Gestational Trophoblastic

Disease
Learning Objectives

Properly diagnose cases of gestational trophoblastic diseases

Outline a plan of management for cases of GTD
Recommend strategies to minimize the risk gor GTN
Explain the importance of beta HCG surveillance
Discuss the management of pregnant patients with a history of GTD
Gestational TROPHOBLASTIC DISEASE
BENIGN MALIGNANT

Hydatidiform Mole Gestational Trophoblastic

Complete Neoplasia
Partial Invasive Mole
Placental Site Nodule Choriocarcinoma
Placental Implantation Site Placental Site Trophoblastic
Tumor
Epithelioid Trophoblastic Tumor
Hydatidiform Mole
• Hydatidiform mole is a general term that includes two distinct
entities: COMPLETE and PARTIAL Hydatidiform Mole. Features
common to both forms include a hydropic state of some or all villi and
trophoblastic proliferation. The two forms, however, differ on the
basis of chromosomal pattern, gross and microscopic histopathology
and clinical course
Pathophysiology
• Can explain the difference in clinical course, histopathology and
prognosis
Question #1
• What is the most common karyotype of a complete hydatidiform
mole?
• A. 46 XX
• B. 46 XY
• C. 69 XXY
• D. 69 XYY
Pathophysiology
Complete Hydatidiform Mole
• 46 XX ( Most Common)
• 46 XX
• 46 XY
Pathophysiology
Partial Hydatidiform Mole
• 69 XXX
• 69XXY
• 69 XYY
Question #1
• What is the most common karyotype of a complete hydatidiform
mole?
• A. 46 XX
• B. 46 XY
• C. 69 XXY
• D. 69 XYY
Risk FACTORS
• Maternal Age
• Paternal Age
• Previous Molar Pregnancy
• Diet
• Oral Contraceptive Use
• Race
Question #2

• A 27 year old, G1P0, 8 weeks amenorrhea consults for vaginal

spotting. Pregnancy test is positive. Examination revealed a boggy
corpus enlarged to 16 weeks with no fetal heart tones. Cervix is
closed. Cul de sac is full. What is your diagnosis?
A. Twin Gestation
B. Pregnancy with myoma uteri
C. Hydatiform Mole
D. Pregnancy with polyhydramnios
Diagnosis
• High Index of suspicion
• Based on the patient’s clinical presentation supported by typical
ultrasonogrophic findings and an elevated hCG titer
DIAGNOSIS
• Vaginal Bleeding
• Uterine Size more than the age of gestation
• Presence of theca lutein cysts
• Hyperemesis Gravidarum
• Preeclampsia
• Hyperthyroidism
• Respiratory Failure
Question #2

• A 27 year old, G1P0, 8 weeks amenorrhea consults for vaginal

spotting. Pregnancy test is positive. Examination revealed a boggy
corpus enlarged to 16 weeks with no fetal heart tones. Cervix is
closed. Cul de sac is full. What is your diagnosis?
A. Twin Gestation
B. Pregnancy with myoma uteri
C. Hydatiform Mole
D. Pregnancy with polyhydramnios
DIAGNOSIS

• Ultrasound
• Overall sensitivity is 50-86%
• Factors that influence diagnosis
• Gestational age
• Operator expertise
• Type of H-Mole
DIAGNOSIS
Ultrasound for Complete hydatidiform mole
Diagnosed in approximately 80% of cases particularly during the second
trimester when the grape-like or hydropic villous change occurs
DIAGNOSIS
Ultrasound for partial hydatidiform mole
Less accurate
As much as 70% of cases may be missed
Two sonographic findings
focal cystic changes in the placenta
a ratio of the transverse to antero-posterior dimension of the
gestational sac >1.5
DIAGNOSIS
Serum Beta hCG
• Correlation of the ultrasonographic findings with beta HCG levels can
further improve the recognition of a molar pregnancy prior to surgical
evacuation
Diagnosis
• Measurement of a high hCG >100,000 U/L is association with vaginal
bleeding and uterine enlargement highly suggests complete
hydatidiform mole
• In contrast partial hydatidiform mole is less commonly associated
with markedly elevated values
DIAGNOSIS
• Gold Standard for diagnosis is still based on histopathologic
evaluation
• Confirmatory Tests
• Cytogenetic Examinations are recommended when the
diagnosis of hydatidiform is in doubt
• Immunostaining may be performed in cases where the
histologic diagnosis is in doubt
• P57kip2
Management
• Complete and partial moles differ histopathologically, cytogenetically
and in clinical behavior. However, management is similar for both
types of hydatidiform mole
MANAGEMENT
Baseline laboratory Examinations
• CBC
• Blood typing, Rh
• BUN, Crea
• SGOT, SGPT
• Quantitative Beta hCG
• Urinalysis
• Chest X-ray
MANAGEMENT
Other examinations
• Serum electrolytes
• 12- lead ECG
• Arterial Blood Gas
• PT, PTT
• FT4, TSH
EVALUATE and TREAT Medical
Complications
• Anemia
• Hyperemesis Gravidarum
• Pre-eclampsia
• Hyperthyroidism
• Respiratory Insufficiency
• DIC
MANAGEMENT
• Evacuation of molar producers
• Definitive therapy
• Confirms pathologic diagnosis
• Relieves symptoms
• Prevents complications
Question #3
• A 27 year old, primigravid, 8 weeks AOG, consulted due to vaginal
spotting. Examination revealed a boggy corpus enlarged to 16
weeks with no fetal heart tones Cervix is closed. Ultrasound
showed a snow storm pattern and beta hCG was 164,000 mIU/ml.
What is the best mode of molar evacuation for her?
A. Medical induction
B. Hysterotomy
C. Suction Curettage
D. Hysterectomy
Management
Suction Curettage Hysterectomy
Preferred method regardless of Option for patients with
the patient’s age and uterine size completed family size
For patients with life threatening
hemorrhage
Decreases the risk for local
invasion
Does not eliminate the need fpr
post-evacuation momnitoring
MAnagement
Hysterotomy Medical Induction
More bleeding More Bleeding
Subsequent operative deliveries Incomplete evacuation
Higher risk of postmolar GTN Higher risk of postmolar GTN
Question #3
• A 27 year old, g1Po, 8 weeks AOG, consulted due to vaginal
spotting. Examination revealed a boggy corpus enlarged to 16
weeks with no fetal heart tones Cervix is closed. Ultrasound
showed a snow storm pattern and beta hCG was 164,000 nIU ml.
What is the best mode of molar evacuation for her?
A. Medical induction
B. Hysterotomy
C. Suction Curettage
D. Hysterectomy
Management
General Guidelines
Cervical ripening done only through mechanical means
Theca lutein cysts are best left alone during laparotomy
Patients who are Rh negative should receive Rh immune globulin at
the time of evacuation because the Rh D factor is expressed on
trophoblast
All tissues obtained during molar evacuation should be submitted
for histologic evaluation
Routine repeat curettage after the diagnosis of a molar pregnancy
is not warranted
prognosis
• Risk of malignant degeneration
• Complete Mole 15-25%
• Partial Mole 0.5-4%

Risk is high especially among those with signs and symptoms of

marked trophoblastic proliferation
PROPHYLAXIS
chemoprophylaxis
• Methotrexate is the drug of choice
• May be useful in situations where
• High risk for postmolar GTD
• Post evacuation surveillance is doubtful

* Does not remove the need for post evacuation surveillance

Chemoprophylaxis
Indications
• Age >= 35 years old
• Gravidity of 4 or more
• Uterine size >= 6 weeks larger than AOG
• Theca Lutein Cysts >= 6 cm
• Medical complications
• Recurrent mole
• Serum BhCG >100,000 mIU/L
• Poor follow up
Follow up
• After molar evacuation, all patients must have serial beta hCG
monitoring to detect malignant degeneration
Molar evacuation
• Serum B hCG after 1 week
• Every 2 weeks until 3 normal titers
• Serum bHCG every month for 6 months
• Serum BhCG every other month to complete 12 months
Follow up
• It is important to use a reliable contraception during the entire follow
up period
• Pregnancy may be allowed after 6 months of normal hCG titers
Future pregnancies
• Risk of another mole 1-2% after complete H. Mole; 15-20% after 2 H.
Mole
• Risk for stillbirth prematurity, spontaneous abortion, and congenital
malformation is similar to that in the general population
Future pregnancies
• An early ultrasound should be performed
• BhCG should be monitored at 6 weeks postpartum
• Placenta should be submitted for histopathogic examination
Indications for referral
• High levels if BhCG more than 4 weeks post evacuation (serum level
of 20,000 mIU/ml; urine level of 30,000 mIU/ml)
• A rise in BhCG of 10% or greater ( 2 consecutive weekly
determinations)
• Plateuing BhCG values (<10% decline or rise) at any time after
evacuation (minimum of 3 consecutive weekly determinations)
INDICATIONS FOR REFERRAL
• Clinical or histologic evidence of metastasis at any site
• Persistently elevated BhCG titer at 14 weeks post evacuation
• Elevation of a previously normal BhCG titer after evacuation provided
the diagnosis of pregnancy is excluded
Gestational trophoblastic neoplasia
• Vaginal bleeding
• Anemia
• Uterine enlargement
• Acute abdomen secondary to tumor perforation
• Signs and symptoms referable to the site of metastasis
Diagnosis
Initial Tests Blood and Urine Tests Metastatic Work-up

Baseline Serum Beta CBC Chest Xray

hCG
Transvaginal Blood typing Whole abdomen CT
ultrasound preferably scan or ultrasound
with Doppler studies
Liver function Teest Chest CT Scan
Renal Function Test Brain CT Scan
Thyroid Function Test
Urinalysis
Diagnosis
• All patients must be staged and scored using the FIGO 2000 Anatomic
Staging and WHO prognostic Scoring System
Management
• Histopathologic confirmation is not necessary to start treatment
• Chemotherapy is the principal mode of treatment
• Suregeru and radiotherapy are adjunctive treatments
Management
• Chemotherapeutic Regimens
Stage I/Stage II or III, Low Risk
• Single Agent Chemotherapy (Methotrexate)
• 2 consolidation therapies
Metastatic, High Risk
• Multi-agent Chemotherapy (EMACO)
• 3 consolidation therapies
Management
Hysterectomy
• Adjunctive Treatment
• Indications
• Remove a resistant focus
• Uterine perforation
• Profuse vaginal bleeding
• Reduce tumor load in a patient with completed family size
Management
• Administered concurrent with chemotherapy
• Done in cases of brain and liver metastasis
• Advantages
• Tumoricidal
• Hemostatic
• Synergistic effect with chemotherapy
hCG monitoring
• Monthly for 6 months
• Every 2 months for 6 months
• Every 3 months for 1 year
• Every 6 months thereafter
Management
• Avoid pregnancy for 2 years
• Reliable contraception
Placental Site Trophoblastic Tumor and
Epithelial trophoblastic Tumor
• Almost always cause irregular uterine bleeding often distant from
a preceeding non molar gestation
• Rarely virilization or nephrotic syndrome
• Uterus is usually symmetrically enlarged
• Serum hCG levels are only slightly elevated
• Histopathologic Examination
• PSTT: implantation type intermediate trophoblast
• ETT: Chorionic Type intermediate trophoblast
Placental Site Trophoblastic Tumor and
Epithelial trophoblastic Tumor
• Immunostaining
• PSTT: diffuse presence of cytokeratin and hPL; focal staining with hCG
Management
• Patients are classified using the FIGO system only
• Hysterectomy is the treatment of choice
• Chemotherapy is given in the for of EMACO
• hCG is used to monitor the disease response to treatment
• Same follow-up protocol as Choriocarcinoma and Invasive Mole