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ORIGINAL ARTICLE
Ann Nucl Med (2008) 22:803–810
DOI 10.1007/s12149-008-0184-6
S. Nishizawa (*) · M. Inubushi · A. Kido · M. Miyagawa ·
T. Inoue · K. Shinohara · M. Kajihara
Hamamatsu Medical Imaging Center, Hamamatsu Medical
Photonics Foundation, 5000 Hirakuchi, Hamakita-ku,
Hamamatsu, Shizuoka 434-0041, Japan
e-mail: sadahiko@hmp.or.jp
Incidence and characteristics of uterine leiomyomas with FDG uptake
Sadahiko Nishizawa · Masayuki Inubushi · Aki Kido
Masao Miyagawa · Takeshi Inoue · Katsura Shinohara
Makoto Kajihara
12 examined more than twice showed substantial changes
in the level of FDG uptake in leiomyomas each year with
FDG uptake disappearing or newly appearing. These
changes were observed frequently in relation with meno-
pause or menstrual phases.
Conclusions Leiomyomas with focal FDG uptake were
seen in both pre- and post-MP women with a higher
incidence in pre-MP women. Abundant cellularity and
hormonal dependency may explain a part of the mecha-
nisms of FDG uptake in leiomyomas. It is important to
know that the level of FDG uptake in leiomyomas can
change and newly appearing FDG uptake does not nec-
essarily mean malignant transformation.
Keywords FDG-PET · MRI · Uterine leiomyomas ·
Genitourinary oncology
Introduction
Positron emission tomography (PET) using
18
F-fluoro-
deoxyglucose (FDG) has been proved to be an effective
diagnostic tool for a variety of malignant tumors and is
frequently used for the management of patients with
such tumors. However, it is true that many benign
tumors and diseases or other physiological conditions
also show focal FDG uptake that mimics that of malig-
nant lesions and leads to misinterpretation of FDG-PET
images [1–3]. Therefore, it is important to understand
those conditions as much as possible to prevent misin-
terpretation. Recent articles showed that, as diagnostic
pitfalls specific to the pelvic organs in women, focal
FDG uptake was frequently seen in the normal uterine
endometrium and ovaries of premenopausal women in
certain phases of the menstrual (or ovarian hormonal)
Received: 18 April 2008 / Accepted: 13 June 2008
© The Japanese Society of Nuclear Medicine 2008
Abstract
Objective Uterine leiomyomas sometimes show focal
18
F-fluorodeoxyglucose (FDG) uptake on positron
emission tomography (PET) images that may result in a
false-positive diagnosis for malignant lesions. This study
was conducted to investigate the incidence and charac-
teristics of uterine leiomyomas that showed FDG
uptake.
Methods We reviewed FDG-PET and pelvic magnetic
resonance (MR) images of 477 pre-menopausal (pre-
MP, age 42.1 ± 7.3 years) and 880 post-MP (age 59.9 ±
6.8 years) healthy women who underwent these tests as
parts of cancer screening. Of 1357, 323 underwent annual
cancer screening four times, 97 did three times, 191 did
twice, and the rest were screened once. Focal FDG
uptake (maximal standardized uptake value > 3.0) in the
pelvis was localized and characterized on co-registered
PET/MR images.
Results Uterine leiomyomas were found in 164 pre-MP
and 338 post-MP women. FDG uptake was observed in
18 leiomyomas of 17 of the 164 (10.4%) pre-MP women
and in 4 leiomyomas of 4 of the 338 (1.2%) post-MP
women. The incidence was significantly higher in pre-
MP women than in post-MP women (chi-square, P <
0.001). Of the 22, 13 showed signal intensity equal to or
higher than that of the myometrium on T2-weighted
MR images, which suggested abundant cellularity,
whereas the majority of leiomyomas without FDG
uptake showed low signal intensity. Of the 13 women,
804 Ann Nucl Med (2008) 22:803–810
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cycle [4–6]. Several case reports also demonstrated that
uterine leiomyomas, although benign, show FDG uptake
on rare occasions that may cause false-positive diagnosis
for malignant lesions [7–10]. The objective of this study
was to investigate the incidence and characteristics of
uterine leiomyomas that showed FDG uptake from data
of a large number of healthy women who underwent
FDG-PET and pelvic magnetic resonance (MR) imaging
as parts of cancer screening.
Materials and methods
Subjects
We included a total of 1357 female subjects in this study,
477 premenopausal (pre-MP, age 42.1 ± 7.3 years) and
880 post-menopausal (post-MP, age 59.9 ± 6.8 years)
women, after excluding those who met the exclusion
criteria: (1) history and/or diagnosis of gynecological
malignancy or surgery, (2) receiving hormonal therapy,
and (3) blood sugar level over 150 mg/ml at the time of
PET examination. They underwent whole-body FDG-
PET and pelvic MR imaging as parts of cancer screening
in the Hamamatsu Medical Imaging Center. Medical
interviews, encompassing prior malignancy and gyneco-
logical surgery, menstrual status, and phase of the men-
strual cycle were conducted with all women. All women
underwent the cancer screening at least once between
August 2003 and December 2006. Of 1357, 323 under-
went the annual cancer screening four times, 97 did three
times, and 191 were screened twice.
Diagnoses of uterine leiomyomas were made on the
basis of findings of MR imaging and results of follow-up
till the end of 2007. Women with findings suggestive of
malignant lesions were referred to local hospitals for
further examinations or periodical follow-ups to obtain
the final diagnosis. Some women with findings suggestive
of leiomyomas were also referred to local hospitals
depending on the size and characteristics on MR images
and symptoms. We checked the occurrence of cancer
including gynecological malignancy 1 year after the
cancer screening by sending a questionnaire to women
who did not receive further examinations or follow-ups.
Written informed consents were obtained from all
women for the study, which was approved by the ethics
committee of the Hamamatsu Medical Photonics
Foundation.
PET imaging
Positron emission tomography imaging was performed
with a dedicated PET scanner (SHR-92000, Hamamatsu
Photonics, Hamamatsu, Japan). The scanner has a long
axial field of view of 685 mm, containing 12 rows of
detector blocks (60 detector blocks in each row), which
produced 336 transverse sections with a section thickness
of 3.2 mm covering from the upper thigh to the top of
the brain in two bed positions with an effective axial
field of view of 1075 mm [11]. Each detector block has a
flat panel position sensitive-photomultiplier (PS-PMT)
(R8400-00-M64, Hamamatsu Photonics) and a 16 × 8
bismuth germanate (BGO) crystal array with a crystal
size of 2.9 mm × 6.3 mm × 20 mm. All women fasted for
at least for 5 h prior to being administered an injection of
FDG. The serum glucose levels were measured just prior
to the injection. All women voided immediately prior to
the scan, which was started 60 min following the injec-
tion of 3 MBq/(kg body-weight) FDG. A lower part of
the body was scanned first to avoid the degradation of
image quality by the urinary activity in the bladder. The
acquisition time was 7 min for one bed position.
Whole-body computed tomography (CT) with low
radiation dose (120 kV, 10 mAs, 0.5 s/rotation, effective
radiation dose of less than 0.5 mSv) was also obtained
with an 8-slice CT scanner (LightSpeed Ultra, GE
Medical Systems, Milwaukee, WI, USA) with holding
breath in an expiration phase, which was used for atten-
uation correction of the PET images. The position
and shape of the body at the time of the CT scan were
reproduced in the PET scanner using the vacuum molded
immobilization mattress (BlueBag Vacuum Cushion,
Medical Intelligence, Schwabmunchen, Augsburg,
Germany) made for each woman, which had been proved
to be a practical device for reproducing the position of
the body [12, 13]. The PET images were reconstructed
by means of a dynamic row-action maximum likelihood
algorithm [14]. Reformatted transaxial, sagittal, coronal,
and maximum intensity projection (MIP) images were
used for the interpretation.
MR imaging
Magnetic resonance imaging was performed with a
1.5-T MR scanner (EXCITE, GE Medical Systems).
A T2-weighted fast spin-echo (FSE) sequence was used
for transaxial [repetition time (ms)/echo time (ms) =
4300/102, 320 × 224 matrix], transaxial fat-saturation
(3700/102, 256 × 192 matrix), and sagittal (2400/102,
320 × 224 matrix) images. Two signals were averaged.
Coronal T1-weighted FSE images (470–570/7.5–8.5,
320 × 224 matrix, one or two signal averaged) were also
obtained. All images were acquired with a 30–36 cm field
of view, a 4–5 mm section thickness, and a 1-mm inter-
section gap.
Ann Nucl Med (2008) 22:803–810 805
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Image analysis
The FDG-PET images were evaluated for focal FDG
uptake in the pelvis visually and with standardized
uptake values (SUVs). The uptake value was corrected
for the injected dose and the body weight to obtain
SUVs, and the maximal SUVs (SUV
max
) of the foci were
recorded. A focal area with FDG uptake showing an
SUV
max
greater than 3 was considered to be positive. The
MR images were used to localize the foci of increased
FDG uptake and to evaluate morphological abnormal-
ity of the lesions. Anatomical correlation of FDG-PET
images with MR images was performed on co-registered
PET/MR images. For this purpose, we referred to CT
images obtained with a low radiation dose for attenua-
tion correction, which could be superimposed closely on
PET images. Anatomical markers such as bony struc-
tures of the pelvis were used for manual co-registration
of CT and MR images. PET images were then co-
registered on MR images.
Leiomyomas with FDG uptake were classified into
three groups according to the level of signal intensity on
T2-weighted MR images as low, almost equal (iso), and
high compared with that of myometrium to see the rela-
tionship between tissue characteristics and FDG uptake.
These were also classified into three groups according to
the levels of FDG uptake: SUV
max
from 3 to 5 as mild
(+), from 5 to 8 as moderate (++), and over 8 as high
(+++), which was correlated with the menstrual status
and/or the phases of menstrual cycle at the examination
in each individual: the menstrual flow phase (M) from
day-1 to day-7 of the cycle, the follicular and periovula-
tory phases (F) from day 8 to 2 days after the expected
day of ovulation, and the luteal phase (L) for the rest of
the cycle.
Results
No woman developed uterine sarcoma in this study
although four women were diagnosed and proved to
have endometrial carcinomas.
Uterine leiomyomas were seen on T2-weighted MR
images in 164 of the 477 pre-MP women and in 338 of
the 880 post-MP women (Table 1). Twenty-two leiomyo-
mas with FDG uptake were found in 21 women. Details
of characteristics and findings of the 22 leiomyomas are
shown in Table 2. Eighteen leiomyomas with FDG
uptake were seen in 17 of the 164 (10.4%) pre-MP women
with the SUV
max
of 5.3 ± 2.9 (range 3.5–16.0) and 4 were
seen in 4 of the 338 post-MP women (1.2%) with the
SUV
max
of 6.1 ± 2.3 (range 3.7–8.0). The incidence of
leiomyomas with FDG uptake was significantly higher
in pre-MP women than in post-MP women (chi-square,
P < 0.001). Especially, the incidence was high in pre-MP
women who were in their 40s.
Of the 22 leiomyomas with FDG uptake, 13 showed
signal intensity almost equal to or higher than that of
the myometrium on T2-weighted MR images, whereas
1147 of 1231 leiomyomas without FDG uptake showed
lower signal intensity. Also noted was that in each indi-
vidual with multiple leiomyomas, the leiomyoma with
FDG uptake showed higher signal intensity on the T2-
weighted MR image than those without FDG uptake
(Fig. 1).
Of the 21 women, 13 with FDG uptake in leiomyomas
underwent the annual screening more than twice
(Table 2). Of the 13 women, 12 showed a substantial
change in a level of FDG uptake in uterine leiomyomas
each year and FDG uptake disappeared or newly
appeared (Fig. 2). FDG uptake in leiomyomas was
greater in a luteal phase than in menstrual flow and
follicular-periovulatory phases in three pre-MP women
and disappeared after menopause in four women. All
leiomyomas, except one (subject no. 1 in Table 2), were
stable in size without apparent growth or shrunk after
menopause.
Discussion
Uterine leiomyomas are the most common benign neo-
plasms arising from the smooth muscle layer of the
uterus, occurring in as many as 30% of women more
than 35 years old [15]. Although these tumors are still a
major indication of surgery or need other treatments
when symptomatic, most of the women with these tumors
are asymptomatic and need no treatment. Leiomyosar-
comas of the uterus are rare malignant smooth muscle
layer tumors that resemble some types of leiomyomas,
Number of subjects With leiomyomas (%) With FDG uptake (%)
Pre-menopausal 477 164 (34.4) 17 (10.4)
Under 39 years 164 26 (15.9) 1 (3.8)
40–44 years 121 49 (40.5) 5 (10.2)
Over 45 years 192 89 (46.4) 11 (12.4)
Post-menopausal 880 338 (38.4) 4 (1.2)
Table 1 Incidence of
leiomyomas in each menstrual
status and age group
FDG
18
F-fluorodeoxyglucose
806 Ann Nucl Med (2008) 22:803–810
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Ann Nucl Med (2008) 22:803–810 807
1 3
and a differential diagnosis with imaging tests is impor-
tant to avoid unnecessary surgery [16, 17]. The initial
report using FDG-PET for the differential diagnosis of
leiomyosarcomas from leiomyomas suggested that
uterine sarcomas which showed FDG uptake could be
clearly differentiated from leiomyomas which did not
accumulate FDG [18]. However, several recent case
reports revealed that FDG uptake could be also seen in
benign uterine leiomyomas [7–10] and indicated that
FDG-PET could not be used for the differential diagno-
sis of leiomyosarcomas from leiomyomas.
In this article, for further understanding of uterine
leiomyomas with FDG uptake, we investigated the inci-
dence and characteristics of those leiomyomas from data
of 1357 healthy women who underwent FDG-PET and
pelvic MR imaging as parts of cancer screening. The
value and feasibility of cancer screening including FDG-
PET for healthy individuals have not been tested and
clarified yet, and a prospective study is now underway
in our center to evaluate annual cancer screening includ-
ing FDG-PET in healthy volunteers [19]. Through the
interpretation of FDG-PET images of healthy women in
this large population, we have encountered many foci of
FDG uptake in the pelvis that should be regarded as
physiological variations and pitfalls [5–6]. Understand-
ing of these physiological and benign FDG uptakes in
such large populations of healthy subjects is of great
importance for correct interpretation of pathological
processes of FDG-PET images.
In this study, we found leiomyomas in about 35% of
both pre- and post-MP women with the prevalence com-
parable with those of published data [15]. Leiomyomas
with FDG uptake were much more common in pre-MP
women as compared with post-MP women. The inci-
dence of 10.4% of pre-MP women with leiomyomas was
significantly higher than that of 1.2% of post-MP women
with leiomyomas (chi-square, P < 0.001). Also noted
were changes in FDG uptake seemingly in relation with
menstrual status and phases. The FDG uptake in leio-
myomas tends to disappear following menopause and to
be seen more frequently and intensely at a certain phase
of the menstrual cycle. It is known that ovarian sex ste-
roidal hormones play an important role in the regulation
and the modulation of leiomyoma growth, especially
progesterone levels suggestively affecting leiomyoma
growth [20–23]. Therefore, FDG uptake in leiomyomas
may be partly explained by increased energy demand for
growth with hormonal dependency.
However, FDG uptake in leiomyomas is an infre-
quent phenomenon and cannot be explained by the
effect of only ovarian hormones. Many types of growth
factors are also believed to be involved in the growth of
leiomyomas [20] and may be related to the increase of
FDG uptake. The FDG uptake in the tumors would be
a
b d c
Fig. 1 The maximum intensity projection (MIP, a) and sagittal (b)
images of
18
F-fluorodeoxyglucose positron emission tomography
(FDG-PET) of a 44-year-old pre-menopausal (pre-MP) woman
showing intense focal FDG uptake in the pelvis. The superimposed
PET/magnetic resonance (MR) image demonstrated that the lesion
with focal FDG uptake corresponded to the posterior wall of the
uterus (c) where the T2-weighted MR image revealed a leiomyoma
with signal intensity almost equal to or slightly higher than
that of myometrium (red arrow, d). The leiomyoma with FDG
uptake showed higher signal intensity than other leiomyomas
without FDG uptake (black arrows) seen in the anterior wall of
the uterus
808 Ann Nucl Med (2008) 22:803–810
1 3
regulated by several factors including expression of
glucose transporter-1 (GLUT-1) and hexokinase, the
number of viable tumor cells, microvessel density, tumor
cell proliferation, and the presence of inflammatory cells
[24], and the combination of factors involved in each
tumor may be different. In breast cancer, for example,
the FDG uptake in the tumors was shown to be the
function of microvasculature, expression of GLUT-1
and hexokinase, number of tumor cells/volume, prolif-
eration rate, number of lymphocyte, and hypoxia-
inducible factor-1 for upregulating GLUT-1 [25].
There are few reports regarding factors that regulate
FDG uptake in leiomyomas. In a recent report of three
cases, histopathological analysis showed increased vas-
cularity as a common finding, but there was no associa-
tion between proliferative activity evaluated by Ki67 and
FDG uptake [9]. In our study, only one woman (subject
no. 14 in Table 2) with multiple leiomyomas underwent
surgery, and immunohistochemical analysis showed
positive for proliferating cell nuclear antigen but there
was no difference in positive indices among leiomyomas
with and without FDG uptake. In this case, signal inten-
sity of the leiomyoma with FDG uptake on T2-weighed
MR images was higher than that of leiomyomas without
FDG uptake. The finding was seen in majority of cases
in our study and seemed to be one of the characteristics
of leiomyomas with FDG uptake.
The finding of increased signal intensity in leiomyo-
mas on T2-weighed MR images is known to suggest
cellular leiomyomas with dense cellular components
with little or no collagen [17]. Cellularity has been
reported as one of the factors that affect FDG uptake in
a
b
d
c
Fig. 2 The MIP (left) and
sagittal (upper right) images
of FDG-PET and T2-
weighted sagittal MR images
(lower right) of a 40-year-old
pre-MP woman who
underwent annual
examinations four times in
April 2004 (a), March 2005
(b), February 2006 (c), and
March 2007 (d) are shown.
Intense FDG uptake was seen
in the large leiomyoma which
showed signal intensity
almost equal to that of
myometrium on the initial
examination that was done in
the late luteal phase of the
menstrual cycle (a). On the
second examination done on
the third day of the menstrual
flow phase, the leiomyoma
showed slight FDG uptake
(b). Intense FDG uptake was
seen again on the third
examination done in the late
luteal phase (c). There was no
FDG uptake on the fourth
examination done in the
periovulatory phase (d). There
was no interval change in the
size of the leiomyoma,
whereas a small leiomyoma
with low signal intensity
without FDG uptake (arrows)
showed a slight increase in
the size (a–d)
Ann Nucl Med (2008) 22:803–810 809
1 3
several kinds of tumors [26–28]. In addition, one article
indicated cellularity has a significant influence on FDG
uptake only in the condition of GLUT-1 glucose trans-
porter strong positive expression [29]. This may explain
why there were also many leiomyomas with increased
signal intensity on T2-weighted MR images that did not
show FDG uptake. In this study, histopathological and
immunohistochemical analyses of leiomyomas with
FDG uptake were not available as, with the exception
of one woman, all women were conservatively followed
up and did not receive surgery because of the benign
nature of the lesions.
The limitation of this study was a lack of histopatho-
logical and immunohistochemical data. Therefore,
further investigations with histopathological and immu-
nohistochemical analyses are needed to clarify the mech-
anism and implications of FDG uptake in leiomyomas.
However, in this study, follow-up data with FDG-PET
and MR imaging up to 3 years were available for more
than 10 women with leiomyomas with FDG uptake and
also for hundreds of women with leiomyomas without
FDG uptake. During the period of this study, most leio-
myomas with FDG uptake were stable in size without
apparent growth, although we observed several leiomyo-
mas without FDG uptake that showed substantial
growth. In the population of healthy women in this
study, FDG uptake in leiomyomas was rather an inci-
dental finding and did not indicate the growth of leio-
myomas or malignant potential. Findings of MR images
co-registered on PET images were helpful to avoid mis-
interpretation by identifying and characterizing the
lesion with FDG uptake.
Conclusions
Uterine leiomyomas with increased FDG uptake were
seen in both pre- and post-MP women with higher inci-
dence in pre-MP women, especially in those women who
were in their 40s. Abundant cellularity and hormonal
dependency may explain a part of the mechanisms of
FDG uptake in leiomyomas. It is important to know
that the level of FDG uptake in leiomyomas can change,
and newly appeared FDG uptake does not necessarily
mean malignant transformation. Careful diagnosis with
the aid of MR imaging should be made to avoid misin-
terpretation and unnecessary surgery.
Acknowledgments The authors thank Hiroyuki Okada, Hironobu
Kodama, and the staff in the Hamamatsu Medical Imaging Center
for technical assistance. We acknowledge Dr. Hiroshi Odani for
providing pathological and immunohistochemical data of the
subject no. 14. We also thank Dr. Keith Bennett for critically
reading the manuscript and providing useful suggestions.
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