Gestational Trophoblastic

Disease

M. Fauzie Sahil – M Rizki Yaznil

• Hipocrates  dropsy of the uterus
• Tombstone of Countess Henneberg (13th
century)
• William Smellie (1700)  the first to use the
terms hydatid and mole
• Velpeau and Boivin  hydatidiform mole as
cystic dilatation of chorionic villi
• Fels, Ehrhart, Roessler, and Zondek (early 20th
century)  demonstrated that an excess of
chorionic gonadotropin hormones could be
identified in the urine of patients with
hydatidiform mole
 A group of conditions which arises from
the fetal chorion
Abnormal (non molar)
villous lesion
Benign non neoplastic Exaggerated placental site,
trophoblastic lesion placental site nodule

Hydatidiform Mole Complete

Partial
Gestational
Choriocarcinoma

Placental Site
Trophoblastic Tumour GTN
Invasive Mole Gestational Trophoblastic Neoplasia

Postmolar GTN
Hydatidiform Mole
 Pathogenesis
• Imprinting
• Paternal genes  placental growth
• Maternal genes  fetal growth
• Y chromatin in only 9 percent of hydatidiform
moles, but 50 percent of invasive moles, and
74 percent of choriocarcinomas (Davis et al,
1984)
 Gestational Trophoblastic Neoplasia

• Spectrum of trophoblastic diseases that are locally

proliferative, have the ability to invade normal tissue,
and the potential to metastasize outside of the
uterus
GESTATIONAL CHORIOCARCINOMA
• Rare, highly malignant neoplasm
• Incidence 1 in 25.000-40.000 pregnancies
• Occur in patients with previous history of
molar pregnancy (50%), abortion (25%),
normal pregnancy (22%) and rarely ectopic
pregnancy
• May also be diagnosed concurrently with a
pregnancy but very rare
Choriocarcinoma. A dark-red,
hemorrhagic mass with a
shaggy, irregular cut surface
diffusely infiltrates the
myometrium
 PLACENTAL SITE TROPHOBLASTIC
TUMOUR (PSTT)
• Neoplasm of intermediate trophoblast derived from
placental site representing the malignant
counterpart of the exaggerated placental site
• Occurs most commonly following a normal
pregnancy or a nonmolar abortion, and may be
present after a latency period of 10 years
• Low or moderately elevated serum hCG levels
• Behave in benign fashion, only 10-15% malignant
(manifested by metastases)
 INVASIVE MOLE
• A variant of GTD in which the hydropic villi
invade the myometrium or blood vessels.
• Metastasis of molar vesicles may occur, and
usually invasive moles will undergo
spontaneous resolution after many months
• Treatment with chemotherapy to prevent
morbidity and mortality caused by uterine
perforation, hemorrhage or infection.
 POSTMOLAR GTN
• Recent recommendations for the diagnosis of
post-molar disease :
– hCG plateau for 4 measurements over 3 weeks or
more
– a rise in hCG for 3 measurements over 2 weeks or
more
– an elevated hCG at 6 months or more
– histological diagnosis of choriocarcinoma
• The most important advances  the standardisation
of terminology, and the concept of risk assignment
based on classification or staging systems which allows
rationalisation of treatment
 HISTORY OF CLASSIFICATION AND
STAGING
• Over the years there have been a variety of
staging and scoring systems
• Various anatomical,clinical and prognostic
scoring systems have been used.
 Early Classifications
• Earlier morphological and histological classifications 
fallen into disuse since, in many patients nowadays,
there is no precise pathological diagnosis
• The decision to treat persistent GTD is usually made on
hCG levels and clinical features
• In 1967  the International Union Against Cancer (UICC)
combined clinical with morphological criteria (table 1)
 A Gestational
B Non-gestational

I CLINICAL DIAGNOSIS
1. Non-metastatic
1. Metastatic
a. Local (pelvic)
b. Extrapelvic (specify location)
1. Other required information
a. Evidence
(i) Morphological
(ii) Non-morphological
a. Antecedent pregnancy – specify duration
(i) Normal
Table 1. GTD Classification (ii) Aborted
(iii) Molar
UICC 1967 4 a. Previous treatment
(i) Untreated
(ii) Treated, specify
II MORPHOLOGICAL DIAGNOSIS
1. Hydatidiform mole
a. Non-invasive
b. Invasive
1. Choriocarcinoma
1. Uncertain
1. Other required information
a. Diagnostic basis – specify
(i) C = curettage
(ii) U = excised uterus
(iii) N = necropsy
(iv) O = other
a. Date of diagnosis (with respect to date of onset of treatment)
b. Subsequent change in morphological diagnosis – specify diagnosis as in II,4a

Source: UICC, International Union Against Cancer, GTD gestational trophoblastic disease
• In the same time  Registration Committee of the
Japan Society of Obstetrics and Gynecology adopted,
and still uses, a morphological classification (table 2)
• If histopathological diagnosis is not available 
patients are classified as having either clinical
invasive mole or clinical choriocarcinoma using a
choriocarcinoma risk score (table 3)
 Table 3. Choriocarcinoma risk score 5

Score of ≤ 4 clinical invasive mole; score of ≥5, clinical choriocarcinoma

 Anatomical Classifications
• In 1982 the FIGO Oncology Committee  promoted
a staging system for GTD
• It is based on the work of Song and associates in
Beijing (table 4 and table 5)
• Unfortunately it was not universally accepted, since
it was soon recognized that prognosis varied greatly
within individual stages, depending on certain clinical
features, leading to under or over-treatment of some
patients
Table 4. GTD Staging FIGO 1982

Table 5. Song’s Classification for GTD

 Clinical Classifications
• Ross et al  identified other features of bad
prognostic  high hCG level, duration of disease
longer than 4 months and the presence of
metastases in the brain and/or liver
• Hammond et al  proposed a clinical
classification for GTD (table 6)  have been used
by many centres in USA because its simplicity and
easy to use.
• Dutch working party group (table 7)
Table 6. Hammond’s Southeastern Trophoblastic
Disease Centre clinical classification for GTD
• Clinical classifications  largely accurate in predicting
prognosis, but they do not take into account the
relative importance of individual prognostic factors
• This is highlighted in the scoring system presented by
Bagshawe in 1976 (table 10), which forms the basis of
the WHO (table 11) and Charing Cross (table 12)
systems
Table 8. Bagshawe Scoring System for GTD
Tabel 9. Sistem skoring WHO
• Bagshawe modification (1988)  due to low
score applied by WHO in their last column,
Bagshawe modified it from score 4 to 6
because concern about undertreatment
• There is still no agreement on which is best and
none has been shown to be superior to others
• The WHO score has generally been found to be
more predictive for prognosis than the FIGO
anatomical staging
• Drawbacks of WHO score  idiosyncratic
variations in the score allotted to the same risk
factors by different investigators and by
difficulties in applying certain scores (ABO group)
• In 1992 FIGO modified their staging system to
include certain risk factor (table 11)  adopted
by UICC in their TNM classification of GTT.
• Soper et al (1994)  retrospective evaluation of
the Hammond Clinical Class, WHO score and
modified FIGO staging  show equal efficiency
• And there some investigator that showed
different prognostic factors to predict failure of
single agent chemotherapy (Lurain et al, Ngan et
al, Bower et al, Kim et al, Nevin et al)
• The large number of existing systems and the fact
that no one system has gained universal acceptance
reflects various deficiencies in all of them  leads to
modification in FIGO staging and WHO scoring
system (2000), table 12

• This classification does not take account of molar

pregnancy not progressing to GTN, that PSTT will be
categorized separately and that chest X-ray will still
be used in the risk scoring of chest metastases.
Table 12. FIGO 2000, GTN Staging