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Keywords:

  • ovarian neoplasms;
  • simple ovarian cyst;
  • ultrasonography;
  • unilocular ovarian cyst

ABSTRACT

  1. Top of page
  2. ABSTRACT
  3. INTRODUCTION
  4. METHODS
  5. RESULTS
  6. DISCUSSION
  7. ACKNOWLEDGMENTS
  8. REFERENCES
  9. Supporting Information

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, 0.48–1.71)) were malignant. The malignancy rate was lower in premenopausal than in postmenopausal women: 0.54% (5/931; 95% CI, 0.17–1.25) vs 2.76% (6/217; 95% CI, 1.02–5.92); 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

  1. Top of page
  2. ABSTRACT
  3. INTRODUCTION
  4. METHODS
  5. RESULTS
  6. DISCUSSION
  7. ACKNOWLEDGMENTS
  8. REFERENCES
  9. Supporting Information

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 pathologist[1] or on the basis of an ultrasound image of the cyst[2-5]. 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 (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 scan[6]. 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 ultrasound[7].

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

  1. Top of page
  2. ABSTRACT
  3. INTRODUCTION
  4. METHODS
  5. RESULTS
  6. DISCUSSION
  7. ACKNOWLEDGMENTS
  8. REFERENCES
  9. Supporting Information

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 protocol[8-10]. 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 definitions[11] 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 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). Fisher's exact test was used to test the statistical significance of differences in binary data; the Mann–Whitney 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

  1. Top of page
  2. ABSTRACT
  3. INTRODUCTION
  4. METHODS
  5. RESULTS
  6. DISCUSSION
  7. ACKNOWLEDGMENTS
  8. REFERENCES
  9. Supporting Information

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, 0.88–6.16)) were classified as unilocular cysts on ultrasound, and of 764 invasive malignancies, six (0.79% (95% CI, 0.29–1.70)) were classified as unilocular cysts on ultrasound.

Of the 1148 unilocular cysts in the IOTA database, 11 (0.96% (95% CI, 0.48–1.71)) were malignant vs 40% (939/2363; 95% CI, 38–42) 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, 0.14–1.01) and that of invasive malignancy was 0.52% (95% CI, 0.19–1.13) (Table S2). The malignancy rate in unilocular cysts was lower in premenopausal women than in postmenopausal women: 0.54% (5/931; 95% CI, 0.17–1.25) compared to 2.76% (6/217; 95% CI, 1.27–5.92); P = 0.009. In premenopausal women, four of 931 unilocular cysts were borderline malignant (0.43% (95% CI, 0.12–1.10)) and one was invasively malignant (0.11% (95% CI, 0–0.60)). The corresponding figures for postmenopausal women were one (0.46% (95% CI, 0.01–2.54)) and five (2.30% (95% CI, 0.75–5.29)) 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, 0.34–3.11) and that in unilocular cysts with another type of cyst fluid, with or without irregular walls on ultrasound, was 0.85% (7/822; 95% CI, 0.34–1.75); the malignancy rate in unilocular cysts with a largest diameter ≤ 5 cm at scan was 0.82% (4/486; 95% CI, 0.22–2.09) and that in unilocular cysts with a largest diameter > 5 cm on ultrasound was 1.06% (7/662; 95% CI, 0.43–2.17).

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).

Table 1. Prospectively collected clinical and ultrasound information for benign and malignant unilocular cysts (n = 1148)
VariableBenign (n = 1137)Malignant (n = 11)P
  • 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.

Clinical characteristics
Age (years)36 (15–90)60 (26–82)0.002
Postmenopausal211 (19)6 (55)0.009
Nulliparous611 (54)6 (55)1
Hysterectomy43 (4)1 (9)0.35
Current hormonal treatment172 (15)1 (9)1
Personal history of ovarian cancer7 (< 1)2 (18)0.003
Personal history of breast cancer23 (2)2 (18)0.02
Family history of ovarian cancer20 (2)0 (0)1
Family history of breast cancer77 (7)0 (0)1
CA 125 (U/mL)*19 (2–3500)20 (7–147)0.50
Ultrasound characteristics
Bilateral165 (15)1 (9)1
Largest diameter (mm)56 (8–760)57 (25–171)0.49
Mean diameter (mm)48 (8–340)48 (23–156)0.49
Volume (cm3)54 (0.2−20 525)58 (7–1940)0.48
Echogenicity of cyst contents
Anechoic322 (28)4 (36)0.52
Homogeneous low level154 (14)1 (9) 
Ground glass412 (36)4 (36) 
Hemorrhagic28 (2)2 (18)0.03§
Mixed221 (19)0 (0) 
Irregular walls161 (14)3 (27)0.20
Fluid in pouch of Douglas162 (14)3 (27)0.20
Fluid in pouch of Douglas (mm)14 (1–61)18 (10–38)0.46
Ascites9 (< 1)0 (0)1
Acoustic shadows169 (15)0 (0)0.38
Color Doppler blood flow
No flow603 (53)5 (45)0.76
Minimal flow384 (34)6 (55) 
Moderate flow138 (12)0 (0)0.38**
Strong flow12 (1)0 (0) 
Venous blood flow only81 (7)2 (18)0.19
Spectral Doppler results
Pulsatility index1.00 (0.13–5.09)1.68 (0.76–3.21)0.41
Resistance index0.61 (0.12–1.00)0.72 (0.52–0.92)0.39
Peak systolic velocity (cm/s)10.20 (0.19–79.85)12.72 (6.18–27.60)0.60
Time averaged maximum velocity (cm/s)6.00 (0.02–52.78)5.85 (1.77–18.20)0.93
Diagnosis on basis of subjective assessment
Certainly benign938 (83)4 (36)<0.001††
Probably benign188 (17)6 (55) 
Uncertain9 (< 1)1 (9) 
Probably malignant1 (< 1)0 (0) 
Certainly malignant1 (< 1)0 (0) 

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 examiner's description and the pathologist's 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 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).

Table 2. Detailed information on the 11 unilocular cysts that proved to be malignant
Age (years)Personal history of ovary cancerPersonal history of breast cancerCA 125 (U/mL)Diagnosis on basis of subjective assessmentLargestdiameter(mm)Echogenicity of cyst fluidFluid inPOD(mm)BilateralIrregular cyst wallsAgreement with macroscopyFinal diagnosis
  1. POD, pouch of Douglas.

42NoNo7Certainly benign58Anechoic0NoNoYesBorderline, mucinous (pseudostratification and atypia), Stage 1
50NoNo14Probably benign128Low-level0NoNoYesBorderline, mucinous, Stage 1
69NoYes26Certainly benign171Ground glass18NoNoYesMature teratoma with microcarcinoma of struma type
60NoNo10Probably benign48Anechoic0NoNoNo (papillations missed)Borderline (focus of atypical cells), serous, Stage 1
41YesNo78Certainly benign53Ground glass0NoNoNo (papillations missed)Borderline, serous, Stage 1
26NoNo13Probably benign140Anechoic0NoNoNo (papillations missed)Borderline, serous, Stage 1
43NoNo147Probably benign45Anechoic38NoNoNo (papillations missed)Seropapillary peritoneal cancer, Stage 3
82NoYes20Probably benign75Ground glass0NoNoNo (solid part missed)Infiltration of neuroendocrine carcinoma in a benign cystic teratoma (previous breast cancer of neuroendocrine type)
62NoNo68Uncertain57Ground glass10YesYesNo (solid part missed)Carcinoma, endometrioid, Stage 3
71NoNo84Certainly benign37Hemorrhagic0NoYesNo (solid tumor)Carcinoma, tubal, Stage 3
65YesNo13Probably benign25Hemorrhagic0NoYesNon-optimal specimenRecurrent mucinous invasive cancer in the ovary, Stage 1
image

Figure 1. Solid lesion misclassified as a unilocular cyst with hemorrhagic cyst contents on ultrasound. The histological diagnosis was tubal carcinoma, Stage 3.

Download figure to PowerPoint

image

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.

Download figure to PowerPoint

DISCUSSION

  1. Top of page
  2. ABSTRACT
  3. INTRODUCTION
  4. METHODS
  5. RESULTS
  6. DISCUSSION
  7. ACKNOWLEDGMENTS
  8. REFERENCES
  9. Supporting Information

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 pre- and 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 situ[4, 5, 14-23]. In studies in which (mostly asymptomatic) women with adnexal cysts judged to be unilocular on ultrasound were recommended for follow-up 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 at eventual operation[5, 14-20, 23]. The clinical course in patients who did not undergo surgery suggests that their unilocular cysts were all benign (Table 3).

Table 3. Malignancy rates in adnexal lesions judged to be unilocular cysts at transvaginal scan and managed by follow-up: literature review
StudyYears of recruitmentMP statusEchogenicity of cyst fluidWall regularitySizeWomen with unilocular cysts (n)Time in follow-upWomen operated on (n)Malignancy in surgical specimen (n/n)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, 0.04–0.28. ‡‡ 95% CI, 0.04–0.24. ?, unequivocal information not available; MP, menopausal.

           
Aubert et al.[14]1991–1996PostMPAnechoic??15–50 mm364–70 months (mean, 31.5 months)00 (0/36)
Auslender et al.[15]1987–1993PostMPHypoechogenicSmooth15–50 mm603–72 months (mean, 31 months)90/90 (0/60)
Conway et al.[16]1990–1994PostMPAnechoicSmooth15–50 mm116 (20 lost to follow-up)5 years (?)180/180 (0/96)
Valentin and Akrawi[17]1991–1998PostMPAnySmooth3–80 mm*1210.3–8 years (median, 3 years)120/120 (0/121)
Castillo et al.[18]1995–2002PostMPAnechoic? (no papillae)1–3219 mL; ≤ 50 mm in 84%149 (153 cysts)≤ 87 months451§ /450.67 (1/149)
Nardo et al.[19]1995–2000PostMP??< 50 mm (18–50 mm)2265 years1382 /1380.88 (2/226)
Sarkar and Wolf[20]1997–2012PostMPAnechoicSmooth, no papillae0.1–860.4 mL (mean, 16.3 mL)314

(378 cysts)

3 weeks–13 years91**   /90.32 (1/314)
Modessit et al.[5]1987–2002> 50 years (mixed)Any?No papillae< 100 mm (mean, 27 mm)2763 (3259 cysts)4 days–14 years (mean, 6 years)1330/1330 (0/2763)
Alcazar et al.[23]1997–2002PreMP??< 60 mm (15–60 mm)3218–94 months (median, 42 months)00/32
Total of nine studies     3797 women (4361 cysts) 364 0.11†† (4/3797 women) (0.09‡‡, 4/4361 cysts)

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, 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 phenomenon[5]). 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.

Table 4. Malignancy rates in surgically removed adnexal lesions judged to be unilocular cysts at transvaginal scan: literature review
StudyYears of recruitmentMP statusEchogenicity of cyst fluidWall regularitySizenMalignancy rate (n/n (%))
PreMPPostMPAll
BordInvAllBordInvAllBordInvAll
  • *

    Cysts with protrusions of solid tissue < 3 mm in height are classified as unilocular (with wall irregularity).

  • 95% CI, 0.98–1.83%. ?, unequivocal information not available; Bord, borderline tumor; Inv, invasive malignancy; IOTA, International Ovarian Tumor Analysis; MP, menopausal.

Kroon and Andolf[26]1983–1992PostMPAnechoic?< 50 mm430/430/430/430/430/430/43
Bailey et al.[27]1987–1995PostMP or > 50 years??< 100 mm450/450/450/45
Granberg et al.[2]1987–1988Mixed???450/450/450/45
Valentin et al.[3]1991–1993Mixed??8–990 mL410/410/410/41
Shalev et al.[24]1988–1993PostMPAnechoicSmooth> 10 mm430/430/430/430/430/430/43
Gramellini et al.[29]2004–2006MixedAnyIOTA*?351/35 (2.6)01/35 (2.6)
Ekerhovd et al.[28]1992–1997MixedAnechoic?18–200 mm6603/413 (0.73)4/247 (1.6)3/660 (0.45)4/660 (0.61)7/660 (1.1)
Osmers et al.[25]1987–1993PreMPAny?> 30 mm6413/641 (0.47)2/641 (0.31)5/641 (0.78)3/641 (0.47)2/641 (0.31)5/641 (0.78)
Osmers et al.[30]1987–1993PostMPAnySmooth> 30 mm1341/134 (0.75)13/134 (9.7)14/134 (10.4)1/134 (0.75)13/134 (9.7)14/134 (10.4)
Total of nine studies      3/641 (0.47)2/641 (0.31)8/1054 (0.76)1/220 (0.45)13/220 (5.9)18/467 (3.9)8/1687 (0.47)19/1687 (1.1)27/1687 (1.6)
Current study1999–2007MixedAnyIOTA*8–760 mm11484/931 (0.43)1/931 (0.11)5/931 (0.54)1/217 (0.46)5/217 (2.3)6/217 (2.8)5/1148 (0.44)6 /1148 (0.52)11/1148 (0.96)
Total of ten studies     28355/1572 (0.32)3/1572 (0.19)13/1985 (0.65)2/437 (0.46)18/437 (4.1)24/684 (3.5)13/2835 (0.46)25/2835 (0.88)38/2835 (1.34)

We present a point estimate of the rate of malignancy in unilocular cysts, but we did not study the malignant potential of unilocular cysts. Others have tried to do so in follow-up studies[5, 14-20, 23]. Such studies are fraught with difficulties. Because unilocular cysts appear and disappear, even in postmenopausal women[5, 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 < 13–14 mm) than in women with no cystic lesions in their ovaries[22].

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 ultrasound[7]. 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.

Table 5. Proportion of borderline and invasive adnexal malignancies classified as unilocular cysts on ultrasound: literature review
StudyProportion of unilocular cysts in malignant adnexal masses (n/n (%))
BorderlineInvasiveAny adnexal malignancy
Exacoustos et al.[31]3/330/823/115
Fruscella et al.[32]4/113No invasive4/113
Valentin et al.[3]0/10/270/28
Gramellini et al.[29]0/50/150/20
Valentin[33]0/50/190/24
Hata et al.[35]0/90/420/51
Jokubkiene et al.[34]0/60/210/27
Granberg et al.[2]No informationNo information0/39
Total of eight studies7/172 (4.1)0/2067/417 (1.7)
Current study5/186 (2.7)6/764 (0.8)11/950 (1.2)
Total of nine studies12/358 (3.4)6/970 (0.6)18/1367 (1.3)

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 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 cysts[1], 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 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 group[11] and a wall irregularity is only a matter of size. There are insufficient published data on the long-term behavior of different types of unilocular cysts to provide an evidence-based statement on optimal follow-up 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 follow-up regimen can be made.

ACKNOWLEDGMENTS

  1. Top of page
  2. ABSTRACT
  3. INTRODUCTION
  4. METHODS
  5. RESULTS
  6. DISCUSSION
  7. ACKNOWLEDGMENTS
  8. REFERENCES
  9. Supporting Information

This work was supported by the Swedish Medical Research Council: grant numbers K2001-72X 11605-06A, K2002-72X-11605-07B, K2004-73X-11605-09A and K2006-73X-11605-11-3; funds administered by Malmö 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’, 2012–2017).

REFERENCES

  1. Top of page
  2. ABSTRACT
  3. INTRODUCTION
  4. METHODS
  5. RESULTS
  6. DISCUSSION
  7. ACKNOWLEDGMENTS
  8. REFERENCES
  9. Supporting Information
  • 1
    Granberg S, Wikland M, Jansson I. Macroscopic characterization of ovarian tumors and the relation to the histological diagnosis: criteria to be used for ultrasound evaluation. Gynecol Oncol 1989; 35: 139144.
  • 2
    Granberg S, Norstrom A, Wikland M. Tumors in the lower pelvis as imaged by vaginal sonography. Gynecol Oncol 1990; 37: 224229.
  • 3
    Valentin L, Sladkevicius P, Marsal K. Limited contribution of Doppler velocimetry to the differential diagnosis of extrauterine pelvic tumors. Obstet Gynecol 1994; 83: 425433.
  • 4
    Roman LD. Small cystic pelvic masses in older women: is surgical removal necessary? Gynecol Oncol 1998; 69: 12.
  • 5
    Modesitt SC, Pavlik EJ, Ueland FR, DePriest PD, Kryscio RJ, van Nagell JR Jr. Risk of malignancy in unilocular ovarian cystic tumors less than 10 centimeters in diameter. Obstet Gynecol 2003; 102: 594599.
  • 6
    Menon U, Gentry-Maharaj A, Hallett R, Ryan A, Burnell M, Sharma A, Lewis S, Davies S, Philpott S, Lopes A, Godfrey K, Oram D, Herod J, Williamson K, Seif MW, Scott I, Mould T, Woolas R, Murdoch J, Dobbs S, Amso NN, Leeson S, Cruickshank D, McGuire A, Campbell S, Fallowfield L, Singh N, Dawnay A, Skates SJ, Parmar M, Jacobs I. Sensitivity and specificity of multimodal and ultrasound screening for ovarian cancer, and stage distribution of detected cancers: results of the prevalence screen of the UK Collaborative Trial of Ovarian Cancer Screening (UKCTOCS). Lancet Oncol 2009; 10: 327340.
  • 7
    Yazbek J, Raju KS, Ben-Nagi J, Holland T, Hillaby K, Jurkovic D. Accuracy of ultrasound subjective ‘pattern recognition’ for the diagnosis of borderline ovarian tumors. Ultrasound Obstet Gynecol 2007; 29: 489495.
  • 8
    Timmerman D, Testa AC, Bourne T, Ferrazzi E, Ameye L, Konstantinovic ML, Van Calster B, Collins WP, Vergote I, Van Huffel S, Valentin L. Logistic regression model to distinguish between the benign and malignant adnexal mass before surgery: a multicenter study by the International Ovarian Tumor Analysis Group. J Clin Oncol 2005; 23: 87948801.
  • 9
    Van Holsbeke C, Van Calster B, Testa AC, Domali E, Lu C, Van Huffel S, Valentin L, Timmerman D. Prospective internal validation of mathematical models to predict malignancy in adnexal masses: results from the international ovarian tumor analysis study. Clin Cancer Res 2009; 15: 684691.
  • 10
    Timmerman D, Van Calster B, Testa AC, Guerriero S, Fischerova D, Lissoni AA, Van Holsbeke C, Fruscio R, Czekierdowski A, Jurkovic D, Savelli L, Vergote I, Bourne T, Van Huffel S, Valentin L. Ovarian cancer prediction in adnexal masses using ultrasound-based logistic regression models: a temporal and external validation study by the IOTA group. Ultrasound Obstet Gynecol 2010; 36: 226234.
  • 11
    Timmerman D, Valentin L, Bourne TH, Collins WP, Verrelst H, Vergote I. Terms, definitions and measurements to describe the sonographic features of adnexal tumors: a consensus opinion from the International Ovarian Tumor Analysis (IOTA) Group. Ultrasound Obstet Gynecol 2000; 16: 500505.
  • 12
    Heintz AP, Odicino F, Maisonneuve P, Beller U, Benedet JL, Creasman WT, Ngan HY, Pecorelli S. Carcinoma of the ovary. Int J Gynaecol Obstet 2003; 83 (Suppl 1) 135166.
  • 13
    Heintz AP, Odicino F, Maisonneuve P, Quinn MA, Benedet JL, Creasman WT, Ngan HY, Pecorelli S, Beller U. Carcinoma of the ovary. FIGO 26th Annual Report on the Results of Treatment in Gynecological Cancer. Int J Gynaecol Obstet 2006; 95 (Suppl 1) 161192.
  • 14
    Aubert JM, Rombaut C, Argacha P, Romero F, Leira J, Gomez-Bolea F. Simple adnexal cysts in postmenopausal women: conservative management. Maturitas 1998; 30: 5154.
  • 15
    Auslender R, Atlas I, Lissak A, Bornstein J, Atad J, Abramovici H. Follow-up of small, postmenopausal ovarian cysts using vaginal ultrasound and CA-125 antigen. J Clin Ultrasound 1996; 24: 175178.
  • 16
    Conway C, Zalud I, Dilena M, Maulik D, Schulman H, Haley J, Simonelli K. Simple cyst in the postmenopausal patient: detection and management. J Ultrasound Med 1998; 17: 369372; quiz 373–364.
  • 17
    Valentin L, Akrawi D. The natural history of adnexal cysts incidentally detected at transvaginal ultrasound examination in postmenopausal women. Ultrasound Obstet Gynecol 2002; 20: 174180.
  • 18
    Castillo G, Alcazar JL, Jurado M. Natural history of sonographically detected simple unilocular adnexal cysts in asymptomatic postmenopausal women. Gynecol Oncol 2004; 92: 965969.
  • 19
    Nardo LG, Kroon N, Reginald PW. Persistent unilocular ovarian cysts in a general population of postmenopausal women: is there a place for expectant management? Obstet Gynecol 2003; 102: 589593.
  • 20
    Sarkar M, Wolf MG. Simple ovarian cysts in postmenopausal women: scope of conservative management. Eur J Obstet Gynecol Reprod Biol 2012; 162: 7578.
  • 21
    Levine D, Gosink BB, Wolf SI, Feldesman MR, Pretorius DH. Simple adnexal cysts: the natural history in postmenopausal women. Radiology 1992; 184: 653659.
  • 22
    Greenlee RT, Kessel B, Williams CR, Riley TL, Ragard LR, Hartge P, Buys SS, Partridge EE, Reding DJ. Prevalence, incidence, and natural history of simple ovarian cysts among women >55 years old in a large cancer screening trial. Am J Obstet Gynecol 2010; 202: 373 e1–9.
  • 23
    Alcazar JL, Castillo G, Jurado M, Garcia GL. Is expectant management of sonographically benign adnexal cysts an option in selected asymptomatic premenopausal women? Hum Reprod 2005; 20: 32313234.
  • 24
    Shalev E, Eliyahu S, Peleg D., Tsabari A. Laparoscopic management of adnexal cystic masses in postmenopausal women. Obstet Gynecol 1994; 83: 594596.
  • 25
    Osmers RG, Osmers M, von Maydell B, Wagner B, Kuhn W. Preoperative evaluation of ovarian tumors in the premenopause by transvaginosonography. Am J Obstet Gynecol 1996; 175: 428434.
  • 26
    Kroon E, Andolf E. Diagnosis and follow-up of simple ovarian cysts detected by ultrasound in postmenopausal women. Obstet Gynecol 1995; 85: 211214.
  • 27
    Bailey CL, Ueland FR, Land GL, DePriest PD, Gallion HH, Kryscio RJ, van Nagell JR Jr. The malignant potential of small cystic ovarian tumors in women over 50 years of age. Gynecol Oncol 1998; 69: 37.
  • 28
    Ekerhovd E, Wienerroith H, Staudach A, Granberg S. Preoperative assessment of unilocular adnexal cysts by transvaginal ultrasonography: a comparison between ultrasonographic morphologic imaging and histopathologic diagnosis. Am J Obstet Gynecol 2001; 184: 4854.
  • 29
    Gramellini D, Fieni S, Sanapo L, Casilla G, Verrotti C, Nardelli GB. Diagnostic accuracy of IOTA ultrasound morphology in the hands of less experienced sonographers. Aust N Z J Obstet Gynaecol 2008; 48: 195201.
  • 30
    Osmers RG, Osmers M, von Maydell B, Wagner B, Kuhn W. Evaluation of ovarian tumors in postmenopausal women by transvaginal sonography. Eur J Obstet Gynecol Reprod Biol 1998; 77: 8188.
  • 31
    Exacoustos C, Romanini ME, Rinaldo D, Amoroso C, Szabolcs B, Zupi E, Arduini D. Preoperative sonographic features of borderline ovarian tumors. Ultrasound Obstet Gynecol 2005; 25: 5059.
  • 32
    Fruscella E, Testa AC, Ferrandina G, De Smet F, Van Holsbeke C, Scambia G, Zannoni GF, Ludovisi M, Achten R, Amant F, Vergote I, Timmerman D. Ultrasound features of different histopathological subtypes of borderline ovarian tumors. Ultrasound Obstet Gynecol 2005; 26: 644650.
  • 33
    Valentin L. Gray scale sonography, subjective evaluation of the color Doppler image and measurement of blood flow velocity for distinguishing benign and malignant tumors of suspected adnexal origin. Eur J Obstet Gynecol Reprod Biol 1997; 72: 6372.
  • 34
    Jokubkiene L, Sladkevicius P, Valentin L. Does three-dimensional power Doppler ultrasound help in discrimination between benign and malignant ovarian masses? Ultrasound Obstet Gynecol 2007; 29: 215225.
  • 35
    Hata K, Akiba S, Hata T, Miyazaki K. A multivariate logistic regression analysis in predicting malignancy for patients with ovarian tumors. Gynecol Oncol 1998; 68: 256262.
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).

Supporting Information

  1. Top of page
  2. ABSTRACT
  3. INTRODUCTION
  4. METHODS
  5. RESULTS
  6. DISCUSSION
  7. ACKNOWLEDGMENTS
  8. REFERENCES
  9. Supporting Information
FilenameFormatSizeDescription
uog12308-sup-0001-Table S1.docWord document58KTable S1 Participating centers and their contribution to the study
uog12308-sup-0002-Table S2.docWord document40KTable S2 Histological diagnosis in unilocular adnexal cysts and other types of adnexal masses (n = 3511)

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