– hemorrhagic mass

CLINICAL FEATURES; Uterine bleeding in first trimester Absence of fetal heart beats Rapid enlargement of the uterus than

expected GA hCG titers greater than expected for

GA Expulsion of grapes like vesicles Hyperemesis

CLINICAL FEATURES Cont

Theca luteal cysts Onset of pre-eclampsia in first trimester

Pathognomonic for hydatidiform mole Other features

Hyperthyroidism Tachycardia

WORK UP History and physical examination USS

Snow stom appearance Visible vesicles Can also detect luteal cyst

B hcg May be of value in diagnosing molar pregnancies

WORK UP CONT…

Chest film R/O lung metastasis - cannon ball opacities

Haematologic survey-WBC, platelet counts Brain CT/MRI - R/O Brain metastasis Abdominal and pelvic ultrasound, R/O

Liver metastasis Luteal cysts

LFTs RFTs Histology-Exam of POC-defn dx is made

TREATMENTMolar pregnancy

i. Suction curettage– Set an IV line for oxytocic infusion only

commenced once evacuation has been completed.

ii. Blood transfusionNote: The procedure may be accompanied with severe haemorrhage

iii. Monitor output

Treatment cont

Choriodenoma destruens     a.  Chemotherapyb.  Elective Hysterectomy

  Prognosis

a.  Good with treatmentb.  75 – 85% > 5 years

Metastatic Gestational Trophoblastic Disease Rx in metastatic disease uses either single-agent

chemotherapy/multiple-agent chemotherapy Several classification systems have been

developed. - National Cancer Institute - World Health Organization (WHO) - Revised FIGO (International Federation on

Gynecology and Obstetrics)

NCI class *Determines if pt will have a good or poor prognosis in response to single-agent chemo.

I. Low risk choriocarcinoma: Characteristics

1. Presents before 4 months postabortion

2. Follows abortion or molar abortion

3. hCG is < 100,000IU/24 hours

4. Mets to the lungs or no mets

NCI class cont…

II: High risk choriocarcinoma: Characteristics

1. Follows term pregnancy

2. Size > 5cm diameter

3. Mets to the brain

4. Blood group AB highest risk

5. Presents > 4 months post delivery

WHO class Scoring system based on an individual's risk

factors. A total score of 0–6 is considered low-risk

and a total score 7 is categorized as high-risk

Revised FIGO (International Federation on Gynecology and Obstetrics) A patient is assigned a stage based on the

anatomic location of disease and given a risk factor score based on the WHO prognostic scoring system.

The goal of the revised FIGO staging is to improve the assessment and clinical management of patients.

Rx

1. Low risk choriocarcinoma(good prognosis)

Methotraxate alone 5-day treatment cycle is given Once negative titers have been achieved, an

additional course is administered

Rx continuation2. High risk choriocarcinoma(poor

prognosis) These patients require prolonged

hospitalization Combined chemotherapy

a. MAC –(Methotraxate, Actinomycin D, chrolambucil)b. EMA/CO (Etoposide, Methotraxate,

Actinomycin, Oncovin (Vincristine), The cycle is repeated every 2 weeks

Rx: Placental-Site Trophoblastic Tumor Generally is resistant to chemotherapy, hysterectomy

is the recommended route of treatment. Partial uterine resection involving the tumor is

possible if the patient desires to retain fertility. EP-EMA is the preferred regimen over EMACO. Good prog if loc to uterus n antecedent pregnancy <2

years

Follow up Clinical Laboratory

FOLLOW UP: Moles Duration = 1 – 2 years Schedule visits plus measure serum hCG in the

following order Weekly during treatment until 3 normal levels (3 weeks) Monthly for 3 months, then 3 monthly for 9 months. Then after every 6 months for one year

Patient should not conceive Contraception

Preferably barrier method otherwise COC Why COC, - because rarely cause abnormal vaginal

bleeding that may be difficult to distinguish from the complication of GTDs

FOLLOW UP: CHORIOCARCINOMA

Duration – 2 years During follow up period1. Measure serum hCG

a. Once weekly during treatment until 3 normal levels (3 weeks)

b. Then every month for 3 monthsc. Then after every 3 months for 9 months.d. Followed by after every 6 monthly for one year

FOLLOW UP cont

2. During follow up clinic visit the following should be done

Take history R/O Abnormal vaginal bleeding, cough, chest pain

Do pelvic assessment: R/O ovarian cystsInvestigate;

CXR R/O lung mets – cannon balls Pelvic USS

3. Patient should not conceive: contraception

Cont… SUMMARY GTD’s

Summary Gestational trophoblastic disease is a spectrum. Molar and Non molar. Invasive and non

invasive. The two main risk factors: extremes of maternal

age and previous GTD Elevated serum hCG concentration. Pv

bleeding,enlarged uterus and pelvic discomfort

Summary Initial evaluation consists of a quantitative

test for hCG and pelvic ultrasound examination.

Dx of complete or partial mole must be confirmed by histologic examination of tissue.

Rx:SE,Hysterectomy,Chemotherapy

References http://www.ncbi.nlm.nih.gov/pubmed/ http://emedicine.medscape.com/article/ http://www.cancer.gov/types/gestational-

trophoblastic/hp/gtd-treatment-pdq Berkowitz RS, Goldstein DP. Chorionic tumors. N

Engl J Med 1996; 335:1740. DC dutta text book of obstetrics 7th edition Current diagnosis and treatment in ostetrics and

gynaecology 10th edition