Mohamed Said El-Shorbagy, MD

 
  To detect ovarian cancer in patients presented with adnexal mass using   Risk of Malignancy Index (RMI) based on menopausal status, ultrasound  findings and serum level of CA125.

 
  Al-Hussein University Hospital, Cairo-Egypt

 
         One hundred and forty women, 30 years or older, admitted with  adnexal mass between September 1998 and February 2002, for laparotomy.

 
  The sensitivity, specificity and positive predictive value of RMI based  on menopausal status, ultrasound findings and CA125 to diagnose ovarian  cancer patients.

 
         Using a cut-off level of 190 to indicate malignancy, the RMI  gave sensitivity of 86.67 %, specificity of 92.5 % and positive  predictive value of 89.66 %.

 
  The risk of malignancy index is able to correctly discriminate between  malignant and benign adnexal mass. It is highly recommended to be  introduced into clinical practice in Egypt to facilitate the selection  of patients for primary surgery at an Gynecologic Oncology Unit.


         Adnexal mass can represent a number of different benign and  malignant conditions. Laparotomy is essential to establish the nature of  adnexal mass. Ovarian cancer is the most lethal of genital malignancy  and surgical staging is recommended by FIGO. Proper staging is the key  to an accurate prognosis.(1) The amount of residual malignant tissue  after primary surgery is among the best prognostic factors in ovarian         cancer (2-4), however, many patients do not receive appropriate  surgery at the time of surgical         diagnosis (5, young).         

The greatest opportunity to influence the natural history of  ovarian cancer occurs at the initial laparotomy. Therefore, patients  with ovarian malignancy should be referred to a special center for  gynecologic oncology.

In practice, the diagnosis of ovarian cancer is often  difficult to make preoperatively and inadequate surgical exploration by  junior or inexperienced surgeon is a regular occurrence.          Sensitive and specific method for preoperative diagnosis of  ovarian cancer would provide a rational basis for referral before  diagnostic laparotomy. Patients with ovarian malignancy would thereby be  ensured of the benefits of thorough surgical staging and cytoreduction  by an experienced surgeon.

A method for better preoperative discrimination of patients  with adnexal mass was introduced by Jacob et al (6)(RMI) based on the  menopausal status, ultrasound findings and serum level of CA125, where,  RMI=M X U X CA125, (M= menopausal status, U= Ultrasound score and         CA125). This method was evaluated by others (7-9).

The purpose of this study was to apply RMI for patients  presented with adnexal mass to examine the sensitivity, specificity and  positive predictive value of the Risk of Malignancy Index in identifying  patients with ovarian cancer         among Egyptian women presented at Al-Hussein University  Hospital, Cairo-Egypt.

 
         Hundred forty patients with adnexal mass were eligible for this study between February 1997 and February 2002.

Preoperative serum CA125 level (IMX, Abbott Laboratories, USA), ultrasound findings and menopausal status were registered.

Ultrasound examination was performed vaginally using 6.5MHz  transducer (Medison, Korea) and extended transabdominally when needed  with 3.5 MHz transducer.

The presence of bilateral lesions, a multilocular cystic  lesion, solid areas, ascites and intraabdominal metastases were  reported. 

Postmenopausal status was defined as more than one year of  amenorrhoea or age older than 50 years in women who had had a  hysterectomy. Patients who did not meet these criteria were classified  as premenopausal.

Based on the data obtained the Risk of Malignancy Index was calculated for each patient.

The calculation was based on a simple regression equation  where total ultrasound score of 0 or 1 gave U=1 and a score >2 gave  U=3.

Premenopausal status gave M=1 and postmenopausal M=2.

The serum level of CA125 was applied directly into the  calculation and Risk of Malignancy Index was calculated as follows: RMI =  U X M X CA125.

All statistical analysis was done in statistical package for social science, SPPS inc. version 5.1.

Chi-square tests were used to test difference in distribution  of age, menopausal status and ultrasound score. The Man-Whitney U test  was applied when testing differences in distribution of CA125 among  women with benign and malignant adnexal mass. 

Sensitivity, Specificity, Positive Predictive value (PPV) and  Negative predictive value (NPV) was calculated for CA125 and RMI in  diagnosis of ovarian cancer.

 
         Out of 140 patients presented with adnexal mass, 60 (%) had malignant disease and 80 (%) benign pathology.

Benign Gynecological conditions included:  functional cysts  (n=30), simple serous cyst (n=16), Dermoid cyst (n=10), tubo-ovarian  abscess (n=5), Endometriosis (n=8), Broad ligament fibroma (n=3),  Hydrosalpinx (n=3), Mucinous cystadenoma (n=3),Ovarian fibroma (n=1) and  tubercloma (n=1).  

Malignant tumors were:  Serous cystadenocarcinoma (n=26),  Mucinous cystadenocarcinoma (n=20), Endometrial adenocarcinoma (n=4),  Borderline mucinous adenocarcinoma (n=2), Undifferentiated carcinoma  (n=5), metastatic breast carcinoma (n=3).

Statistically significant differences were found between the  groups with benign and malignant pathology as far as age, menopausal  status, ultrasound score and serum level of CA125 were concerned         (

). Distribution of patients according to CA125 levels and MRI is shown in         

Sensitivity, specificity, positive predictive value and negative predictive value for CA125 and RMI are shown in         

The best performance was obtained for serum CA125 level of 55  U/ml (sensitivity96.67  %, specificity 96.77  % and PPV 96.77  %) and  for RMI a cut-off value of 190 gave the best performance with  sensitivity of 86.67  %, specificity of 92.5  % and PPV of 89.66%.          The performance of CA125 and RMI is shown in the  receiver-operator characteristic curve         (


         The accuracy of diagnostic tests used to evaluate an adnexal  mass is of great concern to practicing gynecologists. In the  pre-operative assessment of adnexal mass, the major diagnostic tools are  still clinical impression and ultrasound examination. However, due to  limitation of clinical impression and sonographic finding to predict  ovarian malignancy, it is not surprising that gynecologists may detect  an unsuspected ovarian malignancy intraoperatively. Often an improper  incision is made, the bowel is not adequately prepared or the surgeon is  confronted with the need to perform an unplanned cytoredctive surgery.

A scoring system that predict ovarian malignancy can improve  the chance of better preoperative counseling, better preoperative  preparation and where appropriate referring the patients to a  specialized center.

Subsequent to introduction of RMI (6) the same research group  had re-evaluated their diagnostic method in a new group of patients  admitted for pelvic masses and confirmed the sensitivity and specificity  of RMI and its priority compared to the individual criteria (7).

In this study menopausal status had a sensitivity of 71% and  specificity of 87% while ultrasound score had a sensitivity of 70% and  specificity of 82%. The serum levels of CA125 were similar to those  reported in other studies in differentiation between benign and  malignant ovarian mass (21,22).

The main limit of CA125 is that it may be high in benign  disease such as ovarian cysts, endometriosis and pelvic infection. The  combination of serum CA125 with menopausal status (22), other tumor  markers (15) and ultrasound parameters (23) increases the discriminating  power of the method for the two types of ovarian pathology.

The RMI developed by Jacobs et al (6) for distinguishing  benign and malignant pelvic masses pre-operatively at a cut-off level of  200 had a sensitivity of 85.4% and a specificity of 96.9%, Davis et al  (7) found a sensitivity of 87% and specificity of 89% for         this index. In this study RMI at a cut-off 190 gave sensitivity  of   % and specificity of   %, however, Tingulstad et al (8) found a  sensitivity of 71% and specificity of 96% for This RMI and found a  sensitivity of 80% and specificity of 92% for their RMI2 at cut-off  level of 200, also Mogante et al (9) found a sensitivity of 81% and  specificity of 90% using their RMI2 with cut-off level         of 125.

At lower cut off values the sensitivity increases at the  expense of specificity, while at a higher cut off values the specificity  increases at the expense of sensitivity and more benign cases will be  referred as malignant. So the decision of the cut off value (action  line) will balance the sensitivity and specificity on one side and the  local resources and availability of the specialists on the other side.  When there is limitation of referral for specialist care because of  distant resources, the RMI can be increased with some degree of  sacrifices in sensitivity to achieve a higher level of specificity.

 
         The risk of malignancy index provides a quantitative assessment  of the risk of malignancy and can be used to discriminate between benign  and malignant disease. Its application in clinical practice would  provide a rational basis for specialist referral of patients with  malignant disease before diagnostic surgery.


         Distribution of age, menopausal status, ultrasound score and  serum CA125 in 140 women with benign (n=80) and malignant (n=60) adnexal  mass.
         Values are given as n (%)         

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Pre-op Diagnosis of Ovarian Cancer in Patients Presented with Adnexal Mass using the Risk of Malignancy Index