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 Table of Contents  
ORIGINAL ARTICLE
Year : 2016  |  Volume : 5  |  Issue : 2  |  Page : 67-71

Evaluation of risk of malignancy index in the preoperative assessment of ovarian tumors: Study from a tertiary care center


1 Department of Pathology, Regional Cancer Centre, Thiruvananthapuram, India
2 Department of Pathology, Amala Institute of Medical Sciences and Research Centre, Thrissur, Kerala, India
3 Department of Obstetrics and Gynaecology, Government Medical College, Thrissur, Kerala, India

Date of Web Publication25-Oct-2016

Correspondence Address:
Jayasudha Arundhathi Vasudevan
Department of Pathology, Regional Cancer Centre, Thiruvananthapuram - 695 011, Kerala
India
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Source of Support: None, Conflict of Interest: None


DOI: 10.4103/2278-0521.193000

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  Abstract 

Objectives: Risk of malignancy index (RMI) is a mathematical formula using a combination of diagnostic modulations to predict whether an adnexal mass is benign or malignant. The aim of this study was to evaluate the diagnostic performance of RMI in differentiating benign and malignant ovarian tumors, in comparison with histopathology, the gold standard and to identify the patients with likely ovarian cancer for a referral to a specialist gynecological oncologist, for proper surgical staging and treatment. Materials and Methods: The descriptive study was done on 102 patients referred to a tertiary care center for 12 months from June 2006 to May 2007. RMI is the product of menopausal score, ultrasound score, and absolute value of serum CA-125 levels. RMI score was calculated and compared with histopathology, the gold standard. Sensitivity, specificity, positive and negative predictive values, and accuracy were calculated for individual parameters and for RMI to assess malignancy. Chi-square test, Cohen's Kappa, and receiver operator characteristic (ROC) analysis was carried out. ROC curve was drawn to conclude on the cutoff value of RMI. Results: Analyzing the diagnostic performance of RMI, we found that RMI performed better than individual parameters in differentiating benign and malignant ovarian tumors at the cutoff score of 200. The present study gives 195 as best cutoff point for RMI to differentiate benign and malignant ovarian neoplasms. Conclusion: RMI can be used by the general gynecologists at the periphery for referral of suspected ovarian tumors to oncology centers, thus improving the survival and prognosis of women undergoing surgery for ovarian tumors.

Keywords: CA-125, menopausal score, ovarian cancer, risk of malignant index, ultrasound score


How to cite this article:
Vasudevan JA, Nair V, Sukumaran S. Evaluation of risk of malignancy index in the preoperative assessment of ovarian tumors: Study from a tertiary care center. Saudi J Health Sci 2016;5:67-71

How to cite this URL:
Vasudevan JA, Nair V, Sukumaran S. Evaluation of risk of malignancy index in the preoperative assessment of ovarian tumors: Study from a tertiary care center. Saudi J Health Sci [serial online] 2016 [cited 2019 Jun 18];5:67-71. Available from: http://www.saudijhealthsci.org/text.asp?2016/5/2/67/193000


  Introduction Top


Ovarian cancer is the leading cause of mortality among gynecological malignancies. [1] Survival from ovarian cancer depends on stage, histological type, and optimal initial cytoreductive surgery. The disease-free interval and survival are significantly increased for patients whose surgery is performed by a gynecologic oncologist. [2] There is little doubt that early stage ovarian cancer is significantly more curable than late stage disease. An early detection of ovarian cancer and timely reference to gynecologic oncologist is the milestone to reduce the mortality from ovarian cancer. Several diagnostic methods for pelvic mass have been reported such as pelvic examination, ultrasonography, CA-125 tumor marker level. However, none of these methods used individually has shown significantly better performance in detecting malignant ovarian tumor. Hence, this led to the development of a mathematical formula using a combination of these diagnostic modalities to predict whether an adnexal mass is benign or malignant - risk of malignancy index (RMI). RMI was originally developed in 1990, and it was termed RMI 1. [3] This index was defined as the product of menopausal score (M), ultrasound score (U), and the absolute value of serum CA-125 level and reported a sensitivity of 85.4% and specificity of 96.9% at the cutoff value of 200. [3] RMI was developed further in 1996, known as RMI 2 and in 1999, he modified it to form the RMI 3. [4],[5] The difference between the three indices lies in the different scoring of ultrasound findings and menopausal status. Subsequently, RMI 4 was introduced which included tumor size as an additional parameter. [6] Studies comparing the performance of RMI 3 and RMI 4 had concluded that their results were comparable. The best cutoff value of RMI for the distinction between benign and malignant masses has been proved to be 200. This study aims in repeat evaluation of RMI that can be easily used by general gynecologists. The results were matched with histopathology, the gold standard.


  Materials and methods Top


The study was conducted in a tertiary care center for 12 months from June 2006 to May 2007. The cases were collected from the six gynecology units. Systematic sampling was done. Every alternate patient was selected. One hundred and two patients were recruited. Patients more than 30 years of age with ovarian mass as detected by clinical examination and/or ultrasound were included in the study. Exclusion criteria included mass in pregnant women, simple cyst <2 cm in premenopausal, masses that are extraovarian at sonography and inoperable ovarian masses. Of the 362 cases of ovarian masses detected, as per the inclusion criteria, 158 cases were excluded as per the above-mentioned exclusion criteria. From the remaining 204 cases, 102 cases were recruited in our study by a systematic sample of every alternate case. The details of the cases selected for the study were collected using a structured questionnaire. Details collected included age, address, menstrual history, reproductive history, clinical presentations, clinical examination findings, ultrasound score, serum CA-125 levels, menopausal score, intraoperative findings on laparotomy. The menopausal score was calculated for each patient based on menstrual status. Premenopausal cases were given a score of 1 (M = 1). Postmenopausal cases were given a score of 3 (M = 3). Postmenopausal status was defined as more than 1 year of amenorrhea or age older than 50 years in women who had hysterectomy. Cases which do not meet these criteria were classified as premenopausal. Ultrasound study was done using a transvaginal and transabdominal probe. Five ultrasonographic features were studied. It includes unilateral/bilateral, unilocular/multilocular, presence of solid areas, ascites, intraabdominal metastasis. A score of 1 for each criterion was given. The presence of 0/1 criteria was given a score of 1, 2-5 criteria were given a score of 3. The serum CA-125 levels were measured from single ISO 9001 certified laboratory for all the cases in the study group. The second generation CA-125 was used, due to the lesser fluctuation of CA-125 from day to day, when compared to first generation CA-125. The absolute level of CA-125 in U/ml were measured and recorded in the pro forma for further analysis. RMI was calculated using a simplified regression equation obtained from the product of the menopausal score, ultrasound score, and the absolute value of serum CA-125 level. Then RMI was calculated and entered into the pro forma for further analysis. Finally, a staging laparotomy was done for these patients. RMI was compared with histopathology, the gold standard. Observations from prepared pro forma were entered into a personal computer and data were analyzed using Statistical Package for Social Sciences version 10 software (SPSS Inc., Chicago, IL, USA). To elucidate the associations and comparisons between different parameters, Chi-square test was used as nonparametric test. Receiver operator characteristic (ROC) analysis was carried out, and the ROC curve was drawn to conclude on the cutoff the value of RMI. Selection bias was avoided by systematic sampling. To eliminate observer bias, sonogram was analyzed by the senior radiologist before the final opinion; sonologist was unaware of the previous ultrasound reports, serum CA-125 level was estimated from a single ISO 9001 certified laboratory. The sensitivity, specificity, positive predictive value, negative predictive value (NPV), accuracy of menopausal score, ultrasound score, and absolute value of serum CA-125 levels were calculated separately and combined into the RMI, to diagnose ovarian cancer.


  Results Top


In the study group, 24 cases had malignant masses as per the histopathology reports [Table 1]. Out of the 24 malignant ovarian masses, 21 cases were epithelial ovarian tumors, with serous tumor predominating. The age of the patients of the study group ranged from 30 to 85 years. The largest group was in the third and fourth decade, and here the benign lesions constituted the majority. The proportion of malignant cases increases as age advances and the mean age for malignant lesions for the study was 50.3 years. A total of 49 cases were postmenopausal and 53 cases were premenopausal. The majority of masses were seen in the premenopausal (52%). The proportion of malignant to benign masses seen in the postmenopausal group was higher than that of the premenopausal group. This is in agreement with the standard observation that the chance of malignancy is increased in postmenopausal women. In the study population, 17 (16.7%) cases had bilateral masses, and 85 (83.3%) cases had unilateral masses. In this study, bilaterality showed a significant correlation, which is in agreement with standard observations. Analysis of solid areas and multilocularity had significant P value. Hence, these characteristics can be used for the objective analysis of ovarian masses. Ascites was observed in twenty cases in the study population. Of the 24 malignant cases, 14 cases had ascites. Of 78 benign cases, six cases had ascites. The occurrence of ascites in malignant lesions showed significant correlation. Only one case was associated with metastasis. Since the number of cases with metastasis was very low, statistical analysis was not possible.

Analysis of menopausal score revealed that in the study population, 49 cases had menopausal score of 3, out of which 16 cases were malignant. Of the 53 cases with score1, eight cases were malignant [Table 2]. There was a significant correlation between menopausal score of 3 and occurrence of malignancy [Table 3].
Table 1: Histopathology reports

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Table 2: Menopausal score, ultrasound score, serum CA-125 levels, and risk of malignancy index in the study population

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Table 3: Analysis of menopausal score, ultrasound score, serum CA-125 levels, and risk of malignancy index

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In the study population, 37 cases had ultrasound score of 3 out of which twenty cases were malignant. Of the 65 cases, with score 1, four cases were malignant [Table 2]. There was a significant correlation between ultrasound score 3 and occurrence of malignancy [Table 3]. Serum CA-125 levels show statistically significant correlation with malignant lesions. However, the sensitivity and specificity of serum CA-125 level are less when compared to ultrasound score. This decrease in sensitivity and specificity is probably due to conditions such as endometriosis, fibrothecoma ovary with ascites and tuberculosis which also showed elevated levels of CA-125. Elevated CA-125 serum levels in the postmenopausal group were significantly associated with malignancy and had higher sensitivity, specificity, and NPV [Table 2] and [Table 3]. The sensitivity, specificity, and NPV of RMI are much higher than of ultrasound score, menopausal score or serum CA-125 level taken individually [Table 3]. Hence, the diagnostic accuracy of RMI is much better than the other diagnostic tools in detection/screening of malignant ovarian tumors which is in agreement with the standard literature. The Cohen's Kappa value of RMI was 0.621 and showed significant association (P < 0.05). The sensitivity, specificity and the NPV of RMI in postmenopausal group were higher [Table 3]. High RMI value was significantly associated with malignancy in this age group. Best cutoff value for RMI as derived from this study is 195 [Figure 1] and [Table 4].
Figure 1: Receiver operator characteristic curve for risk of malignancy index

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Table 4: Best cut off point for risk of malignancy index as derived from this study is 195

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  Discussion Top


Characterization of adnexal masses to identify patients with malignant ovarian tumors preoperatively for a referral to a cancer center for treatment has been extensively studied. A simple algorithm called RMI has subsequently been tested on retrospective and prospective data with encouraging results. Up to 70% of cases are detected at advanced stages. [7] In the present study, the most common pathological entity among malignant ovarian tumors encountered were epithelial ovarian tumors (87.5%), of which eight cases presented in Stage 1 and 13 cases presented in Stage 3 and 4. Among the benign lesions, serous cystadenoma and mucinous cystadenoma were the most numerous (62.5%). Ovarian cancer is rare before the age of 40, increases steadily thereafter and the peak incidence is at 50-60 years. [8] In the study group, maximum number of cases were in the third and fourth decades and the percentage of malignant masses were low in this age group. The mean age of occurrence of malignant lesion was 50 years. Early menarche and late menopause increase the risk of ovarian cancer. [9] In our study group, there was no significant association between age of menarche and occurrence of malignancy. However, 58% of malignancies were seen in the early menarche age group (11-13 years). With regard to menopausal status, the majority of cases were in the premenopausal group (52%). However, the percentage of malignant tumors was more in the postmenopausal group. As the age of menopause increased, the proportion of malignant lesions also increased. Best accepted cutoff the value of RMI to differentiate benign and malignant adnexal tumors is proved to be 200. [3] In this study, comparing the diagnostic performance, RMI has the highest NPV, sensitivity, and specificity [Table 2]. Analyzing the diagnostic performance of RMI, we found that RMI performed better than any individual parameters in differentiating benign and malignant ovarian tumors at the cutoff score of >200 to indicate malignancy. Of the 102 cases, 29 cases had elevated RMI (>200), of which 20 cases were malignant. The remaining nine cases of false positivity were three cases of endometriosis, one case of tuberculosis, two cases of fibrothecoma ovary with ascites, and three cases of serous cystadenoma. Of the 73 cases with normal RMI, four cases turned out to be malignant. Those malignant cases were mainly nonepithelial tumors (malignant lymphoma, immature teratoma Grade 3, Krukenberg tumor and one case of mucinous cystadenocarcinoma Grade 1). The sensitivity, specificity, and the NPV of the diagnostic performance of RMI were 83.3%, 88.46%, 94.52%, respectively, which was comparable to other studies that ranged from 80% to 91%, 85%-93%, 96%-99%, respectively. [10],[11],[12] The Cohen's Kappa statistics value of the RMI for this study population also showed significant correlation. Best cutoff point for RMI from this study was 195. The actual figures of these diagnostic values might vary from study to study. The difference probably lay on the characteristics of the tumors and the associated findings in each case studied. Another reason probably is the difference in the proportion of benign to malignant tumors in each series. Analysis of the diagnostic performance of RMI in postmenopausal age group was found to be more accurate, probably due to the absence of the benign conditions with elevated serum CA-125 levels (endometriosis, tuberculosis, etc.).


  Conclusion Top


RMI has proved to be a good diagnostic tool to differentiate benign and malignant ovarian tumors. This scoring system due to its simplicity can be used by the general gynecologists at the periphery to refer suspected ovarian cancers to oncological centers and thereby improving the survival and prognosis of women undergoing surgery for ovarian tumors.

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Conflicts of interest

There are no conflicts of interest.

 
  References Top

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Bristow RE, Tomacruz RS, Armstrong DK, Trimble EL, Montz FJ. Survival effect of maximal cytoreductive surgery for advanced ovarian carcinoma during the platinum era: A meta-analysis. J Clin Oncol 2002;20:1248-59.  Back to cited text no. 2
    
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Jacobs I, Oram D, Fairbanks J, Turner J, Frost C, Grudzinskas JG. A risk of malignancy index incorporating CA 125, ultrasound and menopausal status for the accurate preoperative diagnosis of ovarian cancer. Br J Obstet Gynaecol 1990;97:922-9.  Back to cited text no. 3
    
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Tingulstad S, Hagen B, Skjeldestad FE, Onsrud M, Kiserud T, Halvorsen T, et al. Evaluation of a risk of malignancy index based on serum CA 125, ultrasound findings and menopausal status in the pre-operative diagnosis of pelvic masses. Br J Obstet Gynaecol 1996;103:826-31.  Back to cited text no. 4
    
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Tingulstad S, Hagen B, Skjeldestad FE, Halvorsen T, Nustad K, Onsrud M. The risk-of-malignancy index to evaluate potential ovarian cancers in local hospitals. Br J Obstet Gynecol 1999;93:448-52.  Back to cited text no. 5
    
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Yamamoto Y, Yamada R, Oguri H, Maeda N, Fukaya T. Comparison of four malignancy risk indices in the preoperative evaluation of patients with pelvic masses. Eur J Obstet Gynecol Reprod Biol 2009;144:163-7.  Back to cited text no. 6
    
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Mondal SK, Banyopadhyay R, Nag DR, Roychowdhury S, Mondal PK, Sinha SK. Histologic pattern, bilaterality and clinical evaluation of 957 ovarian neoplasms: A 10-year study in a tertiary hospital of Eastern India. J Cancer Res Ther 2011;7:433-7.  Back to cited text no. 8
    
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Purdie DM, Bain CJ, Siskind V, Webb PM, Green AC. Ovulation and risk of epithelial ovarian cancer. Int J Cancer 2003;104:228-32.  Back to cited text no. 9
    
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van den Akker PA, Aalders AL, Snijders MP, Kluivers KB, Samlal RA, Vollebergh JH, et al. Evaluation of the risk of malignancy index in daily clinical management of adnexal masses. Gynecol Oncol 2010;116:384-8.  Back to cited text no. 10
    
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Mohammed AB, Ahuga VK, Taha M. Validation of risk of malignancy index in the primary evaluation of ovarian masses. Middle East Fertil Soc J 2014;19:324-8.  Back to cited text no. 11
    
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Bouzari Z, Yazdani S, Ahmadi MH, Barat S, Kelagar ZS, Kutenaie MJ, et al. Comparison of three malignancy risk indices and CA-125 in the preoperative evaluation of patients with pelvic masses. BMC Res Notes 2011;4:206.  Back to cited text no. 12
    


    Figures

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    Tables

  [Table 1], [Table 2], [Table 3], [Table 4]



 

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