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Management of Complex Ovarian Cysts in Women with Management of Complex Ovarian Cysts in women with
Postmenopausal Bleeding

Abstract
Introduction: Transvaginal ultrasound (TVS) to determine endometrial thickness
is recommended in women with postmenopausal bleeding (PMB). TVS may also
detect extra-endometrial pathology including ovarian cysts. National guidelines
exist regarding management of ovarian cysts in postmenopausal women (RCOG
Green top No54). Cysts are categorized as simple or complex based on
ultrasound and this in conjunction with CA125 is used to calculate a risk of
malignancy index (RMI). Those with simple cysts and a low RMI (<250) maybe
safely managed conservatively whilst those with complex cysts or an increased
RMI (>250) should be offered surgical resection.

Objective: the purpose of this study was to determine whether the RCOG
guidelines on complex ovarian cysts were applicable to a subgroup of
postmenopausal women with PMB.

Methods: Clinical and ultrasound date for consecutive women attending our
PMB clinic from September 2001 to April 2004 were retrieved from a
computerized database. All women with complex cysts were counseled and
offered surgery according to RCOG guidelines. Those with simple cysts were
advised based on RMI. Pathology reports were obtained for all resected samples.

Results: 753 women underwent TVS. 76 women (10.1%) were found to have
ovarian cysts. 59 had simple cysts, CA125 was within the normal laboratory
range giving an RMI of less than 250 in all 59women .17(2.25%) women had
complex cysts: 11women had normal CA125 and thus low RMI and 6 had
elevated CA125 giving an elevated RMI. All women with complex ovarian cysts
were offered surgery. 6 of the 11 with low RMI elected to have surgery and all
had benign disease. The remaining 5 had follow-up CA125 and TVS and all had
ultrasound resolution of their cysts between 6months and 2years. All women
with increased RMI underwent surgery. 5 had primary ovarian malignancy with
one complex benign lesion.
Conclusion: RMI calculations are a reliable predictor of ovarian malignancy in
women with complex ovarian cysts and PMB. RCOG guidelines for the
management of complex ovarian lesion in the postmenopausal population are
safely applicable to this important sub-group of women
Key Words
PMB, TVS, CA125, RMI, ovarian cyst
INTRODUCTION:

Maintenance of postmenopausal health is of paramount importance, if we are to
minimize economic impact on society in this and future millennium1.
Seventy percent of Caucasians and afrocarribean women suffer from hot flushes
and sweats; the commonest menopausal symptom 2,3. Although there are several
immediate and long term consequences of menopause one of the most important
is not to miss endometrial malignancy which may first present with a symptom
of postmenopausal bleeding (PMB).

Vaginal bleeding more than 12 months after menopause occurs is considered
PMB4 . Careful history is important as well as meticulous physical examination.
Bleeding in post-menopausal women can be due to several causes including
genital tract tumour, and other extra-endometrial pathology. It is therefore not
unusual to find other pelvic tumours like bladder and ovarian malignancies,
during the cause of investigation
Transvaginal ultrasound scan (TVS) to determine endometrial thickness is
recommended in women with postmenopausal bleeding (PMB). TVS may also
detect extra-endometrial pathology including ovarian cysts. National guidelines
exist regarding management of ovarian cysts in postmenopausal women (Royal
college of Obstetricians and Gynaecologists: RCOG Greentop Guidelines No.
54). Cysts are categorized as simple or complex based on ultrasound and this in
conjunction with CA125 is used to calculate a risk of malignancy index (RMI).
Those with simple cysts and a low RMI (<250) may be safely managed
conservatively whilst those with complex cysts or an increased RMI ( >250)
should be offered surgical resection.
TVS also offers an opportunity to individualize the management of PMB.
Evidence shows that, women who present with PMB and in whom a TVS has
demonstrated an endometrial thickness of ≤ 4mm have a very small risk of
developing endometrial cancer4 .
.

Objective:
The purpose of this study was to determine whether the RCOG guidelines on
management of complex ovarian cysts were applicable to a subgroup of post-
menopausal women with PMB
Methods
The Royal Alexandra Hospital is a district general hospital that also serves as a
referral center where all the clinical records were kept.
We took the Clinical and ultrasound data for consecutive women attending our
postmenopausal bleeding (PMB) clinic from September 2001 until April 2004
from our computerized database. All women found to have an ovarian cyst had
also serum CA125 measurement and RMI calculated. Those with complex cysts
were counseled and offered surgery according to RCOG No 54 guidelines on the
management of ovarian cysts in postmenopausal women. Those with simple
cysts were advised based on RMI and followed-up until the cyst disappears.
Pathology reports were obtained for all resected samples.
Calculation of RMI was based on the formula menopausal status X CA125 X
ultrasound score (UXMXCA125). A simple cysts was define as monolocular with
smooth inner wall, while a complex cysts was define as a cyst with solid
component, irregular and thick wall.

Results:

Seven hundred and fifty-three women underwent TVS
1.
TVS Findings
76 women (10.1%) were found to have ovarian cysts on TVS, CA125 measurement were obtained in all these women. 59 of the 76 had simple cysts with the remaining 17 had complex lesions. i. 49 were unilocular and 10 were bilocular. CA125 was less than 25 in all cases (mean= 14, range 6-14) . ii. 11 patients had CA125 concentrations within the normal laboratory reference range ( 0-30U/ml). 6 patients had CA125 concentrations above the normal range (mean=144U/ml, range 39-556U/ml) 2. Outcomes
none underwent surgery. All were followed-up with TVS for a median time of 6 months (range 3 months – 1 year). and had repeat TVS. Their cysts resolved during this time and they were discharged. ii. With normal CA125 n=11. 6patients underwent surgery. All were benign disease. 5 did not have surgery (patient refusal n=2, unacceptable anaesthetist risk n=3) and underwent TVS during follow-up (median time 1 year. Range 6 months – 2 years) all cysts resolved spontaneously. With raised CA125, n=6. All underwent surgery. 5 of them had primary ovarian malignancy while one patient had benign tumour. Retrospective correlation of RMI and pathology in patients managed
surgically.

i.
RMI for all subjects was less than 250. All showed benign diseases. ii)
One patient had RMI of 612 – benign pathology. Remaining 5 patients had high
RMI (range 300-5004) and primary ovarian malignant disease .
Table 1
Type of ovarian cysts 76 women
.
Simple Complex Total
59 17 76

Table II
CA125 level in women with complex ovarian cysts
Normal value<30u/ml
Level
<30 6
30-60 4
60-100 5
>100 1
Table III
CA125 assay value, RMI in 5 patients with ovarian cancer and
histological type

Histology
Mucinous cystadenocarcinoma 39 351 Poorly differentiated endometroid sarcoma 5

Table IV
Size of ovarian cysts in relation to ovarian malignancy

Cysts size (diameter) cm
5 Malignant Brenner tumour

Table V correlation between CA125 and RMI
Cysts (complex)


Table VI
Ultrasound characteristics of ovarian cysts in PMB patients

Characteristics
Less than 5cm 49 49 More than 5 cm 22 5 27 Unilocular 49 49
Multilocular 22 5 27



.

Discussion:

Transvaginal ultrasound is recommended in women with post menopausal
bleeding4. It is well known that PMB could be a major symptom in women
suspected of endometrial carcinoma. Women may present with this symptom in
their late 50s or 60s and during the cause of investigation other pathology may be
discovered 1.
The main concern is to be certain that women who present with PMB and may
having other pathology are properly screened and right treatment offered. TVS
may also detect other extra-adnominal including ovarian cysts
Ovarian cysts are divided into both simple and complex cysts base on the
criteria earlier mentioned .Seven-hundred and fifty-three women came to our
clinic with PMB and had TVS – 76 women were found to have ovarian cysts. It
was our practice that all women we discovered during the cause of investigation
and found to have ovarian cysts were also offered biochemical estimation of
CA125. The women who had ovarian cysts were further classified according to
RCOG green top guidelines whether they had simple or complex cysts.
59 women had simple cysts and CA125 value estimation in these women was
within normal limit <30u/ml . We also calculated their risk of malignancy index
( RMI) which was less than 250, their cysts resolve within twelve weeks of
follow-up with CA125 and TVS. As shown in table IV the ovarian cysts in these
patients was mostly less than 5cm 49 were unilocular, while ten were
multilocular
17 women (2.75%) had complex cysts, which were multilocular with thick
septa on the wall. Eleven of these women had normal CA125 level and when
the RMI was calculated it was low. While the balance of 6 of these women had
elevated CA125 which gave them an RMI greater than 250 as shown in table III.
Based on this all the women in this group were offered surgery(laparotomy) and
had total abdominal hysterectomy ,bilateral salphingo-ophorectmy(TAH+BSO)
according to RCOG guidelines and the result showed benign disease, while the
other 5 declined and where therefore followed up using CA125 and TVS and all
had ultrasound resolution of their cysts within 6/12 to 2 years.
The other 6 women with complex ovarian cysts, elevated CA125 and high RMI
also underwent surgery. The results as tabulated in table III, showed 5 women
had primary woman ovarian malignancy. The sixth patient in this group had
histologically confirmed complex benign ovarian lesion. The first patient with
malignant Brenner tumour was elderly 68years with a complex multilocular
cyst, and high CA125 (14U/ml). The other 3patients also had a multilocular
cysts with a diameter of 6-20cm, raised CA125 (>60U/ml) and high RMI.
All these patients had optimum surgery and , were followed up for 2 years with
CA125, pelvic ultrasound and did not have any recurrence .This demonstrated
that CA125 is a reliable indicator in detecting ovarian malignancy in women with
PMB. This is was similar to a study by Jacobs et-al, which shows that using RMI
cut-off level of 250, the sensitivity was 85% and specificity was 95%.
.Ultrasound criteria have been developed and set as standard for differentiating
ovarian cyst on TVS in to those that are likely to be malignant or benign as
follows:

The Ultrasound criteria considered were:
More complex lesions tend to be multilocular with a diameter greater than Morley and Barnett (1970) suggested that gross malignant change was indicated by the pressure of more complex lesion with thick septa and solid areas- this was similar to findings in our studies. This is also supported by Koboyashi (1976) who again suggested the more complex lesion cysts tends to be more to be malignant too. Several studies have shown a relationship between endometrial thickness as measured by TVS and endometrial malignancy on women with PMB 3,4 Several studies demonstrated that, with 4mm as a cut off level TVS of the endometrial on women with PMB can exclude endometrial antibody with reasonable certainty 5,6 Using this standard the 5th patient beside the ovarian cytsadenocarcinoma also had endometrial adenocarcinoma, the endometrial thickness was 10mm. She had TAH+BSO, omentectomy and radiotherapy. Gynaecologist are often confronted with the difficult problem of differentiating malignant tumour from benign and in patients with pelvic masses since Bast et-al discovered monoclonal antibody OC125 for ovarian cancer, use of this antibody to estimate serum CA125 level have become a relatively effective immunodiagnostic method for detecting ovarian malignancy. We use these biochemical methods also in patients with complex ovarian cysts in PMB women to help differentiate those with malignant lesion. Bast et al further define that a CA 125 value greater than 65 U/ml is a positive criteria for the presence of a epithelial ovarian cancer. In all the 5 patients that had detectable histological ovarian cancer they had a CA125 greater than 65 U/ml. When you look at retrospective correlation of RMI with pathology in 6 patients managed surgically; they all had benign disease. These patients had a normal CA125. It is not worthing that the sensitivity of CA125 in detecting patient with epithelial ovarian cancer has been reported as 73-92%.7,8,9 but CA125 has also a high false positive rate and this was demonstrated in one of the patient who despite a CA125 value of <100 she had a benign disease. Chen Di-Xia and colleagues suggested that to reduce the high false positive rate they raised the cut off criteria of CA125 level greater than 194 Ulml .By doing this in their study; they were able to show that the false positive rate drops from 39% to 5.2% Menopausal status, CA125, and Ultrasound scan to calculate RMI is a
criteria effective and useful in distinguishing between benign and
malignant ovarian tumour using a cut-off part of 250 and above, the
sensitivity was 85% and specifically of 97%.using similar criteria we were
able to discover the five cases of ovarian malignancy in this subgroup of
women with PMB (see table V)
Using this criteria than any of the 3 alone plus, clinical impression will
allow discriminating correctly approximated 90% of patients with a benign
or malignant adnexal mass perioperatively 9,10,12 .


The principle advantage of TVS compared to transabdominal is, 12,13,14,15
the latter has improved resolution allowing more accurate endometrial
thickness measurement and better assessment of endometrial malignancy.
It also has the following advantages:
More successful assessment of above patient Ability to clearly define other pelvic pathology and the reason why we employ it and were able to detect the extra-endometrial malignant like ovarian tumor. Using TVS is now considered mandatory in patients presenting with
PMB.15 except where there is an obvious abdominal swelling, when
TAB might be more useful.

Conclusion:

RMI calculations are a reliable predicator of ovarian malignancy in women with
complex ovarian cysts and PMB. RCOG guidelines for the management of
complex ovarian lesions in the postmenopausal population are safely applicable
to this important sub-group of women.


References

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. 4. Bast Rejr. Klug TC, St. John E. Radiosionominossay using a
monoclonal antibody to monitor the course of epithelial ovarian cancer. N
engl. J Med 309: 883:1983
5. Chem Di-XIA. Peter ES. LI XINGUO and Yaung Zhan. Evaluation of CA125 levels in differentiating malignant from benign tumour inpatients with pelvic mone 1988 Obts. & Gyneac. 72 (1) 23-27 6. Marley P. Barnett E (1970) British Journal of radiology 43: 602 8. Granberg S. Friberg L-G, Norstrom A. Wikland M. Endovaginal Ultrasound scanning of women with PMB. J. Ultrasound Med. 1988 (7) ( Supple 10) : 283 .9.Whitehead,MI. The climacteric: In progress in Obstetrics & Gynaecology. Ed. J. Studd, vol 5 . Pg 332 - 356 10. Lied HK, Fruckle WD (1978) 1988 Association of estrace and the development of endromentrial cancinana and obst. Gynaecology 124: 735-740. 11. Traqqiai C, Stanhope R. Disorders of pubertal development. Best pract Res Clin Obstet Gynaecol;17:41-56. 12.Ziel HK,Finkle WD, Association of estrone and the development of endometrial carcinoma.Am J Obst Gynecol 1976;124:735-740 13. Jacobs I.J and Bast RC. The CA125 tumour associated antigen a review of the literature. 1989;HUM Reprod 4. 1-2 14. Jacobs I. Ovam D. Farmbauk J. Turnes), Frosh C. Grudzinskas JG, (1980) a risk of malignancy under incorporating CA125, Ultrasound and menopausal status for the accurate preoperative diagnosis of ovarian cancer .1980; 97:922-929 15. Scottish Intercollegiate Guidelines Network Number 61 September 2002 (SIGN 61).

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