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Ultrasound Obstet Gynecol 2013; 41: 8089

Published online in Wiley Online Library (wileyonlinelibrary.com). DOI: 10.1002/uog.12308

Risk of malignancy in unilocular cysts: a study of 1148


adnexal masses classified as unilocular cysts at transvaginal
ultrasound and review of the literature
L. VALENTIN*, L. AMEYE, D. FRANCHI, S. GUERRIERO, D. JURKOVIC**, L. SAVELLI,
D. FISCHEROVA, A. LISSONI, C. VAN HOLSBEKE***, R. FRUSCIO, S. VAN HUFFEL,
A. TESTA and D. TIMMERMAN***
University Hospital Malmo,
*Department of Obstetrics and Gynecology, Skane
Lund University, Malmo, Sweden; KU Leuven,
Department of Electrical Engineering (ESAT) SCD-SISTA, Leuven, Belgium; IBBT Future Health Department, Leuven, Belgium;
Preventive Gynecology Unit, Division of Gynecology, European Institute of Oncology, Milan, Italy; Department of Obstetrics and
Gynecology, Ospedale San Giovanni di Dio, University of Cagliari, Cagliari, Sardinia, Italy; **Department of Obstetrics and Gynecology,
University College Hospital, London, UK; Gynecology and Early Pregnancy Ultrasound Unit, S. Orsola-Malpighi Hospital, University of
Bologna, Bologna, Italy; Gynecological Oncology Center, Department of Obstetrics and Gynecology, First Faculty of Medicine and
General Faculty Hospital of Charles University, Prague, Czech Republic; Clinica Ostetrica e Ginecologica, Ospedale S. Gerardo,
Universita` di Milano Bicocca, Monza, Italy; Department of Obstetrics and Gynecology, Ziekenhuis Oost-Limburg, Genk, Belgium;
***Department of Development and Regeneration, University Hospitals KU Leuven, Leuven, Belgium; Istituto di Clinica Ostetrica e
Ginecologica, Universita` Cattolica del Sacro Cuore, Rome, Italy

K E Y W O R D S: ovarian neoplasms; simple ovarian cyst; ultrasonography; unilocular ovarian cyst

ABSTRACT
Objectives The aim of this study was to estimate the
rate of malignancy in adnexal lesions described as
unilocular cysts at transvaginal ultrasound examination
and to investigate if there are differences in clinical and
ultrasound characteristics between benign and malignant
unilocular cysts.
Methods A total of 3511 patients with an adnexal mass
underwent transvaginal ultrasound examination between
1999 and 2007. Sonologists used the International
Ovarian Tumor Analysis terms and definitions to describe
their ultrasound findings. Only masses operated on within
120 days after the ultrasound examination were included
in the analysis and the histopathological diagnosis of the
mass was used as the gold standard.
Results Of the 3511 masses, 1148 (33%) were classified
as unilocular cysts on ultrasound. Of these, 11 (0.96%
(95% CI, 0.481.71)) were malignant. The malignancy
rate was lower in premenopausal than in postmenopausal
women: 0.54% (5/931; 95% CI, 0.171.25) vs 2.76%
(6/217; 95% CI, 1.025.92); P = 0.009. More patients
with malignant unilocular cysts had a personal history of
breast cancer (18% vs 2%; P = 0.02) or ovarian cancer
(18% vs 0.6%; P = 0.003). Hemorrhagic cyst contents
on ultrasound were more common in malignant than in
benign unilocular cysts (18% vs 2%; P = 0.03). In seven of

the 11 malignancies judged to be unilocular cysts at scan,


papillary projections or other solid components were seen
at macroscopic inspection of the surgical specimen.
Conclusions The malignancy rate in surgically removed
adnexal lesions judged to be unilocular cysts at transvaginal scan is c. 1%. Postmenopausal status, personal
history of breast or ovarian cancer and hemorrhagic cyst
contents on ultrasound increase the risk of malignancy.
To avoid misclassifying adnexal lesions as unilocular cysts
at scan, it is important to scrutinize unilocular cysts for the
presence of solid components. Copyright 2012 ISUOG.
Published by John Wiley & Sons, Ltd.

INTRODUCTION
The risk of a unilocular ovarian cyst being malignant
is considered to be very low, irrespective of whether
the cyst is described on the basis of macroscopic
inspection by a pathologist1 or on the basis of
an ultrasound image of the cyst2 5 . It has been
suggested that unilocular cysts < 5 cm in diameter in
postmenopausal women do not require intervention
other than possibly follow-up scans. For example, in
the United Kingdom Collaborative Trial on Ovarian
Cancer Screening (UKCTOCS), women with a unilocular
cyst with anechoic contents and a volume < 60 mL

University Hospital Malmo,


20502 Malmo,
Sweden
Correspondence to: Prof. L. Valentin, Department of Obstetrics and Gynecology, Skane
(e-mail: lil.valentin@med.lu.se)
Accepted: 19 September 2012

Copyright 2012 ISUOG. Published by John Wiley & Sons, Ltd.

ORIGINAL PAPER

Risk of malignancy in unilocular cysts


(corresponding to a diameter < 5 cm) are dismissed as
having normal findings, while those with unilocular cysts
with mixed or random echogenicity/irregular walls/solid
elements have a repeat scan6 . On the other hand, Yazbek
et al. reported that 11% (4/35) of borderline tumors and
4% (1/24) of epithelial ovarian cancers were classified
as unilocular cysts at ultrasound examination performed
by an ultrasound expert in a tertiary referral center for
gynecological ultrasound7 .
The aim of this study was to estimate the rate of
borderline and invasive malignancy in ovarian lesions
described as unilocular cysts at ultrasound examination,
and to investigate if there are any differences in clinical and
ultrasound characteristics between benign and malignant
unilocular cysts.

METHODS
This is a retrospective analysis of prospectively collected
information in the International Ovarian Tumor Analysis
(IOTA) database. The IOTA study is a prospective
observational international multicenter study including
21 ultrasound centers in nine countries, in which
patients with adnexal masses were scanned transvaginally
using a standardized research protocol8 10 . Ultrasound
examiners were radiologists or gynecologists highly
experienced in gynecological ultrasound and with a special
interest in adnexal masses. The study was conducted
in accordance with precepts established by the Helsinki
Declaration, the research protocol was ratified by the
local Ethics Committee at each center and all participants
gave informed consent to participate. Recruitment took
place between 1999 and 2007. The IOTA terms and
definitions11 were used to describe ultrasound findings.
Both gray-scale and color/power Doppler ultrasound
examination were carried out, and information on
more than 40 clinical and ultrasound variables was
collected. In addition, the ultrasound examiner classified
each mass as benign or malignant using subjective
evaluation of gray-scale and Doppler ultrasound findings
(subjective assessment) and stated the confidence with
which the classification was made (certainly benign,
probably benign, uncertain, probably malignant, certainly
malignant). In the case of bilateral adnexal masses, the
mass with the most complex ultrasound morphology was
included in the database. If both masses had similar
ultrasound morphology the largest or the one most easily
accessible by ultrasound was included. Only women with
masses who were operated on within 120 days after the
ultrasound examination were included in the analysis.
The gold standard was histological diagnosis of the
surgically removed adnexal mass. Staging of malignancies
was done in accordance with the International Federation
of Gynecology and Obstetrics (FIGO)12,13 .
For the purpose of the current study, the IOTA database
was searched for tumors classified as unilocular cysts
at ultrasound examination. The unilocular cysts in the
database comprised our study population. The IOTA
definition of a unilocular cyst is a cyst with one cyst

Copyright 2012 ISUOG. Published by John Wiley & Sons, Ltd.

81

locule, no solid components and no papillary projections


(papillary projection being defined as a protrusion of solid
tissue into the cyst lumen with a height 3 mm) and with
cyst contents of any type of echogenicity (including the
mixed echogenicity typical of dermoid cysts). Unilocular
cysts with protrusions of solid tissue into the cyst lumen
with a height < 3 mm are classified as unilocular cysts with
irregular walls. The prospectively collected clinical and
ultrasound information was compared between benign
and malignant unilocular cysts. In addition, clinical,
surgical and pathological reports and the ultrasound
images of patients with a malignant unilocular cyst were
retrieved and scrutinized retrospectively.
Statistical analyses were carried out using the SAS
System 9.3 (SAS Institute Inc., Cary, NC, USA). Fishers
exact test was used to test the statistical significance of
differences in binary data; the MannWhitney U-test
was used to test the statistical significance of differences
in continuous data. Two-tailed P-values < 0.05 were
considered statistically significant.

RESULTS
The IOTA database contains information on 3511
patients with at least one adnexal mass. The number
of masses contributed by each center is shown in Table S1
(online) and the histology of the masses in Table S2
(online). Of the 3511 masses, 1148 (33%) were classified
as unilocular cysts on ultrasound examination. The
proportion of adnexal masses classified as unilocular
cysts ranged from 12% to 67% in the different centers.
Of 186 borderline tumors in the entire IOTA database,
five (2.76% (95% CI, 0.886.16)) were classified as
unilocular cysts on ultrasound, and of 764 invasive
malignancies, six (0.79% (95% CI, 0.291.70)) were
classified as unilocular cysts on ultrasound.
Of the 1148 unilocular cysts in the IOTA database,
11 (0.96% (95% CI, 0.481.71)) were malignant
vs 40% (939/2363; 95% CI, 3842) of all other
adnexal masses (P < 0.001). Five of the malignant
unilocular cysts were borderline tumors and six were
primary invasive malignancies, i.e. the rate of borderline
malignancy was 0.44% (95% CI, 0.141.01) and that
of invasive malignancy was 0.52% (95% CI, 0.191.13)
(Table S2). The malignancy rate in unilocular cysts was
lower in premenopausal women than in postmenopausal
women: 0.54% (5/931; 95% CI, 0.171.25) compared
to 2.76% (6/217; 95% CI, 1.275.92); P = 0.009. In
premenopausal women, four of 931 unilocular cysts were
borderline malignant (0.43% (95% CI, 0.121.10)) and
one was invasively malignant (0.11% (95% CI, 00.60)).
The corresponding figures for postmenopausal women
were one (0.46% (95% CI, 0.012.54)) and five (2.30%
(95% CI, 0.755.29)) of 217 unilocular cysts.
The malignancy rate in unilocular cysts with anechoic
cyst fluid and regular walls on ultrasound was 1.22%
(4/326; 95% CI, 0.343.11) and that in unilocular
cysts with another type of cyst fluid, with or without
irregular walls on ultrasound, was 0.85% (7/822; 95%

Ultrasound Obstet Gynecol 2013; 41: 8089.

Valentin et al.

82

Figure 1 Solid lesion misclassified as a unilocular cyst with


hemorrhagic cyst contents on ultrasound. The histological
diagnosis was tubal carcinoma, Stage 3.

CI, 0.341.75); the malignancy rate in unilocular cysts


with a largest diameter 5 cm at scan was 0.82% (4/486;
95% CI, 0.222.09) and that in unilocular cysts with a
largest diameter > 5 cm on ultrasound was 1.06% (7/662;
95% CI, 0.432.17).
Prospectively collected clinical and ultrasound information from the IOTA database for benign and malignant
unilocular cysts is presented in Table 1. Women with
malignant unilocular cysts were older and more were
postmenopausal and had a personal history of breast
or ovarian cancer than women with benign unilocular
cysts. Cyst contents judged to be hemorrhagic on ultrasound were more common in malignant than in benign
unilocular cysts (18% vs 2%; P = 0.03). Irregular internal
cyst walls and fluid in the pouch of Douglas on ultrasound were twice as common in malignant as in benign
unilocular cysts, but these differences, although substantial (both 27% vs 14%), were not statistically significant.
The ultrasound examiner less often assigned a diagnosis
of certainly benign to unilocular cysts that proved to be
malignant than to those that proved to be benign (36%
vs 83%; P < 0.001).
Retrospective analysis of clinical, surgical and pathological reports and ultrasound images showed that, in seven
of the 11 malignancies described as unilocular cysts at
ultrasound examination, there was a discrepancy between
the ultrasound examiners description and the pathologists description of the macroscopic appearance of the
cyst (Table 2). In six cysts the ultrasound examiner had
failed to detect papillary projections (n = 4) or solid components (n = 2) visible at macroscopic inspection by the
pathologist. In the seventh case a lesion described by the
ultrasound examiner as a unilocular cyst with hemorrhagic cyst contents proved to be a completely solid lesion
(Figure 1). For one cyst described as unilocular, with
hemorrhagic contents on ultrasound, the macroscopic
description by the pathologist was unreliable. This cyst
was removed by laparoscopy, and the specimen came out
in pieces unsuitable for macroscopic inspection. In three
cases, ultrasound findings agreed with the macroscopic
description by the pathologist, i.e. the cyst was unilocular
without papillary projections or other solid components
also at macroscopic inspection. One of these cases was a

Copyright 2012 ISUOG. Published by John Wiley & Sons, Ltd.

Figure 2 A 6-cm unilocular cyst for which the histological


diagnosis was mucinous borderline tumor, Stage 1. Macroscopic
inspection of the surgical specimen revealed no solid components
and no papillary projections.

17-cm mature teratoma with a microcarcinoma of struma


type with ground glass echogenicity of the cyst contents
on ultrasound, one was a 13-cm mucinous borderline
tumor with cyst fluid of low level echogenicity on ultrasound and one was a 6-cm mucinous borderline tumor
with anechoic cyst contents at scan (Figure 2).

DISCUSSION
We found the risk of malignancy in surgically removed
adnexal lesions judged to be unilocular cysts at
transvaginal scan to be 0.96%; it was 0.54% in
premenopausal women and 2.76% in postmenopausal
women and the difference in malignancy rate between preand postmenopausal women was statistically significant.
Hemorrhagic cyst contents on ultrasound increased the
risk of malignancy, as did a personal history of ovarian
or breast cancer. However, seven of the 11 malignant
cysts described as unilocular on ultrasound proved to
contain papillary projections or other solid components
at macroscopic inspection of the corresponding surgical
specimen by the pathologist.
The strength of our study is that it is large and
multicenter and that data were prospectively collected
following a standardized research protocol and using
standardized terminology to describe the masses. This
increases the likelihood that our results are generalizable.
A limitation of our study is that it includes only women
who were operated on. The true malignancy rate in cysts
judged to be unilocular on ultrasound is likely to be much
lower than that in our study, because many unilocular
cysts are left in situ4,5,14 23 . In studies in which (mostly
asymptomatic) women with adnexal cysts judged to be
unilocular on ultrasound were recommended for followup with ultrasound examination or were indeed followed
with ultrasound examination for up to 13 years, four of
4361 (0.09%) unilocular cysts in 3797 (0.11%) patients
(most postmenopausal) were found to be malignant

Ultrasound Obstet Gynecol 2013; 41: 8089.

Risk of malignancy in unilocular cysts

83

Table 1 Prospectively collected clinical and ultrasound information for benign and malignant unilocular cysts (n = 1148)
Variable
Clinical characteristics
Age (years)
Postmenopausal
Nulliparous
Hysterectomy
Current hormonal treatment
Personal history of ovarian cancer
Personal history of breast cancer
Family history of ovarian cancer
Family history of breast cancer
CA 125 (U/mL)*
Ultrasound characteristics
Bilateral
Largest diameter (mm)
Mean diameter (mm)
Volume (cm3 )
Echogenicity of cyst contents
Anechoic
Homogeneous low level
Ground glass
Hemorrhagic
Mixed
Irregular walls
Fluid in pouch of Douglas
Fluid in pouch of Douglas (mm)
Ascites
Acoustic shadows
Color Doppler blood flow
No flow
Minimal flow
Moderate flow
Strong flow
Venous blood flow only
Spectral Doppler results
Pulsatility index
Resistance index
Peak systolic velocity (cm/s)
Time averaged maximum velocity (cm/s)
Diagnosis on basis of subjective assessment
Certainly benign
Probably benign
Uncertain
Probably malignant
Certainly malignant

Benign (n = 1137)

Malignant (n = 11)

36 (1590)
211 (19)
611 (54)
43 (4)
172 (15)
7 (< 1)
23 (2)
20 (2)
77 (7)
19 (23500)

60 (2682)
6 (55)
6 (55)
1 (9)
1 (9)
2 (18)
2 (18)
0 (0)
0 (0)
20 (7147)

0.002
0.009
1
0.35
1
0.003
0.02
1
1
0.50

165 (15)
56 (8760)
48 (8340)
54 (0.220 525)

1 (9)
57 (25171)
48 (23156)
58 (71940)

1
0.49
0.49
0.48

322 (28)
154 (14)
412 (36)
28 (2)
221 (19)
161 (14)
162 (14)
14 (161)
9 (< 1)
169 (15)

4 (36)
1 (9)
4 (36)
2 (18)
0 (0)
3 (27)
3 (27)
18 (1038)
0 (0)
0 (0)

0.52

603 (53)
384 (34)
138 (12)
12 (1)
81 (7)

5 (45)
6 (55)
0 (0)
0 (0)
2 (18)

0.19

1.00 (0.135.09)
0.61 (0.121.00)
10.20 (0.1979.85)
6.00 (0.0252.78)

1.68 (0.763.21)
0.72 (0.520.92)
12.72 (6.1827.60)
5.85 (1.7718.20)

0.41
0.39
0.60
0.93

938 (83)
188 (17)
9 (< 1)
1 (< 1)
1 (< 1)

4 (36)
6 (55)
1 (9)
0 (0)
0 (0)

0.03
0.20
0.20
0.46
1
0.38
0.76
0.38**

< 0.001

Data are given as n (%) or median (range). *CA 125 was measured in 742 (65%) patients with a benign mass and in 11 (100%) patients
with a malignant mass. Pulsatility index, resistance index, peak systolic velocity and time-averaged maximum velocity were measured in
cases with detectable color Doppler signals and detectable arterial blood flow, i.e. in 453 (39%) patients with a benign mass and in four
(36%) patients with a malignant mass. Anechoic vs others. Hemorrhagic vs others. No flow vs others. **No or minimal flow vs
moderate or strong flow. Certainly benign vs others.

at eventual operation5,14 20,23 . The clinical course in


patients who did not undergo surgery suggests that their
unilocular cysts were all benign (Table 3).
The rate of histologically confirmed malignancy in
adnexal cysts judged to be unilocular at transvaginal
scan has been described in nine studies (Table 4)2,3,24 30 .
However, the definition of unilocular cyst in the nine
studies is not always clear. Moreover, the definitions are
not uniform, the size of cysts is highly variable and characteristics of the study populations differ. Of the 1687
surgically removed lesions classified as unilocular cysts
on ultrasound, 1.6% were malignant (Table 4). However,

Copyright 2012 ISUOG. Published by John Wiley & Sons, Ltd.

the malignancy rate in the study of Osmers et al.30 is much


higher (10.4%) than that in any other published study.
Possibly their study population was a selected high-risk
group, or possibly some incidental benign unilocular
cysts were associated with seropapillary peritoneal cancer
(which may be a common phenomenon5 ). If we exclude
the study of Osmers et al.30 and consider only the results
of the remaining eight published studies, the malignancy
rate in surgically removed unilocular cysts is 0.84%
(13/1553), which is similar to the 0.96% rate in our study.
We present a point estimate of the rate of malignancy
in unilocular cysts, but we did not study the malignant

Ultrasound Obstet Gynecol 2013; 41: 8089.

Copyright 2012 ISUOG. Published by John Wiley & Sons, Ltd.

No

No

No

41

26

43

82

POD, pouch of Douglas.

Yes

Yes

60

65

No

69

No

No

50

71

No

42

No

No

Age
(years)

62

Personal
history of
ovary cancer

No

No

No

Yes

No

No

No

No

Yes

No

No

Personal
history of
breast cancer

13

84

68

20

147

13

78

10

26

14

CA 125
(U/mL)

Certainly
benign
Probably
benign

Uncertain

Certainly
benign
Probably
benign
Probably
benign
Probably
benign

Probably
benign

Probably
benign
Certainly
benign

Certainly
benign

25

37

57

75

45

140

53

48

171

128

58

Diagnosis on
basis of
Largest
subjective
diameter
assessment
(mm)

Table 2 Detailed information on the 11 unilocular cysts that proved to be malignant

Hemorrhagic

Hemorrhagic

Ground glass

Ground glass

Anechoic

Anechoic

Ground glass

Anechoic

Ground glass

Low-level

Anechoic

Echogenicity
of cyst fluid

10

38

18

Fluid in
POD
(mm)

No

No

Yes

No

No

No

No

No

No

No

No

Bilateral

Yes

Yes

Yes

No

No

No

No

No

No

No

No

Irregular
cyst walls

Non-optimal
specimen

No (solid part
missed)
No (solid tumor)

No (papillations
missed)
No (papillations
missed)
No (papillations
missed)
No (solid part
missed)

No (papillations
missed)

Yes

Yes

Yes

Agreement with
macroscopy

Borderline, mucinous
(pseudostratification
and atypia), Stage 1
Borderline, mucinous,
Stage 1
Mature teratoma with
microcarcinoma of
struma type
Borderline (focus of
atypical cells), serous,
Stage 1
Borderline, serous,
Stage 1
Borderline, serous,
Stage 1
Seropapillary peritoneal
cancer, Stage 3
Infiltration of
neuroendocrine
carcinoma in a
benign cystic
teratoma (previous
breast cancer of
neuroendocrine type)
Carcinoma,
endometrioid, Stage 3
Carcinoma, tubal,
Stage 3
Recurrent mucinous
invasive cancer in the
ovary, Stage 1

Final diagnosis

84

Valentin et al.

Ultrasound Obstet Gynecol 2013; 41: 8089.

Copyright 2012 ISUOG. Published by John Wiley & Sons, Ltd.

PostMP

PostMP

19901994

19911998

19952002

19952000

19972012

19872002

19972002

Auslender et al.15

Conway et al.16

Valentin and
Akrawi17
Castillo et al.18

Nardo et al.19

Sarkar and Wolf20

Modessit et al.5

Alcazar et al.23

> 50 years
(mixed)
PreMP

PostMP

PostMP

PostMP

Any?

Anechoic

Anechoic

Any

Anechoic

Hypoechogenic

Anechoic?

Echogenicity
of cyst fluid

Smooth, no
papillae
No papillae

? (no
papillae)

Smooth

Smooth

Smooth

Wall
regularity

13219 mL;
50 mm in
84%
< 50 mm
(1850 mm)
0.1860.4 mL
(mean, 16.3 mL)
< 100 mm
(mean, 27 mm)
< 60 mm
(1560 mm)

380 mm*

1550 mm

1550 mm

1550 mm

Size

3797 women
(4361 cysts)

314 (378
cysts)
2763 (3259
cysts)
32

226

149 (153
cysts)

116 (20 lost


to follow-up)
121

60

36

4 days14 years
(mean, 6 years)
1894 months
(median,
42 months)

3 weeks13 years

5 years

0.38 years
(median, 3 years)
87 months

470 months
(mean,
31.5 months)
372 months
(mean,
31 months)
5 years (?)

Time in
follow-up

364

133

138

45

12

18

Women
operated
on (n)

0/133

1**/9

2/138

1/45

0/12

0/18

0/9

Malignancy in
surgical
specimen (n/n)

0.11
(4/3797
women)
(0.09,
4/4361
cysts)

0/32

0 (0/2763)

0.32 (1/314)

0.88 (2/226)

0.67 (1/149)

0 (0/121)

0 (0/96)

0 (0/60)

0 (0/36)

Malignancy
rate per
woman in
study
population
(% (n/n))

*Refers to all adnexal lesions included in the study; this study includes also cysts other than unilocular ones. The study includes an additional 39 cysts with more complicated but benign ultrasound
morphology. Not all 12 cysts operated on were unilocular. Squamous cancer in a papillation overlooked at scan in a dermoid cyst. Indication for surgery was cyst growth. **At surgery this cyst
was no longer unilocular; a papillary projection had developed. 95% CI, 0.040.28. 95% CI, 0.040.24. ?, unequivocal information not available; MP, menopausal.

Total of nine
studies

PostMP

19871993

Aubert et al.14

PostMP

19911996

Study

MP status

Years of
recruitment

Women
with
unilocular
cysts (n)

Table 3 Malignancy rates in adnexal lesions judged to be unilocular cysts at transvaginal scan and managed by follow-up: literature review

Risk of malignancy in unilocular cysts


85

Ultrasound Obstet Gynecol 2013; 41: 8089.

26

Copyright 2012 ISUOG. Published by John Wiley & Sons, Ltd.


IOTA*

2835

8760 mm 1148

134

5/1572
(0.32)

3/1572
(0.19)

1/931
(0.11)

2/641
(0.31)

2/641
(0.31)

3/641
(0.47)

13/1985
(0.65)

5/931
(0.54)

8/1054
(0.76)

3/413
(0.73)
5/641
(0.78)

All

2/437
(0.46)

1/217
(0.46)

1/220
(0.45)

18/437
(4.1)

5/217
(2.3)

13/220
(5.9)

13/134
(9.7)

1/134
(0.75)

0/43

0/43

Inv

0/43

0/43

Bord

PostMP

24/684
(3.5)

6/217
(2.8)

18/467
(3.9)

14/134
(10.4)

0/43

4/247
(1.6)

0/43

All

Malignancy rate (n/n (%))

13/2835
(0.46)

5/1148
(0.44)

8/1687
(0.47)

0/45
0/41
0/43
1/35 (2.6)
3/660
(0.45)
3/641
(0.47)
1/134
(0.75)

0/43
0/45

Bord

25/2835
(0.88)

6 /1148
(0.52)

19/1687
(1.1)

0/45
0/41
0/43
0
4/660
(0.61)
2/641
(0.31)
13/134
(9.7)

0/43
0/45

Inv

All

38/2835
(1.34)

11/1148
(0.96)

27/1687
(1.6)

0/45
0/41
0/43
1/35 (2.6)
7/660
(1.1)
5/641
(0.78)
14/134
(10.4)

0/43
0/45

All

*Cysts with protrusions of solid tissue < 3 mm in height are classified as unilocular (with wall irregularity). 95% CI, 0.981.83%. ?, unequivocal information not available; Bord, borderline tumor;
Inv, invasive malignancy; IOTA, International Ovarian Tumor Analysis; MP, menopausal.

Total of ten studies

Any

> 30 mm

641

45
41
43
35
660

43
45

Inv

PreMP
Bord

4/931
(0.43)

19992007 Mixed

Smooth

> 30 mm

?
8990 mL
> 10 mm
?
18200 mm

< 50 mm
< 100 mm

Current study

Any

?
?
Smooth
IOTA*
?

?
?

Size

3/641
(0.47)

19871993 PostMP

Osmers et al.30

Any

?
?
Anechoic
Any
Anechoic

Anechoic
?

Echogenicity Wall
of cyst fluid regularity

Total of nine studies

19871993 PreMP

19831992 PostMP
19871995 PostMP or
> 50 years
19871988 Mixed
19911993 Mixed
19881993 PostMP
20042006 Mixed
19921997 Mixed

Osmers et al.25

Granberg et al.2
Valentin et al.3
Shalev et al.24
Gramellini et al.29
Ekerhovd et al.28

Kroon and Andolf


Bailey et al.27

Study

Years of
recruitment MP status

Table 4 Malignancy rates in surgically removed adnexal lesions judged to be unilocular cysts at transvaginal scan: literature review

86

Valentin et al.

Ultrasound Obstet Gynecol 2013; 41: 8089.

Risk of malignancy in unilocular cysts

87

Table 5 Proportion of borderline and invasive adnexal malignancies classified as unilocular cysts on ultrasound: literature review
Proportion of unilocular cysts in malignant adnexal masses (n/n (%))
Study

Borderline

Invasive

Any adnexal malignancy

3/33
4/113
0/1
0/5
0/5
0/9
0/6
No information

0/82
No invasive
0/27
0/15
0/19
0/42
0/21
No information

3/115
4/113
0/28
0/20
0/24
0/51
0/27
0/39

Total of eight studies

7/172 (4.1)

0/206

7/417 (1.7)

Current study

5/186 (2.7)

6/764 (0.8)

11/950 (1.2)

Total of nine studies

12/358 (3.4)

6/970 (0.6)

18/1367 (1.3)

Exacoustos et al.31
Fruscella et al.32
Valentin et al.3
Gramellini et al.29
Valentin33
Hata et al.35
Jokubkiene et al.34
Granberg et al.2

potential of unilocular cysts. Others have tried to do so in


follow-up studies5,14 20,23 . Such studies are fraught with
difficulties. Because unilocular cysts appear and disappear,
even in postmenopausal women5,21,22 , it is difficult to
ascertain whether an ovarian malignancy in a woman
with previous diagnosis of a unilocular cyst developed
from that particular cyst or whether it developed de
novo while the previous cyst resolved. Lifelong follow-up
would be needed to settle the matter. In any case, the
risk of developing ovarian cancer does not seem to be
higher in women with ovarian unilocular cysts < 10 mL
(i.e. a diameter < 1314 mm) than in women with no
cystic lesions in their ovaries22 .
Yazbek et al. found that 11% (4/35) of borderline
tumors and 4% (1/24) of epithelial ovarian cancers were
described as unilocular cysts on ultrasound7 . These rates
are much higher than those in our study and those
reported elsewhere in the literature (Table 5)2,3,29,31 35 .
Differences in study populations, as well as failure of the
ultrasound examiner to detect papillary projections or
solid components might explain the discrepancies.
In agreement with our results, both Ekerhovd et al.28
and Osmers et al.25,30 found the risk of malignancy in
unilocular cysts to be higher in postmenopausal than
in premenopausal patients. They also stated that the
risk of malignancy increased with cyst size (statistical
significance not reported)25,28,30 , while in our study the
size of benign and malignant unilocular cysts did not differ
(Table 1). Osmers et al. found that the risk of malignancy
was unrelated to the echogenicity of cyst fluid (anechoic
vs echoic)25,30 . Our results suggest that the finding of
hemorrhagic cyst contents on ultrasound is associated
with an increased likelihood of malignancy. The reason is
probably that solid tumor and hemorrhagic cyst contents
may be confused, as happened in one case in our study,
and it may be difficult to detect irregularities and papillary
projections when cyst contents appear hemorrhagic on
ultrasound. Our finding of higher malignancy risk in
unilocular cysts in women with a personal history of
ovarian or breast cancer is also clinically likely. Still, our
numbers are small and therefore our results with regard to

Copyright 2012 ISUOG. Published by John Wiley & Sons, Ltd.

hemorrhagic cyst contents and personal history of ovarian


or breast cancer as being risk factors for malignancy in
unilocular cysts, although statistically significant, need to
be interpreted with caution. To determine which factors
can predict malignancy in unilocular cysts, one would
need a number of malignant unilocular cysts sufficiently
large for multivariate logistic regression analysis to be
possible. The predicting variables in such an analysis
could be menopausal status, personal history of breast or
ovarian cancer, family history of breast or ovarian cancer,
echogenicity of cyst fluid, wall irregularity and possibly the
color content of the cyst wall at color Doppler ultrasound
examination. Approximately 80 malignant unilocular
cysts would be needed to perform a relevant multivariate
logistic regression analysis. However, because it has taken
us 8 years to collect 11 cases of malignant unilocular
cysts from 21 centers, we doubt that it will be possible
to collect data sufficient for an appropriate multivariate
analysis within a reasonable time.
In our study, seven of the 11 malignant cysts
judged to be unilocular on ultrasound contained
papillary projections or solid components at macroscopic
inspection by the pathologist. Because the risk of
malignancy is higher in lesions containing septa and solid
components than in unilocular cysts1 , it is important that
the ultrasound examiner scrutinizes cyst walls for the
presence of papillary projections and thoroughly searches
for solid components in any cyst that appears to be
unilocular at scan. If there are technical problems, e.g.
bowel gas or other factors preventing a detailed view
of the lesion, the patient should be rescanned and the
uncertain nature of the mass should be noted.
Based on the results of our study and our extensive
review of the literature, it seems safe to leave cysts judged
to be unilocular on ultrasound in situ, as long as the
ultrasound examiner feels confident that the presence
of papillary projections or other solid components was
not overlooked. However, one should be aware that
postmenopausal status increases the risk of malignancy,
and that personal history of breast or ovarian cancer as
well as hemorrhagic cyst contents are also likely to do

Ultrasound Obstet Gynecol 2013; 41: 8089.

Valentin et al.

88

so. Another point to be noted is that wall irregularity


was twice as common in malignant than it was in
benign unilocular cysts in our study. Although this
difference did not reach statistical significance, we believe
that the possibility of malignancy should be considered
in unilocular cysts with irregular walls. After all, the
difference between a papillary projection as defined by
the IOTA group11 and a wall irregularity is only a matter
of size. There are insufficient published data on the longterm behavior of different types of unilocular cysts to
provide an evidence-based statement on optimal followup of unilocular cysts left in situ. A large prospective
observational study is needed to elucidate the natural
history of different types of unilocular cysts before an
evidence-based recommendation on the optimal followup regimen can be made.

7.

8.

9.

10.

ACKNOWLEDGMENTS
This work was supported by the Swedish Medical
Research Council: grant numbers K2001-72X 1160506A, K2002-72X-11605-07B, K2004-73X-11605-09A
and K2006-73X-11605-11-3; funds administered by
Malmo University Hospital; two Swedish governmental
grants: ALF-medel and Landstingsfinansierad Regional
Forskning; and Reasearch supported by Research Council
KU Leuven: GOA-MANET; IWT-TBM 070706 (IOTA);
Belgian Federal Science Policy Office: IUAP P6/04
(DYSCO); Research Foundation Flanders (FWO
Vlaanderen, 2151609 N, 1251612 N; research project
grant G049312N); Research Council KUL: GOA MaNet,
IBBT: Future Health Dept., Belgian Federal Science Policy
Office: IUAP P7/ (DYSCO, Dynamical systems, control
and optimization, 20122017).

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SUPPORTING INFORMATION ON THE INTERNET


The following supporting information may be found in the online version of this article.
Table S1 Participating centers and their contribution to the study.
Table S2 Histological diagnosis in unilocular adnexal cysts and other types of adnexal masses (n = 3511).

Copyright 2012 ISUOG. Published by John Wiley & Sons, Ltd.

Ultrasound Obstet Gynecol 2013; 41: 8089.

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