Clinical Radiology (2009) 64, 857e871

REVIEW

Cancer presenting during pregnancy: radiological

perspectives
S. Doylea,*, C. Messioub, J.M. Rutherfordc, R.A. Dineena
a

Department of Radiology, Nottingham University Hospitals NHS Trust, Nottingham, UK, bSection of
Clinical Magnetic Resonance, Institute of Cancer Research and Royal Marsden NHS Foundation Trust,
Sutton, Surrey, UK, and cFoetomaternal Medicine, Nottingham University Hospitals NHS Trust,
Nottingham, UK

Received 22 May 2008; received in revised form 22 July 2008; accepted 25 August 2008

Malignancy presenting during pregnancy is rare. When it does, there are important considerations and challenges for
the radiologist. The physiological changes of pregnancy may mask signs and symptoms of malignancy leading to delayed presentation. Endocrine and physiological changes during pregnancy can interact with tumour biology to alter
the behaviour and patterns of growth of certain tumours. The timing and choice of imaging technique pose potential
risks to the foetus, but this must be weighed against the risks to both mother and foetus of inadequate investigation or
misdiagnosis. This review outlines the general principles and approach to imaging the pregnant patient with suspected
malignancy, following which there is a more detailed discussion of the effects of pregnancy on tumour biology and
presentation of specific tumours. Imaging strategies are discussed for the different entities, and where possible,
evidence-based imaging recommendations are made.
2009 The Royal College of Radiologists. Published by Elsevier Ltd. All rights reserved.

Introduction
Although rare overall, malignancy accounts for up
to one-third of maternal deaths during gestation.
The incidence of cancer in pregnancy has been estimated as affecting 1 in 1000 pregnancies,1 and 1
in 3000e6000 live births.2e4 This is less than in
non-pregnant women of the same age,5 which is
multifactorial. Much of the reduction in incidence
is likely due to infertility associated with the underlying diagnosis/treatment and women with
known cancer avoiding pregnancy. Delays or misdiagnosis of cancer in pregnancy may also be a contributory factor. The latest triennial report of
maternal deaths in the UK by the Confidential
Enquiry into Maternal and Child Health (CEMACH)

found a significant number of cases of delayed diagnosis of malignancy in pregnancy, despite overt
symptoms.6 This is of relevance to radiologists
when making decisions about the appropriateness
of radiological investigations during pregnancy.
In this review we consider the biological factors
that may alter tumour behaviour and diagnosis of
tumours presenting in pregnancy, and where possible, imaging strategies are presented. The
commonest cancers diagnosed during pregnancy
(Table 1) are reviewed, along with selected tumours of the brain and spine, which can behave
differently during pregnancy. The gestational trophoblastic tumours, which can coexist with viable
pregnancy, are also discussed.

Clinical considerations
* Guarantor and correspondent: Department of Radiology,
Nottingham University Hospitals NHS Trust, Queens Medical
Centre, Derby Road, Nottingham, NG7 2UH, UK. Tel.: 44
7976979094.
E-mail address: SDoyle76@aol.com (S. Doyle).

A common cause of delay in the diagnosis of cancer

in pregnancy is the mistaken attribution of
symptoms to the pregnancy itself (Fig. 1). The

0009-9260/$ - see front matter 2009 The Royal College of Radiologists. Published by Elsevier Ltd. All rights reserved.
doi:10.1016/j.crad.2008.08.020

858

S. Doyle et al.

Table 1








Commonest cancers in pregnancy.

Cervix
Breast
Melanoma
Lymphoma
Leukaemia
Thyroid
Ovary

physiological changes in pregnancy include

increased breast density and size, altered biomechanical stress on the spine, and abdomino-pelvic
compression, all of which increase as the pregnancy
progresses and can cause maternal symptoms.
Other common features of pregnancy include nausea and vomiting, particularly in the first trimester.
Therefore, many symptoms are common to both
pregnancy and malignancy, such as vomiting, abdominal pain, back pain, urinary symptoms, and
breast masses, and adequate clinical assessment
and investigation as appropriate are required to distinguish these. Based on analysis of mis- or delayed
diagnosis of malignancy in pregnancy, the latest
CEMACH report highlights concerning symptoms
that were under-investigated or erroneously attributed to other causes (Table 2).

Imaging considerations
Ionizing radiation and the foetus
Deterministic effects in the foetus (those resulting
from cellular damage occurring when a certain
dose threshold is exceeded) include death, malformation, growth restriction, and severe mental
retardation. The predicted thresholds for these
effects are all over 50e100 mGy and typically in
the order of hundreds of Gray. This is well above
the usual doses for most diagnostic radiological
tests (Table 3), and therefore, the advice is that
there is no significant risk of diagnostic medical exposures causing these complications.7,8 Only when
the foetal dose approaches the much higher radiation doses used in therapeutic radiotherapy are
deterministic effects a real concern (Table 4).
Stochastic effects in the foetus result from
radiation-induced modification of cells, and include induction of cancer and hereditary disease.
These are considered to have no dose threshold.
Current guidelines7 calculate the number of excess
cancer cases (both leukaemias and solid tumours)
up to age 15 years following irradiation in utero
as 1/13,000 per mGy for x-rays and gamma rays,

Figure 1 Malignancy masquerading as a complication

of pregnancy. A 35-year-old women presenting at 31
weeks of gestation with seizures and raised liver enzymes, presumed to be due to eclampsia. (a) Enhanced
cranial CT performed following an emergency Caesarean
section showed multiple brain metastases. Whole-body
CT demonstrated a T4 left upper lobe mass (b), subsequently confirmed by biopsy as an adenocarcinoma,
and multiple liver metastases.

from 5e6/52 post-last menstrual period (LMP).

This is on a background of a natural baseline UK
risk of childhood cancer of 1/500. The risk of heritable effects from foetal irradiation is thought to
be the same as that after birth, at 1/200,000 per

Cancer presenting during pregnancy

859

Table 2 Worrying symptoms in pregnancy which require

adequate investigation.







Weeks post-LMP

Severe abdominal or back pain

Sciatica
Urinary incontinence
Haematuria
Unexplained breathlessness
Significant weight loss

mGy for x-rays and gamma-rays. The natural incidence of heritable disease manifesting at birth is
estimated to be at least 1e3%. The predicted stochastic foetal effects from certain imaging tests
are listed in Table 5. The potential stochastic
effects on a pregnancy of up to 5e6/52 post-LMP,
although not zero, are judged much less.
Most radiological examinations in which the
foetus is not exposed directly to the primary x-ray
beam incur a foetal dose of less than 1 mSv, which is
mainly from internal scatter within the patient and
from leakage from the x-ray tube housing. For example, the mean foetal dose from chest computed
tomography (CT) is 0.06 mGy (with a possible maximum of 0.96 mGy), the average foetal dose is,
therefore, less than half the dose from an abdominal radiograph.7 Abdominopelvic shielding with
a lead-rubber apron equivalent to 0.5 mm lead
can significantly reduce dose from leakage radiation, but not the dose from internal scatter.8,10
In essence, the advice is that the majority of
diagnostic ionizing radiation exposures are unlikely
to increase the childhood risks of malignancy or
heritable disease significantly when compared
with the natural risk, and foetal exposure would
not justify the greater risks of invasive foetal
diagnostic procedures to the mother or foetus, or
termination of pregnancy to the mother.7,9 This
should be borne in mind if there is clinical need
Table 3 Maternal and foetal radiation doses from common
imaging tests.7,8,109
Imaging test

Maternal radiation
Foetal radiation
dose (mean effective dose (mGy)
dose mSv)
Mean
Maximum

Chest radiograph
Abdominal
radiograph
Barium enema
CT head
CT chest
CT abdomen
CT pelvis
99mTc bone
scintigram

0.2
1.7

<0.01
1.4

<0.01
4.2

9.0
2.0
9.1
8.0
9.4
5.0

6.8
<0.005
0.06
8.0
25
3.3

24
<0.005
0.96
49
79
4.6

CT, computed tomography.

Table 4
Radiation dose thresholds for foetal deterministic
effects.7,8
Foetal dose Potential deterministic
effects

2e4
>50e
(Pre-implantation)
100 mGy
2e8
>200 mGy
(Organogenesis)
8e15
100e
1000 mGy
After 15th week
>1000 mGy

Spontaneous abortion
but not malformation
Malformations
Severe mental
retardation
Mental retardation

for maternal imaging using ionizing radiation, in

situations where alternative imaging methods will
not suffice. Obviously the choice of investigation
should be the lowest radiation dose test to adequately answer the clinical question. Most work
to date on 2- [18F]-fluoro-2-deoxy-D-glucose
positron-emission (FDG-PET)eCT has excluded
pregnant patients, and although this technique is
being increasingly shown to be valuable in the assessment and staging of some cancers, currently
it has no established role during pregnancy.11
In cases where there is clinical need for imaging
involving direct irradiation of the foetus, current
advice for the radiologist includes taking all
possible technical measures to reduce the dose,
asking a medical physicist to make a preliminary
evaluation of the dose to the foetus, and giving the
mother all available information about the corresponding risk from that dose. If the mother is too
unwell to participate fully in this consenting
process, but urgent imaging is required, the
risk:benefit decision must be taken in consultation
with the referring physician. In such cases, recording the examination dose and performing and
recording an estimation of consequent risk is
recommended.8

Magnetic resonance imaging (MRI) and the

foetus
Although no definite adverse outcomes have been
established from MRI in pregnancy, there are some
Table 5
Risk of stochastic foetal effects from common
imaging tests.7
Mean foetal
radiation dose (mGy)

Risk of stochastic foetal effects

Childhood
cancer

0.005 (Chest radiograph)

<1 in a million
3.3 (99mTc-bone scintigram)1 in 4000
8 (CT abdomen)
1 in 1600
25 (CT pelvis)
1 in 500

Hereditary
disease
<1 in a million
1 in 60,000
1 in 25,000
1 in 8000

860

MRI-specific concerns that currently mean the

existing advice is to use MRI only in cases where
certain conditions are met; namely that the
clinical question cannot be answered by ultrasound; that patient management is likely to be
altered, and that the imaging cannot wait until
after birth.12e14 Despite the current lack of evidence of mutagenic risk in human foetuses, many
advise avoiding MRI exposure, if possible, during
the first trimester of pregnancy, the period of
foetal organogenesis.
One concern is over the potential for foetal
tissue heating, resulting from radiofrequency pulse
energy deposition. The specific absorption rate
(SAR), a measurement of energy deposition in the
patient during MRI examination, increases with the
static magnetic field strength, the number of
radiofrequency pulses, and the flip angle. However, it has been noted that foetal MRI has widely
used spin-echo sequences, which have a high SAR,
compared with low SAR gradient-echo sequences,
without proven detriment.15

Contrast media and the foetus

Another issue of potential safety concern with
both CT and MRI is that of foetal exposure to
contrast media. Both intravenously administrated
iodinated contrast agents and gadolinium chelates
are predominantly distributed in extracellular
water and rapidly excreted via the maternal
kidneys, but small amounts can cross the placenta.
Excretion is via the foetal urinary tract into the
amniotic fluid, which can then be ingested.
Although there is little available safety information currently, to date no adverse foetal effects
have been observed following maternal exposure
to iodinated contrast media or gadolinium chelates. However, foetal abnormalities have been
observed in rats after maternal gadolinium chelate
administration,16 and due to the paucity of human
safety data, exposure to these agents is avoided, if
possible, during pregnancy.17 No adverse effects
have been seen in infants after gadolinium chelate
exposure during pregnancy. Maternally administered iodinated contrast media containing free
iodide can potentially cause foetal or neonatal
hypothyroidism, hence current advice is to check
neonatal thyroid function during the first week of
life in infants exposed in utero.

Minimization of risk of aortocaval compression during imaging

An important consideration for any imaging technique in pregnant patients is correct positioning to

S. Doyle et al.

avoid aortocaval compression, a common phenomenon, particularly in the third trimester. Supine
positioning leads to compression of the inferior
vena cava and lateral displacement of the infrarenal aorta by the gravid uterus,18 which can lead to
a reduction in cardiac output by up to 24%.19 This
can manifest as the supine hypotensive syndrome,
with hypotension causing dizziness, pallor, sweating, tachycardia, and faintness. This can be
avoided by positioning the patient in a 5e10 left
lateral tilt, for example, using a foam insert or
pillow under the patients right side.

Tumours in pregnancy
Cervical
Tumour behaviour
Invasive cervical cancer is the commonest malignancy to occur during pregnancy, accounting for
up to 50% of pregnancy-related cancers, occurring
in around 1/2200 pregnancies.20 Histologically
there is no difference between the cancers of
pregnant versus non-pregnant women, with the
majority (90%) being squamous cell carcinomas.
The majority of women with cervical cancer are
asymptomatic, but can present with pain, vaginal
bleeding, or discharge. Therefore, if present,
symptoms can be masked by pregnancy, leading
to potential delay in diagnosis.21 Most reports
have found that cervical cancer in pregnancy was
more likely to be of lower stage, likely due to
patients undergoing cervical examination during
routine obstetric review.22 The weight of evidence
suggests that maternal survival is not adversely
affected by pregnancy.23
The effect of the cancer on the pregnancy
depends on whether the pregnancy can be continued without excessively delaying definitive treatment, which in turn depends on the stage of
pregnancy and cancer stage at diagnosis. Cervical
cancer spreads by local extension into adjacent
structures including uterus, vagina, and distal
ureters, and via the parametrium towards the
pelvic side wall. Lymphatic spread is initially to
the regional pelvic lymph nodes (parametrial,
obturator, iliac). Distant nodal involvement (e.g.,
para-aortic, inguinal) is a late feature, and distant
visceral metastases are uncommon.
Imaging strategy
Staging is required to plan treatment, which can
range from a watch-and-wait approach until after
birth for early stage disease, to radical surgery,

Cancer presenting during pregnancy

such as hysterectomy and pregnancy termination in

the first trimester, or radical Caesarean hysterectomy in the third trimester, with or without radiotherapy. Abdominopelvic staging is optimally done
using MRI, which can be used to assess the size of
the primary tumour and identify local invasion or
nodal disease, as well as identify distant metastases
within the abdomen and complications such as
hydronephrosis (Fig. 2). T2-weighted sequences
are most useful for delineating local extent and
nodal involvement.24 The commonest sites of distant metastases other than nodes are the lungs
and bones. Chest imaging options include a chest
radiograph or CT chest with abdominal shielding,
with other centres instead advocating the use of
a pulmonary-nodule sensitive MRI sequence such
as turbo spin-echo (TSE) or short tau inversion
recovery (STIR).25 CT is more sensitive than chest
radiography and MRI for detecting lung metastases,
but again the likelihood of findings changing

Figure 2 Cervical cancer presenting in pregnancy. A

24-year-old woman presented at 30/40 gestation with
vaginal bleeding. A suspicious cervical lesion, seen at
colposcopy, was biopsied, histology showed adenocarcinoma. MRI showed widening of the cervical canal but
preservation of the cervical stromal layers, and no local
extension or lymphadenopathy (radiologically FIGO
stage IB1), and the 31/40 fetus in a cephalic presentation (sagittal T2-weighted images shown). At 35/40 the
patient underwent a Caesarean section with subsequent
examination under anaesthesia, radical hysterectomy,
and pelvic lymph node dissection. Histology showed
a 20 mm moderately-differentiated cervical adenocarcinoma with negative nodes and no paracervical involvement (surgically FIGO stage 1B1).

861

management during pregnancy versus the risks of

radiation to both foetus and mother should be considered. If a whole-body skeletal survey for
metastases is required, a whole-body MRI with
turbo-STIR sequence has been advocated as an effective technique, with better sensitivity for bone
metastases than bone scintigraphy while avoiding
foetal radiation dose.26,27

Breast
Tumour behaviour
Pregnancy-associated breast cancer is commonly
defined as that diagnosed during pregnancy or
within 1 year postpartum, as the physiological
changes in breast tissue beginning in pregnancy
continue into the subsequent period of lactation.
Three percent of breast cancers present in women
who are either pregnant or lactating.28 Breast cancer is the second commonest cancer in pregnancy
after cervical cancer, affecting approximately
1/3000e10,000 pregnancies,29 and is the commonest cause of cancer death in women who are pregnant or lactating.30 It is currently seen mainly in
the 32e38 year age group of pregnant patients,
but as the average age at which women conceive
tends to increase, both the incidence and the average age at diagnosis are likely to rise.31,32
Histologically, pregnancy-associated breast cancers are similar to those in non-pregnant women of
reproductive age, with the majority being invasive
ductal carcinomas. The weight of evidence does not
support previous studies showing an excess of inflammatory breast cancer,33,34,30 with an incidence
of 2e4% being found in both populations. In pregnancy there are a relatively high proportion of
oestrogen-receptor negative (54e80%) and progesterone-receptor negative tumours,35 which is similar to the non-pregnant young female population,
although some studies suggest that the number of
oestrogen-receptor negative tumours is higher in
pregnancy than in age-matched controls.33 The relationship between hormonal factors in pregnancy
promoting or inhibiting tumourigenesis is complex,
and, as yet, incompletely understood. Raised serum
levels of oestrogen, progesterone, and prolactin
have been proposed as potential contributory factors,36,37 whereas some other pregnancy-related
hormones (human chorionic gonadotrophin, relaxin)
may inhibit tumour growth.38,39 A Swedish study of
breast cancer cases in women under 40 years suggested that BRCA1/2 mutation carriers were at increased risk of breast cancer during pregnancy,
possibly indicating a role for circulating oestrogens
in accelerating malignant transformation.40
Although some propose a hypothetical increase in

862

tumour aggressiveness in pregnancy, no survival

benefit is seen in those terminating the pregnancy.41
Breast imaging of the pregnant patient occurs
most frequently for evaluation of a palpable lump
(Fig. 3).42 This, combined with the potential masking of breast carcinoma by physiological breast
changes, results in pregnancy-associated cancers
often being larger and of later stage than mammographically detected cancers in the screening
population. Axillary lymph node involvement is
more likely at diagnosis (68 versus 40e50% in
the non-pregnant population).23 However, when
matched for stage and patient age, the overall
survival is similar.43

S. Doyle et al.

Imaging strategy
Historically there have commonly been delays in
diagnosing breast cancer in pregnancy, presumably
largely due to the masking of cancers by physiological changes in breast tissue. In certain series this
delay has been significant, averaging 10 months.44
The physical alterations in breast tissue during pregnancy include proliferation of ductal and glandular
breast tissues, leading to increased breast clinical
and radio-density, breast enlargement, and later,
milk production. The increased breast density persists post-partum until cessation of lactation, with
a radiological return to near the pre-pregnant appearance from 1e5 months post-lactation. Another

Figure 3 A 39-year-old woman presented at 27/40 with a 3 month history of a breast lump in the upper outer right
breast. Clinical examination revealed a 10 mm category B (indeterminate) mass centrally in the upper right breast. (a)
Targeted ultrasound of the right breast revealed a 15 mm category A (sonographically malignant) mass, which was biopsied under ultrasound guidance. (b) Bilateral mammography was normal (bilateral cranio-caudal views shown). Cancer was confirmed at biopsy, provisionally classified as grade 2. MRI was not performed in view of the difficulty of
prone imaging. Wide local excision with axillary node sampling and sentinel node biopsy was performed at 30 weeks.
The mass was radiologically visible on the excision sample. Histology showed clear margins around a 22 mm, grade 3,
invasive ductal carcinoma, with extensive surrounding ductal carcinoma in situ (DCIS) measuring 50 mm extending to
surgical margins. Axillary nodes were negative for tumour (stage 1). A joint decision was made with the obstetric team
to induce at 37e38/40, followed by chemotherapy and subsequent mastectomy.

Cancer presenting during pregnancy

factor delaying diagnoses may be reluctance to perform breast biopsy during pregnancy because of the
increased risk of bleeding, infection, and milk fistulae.45,46 There is evidence that this delay is now
shorter, but remains common.47,48
The differential diagnosis of breast lumps in
pregnancy and lactation is wide, with benign
lesions such as abscesses, galactoceles, and fibroadenomas common. Indications for imaging and
biopsy of pregnancy-associated breast lumps are
the same as for non-pregnant women of the same
age. However, there are some pregnancy-specific
considerations regarding choice of imaging technique. The initial imaging of a palpable breast
lump should be targeted ultrasound, which reliably
distinguishes cystic lesions, such as galactoceles,
from solid lesions. The commonest causes of a solid
breast mass in pregnancy or lactation are fibroadenomas and lactating adenomas, but if ultrasound demonstrates a solid lesion, this should be
biopsied without delay to exclude malignancy.
Core-biopsy is preferred to fine-needle aspiration
(FNA), as the hyperproliferative cellular state of
breast tissue in pregnancy can cause misinterpretation on FNA evaluation.49 The sensitivity of
breast ultrasound for malignancy in pregnancy
has generally been found to be better than that
of mammography, approaching 100%.50 However,
one small series found that sonographic appearances of breast cancer in pregnant women could
be atypical, for example, featuring cystic components and posterior acoustic enhancement.51
After ultrasound of a suspicious lesion, mammography has a role in assessing for synchronous lesions
and the presence of calcifications. There are few
data on the foetal dose received from modern
mammography systems. Older work widely quotes
an estimated foetal dose of 4 mGy from bilateral
two-view mammography, but recent work has found
a significantly smaller dose of less than 0.06 mGy,
which can be further reduced by between two to
seven times by the use of abdominopelvic shielding.52,53 However, mammography is often less useful
than ultrasound in pregnancy-associated breast
cancer, with a significantly higher false-negative
rate. The predominantly glandular background
parenchymal pattern on mammography in this younger population, in addition to the pregnancy-related
additional glandular proliferation, hyperaemia, and
oedema is more likely to obscure a cancer (Fig. 3b).
Reports of mammographic sensitivity for cancer
vary from only 25% up to 87% in pregnant
patients,54e56 but usually less than 70%.57,58 A small
series found that although the mass itself was not
visible on mammography in more than half of cases,
there were often secondary signs suggestive of

863

malignancy, such as axillary lymphadenopathy, suspicious calcifications, or skin thickening.51 In many

cases, the main role of mammography is to exclude
diffuse malignant-type micro-calcifications which
would preclude breast-conserving surgery. In this
scenario, a single projection instead of the standard
two views may be adequate.59
Contrast-enhanced MRI has reduced sensitivity
and specificity for cancer detection in dense
breast tissue, limiting the diagnostic value in
pregnant and lactating women.60 In addition, MRI
of the breasts is optimally performed with the patient lying prone, and therefore, is often impractical in the second half of pregnancy (see case).
Routine staging of asymptomatic patients has not
been shown to improve prognosis and is, therefore,
not indicated routinely. Further imaging is dictated
by symptoms, such as chest radiography for breathlessness. If liver metastases are suspected, ultrasound is an appropriate first investigation without
the safety issues of MRI, although MRI has better
sensitivity for liver metastases and may be required
if ultrasound is negative in cases with strong clinical
suspicion. Bone metastases in breast cancer tend to
predominate in the axial skeleton, and in
pregnancy, are optimally imaged with MRI. Brain
metastases are also optimally imaged by MRI.

Melanoma
Tumour behaviour
Melanoma is one of the commonest cancers in
women of reproductive age and its incidence is
increasing.61 Melanoma comprises 8% of malignancies diagnosed during pregnancy.62 A recent review
article63 attempted to debunk several widely held
beliefs about the relationship between melanoma
and pregnancy, including the beliefs that melanoma is commoner in pregnancy and has a worse
outcome in pregnant patients. This presumed association appears largely based on work from the
1950s, which did not use a control group or analyse
prognosis relative to disease stage.64 Since then,
the weight of evidence indicates that incidence
is unchanged between pregnant and non-pregnant
women,65 and that stage-for-stage the prognosis is
also unchanged.66 Melanomas in pregnant women
have been found in some series to be thicker
than in non-pregnant women66; one theory is that
false beliefs about hormonal effects on nevi result
in delayed investigation of an enlarging nevus. Although pregnancy and oral contraceptives often
cause increased skin pigmentation,67 it is a myth
that they commonly cause nevi to grow or
darken.68 Several series have shown an increased
incidence of lymphatic metastases in pregnant

864

patients compared with non-pregnant controls.69,70 Although the incidence of distant metastases and overall survival does not seem to be
significantly
different
between
the
two
groups,71,66 there are a limited number of longterm follow-up studies.
Imaging strategy
Staging of melanoma (American Joint Cancer Commission staging system) depends on the depth of the
lesion and the presence of regional lymph node or
distant metastases.72 In terms of imaging pregnant
patients with melanoma, the need for whole-body
radiological staging during pregnancy is a concern
only for the minority of patients. Around 85% of melanomas are stage I at diagnosis, with treatment of
localized disease (stages I and II) comprising surgical
excision  local lymph node dissection. Depending
on local practice, chest radiography and liver ultrasound may be used to screen for clinically unsuspected metastases. Stages III IV require
examination of the chest, liver, and regional lymph
nodes. In the first instance chest radiography and ultrasound of the liver and regional lymph nodes may
provide sufficient initial information to enable discussion of prognosis with the patient and to aid
treatment planning. Some patients given a diagnosis
of advanced metastatic melanoma, which has a very
poor prognosis, may decide to terminate the pregnancy. If the primary lesion is on the lower body or
lower extremities, ultrasound may be insufficient
to assess for pelvic nodal disease, in which case
MRI of the abdomen/pelvis would be preferable to
CT to avoid foetal ionizing radiation exposure. In addition, MRI can be helpful due to the characteristic
high T1, low T2 signal of paramagnetic melanin.
The considerations of best investigation for pulmonary metastases are as previously discussed.

Lymphoma
Tumour behaviour
Lymphoma is rare in pregnancy despite being the
fourth most frequent diagnosis of malignancy
made in pregnant women.73 Although less common
than non-Hodgkins lymphoma (NHL) in the general
population, the incidence of Hodgkins disease
(HD) peaks in young adults and is, therefore,
more frequently associated with pregnancy than
NHL, which is commoner in the older population.
HD most commonly presents with peripheral
lymphadenopathy, particularly cervical, and with
non-specific systemic symptoms such as night
sweats, weight loss, and malaise. The clinical
course and long-term survival rates in HD

S. Doyle et al.

(dependent on stage, but often above 80% in

young patients) do not significantly differ in
pregnancy.74,75
The incidence of NHL has increased over the last
few decades, in part due to the association with
human immunodeficiency virus (HIV) infection.
NHL tends to be at a higher stage when diagnosed
and have a worse prognosis than HD.76 Approximately two-thirds of NHL cases during pregnancy
are aggressive subtypes and disseminated (stage
4) disease. Burkitts lymphoma, an uncommon subtype usually occurring in childhood, can occur in
pregnancy. It has been theorized that hormonal
changes and increased blood flow in pregnancy
may aid dissemination of aggressive forms, such
as Burkitts lymphoma, with increased incidence
of breast, uterine, and ovarian involvement.75
An unusual presentation of lymphoma, which is
associated with pregnancy, is bilateral breast
lymphoma, primary or metastatic, most commonly
high-grade/Burkitts lymphoma. Bilateral breast
involvement with acute lymphoblastic leukaemia
has also been documented.77 Breast lymphoma can
present with uni- or bilateral breast enlargement.
Although this is usually clinically gross, far beyond
what might be expected as physiological during
pregnancy, this can initially be misdiagnosed as
mastitis.78,79
Imaging strategy
The staging of lymphoma in the non-pregnant
population is most commonly with CT of the chest,
abdomen, and pelvis  neck depending on the clinical site of disease, although PET-CT is being increasingly used in the staging and follow-up of
treatment response in lymphoma. In the pregnant
patient, the method and timing of staging depends
on whether there is an intention to continue the
pregnancy and the treatment strategy to be
used. A strategy to minimize foetal radiation
dose may include a chest radiograph or chest CT
with abdominopelvic shielding, and MRI without
contrast media of the abdomen and pelvis.

Thyroid
Tumour behaviour
Thyroid cancer is the commonest endocrine
malignancy, with an increasing incidence in the
general population over recent decades.80 Previous neck irradiation and a family history of thyroid
cancer are risk factors. It is approximately three
times commoner in women than men,81 and the incidence in pregnancy has been reported as up to
9e14 per 100,000 live births.82 The majority (up
to 80%) of thyroid cancers are well-differentiated

Cancer presenting during pregnancy

papillary cancers, which have an excellent prognosis with a 30-year survival of approximately 95%.90
Thyroid nodules occur in approximately 2% of
pregnant women, most benign in nature.88 Both
the development of new benign thyroid nodules
and the enlargement of pre-existing benign thyroid
nodules have been observed in pregnancy.83 It has
been proposed that thyroid tissue growth is stimulated during pregnancy due to close similarity between the beta subunit of hCG and that of
thyroid-stimulating hormone (TSH).84 The effects
of pregnancy on thyroid malignancy are not fully
understood. Some studies have suggested an acceleratory effect of pregnancy on the growth of thyroid cancer,85 whereas other series have not
found any such effect.83 The overall prognosis for
thyroid cancer diagnosed during pregnancy has
been shown to be not significantly altered from
cases diagnosed in age-matched, non-pregnant
controls.86,87
Imaging strategy
Approximately 5e13% of thyroid nodules will be
malignant. The prevalence of malignancy is similar
for patients with a solitary nodule as for those with
multiple nodules.89 Ultrasound of both the thyroid
and the cervical lymph nodes is the usual first-line
imaging investigation, with FNA biopsy of lesions as
appropriate. There are no diagnostic sonographic
features of malignancy, but certain features, particularly in combination, increase the likelihood
of malignancy. These include calcifications, solid
rather than cystic composition, hypoechogenicity,
irregular margins, absence of a benign-type
halo, cervical lymphadenopathy, and predominantly central rather than peripheral vascularity.90
Nodule size is not predictive of malignancy, and if
10 mm is used as the threshold before biopsy is
performed then some cancers will be missed. However, this must be balanced with the knowledge
that the majority of thyroid cancers are indolent
in nature, and that the treatment of subcentimetre cancers currently has an unproven effect
on life expectancy.90
Management of thyroid nodules is usually based
on the clinical, sonographic, and cytological findings. Other imaging methods have only a limited
role. Thyroid scintigraphy is contra-indicated in
pregnancy. In the rare cases of poorly differentiated aggressive thyroid cancers in pregnant patients, further radiological staging may be required,
usually comprising chest imaging as the lungs are
the commonest site of metastases. The diagnosis of
an aggressive-type tumour in pregnancy may lead to
elective termination in order to begin aggressive
treatment. The more usual treatment of well-

865

differentiated papillary thyroid cancer often

involves total thyroidectomy, followed by 131I ablation of any residual thyroid tissue. If diagnosed during pregnancy, surgery is either performed in the
early-mid second trimester or delayed until after
delivery depending on the particular clinical
circumstances and local practice. 131I ablation is
delayed until after delivery and breast-feeding if
surgery is performed during pregnancy; it can be
given 3e6 months after delivery if the thyroid cancer is a typical low-grade papillary malignancy.91

Ovarian
Tumour behaviour
Although the second commonest gynaecological
cancer encountered in pregnancy, ovarian cancer
is rare, occurring in the range of 1/9000 to 1/
25,000 pregnancies.92 This is in contrast to the frequent finding of adnexal masses during pregnancy,
commonly during routine obstetric imaging; one
series reported this finding in up to 1/190 pregnancies.93 The vast majority of these prenatally
discovered adnexal masses prove benign, most
being corpus luteum or other functional cysts
that usually resolve by 16 weeks gestation.94 Only
3e5% of adnexal masses are subsequently found
to be malignant.95 Adnexal masses before 16
weeks are usually asymptomatic and found on routine ultrasound; after 16 weeks with the enlarging
uterus adnexal masses are more likely to become
symptomatic, presenting with torsion (15%), pain,
or haemorrhage.94 CA125 levels are not reliable
in pregnant patients for diagnosis or follow-up of
ovarian cancer.
Imaging strategy
Ultrasound, including the use of Doppler, may be
the only required imaging method in the investigation of adnexal masses. Benign characteristics
include asymptomatic unilocular unilateral cysts
under 6 cm in size, which are often physiological
and usually resolve by the end of the first trimester. Worrying features include solid components,
size over 6 cm, bilaterality, ascites, and a low resistive index to blood flow on Doppler assessment,
whereas masses with a high resistive index are very
likely benign even if persisting into the second trimester.96 MRI may be helpful in further characterization in cases where ultrasound is equivocal, but
in the presence of these concerning features examination at laparoscopy or laparotomy is usually
required. In cases with features suspicious for malignancy, initial staging is usually surgical. The majority of ovarian malignancies diagnosed during
pregnancy are at an early stage (FIGO stage I).

866

S. Doyle et al.

The prognosis is similar to that in non-pregnant

women.94

Brain and spine

Tumour behaviour
Tumours of the brain and spinal cord are rare in
pregnancy, with an estimated incidence of 3.6
cases of primary malignant brain tumours per
million live births (a figure that excludes meningiomas, vestibular schwannomas, and pituitary neoplasms).97 The relative frequency of different
types of intracranial tumours is unchanged in pregnancy compared with age-matched non-pregnant
women.98 Thirty-two percent of brain tumours in
pregnancy are gliomas, 29% meningiomas, 15% vestibular schwannomas, and other rarer types (such
as cerebellar astrocytoma and medulloblastoma)
account for 6% or less each. Spinal tumours diagnosed in pregnancy are even rarer, the majority
(61%) of these are benign vertebral haemangiomata, with spinal meningiomas second commonest
(18%).99
Pregnancy can cause rapid enlargement of tumours, particularly meningiomas, pituitary adenomas, vestibular schwannomas, and cerebellar
haemangioblastomas. Proposed mechanisms include
vascular engorgement and increased fluid content,
as well as hormonal effects. Approximately 90% of
meningiomas have high-affinity progesterone receptors and 30% have oestrogen receptors, which may
explain their propensity to grow during pregnancy
(Fig. 4). Postpartum improvement in symptoms has
especially been described in association with meningiomas and spinal vascular tumours,98 although neurological deficit may persist beyond delivery.100
Thirty percent of pituitary macroadenomas enlarge
in pregnancy to the extent that medical or surgical
intervention is needed, either treatment during
pregnancy, or treatment after induction of an early
delivery. In one series 17% of pregnant women with
vestibular schwannomas developed new or worsening symptoms during the last month of pregnancy.101
Small studies have found oestrogen receptors in
44e100% of vestibular schwannomas.102,103
Gliomas most commonly present in the third
trimester of pregnancy. Although the prognosis
stage for stage is similar to non-pregnant patients,
symptoms can be dangerously exacerbated at
birth, with raised intracranial pressure causing
brain herniation (Fig. 5).104 Clinical features of
brain tumours include headache, nausea, and vomiting due to raised intracranial pressure, neurological deficits, and fits. Constant or daily headache
should not be attributed to pregnancy, particularly
in patients with no past history of headache.

Figure 4 Meningioma presenting during pregnancy. A

25-year-old woman with headaches in the third trimester
developed acute deterioration of visual acuity in the
right eye at 35 weeks of gestation. A pituitary cause of
the visual loss was suspected and MRI was performed.
Contrast-enhanced, T1-weighted, (a) coronal and (b)
sagittal images show a meningioma arising from the region of the tuberculum sellae and planum sphenoidale,
with normal appearances of the pituitary gland (short
black arrow). The tumour abuts the optic chiasm (short
white arrow) and displaces the cisternal portions of the
optic nerves superiorly and laterally (long white arrows).

Nausea and vomiting in pregnancy can be mistaken

for morning sickness, although this usually predominates in the first trimester and then tends to
remit, unlike tumour-related sickness. Seizures in
pregnancy, particularly in the second half of pregnancy, are more likely to be due to eclampsia than

Cancer presenting during pregnancy

867

diffusion-weighted imaging, perfusion MRI, and

magnetic resonance spectroscopy can aid tumour
characterization, and should not be withheld if the
information gained from these techniques could
potentially influence treatment decisions.
CT has a valid role for urgent cases in which raised
intracranial pressure is suspected. The average
foetal dose from a CT brain is less than 0.005 mGy,7
which has minimal detrimental implications for the
foetus. Hence for urgent investigation of worrying
neurological symptoms there should be no delay
due to concerns about foetal radiation exposure.
For spinal compression symptoms, again MRI is
the technique of choice. In this context the need
to urgently assess for a remediable cause would, in
practice, outweigh the general advice to avoid MRI
in the first trimester of pregnancy.

Gestational trophoblastic tumours

Figure 5 Glioma presenting in pregnancy. A 23-yearold presented at 19 weeks gestation with headaches
and a single seizure. MRI was performed to exclude
venous sinus thrombosis, but showed a large, bland,
left frontal tumour felt to be consistent with a low-grade
glioma. Coronal T1 images at 31 weeks showed a significant mass effect with midline shift and tumour
displacing the optic chiasm (white arrow), although
this had not changed significantly from the initial MRI.
Following consultation between the neurosurgical and
obstetric teams, elective Caesarean section was
performed at 36 weeks.

brain tumour. As a guide, intracranial tumour

should be considered as a cause for seizures
when seizures are focal or when there are no other
features of eclampsia.100
Vertebral haemangiomas can become symptomatic in pregnancy, most commonly in the thoracic
region.100 Spinal meningiomas are also commoner
in the thoracic region, and like intracranial meningiomas may rapidly grow during pregnancy. Both
symptomatic vertebral haemangiomas and spinal
meningiomas most commonly present in the third
trimester with painless leg weakness and paraesthesia, and later with sphincter disturbance.
Back pain is not typical, but if a pregnant patient
does present with thoracic back pain, this should
not be confused with common pregnancy-related
mechanical lower back pain.
Imaging strategy
MRI is the method of choice for imaging suspected
central nervous system (CNS) tumours in pregnancy,
predominantly for its ability to characterize tumours, showing greater sensitivity and specificity
for brain tumours than CT. Contrast-enhanced MRI,

Tumour behaviour
The gestational trophoblastic tumours (GTT) represent a unique group as they are the only tumours
to arise as a direct consequence of pregnancy. GTT
almost always develops with or following a pregnancy, 50% following a molar pregnancy, 25% after
a pregnancy not carried to term, and 25% after an
apparently normal pregnancy. This equates to an
8% risk of GTT after a complete molar pregnancy,
0.5% risk after a partial molar pregnancy, and
1/50,000 risk after a full-term pregnancy.105
Pathologically the group comprises invasive
hydatidiform mole, placental site trophoblastic
tumour, and choriocarcinoma.106 GTT commonly
present with persistent vaginal bleeding post-partum, but not uncommonly present with metastases, and are usually diagnosed by persistently
high serum b-hCG.
Choriocarcinoma is the most malignant form
with early blood-borne metastases. The incidence
is 0.02e0.2/1000 pregnancies. Vaginal bleeding is
present in only 50e60% of cases. Presentation is
commonly with metastatic symptoms usually in the
late post-partum period, but can be delayed for
months to years following the pregnancy. Metastases are typically hypervascular/haemorrhagic,
with commonest sites being lung (75e87%) and
vagina (50%), with other common sites including
vulva, kidneys, liver, ovaries, brain (3e20% will
have brain metastases at diagnosis), and bowel.
The diagnosis of metastatic choriocarcinoma
should always be considered in women recently
post-partum presenting with cough or haemoptysis, but also in any woman of reproductive age with
haemorrhagic lesions or widespread metastatic
disease of unknown cause.

868

Imaging strategy
Ultrasound with colour Doppler is widely used to
assess GTT for location and degree of myometrial
invasion, although in some centres transvaginal
ultrasound is avoided in known GTT because of the
potential risk of causing bleeding from vaginal
metastases.106 Trophoblastic tumour nodules tend
to be surrounded by neo-vasculature, commonly
with arterio-venous anastomoses. Characteristically on ultrasound the appearance is of hypoechoic
blood lacunae surrounded by irregular echogenic
trophoblastic nodules with multiple intramyometrial vascular shunts. These intramyometrial vessels
typically have low resistive index and high peak systolic velocities.107 These features can also be used
to monitor response to treatment, with the resistance to flow usually inversely proportional to the
serum b-hCG level. Uterine volume can also be measured on ultrasound, which is related to tumour burden and used to aid staging (FIGO 2000). MRI does
not have a routine role in imaging local GTT, but
can be useful in assessing parametrial or other local
invasion, and is the preferred technique for assessing vaginal metastases.106
Further investigation for suspected metastasis is
required following primary treatment if there are
persistently raised b-hCG levels or symptoms of
concern. In the absence of lung or vaginal metastases, other metastatic disease is unlikely, and
therefore, chest imaging either with chest radiograph or CT is an appropriate first investigation for
metastases. In choriocarcinoma, the commonest
cause of metastatic GTT, the haematogenous
pulmonary metastases are typically multiple
rounded soft-tissue densities measuring up to
3 cm in diameter, usually less than 10 in number.
Less common thoracic manifestations include
miliary metastases, intravascular tumour causing
infarction, and airspace opacification due to haemorrhage. Although CT detects more pulmonary
nodules than a chest radiograph, it is not established whether this affects management.106 If CT
is used, low-dose lung CT protocols have shown
adequate levels of detection for accurate staging
purposes, despite not detecting as many small
nodules as standard thoracic CT.108 Imaging of
the brain, chest, abdomen, and pelvis may be
required depending on symptoms. In practice, as
patients found to have lung or vaginal metastases
are at high risk of metastases at other sites,
usually further imaging is appropriate in these
patients, including abdominal CT to assess for liver
metastases, and brain MRI. Liver metastases are
typically multiple hypodense masses on noncontrast CT, which enhance avidly in the arterial
phase. Brain metastases are typically multiple,

S. Doyle et al.

most commonly occurring at the greyewhite matter junction in the parietal lobe.106

Conclusion
Pregnancy should not preclude investigation of
serious symptoms. Investigating pregnant women
for cancer requires careful consideration of the
potential risks and benefits of various imaging
methods. In many cases the pregnant woman can
be adequately investigated and staged without
significant risk to the foetus. This is essential not
only for treatment planning, but also to provide
prognostic information to inform the clinician and
womans decision making.
Effective communication between members of
the multidisciplinary team is critical in the care of
these women. As a key member of this team, the
radiologist has a vital role in communicating the
potential risks and benefits of the various imaging
methods to other professionals, and when appropriate, directly to the patient.

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