Abstract

1. Premenopausal women presenting with high level tumour marker CA-125 and pelvic mass is not necessarily bad news. Case reports and review of literature Essam Hadoura, Magdy Moustafa Royal Alexandra Hospital. Paisley. Scotland. UK, Frimley Park Hospital. Surrey. England. UK Abstract Introduction Discussion Conclusions CA125 and transvaginal ultrasound are the main components of the risk malignancy index (RMI). RMI is a way in triaging women with ovarian cysts into low, moderate or high risk of malignancy and accordingly patients can be managed by general gynaecologist, in a cancer unit or in a cancer institute [1]. Recent observational diagnostic study by Van Calster et al., shows that triaging women using the International Ovarian Tumour Analysis (IOTA) and logistic regression model (LR2) was more accurate than the RMI-based protocol [2]. Case (1) A 45 year old woman, Para 2 was referred with six months history of lower abdominal pain, progressively increasing over the right iliac fossa region in the last three months. Physical examination revealed generalized pelvic tenderness and a mass palpated at the right side. Trans-vaginal ultrasound scan revealed unilocular 8cm right adnexal mass with homogenous low level echogenicity, consistent with endometrioma. Left ovary contains 3cm haemorrhagic cyst. Pelvic computerized tomography (CT) confirmed bilateral ovarian masses with features in keeping with endometriomas. CA125 measured 3102 IU/ml (Normal 0-35 IU/ml). At Laparotomy widespread haemosidren deposition noted over the peritoneum and pelvic organs with large right sided ovarian cyst. She had total abdominal hysterectomy and bilateral salpingoophrectomy and omentectomy. Histolopathological examination confirmed bilateral ovarian endometriomas. Case (2) A thirty years old nulligravida was referred by the urologist because of incidental ultrasound finding of pelvic mass 10X6X10 cm. Her main complaint was lower abdominal pain and urinary frequency. MRI showed bilateral ovarian endometrioma of 8x8 cm (right) & 5x5 cm (left). Examination revealed pelviabdominal mass of about 18 week’s size. CA125 was 1060 IU/ml. She had Laparoscopic bilateral ovarian cystectomy. Histolopathological examination confirmed bilateral ovarian endometriomas with no malignant changes. Repeat CA125 four weeks after surgery was 214 IU/ml. Serum Carbohydrate Antigen 125 (CA-125) is a high molecular weight glycoprotein elevated in 80% of epithelial ovarian tumours. It is useful for the detection of persistence, recurrence and monitoring response to chemotherapeutic agents in patients with epithelial ovarian cancers[3]. It is elevated in benign gynaecological conditions like ovarian endometriomas, serous cystadenoma, pelvic inflammatory disease, pregnancy, menstruation and leiomyoma. CA125 is also elevated in non-gynaecological conditions including cancers of the colon, pancreas, breast and lungs [4]. Since the serum CA-125 levels of more than 1,000 IU/ml was rarely seen in the patients with benign gynaecological diseases, it could be used to differentiate malignant and benign ovarian masses in combination with the other diagnostic methods [5]. Ghaemmaghami et al., 2007 described their experience with CA125 serum level >1,000 IU/ml with uterine leiomyoma and endometrioma without any malignancy [6]. It is not clear the mechanism of significantly raised serum CA125 level in benign ovarian endometriomas, but it has been observed in cases of ruptured endometrioma[7] as evident in case 1. Regression of serum CA125 level was shown after resection of these benign conditions as noted in case 2. Ovarian endometrioma occurs in 50% of women with endometriosis. The typical ultrasound features of endometriomas in premenopausal patients have been described as a unilocular cyst with homogeneous low-level echogenicity of the cyst fluid (ground glass echogenicity) in 53% by Van Holsbeke et al., and 83% Guerriero et al [8-9]. The International Ovarian Tumour Analysis (IOTA) Group described ultrasound characteristic rules for endometriomas. The use of specific ultrasound morphological findings without CA-125 has been shown to have high sensitivity, specificity and likelihood ratios [10].Using these rules, the reported sensitivity was 95%, specificity 91%, positive likelihood ratio of 10.37 and negative likelihood ratio of 0.06. There is no clear consensus regarding the need for further imaging beyond transvaginal ultrasound in the presence of apparently benign disease. However, these additional imaging modalities will have a place in the evaluation of more complex lesions [11]. In conclusion, the combination of ultrasound characteristics and serum tumour marker CA125, and possible other imaging modalities are essential to diagnose the nature of ovarian mass. CA-125 on its own has low specificity in premenopausal women with an adnexal mass even at a very high level. Objective: The clinical value of high level tumour marker CA125 in premenopausal women presenting with Lower abdominal pain and pelvic mass. Methods: Two clinical cases presented with lower abdominal pain, pelvic mass and very high level tumour marker CA125 Results: Case I treated with total abdominal hysterectomy and bilateral salpingoophrectomy. Case II had Laparoscopic bilateral ovarian cystectomy. Histolopathological examination confirmed bilateral ovarian endometriosis with no malignant changes in both cases. Conclusion: Although high level tumour marker CA125 is commonly associated with epithelial ovarian malignancy it is also detected in non malignant gynaecological conditions mainly ovarian endometrioma, stage 4 endometriosis and leiomyoma. Premenopausal women presenting with high level of Tumour marker CA125 with acute pelvic pain and or abnormal vaginal bleeding is not necessarily bad news. References • Green-top Guideline No. 62 RCOG/BSGE Joint Guideline (2011): Management of Suspected Ovarian Masses in Premenopausal Women. • Van Calster B, Timmerman D, Valentin L, et al (2012) Triaging women with ovarian masses for surgery: observational diagnostic study to compare RCOG guidelines with an International Ovarian Tumour Analysis (IOTA) group protocol. BJOG 6:662-671. • Gupta D, Lis CG (2009) Role of CA125 in predicting ovarian cancer survival-a review of the epidemiological literature. J Ovarian Res 2-13. • Eltabbakh GH, Belinson JL, Kennedy AW et al (1997) Serum CA-125 measurements > 65 IU/mL. Clinical value. J Reprod Med 10:617-24. • Van Calster B, Timmerman D, Bourne T, et al (2007) Discrimination between benign and malignant adnexal masses by specialist ultrasound examination versus serum CA-125. J Natl Cancer Inst 99:1706–1714. • Ghaemmaghami F, Karimi Zarchi M ,Hamedi B( 2007) High levels of CA125 (over 1,000 IU/ml) in patients with gynecologic disease and no malignant conditions: three cases and literature review. Arch Gynecol Obstet 276:559–561. • Johansson J, Santala M, Kauppila A (1998) Explosive rise of serum CA125 following the rupture of ovarian endometrioma. Hum Reprod 13:3503–3504. • Van Holsbeke C, Van Calster B, Guerriero S, et al (2010) Endometriosis: their ultrasound characteristics. Ultrasound Obstet Gynecol 6:730-40. • Guerriero S, Mais V, Ajossa S, et al (1995) The role of endovaginal ultrasound in differentiating endometriomas from other ovarian cysts. Clin Exp Obstet Gynecol 1:20-2. • Timmerman D, Testa AC, Bourne T, et al (2008) Simple ultrasound-based rules for the diagnosis of ovarian cancer. Ultrasound Obstet Gynecol 31:681–90. • Ghezzi F, Cromi A, Bergamini V, et al (2008) Should adnexal mass size influence surgical approach? A series of 186 laparoscopically managed large adnexal masses. BJOG 115:1020–7.