Gestational Trophoblastic

Diseases
Dr Adam

11/26/2024 1
 OUTLINE
• Classification of GTT
• GTD .Pathogenesis
• Clinical Features of Premalignant(GTD)
• Management
• Clinical Features of Malignant (GTN)
• Investigations
• Choriocarcinoma, Diagnosis, Investigation, Management

11/26/2024 2
 Introduction

• GTD, is a term used to describe the heterogeneous

group of interrelated lesions that arise from
abnormal proliferation of placental trophoblast.
• GTD Lesions are histologically different and can be
Benign and malignant.

11/26/2024 3
 WHO Classification
GTD
Premalignant Diseases
• Complete Hydatidiform Mole ( C M )
• Partial Hyadatidiform Mole ( P M )

Malignant Diseases (GTN) ,devided into

a) Nonmetastatic
• Invasive Mole
• Placental site trophoblastic tumor ( PSTT )
• Epitheloid tumour
b) Metastatic
• Gestational Choriocarcinoma
11/26/2024 4
 Clinical risk factors for molar pregnancy

Age (extremes of reproductive years)

<15
>40
Reproductive history
prior hydatidiform mole
prior spontaneous abortion
Diet
Vitamin A deficiency
Birthplace
Outside North America( occasionally has this
disease)
11/26/2024 5
 Homozygous 85%

Pathogenesis of complete H Mole

11/26/2024 6
 Heterozygous 15%

Pathogenesis of complete H Mole

11/26/2024 7
Pathogenesis of Partial H. Mole
11/26/2024 8
 GTD

Genetic & Pathology

• C M contains Paternal DNA only, so its androgenic
• Macroscopically like bunch of grapes
• P M are triploidy, two paternal & one maternal sets of
xsomes.
• There is hyperplasia of chorionic villi& embryo usually dies 8-9
weeks of gestation.

11/26/2024 9
 Clinical features
Complete Mole
• common in first trimester or early Second trimester
• Vaginal bleeding 84-97%

• Uterus is larger than POG (28%)

• Presents with the features of threatened abortion; Amenorrhea, pain &

bleeding P/V
• Associated , Hyperemesis Gravidarum

• Preeclampsia 10-15%

• hyperthyroidism 7%

11/26/2024 10
 Clinical features

• Theca leutin cysts

• Beta h CG levels > 100.000mIU/L

O/E
• expulsion of grapes like vesicles
• Pulmonary , cervical, Vaginal metastasis may occur disappears after
evacuation of mole
• Macroscopic features: Bunch of grapes due to villous hypertrophy
• Branching contain hyperplastic cyto & syncytio trophoblast with many
vessels

11/26/2024 11
 Complete Molar Pregnancy
11/26/2024 12
High Risk For Developing Post molar tumor

• hCG Levels > 100,000 mIU/L

• Excessive Uterine Enlargement
• Theca leutin cyst 6cm or larger

11/26/2024 13
 Clinical features

PARTIALMOLE
• Most commonly presents in late Ist or second trimester
• Uterus is often not enlarged more than POA
• More often presents as Missed or incomplete abortion
• Pre evacuation h CG levels are less than 100,000IU/ L
• Macoscopic : villous swelling is less intense ( focal)
• Embryo is present
• Presence of nucleated RBS of embryo in villous structure

11/26/2024 14
 Management Of Molar Pregnancy

There are 2 important basic lines:

1. Evacuation of the mole
2. Regular follow up to detect persistent Trophoblastic
disease

11/26/2024 15
 Management of Molar Pregnancy

For complete mole:

Suction Curettage

11/26/2024 16
 Contraception
• Should NOT conceive until follow up is complete.
• Use Barrier method or COCs
• IUCD should not be used

11/26/2024 17
 Role of hysterectomy
• If the patient desires surgical sterilization, a hysterectomy may
be performed with the mole in situ.
• Hysterectomy does not prevent metastasis; therefore,
patients will require follow up with assessment of hCG levels.

11/26/2024 18
Role of prophylactic chemotherapy
• It may be useful in the high-risk cases when
follow up are unavailable or unreliable.
high risk factors:
 hCG level >100,000 mIU/ml
 Excessive uterine enlargement
 Theca lutien cysts 6 cm in diameter

11/26/2024 19
 Chances of malignant transformation
• Complete H.Mole 16%

• Partial H.Mole 0.5%

11/26/2024 20
 Gestational trophoplastic Neoplasia
Nonmetastatic
Invasive Mole:
Clinical features
• Clinical diagnosis by persistence or rising titers of Beta h CG in the weeks
after molar evacuation & USG
• Persistent bleeding p/v
• Lower abdominal pain due to invasion in myometrium, vulva, vagina or
intra abdominal metastasis
• It may spread to adjacent pelvic structures ,bladder , rectum; hematuria,
bleeding P/ R
• Pulmonary metastasi

11/26/2024 21
 Clinical features

Placental Site Trophoblastic Tumor (PSTT):

• it is rare slow growing tumor
• Women mainly presents with menstrual irregularities & lower abdominal
pain, galactorrhea due to hyperprolactinemia increased h PL
• Little or no h CG is produced ( Free B hCG fragment )

11/26/2024 22
Metastatic Gestational Trophoblastic Neoplasia

 Second most common GTN

 1 in 30,000 pregnancies
 Early haematogenous spread is characterstic of
choriocarcinoma
 40% after molar pregnancy: Easily Diagnosed
 60% non-molar pregnancy: Difficult to Diagnose

11/26/2024 23
 Metastatic Gestational Trophoblastic Neoplasia

 GTN arises when the normal regulatory mechanisms controlling

the proliferation and invasiveness of trophoblastic tissue are lost.
 Diagnosis of the GTN is made on
 Clinical presentation
 Elevated b-HCG
 Evidence of metastasis
 Imaging
 Tissue for Histology.
11/26/2024 24
 Metastatic Gestational Trophoblastic Neoplasia

CHORIOCARCINOMA:
Clinical features
• Occurs mainly following any form of pregnancy, mainly after
CM, others-abortion, normal pregnancy
• bleeding p/v ,
• lower abdominal pain,
• distant metastasis lungs , brain ,liver, skin, etc
• Highly malignant , appears as soft purple largely hemorrhagic
mass

11/26/2024 25
 Clinical features of chorio CA

• Microscopic: implanting blastocyst with central cores of

mononuclear cytotropho surrounded by rim of
multinucleated syncytiotrophoblast & distinct absence of
chorionic villi extensive areas of necrosis & haemorrage
&frequent evidence of tumor in the sinuses
• The hyper vascularity & absence of connective tissue support
are the reason for its highly malignant behaviour

11/26/2024 26
 investigations
• Quantitative beta hCG
• X Ray Chest
• Pelvic Doppler USG
• Abdominal doppler USG to rule out liver & renal metastasis
• CT chest , abdomen
• MRI brain
• Genetic studies

11/26/2024 27
FIGO REQUIREMENT FOR MAKING DIAGNOSIS
OF GTN

1. Four values or more of plateaue hCG over at

least 3 weeks: days 1, 7, 14 and 21.
2. Histologic diagnosis of choriocarcinoma.
3. Persistence of hCG beyond 6 months after
mole evacuation.

11/26/2024 28
 Metastatic disease

Sites: Symptoms:

a. Pulmonary- 80% Chest pain, dyspnoea

b. Vagina- 30% Vagina bleeding , purulent
discharge and nodule.
c. Liver- 10% Epigastric pain, jaundice, hepatic
rupture leading to intraperitoneal
haemorrhage.

d. Brain- 10% Focal neurological deficit.

11/26/2024 29
GTN Vaginal Metastasis

11/26/2024 30
 Management of GTN

 Prognostic score is central to the

management of GTN.
 A single universally accepted, anatomical
staging and prognostic scoring system for
GTN was developed by FIGO in 2000.

11/26/2024 31
FIGO prognostic score (2000)
O 1 2 4
Age (years) <39 >39
Antecedent pregnancy Hydatidi form Abortion Term
mole pregnancy

Interval from index <4 4-6 7-12 > 12

pregnancy, months

Pretreatment hCG < 103 103-104 > 104-105 > 105

(mlU/ml)

Largest tumour size, 3-4 cm 5 cm

including uterus

Site of metastases Spleen, GI tract Brain, liver

kidney
Previous failed Single Two or more
chemotherapy drugs

Low risk (Score 0-6) and high risk (score> 7)

11/26/2024 32
 WORK UP OF GTN

 History & physical examination

 Serial weekly hCG measurement in serum.
 Hemogram, LFT, KFT
 Chest X-ray
 USG whole abdomen pelvis to rule out hepatic and renal
metastasis
 CT or MRI brain
 CSF analysis – in metastatic disease.
 Curette to be done if there is uterine bleeding.

11/26/2024 33
 GTN

FIGO scoring

Low risk (<6) High risk (> 6)

Single-agent Combination
chemotherapy chemotherapy

Resolution
Serial hCG levels
Life-long hCG follow-up

Relapsed/resistant disease
Second-line chemotherapy+ surgical debulking

11/26/2024 34
 Low Risk GTN

 FIGO score 6 or less.

 FIGO stage I, II & III.
 Drugs schedules: single agent chemotherapy

Most commonly used regimen.

Methotrexate: 11/26/2024 35
 Follow up in Low risk GTN

 Weekly hCG titre until normal for 3 consecutive

weeks.
 Monthly  HCG level until normal for 12 consecutive
months.
 Effective contraception during the follow up (OCP)
 FIGO recommends additional 2 courses of
chemotherapy after initial negative  hCG.

11/26/2024 36
 High Risk GTN
.
 Stage I, II, III With FIGO score 7 or greater or Stage IV
.
 Primary intensive combination chemotherapy and
selective use of radiation and surgery.
 Regimes given :
 MAC.
 Modified Bagshawe (CHAMOCA)
 EMA-CO
 EMA-EP.

11/26/2024 37
 Thank You

11/26/2024 38