ORIGINAL ARTICLES Use of the ESCAPE Mnemonic May Help Differentiate Functional Ovarian Masses from Ovarian Neoplasms
Michael G. Kelly, M.D., and Samuel S. Lentz, M.D.
Adnexal masses are often identified incidentally on With the advent of sophisticated imaging tech- physical and pelvic examinations and during cross- niques, including ultrasound, computed tomogra- sectional imaging studies, such as CT scan, being per- phy (CT), and magnetic resonance imaging (MRI), formed for other reasons. it has become routine to Many of these masses are perform one or perhaps functional cysts—these can The ESCAPE mnemonic can be several of these studies be managed conservatively without the need for surgi- useful in the initial evaluation as in patients found to have an adnexal mass on phys- cal intervention. Although well as an adjunct to imaging ical examination. In addi- contemporary management modalities such as pelvic tion, adnexal masses are of adnexal masses often in- often discovered inciden- volves imaging, understand ultrasound in patients with tally during imaging per- ing the pathophysiology of an adnexal mass. formed for other reasons. functional lesions and im- Most adnexal masses plementing the mnemonic detected either on phys- ESCAPE may provide additional information in the ical examination or imaging are ovarian in origin. initial management of a patient with a palpable adnexal The clinician and patient are often faced with mass. This approach, in conjunction with sonographic the decision of whether to proceed with surgical imaging, may further minimize unnecessary surgery in intervention of these incidental ovarian masses. patients with palpable adnexal masses. (J Reprod Med This determination revolves around the nature of 2020;65:335–340) the lesion, i.e., neoplasm versus functional cyst. A functional ovarian mass is the sequelae of normal Keywords: adnexa, adnexal masses, diagnosis, physiologic function during the reproductive years. International Ovarian Tumor Analysis, mnemonic Functional lesions typically resolve spontaneously ESCAPE, ovarian cancer, ovarian neoplasms, pre- with observation over a 6–8-week time period. operative evaluation, risk assessment, ultrasonog- Neoplastic lesions, whether benign or malignant, raphy. may ultimately require surgical intervention. There is no evidence that a 6–8-week time period delay affects prognosis in the setting of an ovarian malig- nancy. Therefore, it may be prudent to reevaluate
From the Department of Obstetrics and Gynecology, Wake Forest University School of Medicine, Winston-Salem, North Carolina. Address correspondence to: Michael G. Kelly, M.D., Department of Obstetrics and Gynecology, Wake Forest University School of Med- icine, One Medical Center Boulevard, Winston-Salem, NC 27157 ([email protected]). Financial Disclosure: The authors have no connection to any companies or products mentioned in this article.
The Journal of Reproductive Medicine® 335 336 The Journal of Reproductive Medicine®
an adnexal mass that is most consistent with a ities, including irregular bleeding or delayed onset functional cyst rather than proceeding with surgical of menses. Pelvic examination typically reveals a excision. tender mass of “doughy” consistency due to the In 1977 Greiss first described use of the mne hematoma in the cyst wall. The main differen- monic ESCAPE for the management of ovarian tial diagnosis with the constellation of these find- lesions. The purpose of this approach was to iden- ings (pelvic pain, menstrual abnormalities, and tify lesions that did not warrant surgical interven- an adnexal mass) is an ectopic pregnancy. This tion.1 We assert that this mnemonic is still valid diagnosis can be readily excluded with a negative today and can be useful in the initial evaluation pregnancy test. as an adjunct to pelvic ultrasound in the assess- Finally, a theca lutein cyst is the result of over ment of ovarian lesions. Additionally, thorough stimulation of the ovary by human chorionic go- understanding of the pathophysiology of function- nadotropin (hCG). The source of hCG can be al lesions of the ovary is crucial in minimizing sur- endogenous, as seen either in gestational tropho- gical intervention in patients with an adnexal mass. blastic disease or exogenous administration asso- ciated with hyperstimulation related to ovulation Pathophysiology of Functional Ovarian Cysts induction. These lesions often require a longer pe- The types of functional ovarian lesions are listed in riod of observation for resolution. For example, in Figure 1. Follicular and persistent corpus luteum a study by Montz et al, when discovered in asso- cysts are the most common of these entities. Each ciation with hydatidiform moles, approximately of these functional lesions is associated with dif- 25% of theca lutein cysts persisted beyond 8 weeks ferent pathophysiology, clinical presentation, and regardless of the course of the trophoblastic dis- differential diagnosis. ease. In this series, theca lutein cysts persisted in The follicular cyst develops as an accumulation 3 patients for 15–18 weeks after hCG regression.2 of serous-type fluid in a follicle that is destined It is suggested that luteoma of pregnancy is to become atretic. This lesion is typically discov- a functional lesion with spontaneous regression ered incidentally in the asymptomatic patient as a postpartum. However, others have reported recur- mobile cystic structure palpated on pelvic exam- rences in subsequent pregnancies associated with ination. The patient, prior to examination, typically maternal virilization.3 Since these lesions are rare does not have any specific symptoms or menstru- and often not diagnosed until after surgical resec- al abnormalities. Vigorous or repetitive examina- tion, this diagnosis should not be considered very tions may actually lead to rupture of the cyst. Cyst often when evaluating a patient with an adnexal rupture causes localized pain for a brief period mass. of time, improving over the ensuing 30–60 min- utes and completely resolving over the next 24 ESCAPE Mnemonic hours. The differential diagnosis includes a benign In addition to understanding the pathophysiology neoplastic process, such as a serous or mucinous of functional lesions of the ovary, the use of the cystadenoma. mnemonic ESCAPE (Figure 2) may also facilitate A persistent corpus luteum cyst involves hem- developing an accurate differential diagnosis for orrhage into a corpus luteum. Unlike the follicu a patient with an adnexal mass. Use of this mne- lar cyst, the persistent corpus luteum cyst may be monic only requires a pertinent history and physi- associated with pain related to either distention cal examination. of the ovarian capsule or peritoneal irritation sec- ondary to leakage. Continued hormonal produc- tion with these cysts leads to menstrual abnormal-
Enlargement Size • Follicular cyst Consistency • Persistent corpus luteum cyst Age • Theca lutein cyst Persistence • Luteoma of pregnancy Endocrine
Figure 1 The types of functional ovarian lesions. Figure 2 The ESCAPE mnemonic. Volume 65, Number 11-12/November-December 2020 337
Enlargement Persistence Typically, when a functional lesion is in the differ- Ovarian lesions that remain unchanged on repet- ential diagnosis, a follow-up examination is indi- itive examinations are not likely functional and cated in 6–8 weeks. A functional lesion should have thus should be considered neoplastic in nature. either resolved completely or at least diminished Certainly, a persistent or stable lesion would be in size on follow-up examination. By contrast, en- more consistent with a benign ovarian neoplasm largement of an ovarian lesion over a 6–8-week time rather than a malignant process. period suggests a neoplastic process. Endocrine Size Ovarian lesions associated with excessive hor- Functional lesions of the ovary are generally 4–8 mone production are neoplastic although gener- cm in diameter, although these lesions may rarely ally benign or of low malignant potential. These reach 10 cm. Certainly, lesions over 8–10 cm are lesions may produce excessive amounts of estro- worrisome for an ovarian neoplasm. gens, such as a granulosa cell tumor or andro- gens characteristic of a Sertoli-Leydig cell tumor. Consistency For example, a patient who presents with rapid Functional lesions are either cystic or “doughy” in onset of virilization associated with an ovarian consistency on examination, indicative of a fluid mass likely has a neoplastic process. or blood-filled structure. In contrast, a solid ovar- The algorithms in Figures 3–4 depict use of the ian mass is usually neoplastic. Most solid ovarian ESCAPE mnemonic in the evaluation of a patient masses are benign neoplasms such as an ovari- with an adnexal mass. The mnemonic is used to an fibroma or cystadenofibroma. Malignant solid aid in the diagnosis of a neoplastic process, with ovarian masses are usually due to metastatic dis- the major concern revolving around identifying a ease from another primary cancer such as colon malignant lesion. As seen in Figure 3, the initial or breast cancer. history and physical examination may denote a neoplastic process (benign or malignant). If a neo- Age plastic process is suspected, a follow-up examina- Ovulatory activity is necessary for development tion in 6–8 weeks is necessary. If the adnexal mass of functional lesions of the ovary. Therefore, pre- has enlarged or has persisted at this point, the mass menarchal or postmenopausal women should not is most likely a neoplasm (Figure 4). have functional ovarian lesions. In fact, Barber de- scribed the postmenopausal palpable ovary syn- Using ESCAPE in Conjunction with Pelvic Sonogram drome based on the principle that the postmeno- Most patients with an adnexal mass will undergo pausal ovary undergoes atrophy and thus typically a pelvic sonogram during initial evaluation. The is not palpable on pelvic examination. Therefore, ESCAPE mnemonic can be used in conjunction any palpable ovary in a postmenopausal patient with ultrasound to further differentiate a function- should raise the suspicion of a neoplastic process, al lesion from a neoplastic one. For example, ultra- although the risk of a malignant lesion is only sound imaging of a persistent corpus luteum may about 10%.4,5 have concerning features for a neoplastic process. In a related clinical situation, any temporary Use of the ESCAPE mnemonic may provide use- suppression of ovulatory function should prevent ful information in the differential diagnosis. In the development of a functional lesion. This would addition, sonography may help differentiate a be- include use of contraceptive hormones and GNRH nign from a malignant neoplasm once a function analogs. However, the frequency of functional al lesion is excluded. For example, a recent ultra- ovarian cysts developing in patients using low- sound study found that the risk of an ovarian dose oral contraceptives (≤35 µg ethinyl estradiol) malignancy was extremely low in postmenopaus- appears to be increased in comparison with those al women with unilocular ovarian cysts under who have used higher-dose pills.6 The incidence of 10 cm.8 At the other end of the age spectrum, functional ovarian cysts is even higher in progestin- Millar et al evaluated the incidence of ovarian only pill users.7 Thus, managing these patients con- cysts in prepubertal females as noted by ultra- servatively with a follow-up examination would be sound and found cysts >2 cm infrequently in young prudent prior to surgical intervention. girls over 2 years of age. They recommended con- 338 The Journal of Reproductive Medicine®
We suggest that patients with an adnexal mass
suggestive of a neoplasm using the ESCAPE mnemonic with IOTA group malignant features be triaged to surgery. Reciprocally, surveillance should be considered in asymptomatic patients deemed to have an ovarian neoplasm with be- nign features using the ESCAPE and IOTA crite- ria. Serial ultrasonographic follow-up is indicated rather than surgical intervention in this clinical situation.13,14 Case A 38-year-old woman presented to the emergency room with left-sided flank pain consistent with nephrolithiasis. The patient had had a subtotal hysterectomy in 2007 for postpartum hemorrhage and an abdominal radical trachelectomy for cer- vical cancer in 2018. In the emergency room a CT scan of the abdomen and pelvis revealed a 1–2 mm punctate kidney stone along the inner margin of Figure 3 Incorporation of the ESCAPE mnemonic into the initial the left distal ureter. There was also an incidental evaluation of a patient with an adnexal mass. finding of a 6.1 cm oval low attenuation cystic
servative follow-up until regression for unilocular
lesions <5 cm, noting no malignancies in their series.9 When a neoplastic process is favored after ap plying the ESCAPE mnemonic, a pelvic sonogram may further differentiate a benign from a malig- nant process. Ultimately, neoplasms with benign- appearing imaging features could be managed con- servatively, thereby further minimizing additional surgical intervention in these patients. For example, the International Ovarian Tumor Analysis (IOTA) group identified 4 reliable sono- graphic predictors of benign neoplasms and 2 re- liable sonographic predictors of malignant neo- plasms.10 However, approximately 20% of the time either both benign and malignant features are present or no features are present. In these incon- clusive cases, more complex algorithms such as the IOTA LR2 model,10 ADNEX (Assessment of Differential Neoplasias in the Adnexa),11 and RMI (Risk of Malignancy Index)12 have been developed to discriminate benign versus malignant processes. These complex algorithms also incorporate clini- cal data such as patient age and CA-125. How- ever, accuracy of these more complex algorithms has not reached a very reliable threshold for use Figure 4 Incorporation of the ESCAPE mnemonic into follow-up in the clinical arena. management of a patient with an adnexal mass. Volume 65, Number 11-12/November-December 2020 339
the first trimester, regressing by approximately 12
weeks’ gestation. Surgical resection of a persistent corpus luteum cyst during this critical time would potentially jeopardize the pregnancy. Hyperthecosis represents another exception to the ESCAPE mnemonic guidelines. This is a clini cal variant of polycystic ovary syndrome charac- terized by more intense androgenization, which can be associated with a rapid onset of virilization and ovarian enlargement, though not a neoplas- tic condition.15,16 Finally, ovarian endometriomas are neither neoplastic nor functional—the ESCAPE mnemonic may not be very helpful with this diagnosis. Symptoms of pelvic endometriosis, including secondary dysmenorrhea, dyspareunia, and dyschezia, associated with an adnexal mass would suggest an endometrioma. Endometriomas also have a characteristic appearance on pelvic sonography. Figure 5 Pelvic sonogram reveals a 6.5 cm hypoechoic to Some adnexal masses will be difficult to classi- anechoic cystic lesion in the left adnexa. fy after utilizing the ESCAPE mnemonic and IOTA group sonographic descriptors. In these cases, pelvic MRI with intravenous contrast should be considered. An IOTA study evaluating MRI per- lesion in the left adnexa. A pelvic ultrasound formance in assessing these masses is currently was performed to further characterize the adnexal ongoing.17 More complex algorithms (IOTA LR2, lesion (Figure 5). The patient’s pain subsequently ADNEX, or RMI) should also be considered when resolved. A follow-up pelvic sonogram 4 months triaging a patient with an indeterminate adnex- later revealed a similar-appearing lesion. Subse- al neoplasm after employing the ESCAPE mne- quently, the patient underwent a laparoscopy con- monic and IOTA sonographic descriptors. Further verted to laparotomy with adhesiolysis and resec- optimization of these models may lead to im- tion of the left adnexa. Final pathology revealed no provement in identification of women with benign evidence of malignancy. ovarian neoplasms who can be spared unnecessary In this case, application of the ESCAPE mne surgery. monic would have led to reassurance in the fol- In conclusion, knowledge of (1) pathophysiol- lowing categories: enlargement, size, consistency, ogy of functional lesions of the ovary and (2) the age and endocrine. The persistence of the cyst ESCAPE mnemonic may be useful, efficient, and suggests a neoplastic process, likely a benign neo- cost-effective tools in the evaluation and man- plasm since the size was stable. On ultrasound agement of patients with an adnexal mass diag- this cyst had IOTA group sonographic predict nosed on examination or incidentally on imaging. ors of a benign mass (with no IOTA group sono- As Greiss stated, “appropriate observation of func- graphic predictors of a malignant process). If the tional ovarian cysts will obviate diagnostic sur- ESCAPE and IOTA group criteria had been used gery 90% of the time, thus permitting an “escape” in this case, this patient may have been spared an from the sequelae of unnecessary and often extir- unnecessary operation. pative operations.”1 The ESCAPE mnemonic can be useful in the initial evaluation as well as an Discussion adjunct to imaging modalities such as pelvic ultra- There are some exceptions to the ESCAPE mne- sound in patients with an adnexal mass. monic. As previously noted, theca lutein cysts References may require somewhat longer than 6–8 weeks to 1. Greiss FC: Ovarian tumors. Am Fam Physician 1977;16(4):170-175 resolve. Similarly, with pregnancy the corpus lute- 2. Montz FJ, Schlaerth JB, Morrow CP: The natural history of theca lutein um is important in gestational support during cysts. Obstet Gynecol 1988;72(2):247-251 340 The Journal of Reproductive Medicine®
3. VanSlooten AJ, Rechner SF, Dodds WG: Recurrent maternal viriliza- ovarian cancer before surgery using the ADNEX model to differen- tion during pregnancy caused by benign androgen-producing ovarian tiate between benign, borderline, early and advanced stage invasive lesions. Am J Obstet Gynecol 1992;167(5):1342-1343 and secondary metastatic tumors: Prospective multicenter diagnostic 4. Barber HRK, Graber EA: The PMPO syndrome [post-menopausal pal- study. Br Med J 2010;341:c6839 pable ovary syndrome]. Obstet Gynecol Surv 1973;28:357-381 12. Jacobs I, Oram D, Fairbanks J, et al: A Risk of Malignancy Index 5. DiSaia PJ, Creasman WT: The adnexal mass and early ovarian cancer. incorporating CA125, ultrasound and menopausal status for the ac- In Clinical Gynecologic Oncology. Sixth edition. St. Louis, Missouri, curate preoperative diagnosis of ovarian cancer. Br J Obstet Gynaecol Mosby, Inc., 2002, pp 272-273 1990;97(10):922-929 6. Lanes SF, Birmann B, Walker AM, et al: Oral contraceptive type and 13. Ekerhovd E, Wienerroith H, Staubach A, et al: Preoperative assess- functional ovarian cysts. Am J Obstet Gynecol 1992;166:956-961 ment of unilocular adnexal cysts by transvaginal ultrasonography: 7. Tayob Y, Adams J, Jacobs HS, et al: Ultrasound demonstration of A comparison between ultrasonographic morphologic imaging and increased frequency of functional ovarian cysts in women using histopathologic diagnosis. Am J Obstet Gynecol 2001;184:48-54 progestogen-only oral contraception. Br J Obstet Gynaecol 1985;92: 14. Nardo LG, Kroon ND, Reginald PW: Persistent unilocular ovarian 1003-1009 cysts in a general population of postmenopausal women: Is there a 8. Modesitt SC, Pavlik EJ, Ueland FR, et al: Risk of malignancy in uniloc- place for expectant management? Obstet Gynecol 2003;102:589-593 ular ovarian cystic tumors less than 10 centimeters in diameter. Obstet 15. Judd HL, Scully RE, Herbst AL, et al: Familial hyperthecosis: Com Gynecol 2003;102:594-599 parison of endocrinologic and histologic findings with polycystic 9. Millar DM, Blake JM, Stringer DA, et al: Prepubertal ovarian cyst for- ovaries. Am J Obstet Gynecol 1973;117:976-979 mation: 5 years’ experience. Obstet Gynecol 1993;81:434-438 16. Speroff L, Glass RH, Kase NG: Anovulation and the polycystic ovary. 10. Froyman W, Timmerman D: Methods of assessing ovarian masses: In Clinical Gynecologic Endocrinology and Infertility. Sixth edition. International Ovarian Tumor Analysis approach. Obstet Gynecol Clin Baltimore, Maryland, Lippincott, Williams, & Wilkins, 1999, pp 497- North Am 2019;46:625-641 498 11. Van Calster B, Van Hoorde K, Valentin L, et al: Evaluating the risk of 17. ClinicalTrials.gov Identifier NCT 02836275
