Volume 38 • Number 7 March 31, 2015

Gynecologic and : Key Imaging Findings, Mimics, and Complications Saro B. Manoukian, MD, Nicholas H. Shaheen, MD, and Daniel J. Kowal, MD

After participating in this activity, the diagnostic radiologist should be better able to utilize ultrasound and MR imaging to help differentiate between gynecologic adenomyosis and endometriosis given their divergent management despite their signifi cant overlap in symptoms.

Adenomyosis of the CME Category: Women’s Imaging Subcategory: Genitourinary Adenomyosis of the uterus represents heterotopic endome- Modality: MRI trial glands and stroma in the with adjacent smooth muscle hypertrophy. The pathogenesis of uterine adenomyosis involves endometrial migration via a basement Key words: Adenomyosis, Endometriosis, Ovarian membrane defect or through lymphatic or vascular channels.1 Women age 40 to 50 years usually are affected. Although patients with uterine adenomyosis are usually asymptomatic, Adenomyosis and endometriosis are gynecologic processes symptoms may include , menorrhagia, and dys- with characteristic pathophysiologic, clinical, and imaging menorrhea. Risk factors for uterine adenomyosis include prior differences. Although adenomyosis refers to the presence of uterine trauma or surgery, multiparity, and hyperestrogene- heterotopic endometrial glands and stroma within the myo- mia. Imaging is important because superfi cial uterine adeno- metrium, endometriosis involves the presence of endometrial myosis responds signifi cantly better to endometrial ablation glands and stroma outside of the uterus (Figure 1). Patients than does deep uterine adenomyosis. On ultrasound imaging, with either adenomyosis or endometriosis can have a similar pseudowidening of the with a poorly defi ned clinical presentation. Imaging can be of great utility in dif- endomyometrial junction often is seen in diffuse uterine ferentiating between these 2 gynecologic pathologic pro- adenomyosis because of heterotopic endometrium extending cesses, thereby guiding appropriate clinical management. into the inner myometrium2 (Figure 2). These heterotopic Accurate diagnosis also is important because endometriosis endometrial glands cause an appearance of subendometrial has potentially more signifi cant complications. Finally, dif- echogenic linear striations.2 Also, the uterus is often globular ferentiating an ovarian endometrioma from its mimics can and enlarged with heterogeneous myometrial echotexture. obviate the need for more invasive procedures, such as lapar- On MRI, diffuse uterine adenomyosis demonstrates oscopy or oophorectomy. thickening of the junctional zone of at least 12 mm. The junctional zone corresponds to the innermost layer of myo- metrium and is visualized as a distinct area of low signal Dr. Manoukian is Radiology Resident, Dr. Shaheen is Radiology Resident, and on T2-weighted MR images, separating the high-signal Dr. Kowal is CT Division Director, Department of Radiology, Saint Vincent endometrium from the intermediate-signal outer myo- Hospital, 123 Summer St, Worcester, MA 01608; E-mail: [email protected]. metrium3 (Figure 3). Although a junctional zone thickness The authors and all staff in a position to control the content of this CME activity greater than 12 mm is diagnostic of uterine adenomyosis and their spouses/life partners (if any) have disclosed that they have no relation- ships with, or fi nancial interests in, any commercial organizations pertaining to (Figure 4), a junctional zone thickness of 8 mm or less effec- this educational activity. tively excludes adenomyosis as a diagnostic consideration.

Lippincott Continuing Medical Education Institute, Inc., is accredited by the Accreditation Council for Continuing Medical Education to provide continuing medical education for physicians. Lippincott Continuing Medical Education Institute, Inc., designates this enduring material for a maximum of 2 AMA PRA Category 1 Credits™. Physicians should only claim credit commensurate with the extent of their participation in the activity. To earn CME credit, you must read the CME article and complete the quiz and evaluation on the enclosed answer form, answering at least seven of the 10 quiz questions correctly. This continuing medical education activity expires on March 30, 2016. 1

CCDRv38n7.inddDRv38n7.indd 1 22/11/15/11/15 10:1810:18 PMPM Figure 3. Sagittal, T2-weighted MR image of the uterus demon- strates its normal zonal anatomy. The outer myometrium (1) is intermediate signal intensity. The inner myometrium (2) (also Figure 1. Adenomyosis represents heterotopic endometrial known as the junctional zone) is hypointense and normally <12 mm glands and stroma in the myometrium. Endometriosis represents in thickness. The endometrium (3) is normally hyperintense. functional ectopic endometrial glands and stroma outside of the uterine cavity, commonly manifesting as an endometrioma. (see Figure 4), and T1-hyperintense punctuate foci indi- cating hemorrhage, all of which are fi ndings that add specifi city to the diagnosis. Because of its superior sensiti- vity and specifi city compared with ultrasound, MRI is the imaging modality of choice for the diagnosis of uterine adenomyosis.2 The defi nitive treatment for diffuse uterine adenomyosis is hysterectomy, particularly in women with debilitating symptoms. Endometrial ablation can be performed for more superfi cial disease, which is best evaluated on MRI.2 Mimics of Focal Adenomyosis. A myometrial contrac- tion could mimic focal adenomyosis, but myometrial con- tractions are transient and change in appearance over time.2 Although typically diffuse, uterine adenomyosis also can occur focally and even appear mass-like as an adenomy- oma. Uterine leiomyomas (fibroids) are well-defined, rounded lesions with mass effect on the endometrium, unlike focal uterine adenomyosis, which is poorly defi ned, elliptical, and without mass effect. Although both uterine Figure 2. Transvaginal ultrasound of the uterus demonstrates fi broids and adenomyosis are hypointense on T2-weighted endometrial pseudowidening (white arrow) with a poorly defi ned MR images, focal uterine adenomyosis contains punctate endomyometrial junction (dashed arrow). Heterogeneity of the hyperintense foci, signifying dilated cystic endometrial myometrium also is present. glands.2 Differentiating the two conditions is clinically rel- Additional MR fi ndings include poorly defi ned junctional evant because of divergent management: uterine conserva- zone margins, intrazonal T2-hyperintense punctate foci tion with myomectomy for leiomyomas versus hysterectomy representing cystic dilatation of heterotopic glands3 for uterine adenomyosis.

The continuing education activity in Contemporary Diagnostic Radiology is intended for radiologists. EDITOR: Robert E. Campbell, MD, Clinical Professor of Radiology, University of Pennsylvania School of Medicine, Philadelphia, Pennsylvania Contemporary Diagnostic Radiology (ISSN 0149-9009) is published bi-weekly by Lippincott Williams & Wilkins, Inc., 16522 Hunters Green Parkway, Hagerstown, MD 21740-2116. Customer Service: Phone (800) 638-3030; FOUNDING EDITOR: William J. Tuddenham, MD Fax (301) 223-2400; E-mail: [email protected]. Visit our website at LWW.com. Publisher, Randi Davis. EDITORIAL BOARD: Copyright © 2015 Wolters Kluwer Health, Inc. All rights reserved. Priority Postage paid at Hagerstown, MD, and at Teresita L. Angtuaco, MD Bruce L. McClennan, MD additional mailing offi ces. POSTMASTER: Send address changes to Contemporary Diagnostic Radiology, Subscription George S. Bisset III, MD Johnny U. V. Monu, MBBS, Msc Dept., Lippincott Williams & Wilkins, P.O. Box 1600, 16522 Hunters Green Parkway, Hagerstown, MD 21740-2116. William G. Bradley Jr., MD, PhD Pablo R. Ros, MD, MPH, PhD PAID SUBSCRIBERS: Current issue and archives (from 1999) are available FREE online at www.cdrnewsletter.com. Liem T. Bui-Mansfi eld, MD William M. Thompson, MD Valerie P. Jackson, MD Subscription rates: Individual: US $692.00 with CME, $542.00 with no CME; international $1013.00 with CME, $743.00 with no CME. Institutional: US $1001.00, international $1139.00. In-training: US resident $139.00 with Opinions expressed do not necessarily refl ect the views of the Publisher, Editor, no CME, international $162.00. GST Registration Number: 895524239. Send bulk pricing requests to Publisher. or Editorial Board. A mention of products or services does not constitute Single copies: $43.00. COPYING: Contents of Contemporary Diagnostic Radiology are protected by copyright. endorsement. All comments are for general guidance only; professional coun- Reproduction, photocopying, and storage or transmission by magnetic or electronic means are strictly prohibited. sel should be sought for specifi c situations. Indexed by Bio-Science Information Services. Violation of copyright will result in legal action, including civil and/or criminal penalties. Permission to reproduce in any way must be secured in writing; go to the journal website (www.cdrnewsletter.com), select the article, and click “Request Permissions” under “Article Tools,” or e-mail [email protected]. Reprints: For commercial reprints and all quantities of 500 or more, e-mail [email protected]. For quantities of 500 or under, e-mail [email protected], call 866-903-6951, or fax 410-528-4434. 2

CCDRv38n7.inddDRv38n7.indd 2 22/11/15/11/15 10:1810:18 PMPM A

Figure 4. T2-weighted MR image demonstrates a poorly defi ned, widened junctional zone (box) containing hyperintense punctate foci (arrow), representing cystic dilatation of heterotopic endometrial glands in diffuse uterine adenomyosis. B

Endometriosis Figure 6. Endometrioma. A: T1-weighted, fat-suppressed MR Endometriosis represents functional ectopic endometrial image demonstrates a homogeneously hyperintense adnexal lesion (arrow), consistent with an endometrioma. This lesion is glands and stroma outside of the uterine cavity. Endometriosis classically described as “light bulb bright.” B: T2-weighted MR is in some ways similar to uterine adenomyosis, which was image demonstrates corresponding hypointensity (dashed arrow) formerly referred to as endometriosis interna.1 The most because of the high concentration of iron, protein, and viscosity. accepted theory of the pathogenesis of endometriosis is that This fi nding is classically referred to as “T2-shading.” it results from metastatic implantation of endometrial tissue into the peritoneal cavity from retrograde menstruation.4 .4 Less commonly, endometriomas may dem- Endometriosis is seen predominantly in women of childbear- onstrate echogenic wall nodularity and have thin or thick ing age, with an overall prevalence of 10%. In addition, 5% septations.6 Ultrasound is highly sensitive and specifi c in the of cases are seen in postmenopausal women.5 The most com- evaluation of endometriomas. However, ultrasound is extremely mon presenting symptoms are pelvic pain and . Risk poor in evaluating the other forms of endometriosis (i.e., factors include age and prolonged exposure to menstruation, endometrial implants and deep pelvic endometriosis with such as early menarche, nulliparity, short menstrual cycles, adhesions),6 which are thought to be the principal causes of and prolonged menstrual fl ow.4 Endometriosis can present pelvic pain and infertility in affected patients. in three forms: ovarian endometriomas, endometrial implants, The most common and specifi c MR appearance of endo- and deep pelvic endometriosis with adhesions. metriomas is the presence of lesions that are homogeneously Endometriomas are chronic cysts that occur within the T1-hyperintense (referred to as “light bulb bright”) and T2- from repeated cyclic hemorrhage. These ovarian endo- hypointense (referred to as “T2 shading”)5 (Figures 6A and metrial cysts are referred to as “chocolate cysts” because 6B). T2 shading occurs because of the high concentration of they contain thick, dark, degenerated blood products.4 On iron and protein and increased viscosity and protein cross- ultrasound, endometriomas contain homogeneously diffuse linking within the lesion.6 Less commonly, endometriomas low-level echoes (Figure 5), a fi nding observed in 95% of can appear T2-hyperintense because of differences in con- centration of blood products. A defi nitive diagnosis of an endometrioma is made if there is a T1-hyperintense lesion with T2 shading or if multiple T1-hyperintense cysts are visualized, regardless of their signal intensity on T2-weighted images.6 MRI is the most specifi c modality for diagnosis of endometriosis, with a sensitivity of 90% and a specifi city of 98%.6 A T1-weighted, fat-suppressed sequence further Figure 5. Endometrioma. improves sensitivity, as fat suppression narrows the dynamic Transvaginal ultrasound of an adnexal lesion with homogene- signal range and increases lesion conspicuity, allowing detec- ously low-level internal echoes, tion of endometriomas and endometrial implants as small as consistent with endometrioma. 5 mm (Figure 7).6 3

CCDRv38n7.inddDRv38n7.indd 3 22/11/15/11/15 10:1810:18 PMPM Figure 8. Axial CT scan dem- onstrates thoracic endome- trial seeding with pleural thickening (calipers), round atelectasis (circle) secondary to chronic pleural irritation, and a pleural effusion found to be a hemothorax.

A are part of the differential diagnosis, but there are useful imaging characteristics that can help differentiate these mimics from endometriomas. Hemorrhagic cysts are usually solitary, unilocular, evolve into more complex-appearing cysts over time, and resolve within 6 weeks, unlike endo- metriomas that persist.7 On ultrasound, hemorrhagic cysts typically demonstrate a reticular pattern of echogenic

B

Figure 7. Multiple endometriomas. A: T1-weighted MR image shows a right adnexal hyperintense lesion (dashed arrow), consistent with an endometrioma. B: T1-weighted, fat-suppressed MR image reveals a punctate left adnexal hyperintense lesion (solid arrow), also an endometrioma that could not be visualized on the sequence without fat suppression.

There are numerous potential sites of implantation in endo- metriosis. The gastrointestinal (GI) tract is the most common site, occurring in 12% to 37% of cases, most commonly the rectosigmoid colon. Serosal, and less commonly, transmural implantation may occur, with patients experiencing bloating, cramping, and pain during defecation.7 The urinary tract is the next most common site of involvement in up to 20% of cases, typically involving the urinary bladder, followed by A the ureters. Patients may present with urinary urgency, dys- uria, and gross hematuria.7 Up to 30% of women with endo- metriosis have involvement at , with likely occurring secondary to adhesions. Hematosalpinx appears as a T1-hyperintense tubular adnexal structure and may be an isolated fi nding in a patient with endometriosis. The thorax is a rare site of involvement but is the most frequent form of extra-abdominal endometriosis. The thoracic endometriosis syndrome manifests as catame- nial pneumothorax, hemothorax, and lung nodules (Figure 8). Women with thoracic endometriosis can present with pleuritic chest pain, pleural effusions, or cyclic hemoptysis.7 The treatment for endometriosis is medical when symp- toms include pelvic pain or , usually with anti- infl ammatory agents or hormonal therapy. In the case of BC infertility, treatment is surgical, which involves the removal of endometriomas or lysis of adhesions in a patient with deep Figure 9. Hemorrhagic ovarian cysts. Transvaginal ultrasound (A) 7 of an adnexal lesion with low-level echoes and thin, reticular, pelvic endometriosis. echogenic strands representing clot and fi brin within a hemor- Mimics of Endometriosis. Hemorrhagic cysts, mature rhagic cyst. On MRI, hemorrhagic ovarian cysts are usually soli- cystic teratomas, and ovarian mucinous epithelial neoplasms tary T2-hyperintense (B) and T1-hyperintense (C) lesions (arrows). 4

CCDRv38n7.inddDRv38n7.indd 4 22/11/15/11/15 10:1810:18 PMPM Figure 13. Clear cell carcinoma of the ovary. Ultrasound of a cystic adnexal lesion with papil- lary projections (arrow) demon- strates intranodular Doppler fl ow, raising suspicion for malig- nant transformation. This lesion was a pathology-proven clear cell carcinoma, the second A B most common malignancy to arise from endometriosis. Figure 10. Mature cystic teratoma. A: Ultrasound of a large cystic adnexal lesion demonstrates low-level internal echoes with the appearance of an endometrioma. B: On an axial CT scan, this lesion demonstrates fat and calcium density (dashed arrow) within Figure 14. Scar endometriosis. a Rokitansky nodule characteristic of a mature cystic teratoma. Axial CT scan of a biopsy- proven subcutaneous endome- trial implant (dashed arrow) Figure 11. Borderline muci- along a transverse incision site nous epithelial ovarian tumor. secondary to iatrogenic spread Transvaginal ultrasound of an from a cesarean delivery. adnexal lesion demonstrates low-level echoes, resembling an endometrioma. However, Rokitansky nodule pathognomic for a dermoid cyst typically this lesion is larger than a is visible on CT (Figure 10B) and especially MRI. On MRI, typical endometrioma and T1 fat-suppressed imaging differentiates dermoid cysts from is a pathology-proven bor- 7 derline mucinous epithelial endometriomas with high specifi city. ovarian tumor, which could be characterized more defi nitively Borderline mucinous epithelial ovarian tumors may dem- on MRI. onstrate low-level echoes on ultrasound because of loculated mucin and, therefore, may resemble endometriomas (Figure 11). However, these tumors are typically much larger than endometriomas. On MRI, these lesions may be multilocular, have enhancing solid components, or have a “stained glass” appearance because of variations in mucin concentration within loculi.6 Complications of Endometriosis. Malignant transforma- tion is rare in endometriosis, occurring less than 1% of the time. The most common malignancies arising from endometriosis are endometrioid carcinoma (Figure 12) fol- lowed by clear cell carcinoma6 (Figure 13). The most reliable imaging fi nding in evaluating for malignant transformation of an endometrioma is the presence of an MRI contrast-enhanc- ing or Doppler-positive mural nodule (see Figure 13).4 On MRI, enhancing mural nodules are sensitive (97%) but not specifi c (56%) for malignant transformation.5 Other, less reliable imaging features suggesting malignant transforma- tion include loss of T2 shading and interval increase in size.5 Figure 12. Endometrioid carcinoma. Axial CT scan of a large bilobed right . This was a pathology-proven endo- Scar endometriosis represents iatrogenic spread of endo- metrioid carcinoma, the most common malignancy to arise from metrial tissue related to surgery, a complication seen in 1% endometriosis. In addition, there is synchronous endometrial of all patients who have had a cesarean delivery. Patients can hyperplasia, a fi nding that occurs in 30% of patients with endo- present with a palpable mass or cyclical pain weeks to years metrioid carcinoma. after surgery.6 On ultrasound, a solid hypoechoic mass is seen with internal vascularity on Doppler imaging. On CT, fi brin strands (Figure 9A), as opposed to the homogeneous a soft tissue density is encountered in the subcutaneous tis- low-level echoes of endometriomas.7 On MRI, hemor- sues of the abdominal wall in the expected region of a rhagic cysts are usually both T1- and T2-hyperintense Pfannenstiel incision6 (Figure 14). Tissue sampling typically (Figures 9B and 9C). Moreover, hemorrhagic cysts are clot- is required to confi rm the diagnosis. forming rather than viscous and contain little iron (i.e., no “T2 shading”).7 Conclusion Mature cystic teratomas (dermoid cysts), particularly those Uterine adenomyosis and endometriosis are gynecologic with high sebum content, may mimic endometriosis on ultra- processes with often overlapping clinical symptoms. This sound and appear as cystic masses with low-level internal CME activity emphasizes the key imaging differences echoes similar to an endometrioma (Figure 10A). If not between these two entities and differentiates them from their detected on ultrasound, the fat and calcium-containing mimics, thereby guiding appropriate therapy. 5

CCDRv38n7.inddDRv38n7.indd 5 22/11/15/11/15 10:1810:18 PMPM References 4. Bennett GL, Slywotzky CM, Cantera M, et al. Unusual manifestations and 1. Tamai K, Togashi K, Ito T, et al. MR imaging fi ndings of adenomyosis: cor- complications of endometriosis—spectrum of imaging fi ndings: pictorial relation with histopathologic features and diagnostic pitfalls. Radiographics. review. AJR Am J Roentgenol. 2010;194:WS34-WS46. 2005;25:21-40. 5. McDermott S, Oei TN, Iyer VR, et al. MR imaging of malignancies arising in 2. Reinhold C, Tafazoli F, Mehio A, et al. Uterine adenomyosis: endovaginal endometriomas and extraovarian endometriosis. Radiographics. 2012;32:845-863. US and MR imaging features with histopathologic correlation. Radiographics. 6. Woodward PJ, Sohaey R, Mezzetti TP Jr. Endometriosis: radiologic- 1999;19:S147-S160. pathologic correlation. Radiographics. 2001;21:193-216. 3. Novellas S, Chassang M, Delotte J, et al. MRI characteristics of the uterine 7. Chamie LP, Blasbalg R, Pereira RM, et al. Findings of pelvic endometriosis junctional zone: from normal to the diagnosis of adenomyosis. AJR Am J at transvaginal US, MR imaging, and laparoscopy. Radiographics. Roentgenol. 2011;196:1206-1213. 2011;31:E77-100.

CME QUIZ: VOLUME 38, NUMBER 7 To earn CME credit, you must read the CME article and complete the quiz and evaluation on the enclosed answer form, answering at least seven of the 10 quiz questions correctly. Select the best answer and use a blue or black pen to completely fi ll in the corresponding box on the enclosed answer form. Please indicate any name and address changes directly on the answer form. If your name and address do not appear on the answer form, please print that information in the blank space at the top left of the page. Make a photocopy of the completed answer form for your own fi les and mail the original answer form in the enclosed postage-paid business reply envelope. Only two entries will be considered for credit. Your answer form must be received by Lippincott CME Institute, Inc., by March 30, 2016. At the end of each quarter, all CME participants will receive individual issue certifi cates for their CME participation in that quarter. These individual certifi cates will include your name, the publication title, the volume number, the issue number, the article title, your participation date, the AMA credit awarded, and any subcategory credit earned (if applicable). For more information, call (800) 638-3030. All CME credit earned via Contemporary Diagnostic Radiology will apply toward continuous certifi cation requirements. ABR continuous certifi cation requires 75 CME credits every 3 years, at least 25 of which must be self-assessment CME (SA-CME) credits. All SAM credits earned via Contemporary Diagnostic Radiology are now equivalent to SA-CME credits (www.theabr.org). Online quiz instructions: To take the quiz online, log on to your account at www.cdrnewsletter.com, and click on the “CME” tab at the top of the page. Then click on “Access the CME activity for this newsletter,” which will take you to the log-in page for http://cme.lww.com. Enter your username and password. Follow the instructions on the site. You may print your offi cial certifi cate immediately. Please note: Lippincott CME Institute will not mail certifi cates to online participants. Online quizzes expire on the due date.

1. Which one of the following MR imaging fi ndings is most sus- 6. Which one of the following is the most common site of GI picious for malignant transformation of an endometrioma? involvement in endometriosis? A. Calcifi cations A. Rectosigmoid colon B. Increase in size B. Cecum C. Loss of T2 shading C. Terminal ileum D. Enhancing mural nodule D. Appendix E. Faint peripheral enhancement E. Duodenum 2. A 42-year-old woman experiences debilitating symptoms 7. Which one of the following MR sequences is most sensitive caused by diffuse uterine adenomyosis. The treatment for at detecting tiny endometrial implants? this patient should be A. T1-weighted A. radiation therapy B. T1-weighted, opposed-phase B. hysterectomy C. T1-weighted, fat-suppressed C. focal excision D. T2-weighted D. chemotherapy E. Diffusion-weighted E. analgesics 8. Ultrasound examination of a 45-year-old woman reveals an 3. Which one of the following is the most common site of urinary adnexal mass with homogeneously low-level echoes. The tract involvement in a patient with endometriosis? differential diagnosis of the adnexal mass could include all A. Kidneys of the following lesions, except B. Proximal ureters A. endometrioma C. Distal ureters B. mature cystic teratoma D. Urethra C. borderline mucinous ovarian tumor E. Urinary bladder D. clear cell carcinoma E. hemorrhagic cyst 4. Which one of the following uterine junctional zone measure- ments (thickness) on MRI is diagnostic of uterine adenomyosis? 9. The term “light bulb bright” refers to an endometrioma seen A. 4 mm on which one of the following MR sequences? B. 6 mm A. T1-weighted C. 8 mm B. T2-weighted D. 10 mm C. Short-tau inversion recovery E. ≥12 mm D. Proton density E. Diffusion-weighted 5. Which one of the following is a chronic, nonresolving that occurs from repeated cyclic hemorrhage? 10. Which one of the following conditions refers to heterotopic A. Endometrial implant endometrial glands and stroma within the myometrium? B. Endometrioma A. Leiomyoma C. Deep pelvic endometriosis B. Adenomyosis D. Hemorrhagic cyst C. Endometrioma E. Dermoid cyst D. Endometriosis E. Hemorrhagic cyst 6

CCDRv38n7.inddDRv38n7.indd 6 22/11/15/11/15 10:1810:18 PMPM