Ann Nucl Med (2009) 23:107–112
DOI 10.1007/s12149-008-0227-z
REVIEW ARTICLE
Benign ovarian and endometrial uptake on FDG PET-CT:
patterns and pitfalls
Yiyan Liu
Received: 14 October 2008 / Accepted: 27 November 2008
© The Japanese Society of Nuclear Medicine 2009
Abstract Increased ovarian or endometrial uptake may
cause a dilemma in the interpretation of whole body
F18-fluorodeoxyglucose-positron emission tomography
(FDG-PET) imaging or even misdiagnosis of malignant
disease. Knowledge of benign FDG uptake of the ovaries
and uterus is important for daily practice of nuclear
medicine radiologists. Increased uptake in the ovaries or
uterus indicates a pathologic or neoplastic process in
postmenopausal patients. In premenopausal women,
increased ovarian or endometrial uptake can be func-
tional or malignant. Benign functional uptake of pre-
menopausal ovaries or uterus is related to the menstrual
cycle; therefore, information about the patient’s men-
strual status is crucial for interpretation. In addition,
correlation with computed tomography (CT), especially
diagnostic CT acquired at the same time of PET/CT is
very useful in clarifying the location of the uptake
and the existence or disappearance of the discrete
lesion. Increased ovarian uptake may also be identified
in histologically different benign tumor entities. Non-
menstrual-related endometrial uptake may be present in
many benign diseases as well.
Keywords FDG-PET · Ovaries · Endometrium ·
Menstrual cycle
Y. Liu
Nuclear Medicine Service, Department of Radiology, New
Jersey Medical School, Newark, New Jersey
Y. Liu (*)
Nuclear Medicine, University Hospital, H-141, 150 Bergen
Street, Newark, NJ 07103, USA
e-mail: liuyl@umdnj.edu
Introduction
Positron emission tomography (PET) with a labeled
glucose analog, F18-fluorodeoxyglucose (FDG) is a
valuable diagnostic tool that is widely used to survey
malignant and inflammatory disease [1, 2]. FDG-PET is
an imaging modality for abnormality of function or
metabolism in tissue and organs, which usually precedes
anatomic change. Another significant advantage of posi-
tron emission tomography-computed tomography (PET-
CT) imaging over anatomic imaging modalities is routine
whole body acquisition without additional radiation
exposure to patients. But on the other hand, radiotracer
FDG is for the measurement of glycolysis and not spe-
cific in accumulation for malignancy. On whole body
imaging of women patients of active reproductive age, it
is not uncommon for focal uptake to exist in the ovaries
or uterus, which may cause a dilemma in interpreting the
scan and even lead to false-positive results. Therefore,
knowledge of some benign FDG uptake of the ovaries
and uterus is important for daily practice of nuclear
medicine radiologists.
In the pelvis, physiologic uptake is often noted in the
alimentary or genitourinary tract on FDG PET-CT
scan. Most of this uptake is easily identified with its lin-
earity and confinement to the colon, ureter or urethra.
In the cases of focal uptake, correlation with CT images
can help to identify location of the uptake and exclude
pathology [3]. Uptake in the reproductive tract of a
woman patient is relatively more treacherous in inter-
pretation. In this article, we discuss and illustrate some
patterns and pitfalls of benign ovarian and endometrial
uptake, as well as compare benign with malignant
uptake.
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Ovarian uptake
In general, normal postmenopausal ovaries have no
visible FDG uptake. Lerman et al. [4] reported that
increased ovarian uptake was not noted in any of the 134
postmenopausal patients without known gynecologic
malignancy. Nishizawa et al. [5] prospectively studied
FDG-PET scans of 55 postmenopausal women volun-
teers and no uptake was identified either. Zhu et al.’s
serial FDG-PET scans for 10 postmenopausal women
with non-gynecological malignancies also confirmed
lack of ovarian uptake [6]. Therefore in postmenopausal
women, any focal uptake in the region of the ovaries or
adnexa usually indicates malignancy and should be con-
sidered pathologic until proven benign.
In contrast, in premenopausal women focal FDG
uptake is often identified in the normal ovaries in corre-
lation with the menstrual cycle, which resembles a patho-
logic uptake, for example, lymph node and could cause
misinterpretation of the FDG PET-CT scan.
There were scattered case reports about focal uptake
of normal ovulating ovaries, ovarian torsion and hemor-
rhage as well as corpus luteal cysts [7–13]. In a few series
studies, Lerman et al. [4] observed increased FDG uptake
in the ovaries of 21 of 112 premenopausal patients
without known gynecologic malignancy. Fifteen of these
patients were imaged near the time of ovulation as
judged by the presence of functional ovarian cysts on
CT. In Nishizawa et al.’s prospective study, 26 of 78
premenopausal women had focal ovarian uptake during
the late follicle to early luteal phase [5]. Zhu et al. [6] did
serial follow-up FDG-PETs (two to four scans) for the
same patient with different menstrual status in a total 14
premenopausal subjects. The findings confirmed that
prominent ovarian uptake was only seen in the midcycle
Fig. 1 Transaxial computed tomography (CT) (left), F18-fluoro-
deoxyglucose-positron emission tomography (FDG-PET) (middle)
and fusion (right) images of the pelvis in a 39-year-old woman with
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Ann Nucl Med (2009) 23:107–112
of the menstruation. Kim et al. [14] retrospectively
reviewed FDG PET-CT findings in 449 women patients
with breast cancer, cervical cancer, and endometrial
cancer or for regular checkup. They found that there was
focal ovarian uptake in 19 cases, 15 of which did not
have FDG uptake anymore on short-term follow-up
PET-CT. Three patients underwent oophorectomy com-
bined with hysterectomy for cervical or endometrial
cancer, and pathology of the ovaries with uptake was
either normal (two cases) or hemorrhage corpus luteum
(one case). All noted ovarian uptake attributed normally
developed ovarian follicles and corpora lutea between
the 10th and 25th days of the menstrual cycle.
Physiologic FDG uptake in the ovaries is usually
observed in the late follicular to early luteal phase [4–6,
14]. Typically, this kind of benign ovarian uptake is
spherical or discoid, exhibits a smooth margin and
locates above the urinary bladder and around the uterus
(Fig. 1). The uptake is most unilateral [5]. Corpus luteal
uptake is usually more intense than an ovulating ovary.
In contrast, lymph node uptake is more peripheral and
close to pelvic wall in location, typically along the iliac
vessels (Fig. 2).
A periovulatory process is involved in an inflamma-
tory reaction and/or increased energy demands. It was
reported that ovarian glucose uptake increases in mid-
cycle to meet metabolic demands of the growing follicle
and ovulated cumulus enclosed oocyte, with enhanced
Glut3 expression [15]. The rupture of the follicle is also
considered to be an inflammatory reaction mediated by
cytokine [16].
Corpus luteal cysts are normal physiologic ovarian
structures formed following ovulation by the dominant
follicle when the follicular wall becomes vascularized,
thickened, and partially collapsed [17]. Corpus luteum
breast cancer at the menstrual cycle day (MCD) 17. A right adnexal
low density structure is visualized with intense uptake, consistent
with a corpus luteal cyst
Ann Nucl Med (2009) 23:107–112
Fig. 2 A case with surgical pathology confirmed right external iliac
nodal metastasis in a 46-year-old woman newly diagnosed with
cervical cancer. The patient’s MCD was unclear owing to vaginal
bleeding. Transaxial CT (left) of the pelvis demonstrates a discrete
development is a complex process involving mechanisms
that are similar to wound healing and tumor formation.
An essential component of corpus luteum development
is the recruitment of blood supply [18]. In addition, cyto-
kines are also thought to be involved in angiogenesis of
the corpus luteum [16].
To avoid significant uptake of the ovaries, it is prefer-
able to schedule FDG PET-CT scans of premenopausal
women just subsequent to menstruation [14]. When focal
uptake is visualized in the adnexal region, information
about the patient’s menstrual status is crucial for inter-
pretation. However, be aware that some patients with
current radiation and/or chemotherapy may have a very
irregular menstrual cycle. In addition, physiologic FDG
uptake is also observed in the ovaries of women of repro-
ductive age even subsequent to hysterectomy [19]. There-
fore, it is not practical to obtain reliable information
about menstrual cycle status from all patients. The next
for interpretation is correlation with CT images, espe-
cially contrast-enhanced CT acquired at the same time
as the PET-CT examination. The characteristic pattern,
location of the uptake and lack of a discrete lymph node
on CT are very helpful to verify the benign nature of the
uptake and exclude malignancy. Sometimes magnetic
resonance imaging (MRI) may be needed for evaluating
characteristics of the nature. For some cases, the disap-
pearance of the uptake on a follow-up scan following
subsequent menstruation can confirm benign uptake of
the ovaries in the earlier scan.
Increased ovarian uptake may be also identified in
benign tumors in both premenopausal and postmeno-
pausal women. Even though some authors found 100%
specificity of FDG PET-CT for benign ovarian tumors
[20], false-positive results of FDG PET-CT were reported
in histologically different tumor entities (both cystic and
solid) in most series [21–23]. The uptake of benign
109
1.1 cm right external iliac node with intense uptake (FDG-PET in
the middle and fusion on the right), suggestive of a metastatic nodal
lesion rather than benign uptake
ovarian tumor is likely influenced by the proportion of
inflammatory processes, which usually have a markedly
elevated glucose metabolism [23].
When interpreting FDG-PET images, in addition to
differentiating between benign ovarian uptake and
pathologic lymph node, sometimes there is a dilemma
owing to a physiological intestinal uptake. In general,
physiologic bowel uptake confines to a linear pattern. In
the case of hypermetabolic focus, correlation with the
CT portion of the combined PET-CT examination can
help in identifying the location of the focus. Although a
variety of imaging protocols are used for PET-CT, it is
recommended to use a negative oral contrast agent for
improved bowel distention and eliminating potential
artifacts caused by high-density oral contrast agents [24,
25] at the same time. Another potential pitfall is bowel
motility in correlating PET to corresponding CT images.
As CT and PET imaging is not obtained simultaneously,
the bowel uptake on PET may not match with the intes-
tine loops on CT. Therefore, a definite anatomic differ-
entiation between bowel loops and adnexal structures
may not always be possible.
Endometrial uptake
Similar to normal ovarian uptake in postmenopausal
women, normal endometrial uptake in postmenopausal
patients is minimal. Lerman et al. [4] studied FDG-PET
images of 116 postmenopausal patients without known
gynecologic malignancy. All subjects including those in
hormonal therapy had very mild FDG uptake [mean
standard uptake value (SUV) about 1.6]. Hormonal
therapy was not associated with a significant alteration
in endometrial FDG uptake. Five additional cases with
increased endometrial uptake (mean SUV 4.5) were
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Fig. 3 Transaxial CT (left), FDG-PET (middle) and fusion (right)
images of the pelvis in a 40-year-old woman with gastric carci-
noma. The patient was on the second day of menstruation. There
Fig. 4 CT (left), FDG-PET (middle) and fusion (right) images in a 56-year-old postmenopausal woman newly diagnosed with endometrial
carcinoma. There is intense endometrial uptake and lack of fluid collection in the uterine cavity on CT
found to have benign uterine pathology (fibroids
or polyp). Nishizawa also reported that all 55 healthy
postmenopausal women volunteers had no endometrial
uptake with the exception of two, one with a neglected
intrauterine device and another with uterine myoma
[5]. Therefore, in postmenopausal women, all increased
endometrial uptake is of clinical significance and
further investigation of the uterine pathology is
advised.
In premenopausal women, endometrial uptake is
related to the menstrual cycle. The endometrial uptake
is highest in the menstrual flow phase, followed by the
ovulating phase [4, 26]. It was also reported that there
was no significant endometrial uptake in women around
the presumed day of ovulation [5]. Typically, endome-
trial uptake during menstruation appears as an inverse
triangle on axial images and curvilinear or ellipsoid over
the urinary bladder on sagittal images (Fig. 3). It is not
easy to differentiate physiologic from malignant endo-
metrial uptake on the basis of intensity or extent of the
uptake on FDG-PET images only (Fig. 4). A combina-
tion of the patient’s menstrual status and fluid collection
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Ann Nucl Med (2009) 23:107–112
is intense uptake corresponding to fluid of the uterine cavity, sug-
gesting menstruation
rather than mass lesion in the uterine cavity on CT can
help to verify the benign nature of the uptake in the
menstrual flow phase. In the patient using a tampon,
intense uptake may be visualized in the vagina.
Endometrial FDG uptake during menstruation may
be related to the peristaltic movements of the subendo-
metrial myometrium that help to discharge menstrual
bleed [27, 28].
The endometrial uptake in premenopausal patients
using oral contraceptives resembles that in nonovulat-
ing, nonmenstruating premenopausal subjects [4], which
is likely secondary to the effect of oral contraceptives
including suppression of glands and atrophic introduc-
tion of the endometrium [29]. It was reported that intra-
uterine devices might cause increased endometrial uptake
secondary to an inflammatory process [5, 30].
On the basis of Lerman’s observation, among the
premenopausal patients with menstrual cycle abnormali-
ties, patients with amenorrhea had minimal endometrial
uptake, whereas patients with oligomenorrhea had
slightly increased uptake similar to the ovulatory phase
[4].
Ann Nucl Med (2009) 23:107–112
In patients with known cervical cancer, endometrial
uptake may be increased even though no endometrial
invasion or involvement really exists, because the uterine
fluid collection secondary to cervical stenosis may result
in increased endometrial uptake [4, 31]. In addition,
local cytokine environment of the cervical lesion may
affect the adjacent endometrium [32]. Therefore FDG
PET-CT is not reliable for adequate evaluation of
endometrial extension of the cervical cancer. Contrast-
enhanced MRI is considered to be the most accurate
imaging modality for determining parametrial involve-
ment [33, 34].
Similar to endometrial uptake in postmenopausal
women, nonmenstrual-related endometrial uptake in
premenopausal patients is worrisome for a pathological
process especially neoplasm. Nonmenstrual-related
endometrial uptake is either focal or diffuse, and typi-
cally locates in the wall rather than the central cavity. In
addition, there is usually no corresponding cavity fluid
collection in the uterus on CT images.
High-grade FDG uptake usually represents a malig-
nant process, but many benign diseases may also
demonstrate increased uptake, such as endometrial
inflammation, leiomyomas, endometrial hyperplasia,
endometrial polyp, pyometria, etc. Leiomyomas are the
most common human uterine neoplasm and are com-
posed of smooth muscle with varying amounts of fibrous
connective tissue. In most cases, leiomyomas show
minimal or mild FDG uptake, less or equal to that of
the liver, which is differentiated from high-grade uptake
in leiomyosarcomas [35, 36]. In addition, FDG uptake
in uterine leiomyoma declines with age [37]. But there
are some case reports of intense FDG uptake in large or
degenerated benign leiomyomas [36, 38–41]. Reported
high uptake in the leiomyomas might be owing to
increased vascularity [40] or large sizes of the tumors
[41]. In addition, high levels of growth factors and recep-
tors related to proliferation of smooth muscle may play
a role in FDG accumulation [38]. Therefore, nonmen-
strual-related endometrial uptake may represent either
benign or malignant process. MRI correlation is usually
helpful for differentiation [39, 40].
Conclusions
In postmenopausal women, there is minimal FDG
uptake in normal ovaries or uterus. Any increased
ovarian or endometrial uptake is of clinical significance
and may represent a neoplastic process. For premeno-
pausal women, increased ovarian or endometrial uptake
could be functional or malignant. Benign functional
uptake of premenopausal ovaries or uterus is related to
111
the menstrual cycle; therefore, information about the
patient’s menstrual status is crucial for interpretation of
a whole body FDG PET-CT imaging. In addition, cor-
relation with CT about the characteristic pattern, loca-
tion of the uptake and lack of a discrete lesion is very
helpful to verify the benign nature of the uptake and
exclude malignancy. Increased ovarian uptake may also
be identified in histologically different benign tumor
entities. Some potential pitfalls are helpful in an ana-
tomic differentiation between bowel loops and adnexal
structures. When you hesitate in the interpretation of
physiological, benign or malignant uptake of the ovaries
and uterus on FDG PET-CT, further investigation of
contrast-enhanced MRI and pathological examination
is recommended.
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