Extremely elevated CA 125, usually suggestive of ovarian malignancy, can be found in physiological or benign conditions such as endometriosis. We present a case of an extremely elevated serum CA 125 level in a patient with stage four endometriosis and bilateral unruptured ovarian endometriomas, with evidence of leakage unilaterally. To avoid costly and unnecessarily invasive tests and procedures it is important to consider the differential diagnosis of endometriosis and/or leaking endometrioma in patients with a profoundly elevated CA 125 level.
The cancer antigen (CA) 125 is a high molecular weight glycoprotein, which originates from coelomic epithelium, which is expressed by normal tissues such as the endometrium, peritoneum, pericardium, and epithelial ovarian carcinomas (EOCs) [
A 27-year-old nulliparous woman presented to the emergency department complaining of abdominal pain on the background of chronic pelvic pain.
On admission, an enlarged right ovary 150cc in volume with a cyst measuring 6.5cm and low internal echoes was demonstrated on pelvic ultrasound. Abdominopelvic computed tomography (CT) scan also demonstrated a 6.5cm dense right ovarian cyst with a moderate volume of free fluid and no evidence of appendicitis. Tumour markers taken at the time of acute presentation demonstrated a serum CA 125 level of 8142 U/ml (reference range: <35 U/ml) which had significantly increased from 115 U/ml when performed 12 months prior. Serum alpha fetoprotein (AFP) and human chorionic gonadotropin (hCG) levels were both <2 U/ml.
She was referred to the gynaecology clinic at Westmead hospital for further urgent review and management. An ultrasound scan for deep infiltrating endometriosis (DIE) verified the presence of a right ovarian cyst (6.3 x 5.0 x 4.4cm) with bowel adherent to the posterior aspect of the uterus. A gynaecological oncological opinion was sought at this time in light of the significantly raised CA 125 recommending a repeat level in 2 weeks on the provisional diagnosis of endometriosis after reviewing the ultrasound images and patients history of initial presentation. Repeat measurement of serum CA 125 level taken two weeks from her initial presentation demonstrated a lower but still significantly elevated level of 2038 U/ml (day 12). Serum carcinoembryonic antigen (CEA) and CA 19.9 were <2 U/ml and 430 U/ml (reference range: <37 U/ml), respectively.
A multidisciplinary discussion with a gynaecologist oncologist was conducted to determine further management. Based on the images and decreasing serum CA 125 level an endometriotic leak from an ovarian endometrioma was considered most likely, with ovarian malignancy being the main differential and unlikely diagnosis.
At laparoscopy on day 58, stage four endometriosis and bilateral unruptured ovarian endometriomas, with features suggestive of leakage unilaterally, were revealed. Widespread endometriotic deposits were found at the upper and anterior abdominal wall, omentum, and bilateral uterosacral ligaments, likely secondary to leaking endometrioma (Figures
Histopathological examination confirmed the diagnosis of endometrioma. The patient recovered uneventfully and was discharged on the third postoperative day. At the third postoperative week the patient remained in a stable condition and routine follow-up with the general practitioner was recommended.
CA 125 was first identified as an ovarian cancer antigen in 1981 [
Patients with endometriosis often do not have CA 125 levels > 100 U/ml [
Extremely elevated CA 125 levels have been reported in the presence of both ruptured [
Summary of cases of ruptured endometrioma with elevated CA 125 levels†.
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Johansson J et al. (1998) [ | Case report n = 1 | 9300 | Abdominal pain | USS: Rt homogeneous ovarian 7x10cm | Laparotomy, Excision of endometrioma |
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Kashyap RJ. (1999) [ | Case report n = 1 | 6114 | Abdominal pain, Nausea | USS: 11 cm complex cyst | Laparotomy, Rt oophorectomy |
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Kurata, H et al. (2002) [ | Case report n = 1 | 9537 | Abdominal pain | USS: homogenous bilateral ovarian cysts, FF in pelvis | Laparoscopy, enucelation of cysts |
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Cengiz et al. (2012) [ | Case report n = 1 | 174.87 | Abdominal pain, Nausea | USS: Lt heterogenous adnexal mass 6x8cm, FF in pelvis | Laparoscopy, Enucleation of cyst |
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A.K. Rani et al. (2012) [ | Case report n = 1 | 9391 | Abdominal pain | USS: Rt homogenous adnexal mass 10.5x7cm, moderate ascites | Laparotomy, excision of endometrioma |
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Duran M et al. (2013) [ | Case report n = 1 | 2556 | Pelvic and Abdominal pain, Dysuria | USS & CT: Lt heterogenous adnexal mass 5x5cm | Laparoscopy, Excision of endometrioma |
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Dereli et al. (2014) [ | Case report n = 1 | 143.72 | Bilateral pelvic masses | USS: hypoechoic bilateral adnexal masses | Laparoscopy, Rt adnexectomy, Lt cystectomy |
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X. Dai et al. (2015) [ | Retrospective cohort | 797.89 ± 1106.52 | Abdominal pain, Pelvic mass, Asymptomatic | - | Laparoscopy/ Laparotomy |
USS: ultrasound; CT: computerised tomography; MRI: magnetic resonance imaging; FF: free fluid; PoD: pouch of Douglas.
†In all cases reviewed endometrioma was confirmed histologically.
Summary of cases of unruptured endometrioma with elevated CA 125 levels†.
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Yilmazer M et al. (2003) [ | Case report n = 1 | 1741.8 | Abdominal pain, Bilateral adnexal masses | USS & CT: bilateral adnexal cystic masses | Laparoscopy, B/L cystectomy |
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Shiau C-S et al. (2003) [ | Case report n = 1 | 6310 | Pelvic mass, Abdominal pain, Nausea | USS & CT: homogenous Lt adnexal cystic mass 75mm | Laparotomy, Enucleation & excision of cyst |
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Atabekoglu C et al. (2003) [ | Case report n = 1 | 3890 | Abdominal pain, Dysmenorrhea | CT: right cystic ovarian mass of 12x10 cm | Laparotomy, Rt adnexectomy |
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Kahraman K et al. (2007) [ | Case report n = 1 | 7900 | Adnexal mass | USS & MRI: homogeneous Lt adnexal cystic mass | Laparoscopy, Cystectomy, U/L salpingectomy |
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Hosseini, M et al. (2009) [ | Case report n = 1 | 2000 | Abdominal pain, Dysmenorrhea | USS: bilateral ovarian cystic masses | Laparotomy, B/L cystectomy |
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Peker N et al. (2013) [ | Case report n = 1 | 1061 | Pelvic mass | USS: homogenous left ovarian cystic mass, FF at PoD | Laparotomy, Enucleation of cyst |
USS: ultrasound; CT: computerised tomography; MRI: magnetic resonance imaging; FF: free fluid; PoD: pouch of Douglas
†In all cases reviewed endometrioma was confirmed histologically.
There are multiple theories behind elevated serum CA 125 levels in endometriosis. The fluid within an endometriotic cyst [or endometrioma] is thought to be rich in CA 125 with concentrations reported to be > 10000 U/ml [
The reason for high CA 125 concentrations in cyst fluid compared to serum levels is attributed to the thick wall of the endometriotic cyst preventing large CA 125 glycoprotein molecules from diffusing out of the cyst and reaching systemic circulation; however, this inhibition of CA 125 molecules is not believed to be absolute [
While there have been several reports of elevated serum CA 125 levels in both ruptured and unruptured endometriomas, the present case reports a rare finding of an extremely elevated serum CA 125 level in the context of bilateral endometriomas, with evidence of leakage unilaterally. This case demonstrates that serum CA 125 levels can be extremely elevated due to an unruptured leaking endometrioma and highlights the importance of considering the differential diagnosis of endometriosis and or endometrioma in patients with an elevated CA 125, when suspecting ovarian carcinoma as the cause of an adnexal mass.
Patient has given written informed consent for this case to be published in a medical journal.
The authors declare that they have no conflicts of interest.