1. Clinical Radiology (2006) 61, 301–313
Radiology of gestational trophoblastic neoplasia
S.D. Allena, A.K. Lima, M.J. Secklb, D.M. Blunta, A.W. Mitchella,*
Departments of aRadiology, and bMedical Oncology, Charing Cross Hospital, Hammersmith Hospitals NHS
Trust, London, UK
Received 5 September 2005; received in revised form 26 October 2005; accepted 5 December 2005
Gestational trophoblastic neoplasia (GTN) encompasses a broad spectrum of placental lesions from the pre-malignant
hydatidiform mole (complete and partial) through to the malignant invasive mole, choriocarcinoma and rare placental
site trophoblastic tumour (PSTT). Ultrasound remains the radiological investigation of choice for initial diagnosis, and it
can also predict invasive and recurrent disease. Magnetic resonance imaging is of invaluable use in assessing extra-
uterine tumour spread, tumour vascularity, and overall staging. Positron emission tomography and computed
tomography undoubtedly have a role in recurrent and metastatic disease, while angiography has a place in disease and
complication management. This review will describe the relevant pathophysiology and natural history of GTN, and the
use of imaging techniques in the diagnosis and management of these conditions.
Q 2006 The Royal College of Radiologists. Published by Elsevier Ltd. All rights reserved.
Introduction 0.5–1/1000 and PHM are 3/1000 pregnancies in
Europe, though in Southeast Asia they are highest,2
Gestational trophoblastic neoplasia (GTN) com- up to 8/1000 in Thailand.3 The reason for this
prises a spectrum of placental lesions that arise variation is not understood, though genetic, as well
from pregnancy and vary considerably in their as socio-economic/dietary and environmental
clinicopathological behaviour. Hydatidiform factors, have been implicated.3,4
moles, which often behave benignly, are best Increased risk of CHM and PHM occurs at the
regarded as pre-malignant because 16% of complete extremes of reproductive life, with women over 40
(CHM) and 0.5% of partial moles (PHM) can trans- years having at least a ﬁvefold increase in risk.5
form into the malignant forms of GTN, which Also, a previous molar pregnancy is a predisposing
include invasive mole, choriocarcinoma and pla- factor.6 Choriocarcinoma and PSTT can arise after
cental site trophoblastic tumour (PSTT).1 The latter any type of pregnancy including CHM, PHM,
disorders are also termed collectively as gestational miscarriage and term delivery.7,8 The incidence of
trophoblastic tumours (GTT). choriocarcinoma arising after miscarriage or term
It is important to recognize GTN, as it is almost delivery is estimated to be 1/50,000 pregnancies.
always curable with preservation of fertility. The PSTT is so rare that accurate data on its incidence
many roles of imaging in this disease, from diagnosis or prevalence are not available.
to treatment, are discussed. Clinical assessment is difﬁcult particularly early
in the course of the disease, as few clinical
characteristics are present to distinguish it from a
Background normal pregnancy. GTN is suspected in patients
with vaginal bleeding and a clinically enlarged
The frequency of GTN varies tremendously with uterus, though these features are non-speciﬁc.
geography. Rates of CHM are approximately The presence and course of the disease is monitored
with quantitative levels of serum beta human
chorionic gonadotrophin (hCG), which provides a
* Guarantor and correspondent: A.W. Mitchell, Department of
valuable evaluation of the amount of trophoblastic
Radiology, Charing Cross Hospital, Hammersmith Hospitals NHS
Trust, Fulham Palace Road, London W6 8RF, UK. Tel.: C44 20
disease present.9 The radiological diagnosis of CHM
8846 1863; fax: C44 20 8846 1885. and PHM is also often made at an early pregnancy
E-mail address: email@example.com (A.W. Mitchell). ultrasound scan.
0009-9260/$ - see front matter Q 2006 The Royal College of Radiologists. Published by Elsevier Ltd. All rights reserved.
2. 302 S.D. Allen et al.
The majority of CHM have a 46XX diploid slow growing, tends to spread locally through the
chromosomal pattern and occur most commonly uterus and can involve lymph nodes (a very rare
when a single haploid sperm fertilizes an ovum ﬁnding for choriocarcinoma) before metastasizing
lacking maternal genes, and then undergoes dupli- elsewhere. PSTT also tend to be relatively poorly
cation. Macroscopically CHM classically resembles a vascularized tumours.17,19 Due to the lack of
bunch of grapes, due to generalized swelling of syncytiotrophoblastic tissue, serum hCG levels
chorionic villi, and pathologically, is composed of are often only modestly elevated, although we
syncytiotrophoblastic and cytotrophoblastic have never had a case at our institute where the
cells.10 These are usually intrauterine in site, hCG was not elevated. PSTT are also relatively
though may contain some foetal tissue if coexistent chemoinsensitive, so when the disease is localized
with a normal foetus and placenta in a dizygotic to the uterus hysterectomy is recommended.
twin pregnancy. This can be a cause of pathological However, women with metastatic disease can
misdiagnosis, as they may be classiﬁed as PHMs.11 still be cured with aggressive chemotherapy. The
PHMs are genetically triploid, most commonly main factor in determining outcome is the
the result of fertilization of a normal egg by two duration from the causative pregnancy: those
sperm.12 Villous swelling is less intense, and an treated within 4 years are nearly always cured
embryo is usually present, which may live into the whilst those diagnosed beyond this time have so
early second trimester. However, the villous far had a 100% death rate.
swelling and trophoblast may be so subtle, that Several systems have been used to classify the
many PHM are missed during evacuation for a severity of GTN, including the Bagshawe scoring
“miscarriage”, or during spontaneous abortions.10 system,20 WHO score,21 and Charing Cross Hospi-
Flow cytometry can be useful to distinguish these tal prognostic scoring system.22 These all use
from hydropic abortions and other non-molar factors that have long been recognized as
chromosomal duplication syndromes.13 predictive of poor outcome. More recently a
A CHM or PHM that invades the myometrium is new International Federation of Gynaecologists
termed an invasive mole and can be diagnosed on and Obstetricians (FIGO) scoring system has been
ultrasound and on a rising hCG after uterine developed and most centres use this to enable
evacuation. Choriocarcinoma encompasses many better comparison of patient response and
abnormal karyotypes and can arise following any outcome (Fig. 1).23
pregnancy, including PHMs. It is highly malignant, The scoring systems have enabled simple strati-
necrotic and haemorrhagic, microscopically resem- ﬁcation of patients into two therapeutic groups.
bling an implanting blastocyst containing cytotro- Those with a low FIGO score (%6) have a low risk of
phoblastic elements and absent chorionic villi. It is developing disease resistant to single drug therapy
locally angio-invasive.10 Choriocarcinoma arising (methotrexate or actinomycin D) whilst those with
after a miscarriage or term delivery may not a high score (O6) require multi-agent combination
present for many years, can be normal on pelvic chemotherapy (Table 1 and Fig. 1). The FIGO
ultrasonography and simply display as distant staging carries little prognostic signiﬁcance and is
metastatic disease with an elevated hCG. It is noted but not used to determine therapy. It should
typically highly vascular and patients may present be noted that PSTT are not classiﬁed under this
with signs of haemorrhage at any involved sites.14 scoring system and those patients with metastatic
Rarely patients may present with concurrent PSTT require very aggressive multi-agent
metastatic disease, most commonly in the lung chemotherapy.
and vagina, but this can occur anywhere, including Approximately 84% of patients with CHM and
the liver and brain. 99.5% of patients with PHM will be cured after
PSTT is the rarest form of GTN, but deserves suction evacuation of the uterus.7,24 Other surgi-
separate consideration, as it behaves in a distinct cal techniques such as hysteroscopy and hyster-
fashion.15 This represents a neoplastic prolifer- ectomy are not favoured as they signiﬁcantly
ation of intermediate trophoblasts that invade the increase the likelihood of the need for chemother-
myometrium at the placental site after preg- apy, thought to be due to the uterine manipu-
nancy.16 They may develop from an antecedent lation. Second evacuation is only rarely successful
normal pregnancy, abortion or after either a CHM at reducing the risk for chemotherapy and is
or PHM,8 though the foremost is the commonest generally not recommended. 10 Patients with
scenario.17 Clinical presentation is often with malignant disease following CHM or PHM are
irregular vaginal bleeding but may be a conse- usually at low risk of developing disease that is
quence of metastatic disease.18 Unlike other resistant to treatment with a single drug (metho-
forms of malignant GTN, PSTT is often more trexate or actinomycin D) and overall have an
3. Radiology of gestational trophoblastic neoplasia 303
Figure 1 Algorithm for the management of gestational trophoblastic neoplasia.
almost 100% cure rate.25 However, patients with Imaging features
high scoring disease that receive multidrug
combination chemotherapy with etoposide, meth- Ultrasound
otrexate, adriamycin, alternating weekly with
cyclophosphamide and vincristine (Oncovin) Ultrasound is the radiological investigation of choice
(EMA–CO) have an 80–90% cure rate.25–27 for initial diagnosis of GTN. As well as identiﬁcation
Table 1 The revised FIGO 2000 scoring system.
FIGO score 0 1 2 4
Age (years) !40 R40 – –
Antecedent pregnancy Mole Abortion Term –
Interval months from index pregnancy !4 4–6 6–12 O12
Pre-treatment hCG (mIU/ml) !1000 1000–10,000 10,000–100,000 O100,000
Largest tumour size including uterus (cm) !3 3–5 O5 –
Site of metastases Lung Spleen, kidney Gastro-intestinal Liver, brain
Number of metastases – 1–4 5–8 O8
Previous failed chemotherapy – – Single drug Two or more drugs
FIGO staging for gestational trophoblastic neoplasia 2000. FIGO Oncology Committee. Int J Gynaecol Obstet 2002;77:285–7. Low risk
patients scoring 6 or less receive single drug therapy with either methotrexate or actinomycin D and those scoringO7 are treated
with multi-agent EMA/CO chemotherapy.
4. 304 S.D. Allen et al.
after evacuation of the molar tissue. However,
this distinction does not affect the management as
both need to be evacuated. Classically with PHM,
the placenta is enlarged and thickened and contains