GESTATIONAL TROPHOBLASTIC TUMORS

(GTT)GESTATIONAL

TROPHOBLASTIC Disease (GTD)

Learning Objective

At the end of this session, I would like you to be able to:

1. Have an idea about GTT2. Diagnose GTT3. Know how to manage GTT4. Know how to monitor GTT

It is a diverse group of tumors 80%- 90% benign.

Abnormalities of trophoblasts

Resulting from abnormal events occurring at or shortly after fertilization

GTT follow normal or abnormal pregnancy

Contains paternal genes

Types:Benign Hydatidiform mole 80%-90% Malignant Invasive mole Persistent trophoblastic tumor Choriocarcinoma Placental site tumors (Rare)

Unique about GTT Cure almost 100% Sensitive marker- secreted by all types Allow:- Accurate assessment- Follow-up

Epidemiology: - Varies- More in far east- Diet- More in extreme of reproductive ages- Risk of having another mole is 1- 3%

Hydatidiform mole:Results from abnormal events occur at or

shortly after fertilization, ? Abnormal gametogensis

Types: Histoligically Cytogenically - Complete mole - Partial mole

Genetic composition Complete (diploid karyotype

&paternal in origin• Chromosomes = 46 xx• Both xx, are paternally derived Fertilization of abnormal egg- no nucleus Haploid sperm 23x empty egg sperm

duplicate 46xx diploid(>90%)

< 20% empty ovum fertilized by 2 sperm resulting in 46xy

12- 25 % progress to Gestational Trophoblastic Tumor

Partial mole Chromosomes, triploid 69 xxy (80%) Minority triploid 69 xxx 20%(dispermic) Maternal& paternal genes Often present with fetal tissue - Fetus may be abnormal - Rarely reach term 5% progress to persistent gestational

trophoblastic tumor

Hydatidiform mole: - Confined to the uterine cavity - Occasionally trophoblastic-Embolic to

lungsPartial mole• some hydropic villi.• other villi normal. • less hyperplasia of trophoblast.• some fetal vessels or fetal Rbc.

Complete mole• all villi hydropic oedematous•all trophoblast are hyperplasia• absence of fetal blood vesselsGreater risk of becoming malignant

Hydatidiform mole:Symptoms: • majority >90% have irregular vaginal

bleeding 1st, 2nd trimester (does not indicate a problem)

• bleeding is painless• may expel vesicles • 1/3 excessive nausea/ vomiting, Why?? hyperemesis gravidarum 25%• pre-eclampsia occurs Early <24 weeks

gestation 3-12%What other conditions in pregnancy, when PET

occurs early???•hyperthyroidism 2- 10%, test before surgery• Theca luteal cysts, bilateral

Signs: Pale complexion Tachycardia sign of thyrotoxicosis Tachypnea- sign of pulmonary Embolism Uterus: Enlarged 50% Theca luteal cyst, 10-15% Secondary post partum bleeding (PPH) Persistent bleeding , should always

think GTT/GTD What should you do??

Partial Mole

More common May be undetected May not appear abnormal on

Ultrasound (USS) USS ordered for ?? Histopathology of Retained

product of conception (RPOC) partial or complete.

SNOWSTORM APPEARANCE OF MOLAR PREGNANCY

Requirement for chemotherapy

H mole may not regress spontaneously and require chemotherapy, more common with??

10-17% of H. mole result in invasive mole

3% of mole progress to choriocarcinoma

Diagnosis: High index of suspicious from clinical

data Quantatative beta-hCG Ultrasound shows _______ appearanceDifferential diagnosis:1. ________________2. ________________ Chest x-ray ??

Laboratory investigations: Full blood count? Blood group – Rh________? Coagulation profile? Liver function test Renal function test base line? Chest film

Treatment: Pre-requisites1. ____________2. ____________

Surgery

Blood cross match in theatre Syntocinon infusion

Dilation – suction evacuationComplication 1. ___________?2. ___________?Hysterectomy:When _________? _________?

Complication: Uterine perforation Uterine haemorrhage

Monitoring: Serum- β human chronic gonadotrophin What happens to βhCG ?- Initially- Post evacuation – immediate - 6-8 weeks post evacuation

Follow-up- Weekly βhCG, until 3 consecutive normal values - Monthly βhCG , until 6 months- Contraception??- History of molar pregnancy, Postpartum check

βhCG at delivery, 6 and 10 weeks- Repeat H> mole occur in 1-3 %, have greater risk

of invasive or choriocarcinoma

Chemotherapy: Prophylactic not justified >79%

spontaneous remission

When does chemotherapy is indicated in hydatidiform mole?

Invasive mole: Villi penetrate myometrium 5 – 10 % preceded by hydatidiform

mole βhCG persistently high after

evacuation of hydatidiform mole Locally invasive Rarely metastases to:- Vagina- Lung- Brain

Placental site trophoblast tumor Extremely rare Occur after non-molar pregnancy Sheets of cytotrophoblasts only When melastasis occur – fatal βhCG levels are relatively low Relatively chemotherapy-resistant Surgery has been the main stay of

treatment

Choriocarcinoma: Metastastatic Non-metastataticHistopathology: - Invade uterine wall- Metastasis- Sheet of cytotrophoblast and

synchiotriphoblast No identifiable villi

Choriocarcinoma: 50% of choriocarcinoma have

preceding hydatidiform mole 50% of choriocarcinoma follow:- Ectopic - Abortion - Normal pregnancy • Trophoblast after normal pregnancy

almost always choriocarcioma

Choriocarcinoma Subdivided into:Good Poor prognosisLow risk and high risk

Depending on:Site Size of metastasisClinical variables

Good Prognostic Factor:1. Initial βhCG < 40,000 miu/L 2. Therapy started within 4 months of

antecedent pregnancy3. Metastasis only to lung or pelvis4. No prior chemotherapy.

Poor Prognostic Factor: βhCG > 40,000 miu/L (initial) Therapy > 4 months from the

pregnancy Metastasis to brain or liver failed response to a single agent of

chemotherapy Choriocarcinoma following full term

pregnancy.

FIGO Staging for GTT

StageDescription

Chemotherapy

Methotrexate Etoposide Actinomycin D Cyclophosphomide Oncovin Folinic acid IM

Further Reading

www.hmole-chorio.org.uk www.swot.org.uk www.rcog.org.uk/guidelines

Questions time

Molar pregnancy Never include a fetus Commonly present with vaginal bleeding in

early pregnancy If complete contains only paternal genes HCG levels will lower than normal in early

pregnancy May result in a need for chemotherapy

GTT

There is a decreased incidence with increasing age

It gives typical USS appearance It is monitored post evacuation by

urinary oestriol It can be treated with trimthoprate

Following a diagnosis of a molar pregnancy

Serum hCG level should fall to within normal range in the first 4 weeks

Pregnancy should be avoided by inserting IUCD

Hysterectomy reduces the necessity for hCG monitoring

Clinical case scenario

Mrs. F is a 22 years old ward clerk. She is 8 weeks pregnant, and is complaining of severe nausea and vomiting, the uterus is compatible with 14 weeks. What is the differential diagnosis??