CT Imaging Findings of Ruptured Ovarian Endometriotic Cysts: Emphasis on the Differential Diagnosis with Ruptured Ovarian Functional Cysts

The reproductive tract is the commonest source of spontaneous hemoperitoneum in women of childbearing age. After ruling out an ectopic pregnancy, rupture of an CT Imaging Findings of Ruptured Ovarian Endometriotic Cysts: Emphasis on the Differential Diagnosis with Ruptured Ovarian Functional Cysts Young Rae Lee, MD Department of Radiology, Kangbuk Samsung Hospital, Sungkyunkwan University School of Medicine, Seoul 110-746, Korea

The purpose of this study is to assess the prevalence of abnormal CT fi ndings in patients with surgically proven ruptured endometriotic cysts, as compared with those abnormal CT fi ndings of ruptured ovarian functional cysts.

This study included 13 retrospectively identified patients with surgically confirmed ruptured ovarian endometriotic cysts and who had also undergone preoperative CT scanning during the previous seven years. As a comparative group, 25 cases of surgically confi rmed ruptured ovarian functional cysts were included. We assessed the morphologic features of the cysts and the ancillary fi ndings based on CT.

For the endometriotic cysts, the mean maximum cyst diameter was signifi cantly larger than that of the functional cysts (70.1 mm versus 36.4 mm, respectively, p < 0.05). The endometriotic cysts frequently had a multilocular shape and a thicker cyst wall, as compared to that of functional cysts, and these differences were statistically signifi cant. Among the ancillary fi ndings, endometriotic cysts showed a signifi cantly higher prevalence of loculated ascites, ascites confi ned to the pelvic cavity without extension to the upper abdomen, and peritoneal strandings and infi ltrations (p < 0.05). Although 11 of the 25 cases of functional cysts showed active extravasation of contrast material at the ovarian bleeding site, only one of 13 cases of endometriotic cysts showed active extravasation.

The diagnosis of ruptured endometriotic cyst should be suspected for a woman in whom CT reveals the presence of multilocular or bilateral ovarian cysts with a thick wall and loculated ascites confi ned to the pelvic cavity with pelvic fat infi ltrations. Index terms: Endometriosis; Ovary; Cysts; Computed tomograpy (CT); Comparative studies; Pelvis Received April 28, 2010; accepted after revision August 9, 2010. Corresponding author: Young Rae Lee, MD, Department of Radiology, Kangbuk Samsung Hospital, Sungkyunkwan University School of Medicine, 108 Pyeong-dong, Jongno-gu, Seoul 110-746, Korea. • Tel: (822) 2001-2337 • Fax: (822) 2001-1030 • E-mail: [email protected] This is an Open Access article distributed under the terms of the Creative Commons Attribution Non-Commercial License (http://creativecommons.org/licenses/by-nc/3.0) which permits unrestricted non-commercial use, distribution, and reproduction in any medium, provided the original work is properly cited. Original Article DOI: 10.3348/kjr.2011.12.1.59 pISSN 1229-6929 · eISSN 2005-8330 Korean J Radiol 2011;12(1):59-65 ovarian cyst is the most common cause of spontaneous hemoperitoneum in nonpregnant patients (1-3). Ovarian cyst rupture and hemorrhage are basically physiological events that involve the follicle or corpus luteum, but when the hemorrhage is large or a considerable quantity of fl uid is released from a cyst into the peritoneal cavity, this may

in acute abdominal pain and/or pelvic pain from peritoneal irritation (2, 4). While ovarian endometriosis is a very common condition in women of reproductive age, endometriotic cyst associated with rupture is an uncommon condition. Nevertheless, this condition is important because it may require emergency surgery due to the severe abdominal pain secondary to chemical peritonitis when the fl uid contents fl ow out of the cysts (5). Although the imaging fi ndings of ovarian endometriotic cysts have been extensively described, less attention Korean J Radiol 12(1), Jan/Feb 2011 www.kjronline.org60 Young Rae Lee retrospectively assessed 25 cases of surgically confi rmed ruptured ovarian functional cysts during the same period, and these cases included 21 cases of corpus luteal cysts and four cases of follicular cysts. All these patients had undergone pelviscopic laparotomy or open oophorectomy within one week after CT scanning. Ever since 2005, the CT scans were performed by a 40-slice Brilliance CT scanner (Philips Medical Systems, Cleveland, OH) using a 0.5 mm detector collimation with 3 mm reconstruction. For the contrast-enhanced scans, 120 mL of nonionic contrast medium was administrated at a rate of 3 mL/s, with a scan delay of 60s. Prior to 2005, a GE HiSpeed Advantage CT (Milwaukee, WI) with helically acquired images at a collimation of 7 mm and a pitch of 1.0 was used. The clinical and laboratory data for age, the presence of leukocytosis and an abnormal hemoglobin level and hematocrit was obtained by a retrospective review of the medical records: leukocytosis was a serum white cell blood count higher than 10.2 x 10 3 /mm 3 , an abnormal hemoglobin level was a serum hemoglobin level lower than the standard value (11.0 g/dL) and an abnormal hematocrit was a serum hematocrit level lower than 34%. A single attending radiologist who specialized in genitourinary radiology and who had more than 15 years of experience and who was without knowledge of the clinical and pathologic fi ndings recorded the morphologic features of the cysts and the ancillary fi ndings based on the CT: the maximum cyst diameter, bilaterality, multilocularity, the cyst has been given to the imaging fi ndings of ruptured endometriotic cysts. Although ultrasound (US) and magnetic resonance imaging (MRI) remain the primary imaging modalities for assessing women with suspected gynecologic pathology, computed tomography (CT) is frequently performed as the fi rst imaging modality for the evaluation of abdominal and pelvic pain of an unknown etiology (6). The possibility of endometriosis is often overlooked as a cause when both ascites and a pelvic mass are found in the same patient, and this is because the majority of ovarian cysts presenting with rupture or hemorrhage are functional cysts. As patients with endometriotic cysts frequently have multiple associated peritoneal adhesions (7, 8), establishing the correct diagnosis of ovarian cyst is crucial to help guide the surgical planning. The purpose of this study is to assess the prevalence of abnormal CT fi ndings of patients with surgically proven ruptured endometriotic cysts, as compared to the abnormal CT fi ndings of patients with ruptured ovarian cysts.

The study population consisted of 13 patients with surgically confi rmed ovarian endometriotic cysts associated with rupture and who underwent preoperative CT from January 2003 to December 2009, and the patients were assessed through a retrospective review of the hospital records and the operation database at Kangbuk Samsung Hospital (Seoul, Korea). As a comparative group, we Table 1. Morphologic Characteristics of Ovarian Cysts and Prevalence of Ancillary Findings on CT Imaging of Women with Ruptured Endometriotic Cysts and Functional Cysts CT Findings Endometriotic Cysts (n = 13) Functional Cysts (n = 25) P value Maximum diameter (mm) 70.1 36.4 0.007* Cyst density on noncontrast scan (HU) 35.07 22.33 0.977 Maximum cyst wall thickness (mm ± SD) 2.92 (1.89) 2.14 (0.72) 0.002* Bilaterality 4 2 0.07 Multilocularity 7 2 0.002* Cyst wall enhancement 11 25 0.202 Disrupted cyst wall 4 16 0.07 Active extravasations 1 11 0.02* Abdomen ascites 3 17 0.023* Loculated ascites 10 1 0.000* Peritoneal infi ltrations 7 3 0.002* Note.— *P values < 0.05 were considered statistically signifi cant. HU = Hounsfi eld unit, SD = standard deviation Korean J Radiol 12(1), Jan/Feb 2011www.kjronline.org 61 CT Findings of Ruptured Ovarian Endometriotic Cysts density on the noncontrast scans, cyst wall enhancement, the maximum thickness of the cyst wall, discontinuity or disruption of the cyst wall, active extravasations of intravenous contrast media around the cyst, the extent of ascites, loculated ascites and the presence of peritoneal infi ltrations. Statistical analysis was performed to compare the differences of the CT fi ndings. Differences in proportions were analyzed by Fisher’s exact test, whereas continuous variables were assessed by the t test. A p value of < 0.05 was considered signifi cant. All the analyses were performed using the SPSS program (SPSS version 17.0 software for Window; SPSS, Chicago, IL).

For the endometriotic cysts, the mean age of the patients with endometriotic cysts was older than that of the patients with functional cysts (32.7 ± 7.30 years and 26.8 ± 6.95 years, respectively), but the difference was not statistically signifi cant. The prevalence of leukocytosis and a decreased hemoglobin or hematocrit level was not different between the two groups. The morphologic characteristics of the ovarian cysts and the prevalence of the ancillary CT fi ndings of the ruptured endometriotic cysts and functional cysts are listed on Table 1. For the endometriotic cysts, the mean maximum cyst diameter was signifi cantly larger than that of the functional cysts (70.1 mm and 36.4 mm, respectively, p = 0.007). The A C B Fig. 1. Ruptured left ovarian endometriotic cysts in 30-year-old woman with sudden onset of abdominal pain. Laboratory tests detected serum CA-125 level that was elevated to 4034 IU/ml. A. Enhanced CT image shows 13-cm-sized cystic lesion in left ovary with crenulated hyperdense cyst wall with focal disruption on right posterior wall (arrows), which all suggested rupture. B. Image more caudal to A shows other cystic lesions of both ovaries with “kissing ovary sign” (arrows). C. Coronal reformatted enhanced image shows large fl uid collections in pelvic cavity (asterisks) and left ovarian cystic lesion with crenulated hyperdense cyst wall (arrows). Note haziness and strandings of mesenteric fat tissue suggesting associated infl ammatory reactions (white arrows). Korean J Radiol 12(1), Jan/Feb 2011 www.kjronline.org62 Young Rae Lee endometriotic cysts had a multilocular shape and a thicker cyst wall than did the functional cysts, and these differences were statistically signifi cant. Seven of 11 patients with endometriotic cysts had bilateral endometriotic cysts (Fig. 1), and only two of the 25 patients with functional cysts had bilateral functional cysts, but this difference was not statistically signifi cant (p = 0.07). Seventeen of 25 functional cysts (68%) had ruptures from the right adenxa, whereas fi ve of 13 endometriotic cysts (38%) had a right sided rupture and one patient had bilateral rupture, but the difference was not statistically signifi cant. Among the ancillary fi ndings, there was a signifi cantly different prevalence of loculated ascites (Fig. 2), ascites confi ned to the pelvic cavity without extension to the upper abdomen, and peritoneal strandings and infi ltrations in the patients with endometriotic cysts as compared to that of the patients with functional cysts (Fig. 1). Although 11 of 25 cases of functional cysts showed active extravasation of contrast material at an ovarian bleeding site, only one of 13 cases of endometriotic cysts showed active extravasation (Fig. 3). Focal discontinuity or a disrupted wall was more prevalent in the ruptured functional cysts than that of the endometriotic cysts, but this difference was not statistically signifi cant. AB Fig. 2. Ruptured left ovarian endometriotic cysts in 27-year-old woman. A. Enhanced CT image shows localized pelvic ascites in posterior cul de sac (asterisk). B. Image more cranial to A shows multiple cysts or multilocular cyst of left ovary with hyperdense wall and focal wall disruption (arrow). Laparoscopic wedge resection of left ovary was performed and lesion proved to endometriotic cyst. AB Fig. 3. 20-year-old woman presented with severe pelvic pain and negative β HCG test. A. Enhanced CT image at level of uterus shows large amount of high-attenuation fl uid in pelvis due to hemoperitoneum (asterisks). B. Enhanced scan more cephalad to A depicts jet of contrast material from right ovarian cyst wall (arrows), suggesting active bleeding site. Surgery confi rmed ruptured corpus luteal cyst of right ovary. Korean J Radiol 12(1), Jan/Feb 2011www.kjronline.org 63 CT Findings of Ruptured Ovarian Endometriotic Cysts

Endometriosis corresponds to the ectopic endometrial glands and stroma outside the uterine cavity. The clinical symptoms include dysmenorrhea, dyspareunia, infertility, painful defecation or cyclic urinary symptoms (7). Endometriotic cysts generally occur within the ovaries and they are the result of repeated cyclic hemorrhage within a deep implant. These cysts can completely replace the normal ovarian tissue (8). Focal leaks with infl ammation, fi brosis and adhesion formation are characteristics of endometriosis, whereas acute cyst rupture is a relatively uncommon complication (8). Such cases of acute cyst rupture are rare, but they may be associated with severe peritonitis and systemic disturbance, followed by adhesion formation (9, 10). A theory on the formation of ascites in endometriosis was postulated by Bernstein et al. (11), who suggested that the blood and endometrial cells shed into the peritoneal cavity may irritate and stimulate the peritoneum, thereby resulting in ascites. Other authors have reported that rupture of endometriotic cysts with subsequent peritoneal irritation and the production of reactive exudates may provide an explanation (12). Ruptured endometriotic cysts sometimes present a diagnostic problem and surgical challenge because patients with a ruptured cyst present with symptoms of an acute abdomen associated with severe abdominal pain and unstable vital signs (8). Ruptured ovarian endometriotic cysts can sometimes mimic ovarian malignancy because of the extremely elevated serum CA 125 concentration (9, 13). The US and MRI aspects of endometriosis, as reported in the literature, are variable depending on many structural and morphologic factors (8, 14 -16). The CT appearance of endometriotic cysts is nonspecifi c and this includes a spectrum from simple cystic to complex cystic masses (8, 17, 18). Buy et al. (19) reported that the CT fi ndings of a hyperdense focus inside an ovarian cyst are suggestive of endometriotic cysts. However, this is nonspecifi c because other hemorrhagic lesions, such as hemorrhagic cysts, may also demonstrate this fi nding (8). Multiple lesions increase the specifi city for the diagnosis of endometriomas because endometriomas are often multiple (20). Endometriotic cysts are more often multiple or bilateral, as opposed to other hemorrhagic cysts that are usually unilateral (8, 21); when associated with interovarian adhesions, endometriotic cysts are often described as “kissing” ovaries (22). In our study, seven of the 13 cases of ruptured endometriotic cysts showed bilateral lesions, as compared to only two cases of bilateral functional cysts. According to the results of this study, the endometriotic cysts are multilocular and they have a thicker cyst wall as compared to that of functional cysts. The multilocular- appearing endometriotic cyst may actually consist of multiple separate cysts (8). Thin or thick septations may be present between these loculi. One study showed that in the absence of wall nodularity and in the presence of diffuse low-level echoes, a multiloculated mass was 64 times more likely to be an endometriotic cyst (23). When using diagnostic MRI criteria such as T1 hyperintense cysts with T2 shading or multiple T1 hyperintense cysts regardless of the T2 signal intensity, the sensitivity and specifi city for making a defi nitive diagnosis of endometriotic cysts have been reported to be as high as 90% and 98%, respectively (15). The mean maximum diameter of the ruptured endometriotic cysts is 70.1 mm in this study, which is larger than that of the uncomplicated ovarian endometriotic cysts reported in the previous studies. Kinkel et al. (7) reported that 81% of ovarian endometriotic cysts ranged between 30 mm and 59 mm for the maximum diameter. If endometriotic cysts get large enough or if trauma occurs, then they can rupture and their contents spill into the pelvic cavity. Unruptured corpus luteal cysts are typically less than 3 cm in diameter (24). The cyst walls in endometriotic cysts are generally thick and fi brotic, and they commonly have areas of discoloration and dense fi brous adhesions. The US appearance of the endometrial cyst wall can be variable, but this deserves special attention (8). Diffuse wall thickening, wall nodularity and echogenic foci within the cyst wall of endometriotic cysts have all been observed (23). Patel et al. (23) found no diagnostic value in assessing the wall thickness for differentiating between endometriotic cysts and other ovarian masses. On MR imaging, administration of gadolinium-based contrast material is not particularly useful for evaluating endometriotic cysts (8). When contrast

is used, the cyst wall demonstrates a nonspecifi c, variable pattern of enhancement that does not differentiate it from other benign and malignant processes (25). In our study, the relatively high incidence of enhancement of the cyst wall after intravenous contrast administration (11 of 13 cases) was suggestive of active infl ammatory changes due to cyst rupture. In patients with ruptured corpus luteal cysts, CT typically reveals hemoperitoneum and an adnexal Korean J Radiol 12(1), Jan/Feb 2011 www.kjronline.org64 Young Rae Lee cyst, with a ring of peripheral contrast enhancement (2). This ring of contrast enhancement may be due to the increased vascularity during the luteal phase, which predisposes the cyst to rupture (26). In a patient suffering from hemoperitoneum, active bleeding as depicted at CT by the active arterial extravasation of intravenous contrast with a measured attenuation value higher than that of free or clotted blood is indicative of the need for prompt surgical intervention (4). A focus of active bleeding may appear as a serpiginous or amorphous high attenuation area that is intermixed with or surrounded by a large hematoma (1). The wall of an endometriotic cyst is mostly fi brotic tissue with a paucity of vascularity; therefore, only one of the 13 cases of endometriotic cysts in our study showed active extravasation, while 11 of the 25 cases of functional cysts showed this fi nding. In patients with ruptured endometriotic cysts, the ascites is usually confi ned to the pelvic cavity with a loculated contour, and this suggests associated pelvic adhesion, which is an extremely common and important complication of endometriosis (8). After a corpus luteal cyst ruptures, hemoperitoneum will be present within the pelvis and possibly throughout the abdomen, as was shown in this study. Higher attenuation blood is typically present within the pelvis, as compared with being present the abdomen, and blood may be present adjacent to the cystic lesion, indicating that the source of the hemoperitoneum is cyst rupture (2). Several limitations of our present study must be considered. First, it was a retrospective evaluation with a relatively small number of patients. Second, the present study was confi ned to patients with functional cysts as a comparative group, and we did not include any patients with conditions such as tuboovarian abscess or ovarian tumor that might potentially overlap with ovarian endometriotic cysts on CT. Third, the patients with ruptured corpus luteal cysts and who had a small amount of hemoperitoneum confi ned to the pelvic cavity were managed conservatively, and this may have caused a selection bias. Fourth, the CT protocol was not identical for all the enrolled patients. Finally, in this study, the images were reviewed and analyzed by only a single reader. That being said, the CT appearance of ruptured endometriotic cysts is relatively distinctive compared to that of ruptured functional cysts, and the accurate preoperative characterization of ovarian cyst via CT will help the surgical planning. In conclusion, the diagnosis of ruptured endometriotic cyst should be suspected for a woman in whom CT reveals the presence of multilocular or bilateral ovarian cysts with a thick wall and loculated ascites confi ned to pelvic cavity with pelvic fat infi ltrations.

1. Lubner M, Menias C, Rucker C, Bhalla S, Peterson CM, Wang L, et al. Blood in the belly: CT fi ndings of hemoperitoneum. Radiographics 2007;27:109-125 2. Hertzberg BS, Kliewer MA, Paulson EK. Ovarian cyst rupture causing hemoperitoneum: imaging features and the potential for misdiagnosis. Abdom Imaging 1999;24:304-308 3. Hertzberg BS, Kliewer MA, Bowie JD. Adnexal ring sign and hemoperitoneum caused by hemorrhagic ovarian cyst: pitfall in the sonographic diagnosis of ectopic pregnancy. AJR Am J Roentgenol 1999;173:1301-1302 4. Bottomley C, Bourne T. Diagnosis and management of ovarian cyst accidents. Best Pract Res Clin Obstet Gynaecol 2009;23:711-724 5. Coulier B, Malbecq S, Brinon PE, Ramboux A. MDCT diagnosis of ruptured tubal pregnancy with massive hemoperitoneum. Emerg Radiol 2008;15:179-182 6. Swart JE, Fishman EK. Gynecologic pathology on multidetector CT: a pictorial review. Emerg Radiol 2008;15:383-389 7. Kinkel K, Frei KA, Balleyguier C, Chapron C. Diagnosis of endometriosis with imaging: a review. Eur Radiol 2006;16:285- 298 8. Woodward PJ, Sohaey R, Mezzetti TP Jr. Endometriosis: radiologic-pathologic correlation. Radiographics 2001;21:193- 216 9. Johansson J, Santala M, Kauppila A. Explosive rise of serum CA 125 following the rupture of ovarian endometrioma. Hum Reprod 1998;13:3503-3504 10. Evangelinakis N, Grammatikakis I, Salamalekis G, Tziortzioti V, Samaras C, Chrelias C, et al. Prevalence of acute hemoperitoneum in patients with endometriotic ovarian cysts: a 7-year retrospective study. Clin Exp Obstet Gynecol 2009;36:254-255 11. Bernstein JP, Perlow V, Brenner JJ. Massive ascites due to endometriosis. Am J Dig Dis 1961;6:1-7 12. el-Newihi HM, Antaki JP, Rajan S, Reynolds TB. Large bloody ascites in association with pelvic endometriosis: case report and literature review. Am J Gastroenterol 1995;90:632-634 13. Göçmen A, Karaca M, Tarakçiog˘lu M. A ruptured ovarian endometrioma mimicking ovarian malignancy: case report. Eur J Gynaecol Oncol 2003;24:445-446 14. Carbognin G, Guarise A, Minelli L, Vitale I, Malagó R, Zamboni G, et al. Pelvic endometriosis: US and MRI features. Abdom Imaging 2004;29:609-618 15. Togashi K, Nishimura K, Kimura I, Tsuda Y, Yamashita K, Shibata T, et al. Endometrial cysts: diagnosis with MR Korean J Radiol 12(1), Jan/Feb 2011www.kjronline.org 65 CT Findings of Ruptured Ovarian Endometriotic Cysts imaging. Radiology 1991;180:73-78 16. Kupfer MC, Schwimer SR, Lebovic J. Transvaginal sonographic appearance of endometriomata: spectrum of fi ndings. J Ultrasound Med 1992;11:129-133 17. Fishman EK, Scatarige JC, Saksouk FA, Rosenshein NB, Siegelman SS. Computed tomography of endometriosis. J Comput Assist Tomogr 1983;7:257-264 18. Umaria N, Olliff JF. Imaging features of pelvic endometriosis. Br J Radiol 2001;74:556-562 19. Buy JN, Ghossain MA, Mark AS, Deligne L, Hugol D, Truc JB, et al. Focal hyperdense areas in endometriomas: a characteristic fi nding on CT. AJR Am J Roentgenol 1992;159:769-771 20. Bennett GL, Harvey WB, Slywotzky CM, Birnbaum BA. CT of the acute abdomen: gynecologic etiologies. Abdom Imaging 2003;28:416-432 21. Yamashita Y, Torashima M, Hatanaka Y, Harada M, Sakamoto Y, Takahashi M, et al. Value of phase-shift gradient-echo MR imaging in the differentiation of pelvic lesions with high signal intensity at T1-weighted imaging. Radiology 1994;191:759-764 22. Ghezzi F, Raio L, Cromi A, Duwe DG, Beretta P, Buttarelli M, et al. “Kissing ovaries”: a sonographic sign of moderate to severe endometriosis. Fertil Steril 2005;83:143-147 23. Patel MD, Feldstein VA, Chen DC, Lipson SD, Filly RA. Endometriomas: diagnostic performance of US. Radiology 1999;210:739-745 24. Borders RJ, Breiman RS, Yeh BM, Qayyum A, Coakley FV. Computed tomography of corpus luteal cysts. J Comput Assist Tomogr 2004;28:340-342 25. Ascher SM, Agrawal R, Bis KG, Brown ED, Maximovich A, Markham SM, et al. Endometriosis: appearance and detection with conventional and contrast-enhanced fat-suppressed spin- echo techniques. J Magn Reson Imaging 1995;5:251-257 26. Lucey BC, Varghese JC, Anderson SW, Soto JA. Spontaneous hemoperitoneum: a bloody mess. Emerg Radiol 2007;14:65-75