Gestational trophoblastic disease 2 pdf - All Lectures

Gestational Trophoblastic

Disease (GTD)

GTD Overview

• Heterogeneous

group of related lesions

• Arise from abnormal proliferation of

trophoblast of

the placenta

• Can

follow any gestational event

– abortion,

miscarriage, ectopic, normal pregnancy

• Unique

because the maternal lesions arise from

fetal (not maternal) tissue

• Most GTD lesions produce

(B-hCG)

• Can be cured

even in the presence of widespread

metastases

Overview

Hydatidiform Mole:
• Complete
• Partial

** Benign

Gestational Trophoblastic Neoplasia (GTN):
• Persistent/Invasive Mole
• Choriocarcinoma
• Placental-Site Trophoblastic Tumor (PSTT)

** Malignant

Relationship of HM. IM. CH

hydatidiform therapeutic or

mole

spontaneous abortion

term pregnancy

ectopic

invasion mole choriocarcinoma.

Hydatidiform mole

Hydatidiform Mole

• North America: 0.6-1.1 per 1000 pregnancies
• Asia: 2-10 per 1000 (3x Western countries)
• Difference possibly related low dietary intake

of carotene (vitamin A deficiency) and animal
fat

• More common at reproductive extremes in

age (>35y or <20y)

Hydatidiform Mole

Risk Factors:
• History of previous GTD

– If one previous mole, 1% chance of recurrence

(vs. 0.1% in general population)

– If 2 previous moles, risk of recurrence increases

to 16-28%

• Smoking
• Vitamin A deficiency
• Blood type:

– A or AB are at slightly higher risk than those with

type B or O

Hydatidiform mole

1. Complete mole

23X

sperm

empty egg

23X

46,XX

23X

sperm

empty egg

23Y

23X

46,XY

23Y

sperm

Hydatidiform mole

2. Partial mole

23X

sperm

normal egg

23Y

23X

69,XXY

23Y

sperm

23X

sperm

Normal egg

23X

69,XXX

23X

sperm

23X

Hydatidiform Mole

Clinical Manifestations:
• Vaginal bleeding

(97%)

/anemia

• Enlarged uterus (size > dates)
• Pelvic pain
• Theca lutein cysts
• Hyperemesis gravidarum
• Hyperthyroidism
• Preeclampsia <20 weeks gestation
• Vaginal passage of hydropic vesicles
• Partial mole usually presented as incomplete or

missed abortion

Diagnosis

• Complete :

U/S usually very sensitive – generalized

swelling (snow-storm )

• partial mole

U/S may detect focal cystic spaces of varying

diameter

Diagnosis on histology of curettings

Complete vs. partial mole

Partial

Complete

Feature

Triploid

(69,xxx or 69,

xxy)

Diploid(usually

46,xx or rarely

46,xy)

Karyotype

focal

diffuse

Swelling of chorionic villi

focal

diffuse

Trophoblastic hyperplasia

Present

absent

Embryonic tissue

usually<

100,000

Often > 100,000

hCG

<5%

15 - 20%

Trophoblastic sequelae

Rare

Up to 25%

Theca lutein cysts

Rare

Up to 25%

Medical complications

Small for dates

50% large for dates

Uterine size

Hydatidiform Mole Treatment

• Evaluate for coexisting conditions:

- History and physical
- CBC, coagulation profile, serum chemistry
- thyroid function
- blood type and cross match
- chest radiography
- pelvic ultrasonography

• Evacuation of mole

Suction curettage

Hysterectomy

if completed childbearing

• If Rh negative, give rhogham

Hydatidiform Mole Treatment

chemotherapy

HM don’t need usually chemotherapy

because HM is benign disease.

Follow-Up Care – Molar Pregnancy

• 80% of patients cured by evacuation
• Follow B-hCG levels every two weeks until 3 consecutive tests

negative

• Then monthly B-hCG every month for 6-12 months
• More than half of patients will have complete regression of

hCG to normal within 2 months of evacuation.

• Avoid pregnancy for at least 6 months after first normal B-hCG

(oral contraceptive pills is preferable)

• Subsequent Pregnancies:

– Send placenta for pathology
– Check B- hCG 6 weeks postpartum

Prognosis

• Complete mole has the latent risk of local

invasion or telemetastasis

• The high-risk factors includes

– β-HCG>100000IU/L
– uterine size is > 20 weeks size.
– the luteinizing cyst is >6cm
– If >40 years old,the risk of invasion and metastasis

may be 37%, If >50 years old,the risk of invasion
and metastasis may be 56%.

– repeated mole: the morbidity of invasion and

metastasis increase 3~4 times

Gestational Trophoblastic Neoplasia

(GTN)

• Persistent/Invasive Mole
• Choriocarcinoma
• Placental-Site Trophoblastic Tumor (PSTT)

** Malignant

Risk Factors for GTN After Mole

• Preevacuation uterine size greater than

gestationl age or larger than 20 weeks
gestation

• Theca-lutein cysts larger than 6 cm
• Age > 40 years
• Serum hCG levels > 100,000 mIU/mL
• Previous hydatidiform mole

Invasive Mole

• Myometrial invasion by hydatidiform mole
• Formerly known as

chorioadenoma destruens

• 1 in 15,000 pregnancies
• 10-17% of hydatidiform moles will progress to

invasive moles

Persistent Mole

Definition of persistent molar disease and need for
chemotherapy (at least one of the following):

– B-hCG plateau for ≥ 4 values for ≥ 3 weeks
– B-hCG increase of ≥ 10% for ≥ 3 values for ≥ 2

weeks

– B-hCG persistence 6 months after molar

evacuation

– Histopathologic diagnosis of choriocarcinoma
– Presence of metastatic disease

Choriocarcinoma

• Most aggressive type of GTN
• Abnormal trophoblastic hyperplasia

• Absence of chorionic villi

• Direct invasion of myometrium
• Most often develops from a

complete

hydatidiform mole

• Vascular spread to distant sites:

– Lungs
– Brain
– Liver
– Pelvis and vagina
– Spleen, intestines, and kidney

Choriocarcinoma

• May come from any type of pregnancy

- 25% follow abortion or tubal pregnancy
- 25% with term gestation
- 50% from hydatidiform moles

• 2-3% of moles progress to choriocarcinoma
• Incidence 1 in 40,000 pregnancies

– Rarely, choriocarcinomas can develop in other parts of the

body in both men and women. These are not related to
pregnancy as ovaries and testicles

• Nongestational choriocarcinoma tends to be less

responsive to chemotherapy and has a less favorable
prognosis than the gestational variant

Placental-Site Trophoblastic Tumor

(PSTT)

• Originate from intermediate cytotrophoblast

cells

• Secrete

human placental lactogen

(hPL)

• B-hCG often

normal

• Less vascular invasion, necrosis and

hemorrhage than choriocarcinoma

• Lymphatic spread

• Arise months to years after term pregnancy

but can occur after spontaneous abortion or

molar pregnancy

Placental-Site Trophoblastic Tumor

(PSTT)

• Most common symptom is vaginal bleeding
• Tend to:

- Remain in uterus
- Disseminate late
- Produce low levels of B-hCG compared to

other GTN
- Be resistant to chemotherapy (treat with

surgery)

Signs & Symptoms GTN

• Continued uterine bleeding, uterine

perforation, enlarged irregular uterus,
persistent bilateral ovarian enlargement

• From metastatic lesions: abdominal pain,

hemoptysis, melena, increased intracranial
pressure (headaches, seizures, hemiplegia),
dyspnea, cough, chest pain

Diagnosis of GTN

• Increase or plateau in B-hCG after molar

pregnancy

• Pathologic diagnosis by D&C or biopsy of

metastatic lesions

• WARNING: biopsy of metastatic lesions can

result in massive hemorrhage

• Metastatic workup: CXR (or CT chest), CT

abdomen/pelvis +/- CT/MR of brain

Classification & Staging of GTD

• FIGO Staging

– Describes anatomic distribution of disease

• World Health Organization (WHO) Scoring

Index

– Describes prognosis

FIGO Staging

Stage

Description

Disease confined to the

uterus

Disease extends outside the uterus but

limited to genital structures

(adnexa,

vagina, and broad ligament)

III

Disease extends to the

lungs

with or

without genital tract involvement

Disease involves any

other metastatic sites

The World Health Organization (WHO) scoring

system for GTD

WHO Prognostic Score Index

Score

Characteristic

Age

<40

≥40

Antecedent preg

Mole

Abortion

Term

Pregnancy to
treatment
Interval (months)

months

4-6

months

7-12 months >12 months

Pretreatment hCG

<10

- 10

-10

>10

Largest tumor size
(including uterus)

< 3cm

3-4 cm

≥5cm

Site of metastases

Lung

Spleen,

kidney

GI tract

Liver, brain

Number of metastases

1-4

5-8

Previous failed
chemotherapy

Single drug

≥2 drugs

Therapy for GTN

• Single agent therapy for nonmetastatic

(stage I) or low-risk metastatic (stage II and
III) with score <7 → survival rates ~ 100%

• Combination chemotherapy +/- radiation

and/or surgery for high-risk metastatic
disease with score ≥7

Therapy: Nonmetastatic GTN

• Single-agent with either methotrexate or

dactinomycin

• Chemotherapy continued until hCG values normal

and then

2-3 cycles beyond

• Change to alternative single-agent for hCG plateaus

above normal or toxicities

• If significant elevation of hCG or new metastases,

switch to multiagent

• 85-90% cured with initial regimen, <5% will require

hysterectomy for cure

Therapy: Low-risk Metastatic GTN

• Low-risk metastatic disease can be treated

with single-agent therapy with 5-day
regimens

• Cure rates ~100% but 30-50% will be develop

resistance to first agent

• If resistance to sequential single-agent

chemotherapy (5-10% of patients), switch to
multiagent chemotherapy

Therapy: High-risk Metastatic GTN

• Stage IV
• Stage II/III with score > 7
• Disease refractory to single-agent chemotherapy

Combination Chemotherapy:
• EMACO:

– Day 1: Etoposide, Methotrexate and Dactinomycin
– Day 8: Cyclophosphamide and Vincristine

(Oncovorin)

– Repeat q2 weeks until remission
– Continue for at

least 2-3 cycles beyond first normal

hCG

• MAC (Methotrexate, Dactinomycin, Cyclophosphamide)
• EMA/EP – EMA + Etoposide and Cisplatin

Metastatic Gestational Trophoblastic Tumors

• Surgery

– It is indicated for tumor resistant to

chemotherapy and single metastases persisting
despite chemotherapy.

• RT

– RT, in combination with chemotherapy, is clearly

indicated for the primary management of patients
with brain metastases.

PSTT Therapy

• Hysterectomy
• Chemotherapy for metastatic disease or

nonmetastatic disease with poor prognosis:
- Interval from index pregnancy > 2 years
- Deep myometrial invasion
- Tumor necrosis
- Mitotic count > 6 per 10 high-power fields

• Survival rates:

– ~100% for nonmetastatic disease
– 50-60% for metastatic disease

Follow-up Care

• After completion of chemotherapy, follow

serial hCG every 2 weeks for three months,
then monthly for one year

• Physical examinations every 6-12 months and

imaging as indicated

Reproductive Performance

• Most women resume normal ovarian

function

• Women who undergo chemotherapy are

advised not to conceive for one year after
completion of treatment

• No increase risk of stillbirths, abortions,

congenital anomalies, prematurity, or major
obstetric complications

False Positive Serum hCG

• Phantom hCG syndrome/ phantom

choriocarcinoma

• 3-4% of healthy individuals have human-antimouse

antibodies that can mimic hCG immunoreactivity

• To verify:

– Urine hCG should be negative
– Should not show parallel decrease with serial dilutions
– Test at national B-hCG reference lab

Summary

• Hydatidiform mole is a benign condition, 80%

cured with suction D&C

• Malignant GTN:

– Persistent or invasive mole
– Choriocarcinoma
– PSTT

• WHO score > 7 represents high-risk disease
• GTN very sensitive to chemotherapy

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