LECTURE NOTE

Gestational Trophoblastic Diseases

Ifebi Okechukwu Chidiebere
MBBS(NIG), FWACS
• Learning points
• Pathophysiology of molar gestation
• Tumour markers in molar pregnancy
• Mgt/follow up for GTN
• Pathophysiology of malignant GTN
• Epidemiological risk factors
• Risk assessment
• Follow up in choriocarcinoma
• PSST
 Introduction
• Gestational trophoblastic disease (GTD)
include a spectrum of interrelated tumors,

• including complete and partial hydatidiform

mole, invasive mole,
 Introduction
• choriocarcinoma, placental site trophoblastic
tumor (PSTT),

• and epithelioid trophoblastic tumor (ETT) that

have varying propensities for local invasion
and metastasis.
 Introduction
• Persistent GTD, also called gestational
trophoblastic neoplasia (GTN), is among the
rare human malignancies that can be cured in
the presence of widespread metastases.
• With the exception of PSTT and ETT, all GTN
arise from the cytotrophoblast and syncytial
cells of the villous trophoblast, and produce
abundant amount of human chorionic
gonadotropin (hCG).
 Introduction
• Measurement of hCG levels serves as a
reliable tumor marker for diagnosis,
monitoring of treatment response, and follow-
up to detect recurrence.

• PSST and ETT originate from the intermediate

cells of extravillous trophoblast and produce
hCG sparsely, making its use as a tumor
marker less reliable
 Introduction
• All GTN most commonly ensues after a molar
pregnancy, it may follow any gestational
event.
• Including therapeutic or spontaneous abortion
and ectopic or term pregnancy.
 Introduction
• Prior to the development of effective
chemotherapy in 1956, the majority of
patients with disease localized to the uterus
were cured with hysterectomy, and metastatic
disease was almost always fatal.
• Most women can now be cured and their
reproductive function preserved if they are
managed according to well-established
guidelines.
 Epidemiology
• Extremes of maternal age; under 20/more
than 35yrs
• Race; commoner among the Asians
• Low socio-economic status
• AB blood group/worse prognosis
• Diet deficient in animal fat or B-carotenes
• Previous history
 Hydatidiform Mole
• This is characterized by focal or generalized
placental hyperplasia and hydropic
degeneration of the placental villi depending
on the nature of oocyte fertilized.
• Hydatidiform moles may be categorized as
either complete or partial moles on the basis
of gross morphology, histopathology , and
karyotype.
 Hydatidiform Mole
• In complete mole, the oocyte is empty, while
in partial mole it contains defective genetic
material.

• Hydatidiform mole occur in 1 in 184 to 1 in

401 pregnancies
Features of Complete and Partial Moles

Complete Mole Partial Mole

• Fetal or embryonic tissue – • Fetal or embryonic tissue –
absent present
• Hydatidiform swelling of • Hydatidiform swelling of
chorionic villi – diffuse chorionic villi – focal
• Trophoblastic hyperplasia – • Trophoblastic hyperplasia –
diffuse focal
• Scalloping of chorionic villi - • Scalloping of chorionic villi -
absent present
Features of Complete and Partial Moles

Complete Mole Partial Mole

• Trophoblastic stromal • Trophoblastic stromal
inclusions – Absent inclusions – Present
• Karyotype – 46XX; 46XY • Karyotype – 69 XXY; 69XYY
• Risk for persistent GTD – • Risk for persistent GTD –
20%-30% <5%
• B- hCG- Elevated > 50,000 • B-hCG- Slightly elevated <
iu/ml 50,000 iu/ml
• Fetal RBCs - Absent • Fetal RBCs - Present
 Clinical features
• Exaggerated early pregnancy symptoms, including
hyperemesis gravidarium
• Symptoms and signs of hyperthyroidism
• Preeclampsia
• Vaginal bleeding
• Uterine size may be > gestational dates
• Uterus doughy on palpation
• No FHT, bilateral theca lutein cyst may or not be
palpable
 Investigations
Quantitative serum B-hCG
Urine B-hCG in serial dilution
FBC, SE/U/Cr, LFT, clotting profile, urinalysis
Abd-pelvic scan ; shows the classic snow storm
appearance
Chest X-ray as part of baseline investigations
 Treatment
• Uterine evacuation under oxytocin cover using
low preasure electric suction machine,
Evacuation is completed with sharp curette to
ensure complete removal of molar tissue.
 Complication
• Uterine perforation
• Trophoblastic embolization leading to acute
respiratory distress
• Haemorrhage
• DIC
• Malignancy
 Follow up
• Usually done using serum B-hCG, which is very
sensitive, however, urine B-hCG is an
alternative where finance is a problem
• Patient is advised to use effective
contraceptive method during follow up
• Indications for initiating chemotherapy in pxs
with GTD
• Rising B-hCG in 2 or plateaued in 3
consecutive sample
• Raised B-hCG 6/12 after evacuation
• Histological evidence of choriocarcinoma
• Metastases to the brain, liver, GIT, spleen,
kidneys or other solid organs
• hCG > 20,000 iu/l > 4/52 after evacuation
• Heavy vaginal bleeding or GIT/intraperitoneal
bleeding
• Lung or vaginal metastases > 2cm
 Invasive mole
• Also called chorioadenoma destruens and
shares same histological characteristics with
molar gestation

• but with marked haemorrhage, necrosis and

local invasion of the myometrium.
• The diagnosis is often made on hysterectomy,
specimen from dilatation and curettage may
not show evidence of invasive mole
 Choriocarcinoma
• This represents one of the entities at the
malignant end of the spectrum,

• it follows different forms of pregnancies and

the basic pathology here is that of the
widespread necrosis of trophoblastic tissues
with extensive haemorrhage.
• Histologically pile of trophoblats but not villi
are seen,

• it tends to metastasize early, characteristically

they are aneuploid but may be heterozygous
 Epidemiology

• It is reported in 2-5% of all cases of GTN

• In about 50% of all cases of choriocarcinoma,

the antecedent gestational event is
hydatidiform mole

• 25% follow term pregnancy while 25% follow

abortion
 Risk factors
• Commoner in older women >40yrs
• Previous molar pregnancy
• Race; higher among Asians
 Clinical features
• It metastasizes early in pregnancy and when
this occurs, the symptoms and signs may be
those referable to the organs affected
• Asymptomatic, if picked up from monitoring
post molar pregnancy and hCG levels plateus or
begins to rise
• Pulmonary-cough, hemoptysis
• Vaginal deposits- (sub-urethral), vaginal
bleeding
• Liver-jaundice
• GIT-Ascites, tenderness, guarding and rebound
tenderness
• Brain – coma
• Weight loss, anorexia, weakness etc.
 Investigations
• Serum B-Hcg
• FBC, LFT, SE/U/Cr
• Chest X-ray, or CT-scan
• Abdominal CT
• MRI- Brain ( skull x-ray in low resource setting)
• Histology if D and C or hysterectomy was
performed
 Metastasis
• Metastasizes early via haematogenous and
lymphatic channels, local extension also occurs
• Common sites;
• Lung -- 80%
• Vagina --- 30%
• Liver ----20%
• Brain ----20%
• Kidney -- 20%
 Staging
i --- confined to the uterus
ii --- GTN extends outside of the uterus but
limited to the genital structures (adnexa,
vagina, broad ligament)
iii --- GTN extends to the lungs, with or
without known genital tract involvement
Iv ---- All other metastasis
 WHO/FIGO scoring system
Score 0 1 2 4
Age <40 >40 - -
Antecedent preg. Mole Abrtn Term -
Interval month <4 4-<7 7-<13 >13
Index preg
Pretreatment <103 103-<104 104-<105 >105
Serum B-hCG
Largest tumour - 3-<5cm >5cm
Size
Site of metastasis lungs spleen/kidney GIT Liver/Brain
Number of metastasis --- 1-4 5-8 >8
Previous failed
Chemotherapy - - single agent 2 or more
 Management
• Involves optimization of the patients clinical
condition, resuscitation, correcting anaemia,
treating infection
• Definitive treatment will depend on her risk
assessment using the WHO/FIGO risk
assessment/prognostication score
• Score of 6 and less are classified as low risk
while 7 and above are high risk.
 Low Risk
• Single agent chemotherapy is recommended
and the regimen includes:

• Methotrexate/folinic acid is commonly used;

• Im methotrexate at 1 mg/kg on days 1,3,5, and

7 and im folinic acid on days 2,4,6, and 8 at 0.1
mg/kg repeat every 2/52
• Methotrexate 30-60 mg/m2 im once a week
• Methotrexate 0,4 mg/kg/d iv or im for 5/7
repeat every 14/7
• Actinomycin-D 1-2.5mg/m2 iv every 14/7
• Actinomycin-D 10-12 mcg/kg/d iv for 5/7
• Actinomycin –D is preferable if the liver
function is not optimal
• Add intrathecal methotrexate to minimize the
risk of CNS metastasis if there is evidence of
lung metastasis on chest x-ray.
 Treatment of High Risk
• Currently EMACO ( etoposide, methotrexate,
• actinomycin-D, cyclophosph
amide, and vincristine)
Chemotherapy provide the best response rate
EMACO
Day 1 Etoposide 100mg/m2 iv
(infused over 30
min)
• Actinomycin –D 0.5mg iv bolus
• Methotrexate 100 mg.m2 iv bolus
• 200mg/m2(infused
over 12 hrs)
Day 2 etoposide 100mg/m2 iv(infused
over 30 min)
actinomycin –D 0.5 mg iv bolus
folinic acid 15mg im or orally every
12hrs for 4 doses 12 hrs
after start of methotrexate
• Day 8 cyclophosphamide 600mg/m2 iv
infusion
vincristine 1mg/m2 iv
bolus
Other regimen; MAC, EP-EMA, BEP
 Surgical management
• Subu-rethral deposits ---- apply under running
• sutures
• Solitary lung lesion ------- pulmonary
• lobectomy
• Uterine lesion --------- hysterectomy if family
• size is completed
• Intractable brain nodules--- craniotomy
• Haemorrhage from liver ----- embolization of
metastasis hepatic artery
 Radiotherapy
Liver metastasis
Multiple brain lesions
 Complications
• Anaemia
• Infections
• Haemorrhage
• Liver failure
• Renal failure
• Death
 Follow up
• Weekly, till 4 consecutive normal serum B-Hcg
values, thereafter for
• Stage I disease ---- monthly for 1 year
• Stages 2-4 ------monthly for 2 years
• Advise patient to prevent pregnancy during
this period with effective contraception
 PSTT
• This is a very rare disease. Unlike CC, PSTT has
human placental lactogen (HPL) as the tumour
marker.

• In this condition intermediate trophoblasts

rich in HPL invade the myometrium destroying
it and causing necrosis.
• . Majority of the patients have low levels of
Hcg, often times below 100 miu/mls.

• Treatment is by hysterectomy with

conservation of the ovaries if the patient is
premenopausal.
• For recurrent tumour or tumour with
metastasis, chemotherapy may be employed.
• If applicable, radiotherapy may aid in control
of local lesion
• THANK YOU FOR YOUR ATTENTION