FERTILITYAND

Vol.68,No.3,September

STERILITY@

Copyright

o 1997 American

Published

by Elsevier

Society for Reproductive

Medicine

Printed

on

1997

acid-freepaper m U. S. A

Science Inc.

The growth pattern of ovarian dermoid cysts: a prospective study in premenopausal and postmenopausal women Benjamin Caspi, M.D.*? Zvi Appelman, M.D.* David Rabinerson, M.D.* Department

of Obstetrics

Yaron Zalel, M.D.* Togas Tulandi, M.D.8 Zeev Shoham, M.D.*

and Gynecology,

Kaplan Medical Center, Rehovot, Israel

Objective: To evaluate prospectively the evolution of ovarian dermoid cysts and the safety of nonsurgical management in premenopausal women. Design: A prospective study. Setting: Tertiary hospital-based ultrasonographic unit. Patient(s): Between 1985 and 1994, 72 premenopausal and 14 postmenopausal women had ovarian dermoid cysts <6 cm in diameter diagnosed by ultrasound and were followed up at Kaplan Medical Center in Israel. Intervention(s): Ultrasound examination was scheduled at 3 and 9 months after the initial diagnosis and then annually. Every cyst was measured in three planes. The growth rate of the cysts was calculated from the data gathered. Main Outcome Measure(s): Prospective evaluation of the evolution of dermoid cysts and the safety of nonsurgical management in premenopausal women by an ultrasonographic follow-up. Result(s): For the premenopausal and postmenopausal women, the mean age (tSD) at diagnosis was 32.3 2 8.2 and 61.1 ? 6.9 years, the mean duration of follow-up was 34.5 ? 21.6 and 35.3 + 26.8 months, the mean cyst size at diagnosis was 3.7 5 1.2 and 4.1 t 1.5 cm, and the calculated mean growth rate was 1.77 ? 3.86 and -1.59 +- 2.48 mm/y, respectively. The difference in the mean growth rate of the cysts between the two groups was statistically significant. The mean growth rate was significantly different from zero in the premenopausal group but not in the postmenopausal group. Twenty-eight women were delivered of 35 healthy infants without complications attributable to the dermoid cysts. The cysts were removed surgically in 24 of the 86 women (27.9%), and benign cystic teratomas were confirmed by histologic examination in all cases. Conclusion(s): Premenopausal women with ovarian dermoid cysts of <6 cm in diameter can be safely managed expectantly, especially if pregnancy is desired. The mean growth rate of dermoid cysts in premenopausal women is 1.8 mm/y. (Fertil Sterile 1997;68:501-5. 0 1997 by American Society for Reproductive Medicine.) Key Words: Dermoid cyst, ovary, teratoma, malignancy, follow-up, premenopausal, postmenopausal

Dermoid cysts, or mature cystic teratomas, are the most common ovarian neoplasms that develop during the reproductive years (1, 2). Ovarian dermoid ReceivedDecember5,1996; revisedand acceptedMay 7,1997. Presentedin part at the 52nd Annual Meeting of American Society for ReproductiveMedicine, Boston, Massachusetts,No-

cysts have pathognomonic features on ultrasound (US) examination that facilitate their diagnosis. Recently, two groups of investigators (3, 4) reported highly accurate rates of US diagnosis of dermoid cysts (97.4% and lOO%, respectively). Possible complications of dermoid cysts include torsion, infection, rupture, and malignant transfor-

vember 2 to 6, 1996. * Department of Obstetrics and Gynecology, Kaplan Medical Center (Affiliated with the Hebrew University, Hadassah Medical School), Jerusalem, Israel. t Reprint requests: Benjamin Caspi, M.D., Department of Obstetrics and Gynecology, Kaplan Medical Center, Rehovot 76100, Israel (FAX: 972-8-9411944).

$ Department of Obstetrics and Gynecology, Rabin Medical Center, Beilinson Campus, Petah Tikva, Sackler School of Medicine, Tel Aviv University, Tel Aviv, Israel. 5 Department of Obstetrics and Gynecology, Royal Victoria Hospital, McGill University, Montreal, Quebec, Canada.

0015-0282/97/$17.00 PI1 SOO15-0282(97)00228-8

501

mation. Malignancy typically occurs in older women and women with large tumors (5). The traditional treatment is surgical excision by laparotomy or laparoscopy (6-11). Reports have shown that ovarian wedge resection causes pelvic adhesions that subsequently impair fertility (12-14). The incidence of adhesion formation after ovarian dermoid cystectomy remains unknown. However, spillage of dermoid material during the operation may increase the severity of the adhesions, potentially resulting in impaired fertility. Therefore, we initiated a program of expectant management for selected patients at our center, postponing operation until the completion of family planning. The program consisted of strict US followup. To the best of our knowledge, this is the first prospective report of nonsurgical management of ovarian dermoid cysts in a large number of women. MATERIALS AND METHODS Patient Characteristics and Selection

Between 1985 and 1994, 86 women entered the expectant management program at the Kaplan Medical Center. Ultrasonographic diagnosis of a dermoid cyst was based on the presence of one or more of the pathognomonic echogenic patterns of dermoid cysts. The three basic pathognomonic echogenic patterns required for the diagnosis of a dermoid cyst were an echogenic adnexal mass of varying density and shadowing, a cyst containing thin band-like echoes, and a cyst containing a fat-fluid level (3). The participants were derived from three sources: [l] patients with various indications referred from our department of obstetrics and gynecology to the ultrasound unit for pelvic US; 121patients referred for a second opinion regarding an unidentified adnexal mass by gynecologists in the community who were affiliated with our hospital; and 131 patients referred for confirmation and further follow-up of a previously diagnosed dermoid cyst. Exclusionary criteria included a mean cyst diameter of >6 cm, proximity to menopause, an annual cyst growth rate of >2 cm, and persistent abdominal pain. Additional criteria were patient refusal and an abnormal serum CA-125 concentration (since 1990). Fourteen women (16.3%) who had reached menopause but nevertheless declined operation also were included in the study. The cysts were measured in three right-angle planes. The largest of the diameters measured, the mean diameter, and the woman’s age were recorded for analysis. Follow-up visits were scheduled for 3 and 9 months later, and then annually. At each follow-up visit, the cysts were measured and the data were recorded. 502

Caspi et al. Expectant management of dermoid cysts

The possible benefits and risks involved in expectant management were discussed thoroughly with each participant. Our program of expectant management was approved by the Institutional Review Board at the Kaplan Medical Center. Statistical Analysis

The US values are expressed to the first decimal point because of the statistical calculation and are not representative of the actual accuracy of the US measurements. Statistical analysis was performed by creating a regression line for each patient, which represented the growth rate of the cyst versus the number of months of follow-up. Because the distribution of the regression slopes was abnormal, significance from zero was tested separately in the premenopausal and postmenopausal women by Wilcoxon’s rank sum test. Comparison between the premenopausal and postmenopausal women was performed using the Mann-Whitney test. P values of ~0.05 were considered statistically significant. Values are presented as means + SD. RESULTS

Bilateral ovarian cysts were encountered in 10 (11.6%) of the 86 women entered into the study. In 78 (90.7%) of the women, the cysts were not palpated during bimanual pelvic examination but were found incidentally during US evaluation. At our institution, as well as at the gynecologic clinics affiliated with our department, pelvic US is considered to be an almost integral part of the routine pelvic examination. In the premenopausal group of patients, 72 women with a mean age (+SD) of 32.2 + 8.2 years were found to have 82 dermoid cysts. The mean duration (?SD) of follow-up was 34.8 _+21.6 months, and the initial mean diameter (+SD) of the cyst was 3.7 + 1.2 cm. In the postmenopausal group of patients, 14 women with a mean age (?SD) of 61.1 + 6.9 years were found to have 14 dermoid cysts. The mean duration (+SD) of follow-up was 35.3 t 26.8 months, and the initial mean diameter (&SD) of the cyst was 4.1 + 1.5 cm (no statistically significant difference compared with the premenopausal group). The tumor growth rate was significantly greater in the premenopausal group than in the postmenopausal group (1.77 + 3.86 versus -1.59 + 2.48 cm/y, respectively; P < 0.001). Although the growth rate was slow in both groups, it was significantly different from zero in the premenopausal group (Table 1). The comparative growth rates of the dermoid cysts in the two groups is shown in Figure 1. Twenty-four women (27.9%) underwent operation (20 from the premenopausal group and 4 from the Fertility and Sterility@

Table

1

Characteristics of Patients and Cysts

No. of patients No. of cysts Patient age (y) Duration of follow-up (mo) Initial cyst size

(cm)

Cyst growth rate

(mm/y)

P value$

P value?

Premenopausal

Postmenopausal

72 82 32.3 2 8.2 (14 to 48)

14 14 61.1 2 6.9 (52 to 73)

34.5 2 21.6 (12 to 107)

35.3 2 26.8 (12 to 91)

NS

3.7 k 1.2 (0.8 to 6.5)

4.1 + 1.5 (1.2 to 5.8)

NS

1.77 2 3.86 (-5.2 to 16.8) 0.0001s

-1.59 2 2.48 (-6.35 to 3.00) 0.058j

0.0001

0.001

Note: NS = not significant. Values are means t SD with ranges in parentheses. t Difference between premenopausal and postmenopausal women. $ Difference from zero.

postmenopausal group), with histopathologic confirmation of benign cystic teratomas in all cases. Twenty-one of the women met our criteria for operation (i.e., tumor growth rate of >2 cm/y>. In 3 of the women, the cysts were excised during cesarean delivery for obstetric reasons. None of the women were operated on because of the classic complications attributed to dermoid cysts, such as torsion, infection, malignant transformation, or rupture. During the follow-up period, 28 women conceived with the dermoid cysts in situ; 5 of them conceived twice, and 1 conceived three times. Twenty-three women conceived spontaneously, and 5 conceived after ovulation induction. Two of the latter 5 women received therapy for ovulation induction with gonadotropin, and 3 conceived after M?-ET. Ovulation was induced by treatment with GnRH agonists and gonadotropin. In all 5 patients, the size of the dermoid cysts remained stable during treatment. In the 3 patients who were treated with IVF-ET, the dermoid cysts were not punctured during the procedure. All the pregnancies were uneventful and resulted in healthy infants; there were no miscarriages.

was practically zero. Nevertheless, the difference in the growth rate between the two groups was statistically significant. This difference may be attributed to the hormonal changes that accompany menopause, mainly estrogen or P deprivation. It has been suggested that ovarian dermoid cysts increase in size after puberty because of the hormonal changes of puberty that stimulate the sebaceous glands that these tumors contain (15). In our study, the initial mean diameter (?SD) of the dermoid cysts in the premenopausal group was 3.7 + 1.2 cm, considerably smaller than the 6.4 cm reported in a recent series (16). This difference may reflect the superior accuracy of US in the detection of these tumors compared with bimanual pelvic examination. In 78 of our patients (90.7%), the tumors were not detected by palpation before US examination. The fact that so many tumors were detected incidentally can be attributed to the widespread and liberal use of US in Israel as an integral part of the gynecologic examination. However, the primary considerations should relate to the safety of our expectant management program. The potential risk of missing a malignant tumor is worrisome, but this did not occur in our study. Complications of dermoid cysts, such as malignant transformation (1% to 2%) and torsion (15%), have been reported (5). However, these findings come from old series of large tumors. In two series comprising 48 women who had dermoid cysts with malignant transformation, the mean size of the tumors was 17 cm (17, 18). In a recent clinicopathologic study of 517 women with mature cystic teratomas (161, the mean cyst diameter was 6.4 cm. In this study, low rates of malignant transformation (0.17%) and torsion (3.4%) were found. In comparison, in our study, the mean cyst diameter (+SD) was 3.7 + 1.2 cm in the premenopausal

m

Premenopausal

Postmenopausal

wr

DISCUSSION

In this prospective study, we evaluated the growth rate of ovarian dermoid cysts and the safety of longterm expectant management in premenopausal women. We also evaluated 14 postmenopausal women who refused operation but agreed to participate in the follow-up program. Even though the growth rate of the cysts in these two groups was minimal (1.8 mm/y>, it was significantly different from zero in the premenopausal group. In the postmenopausal group, the growth rate Vol. 68, No. 3, September 1997

c-o.3

-0.3-0.0

0.0-0.3

Growth

0.3-0.6

0.6-0.9

OS-12

12-1.5

Rate (mm/month)

1 Distribution of premenopausal and postmenopausal women with ovarian dermoid cysts in relation to the growth rate of the cysts.

Figure

Caspi et al.

Expectant

management

of dermoid

cysts

503

women, smaller than that reported by Comerci et al. (16). Hence, even lower rates of malignant transformation and torsion can be expected. No patient in our study had any evidence of torsion or malignancy. In view of all these factors, the risk of malignancy in our study probably was 2 cm/y> threshold criteria selected for surgical intervention stem from the following rationale. The upper limit of 6 cm was based on observations in the literature in which malignant transformation typically was associated with dermoid cysts of >6 cm in diameter (17,lS). The growth rate limit of 2 cm/y was chosen arbitrarily because we wanted to detect rapidly growing tumors at the first scheduled follow-up visit (at 3 months). As another safety measure in our study, serum CA-125 concentrations were measured. It is well known that serum CA-125 concentrations are an unreliable indicator of malignancy, producing high rates of false-positive and false-negative results. Nevertheless, we used positive test results for CA-125 as an additional criterion for the exclusion of patients from our program. In theory, some malignant ovarian dermoid cysts may be malignant from the beginning. All the published series rarely have shown malignant tumors measuring <6 cm. This supports the possibility that malignant transformation is associated with large tumors. Unfortunately, there are practically no data on the incidence, appearance, or growth rate of such tumors. An important question relates to the expected benefit of nonsurgical management in regard to fertility. Toaff et al. (12) and Weinstein and Polishuk (13) have shown that wedge resection of the ovaries at laparotomy may cause severe adhesions, resulting in mechanical infertility. The incidence of adhesion formation after ovarian dermoid cystectomy remains unknown. However, spillage of dermoid material during operation may increase the severity of adhesions related to ovarian cystectomy. Cystectomy typically is performed by laparoscopy, and the impact of this relatively new technique on fertility is not known. Therefore, women with small dermoid cysts who would like to become pregnant may benefit from postponing operation. Our study shows that the mean growth rate of 504

Caspi et al.

Expectant

management

of dermoid

cysts

dermoid cysts in premenopausal women is 1.8 mm/y. In view of this finding, we suggest that premenopausal women with dermoid cysts of <6 cm in diameter can be safely followed up conservatively as long as the tumor growth rate is <2 cm/y. No complications occurred in the 14 postmenopausal women who were followed up for a mean of 34 months in our study. Positive identification of a malignant teratoma would be the goal of any diagnostic procedure. However, US examination can provide only indicative evidence of malignancy, primarily through the detection of large tumor size or rapid growth rate, irregular tumor borders, or ascites. Therefore, any program of conservative follow-up of ovarian dermoid cysts should be subject to the strict criteria on which our program is based. In conclusion, we have shown that the growth rate of small ovarian dermoid cysts is very slow and the complication rate is low. This makes conservative nonsurgical management possible in young women who have not completed their family planning. By postponing surgical intervention, we may avoid possible impairment of fertility.

Acknowledgment. The authors thank Hillary Voet, Ph.D., from the Department of Statistics, Faculty ofAgriculture, Hebrew University, Rehovot, for her statistical assistance.

RJWEXENCES 1. Petersen WF, Prevost EC, Edmunds Fl’, Hundley JM, Morriss FK. Benign cystic teratomas of the ovary. Am J Obstet Gynecol 1955; 70:368-82. 2. Pantoja E, Noy MA, Axtmayer RW, Colon FE, Pelegrina I. Ovarian dermoids and their complications: comprehensive historical review. Obstet Gynecol Surv 1975;30:1-20. 3. Caspi B, Appelman Z, Rabinerson D, Elchalal U, Zalel Y, Katz Z. Pathognomonic echo patterns of benign cystic teratomas of the ovary: classification, incidence and accuracy rate of sonographic diagnosis. J Ultrasound Obstet Gynecol 1996;7: 275-9. 4. Bronstein M, Yoffe N, Brandes JM. Hair as a sonographic marker of ovarian teratomas: improved identification using transvaginal sonography and simulation model. J Clin Ultrasound 1991; 19:3X-5. 5. Talerman A, Path F. Germ cell tumors of the ovary. In: Kurman RJ, editor. Blaustein’s pathology of the female genital tract. 3rd ed. New York: Springer-Verlag, 1987:654-727. 6. Lin P, Falcone T, Tulandi T. Excision of ovarian dermoid cyst by laparoscopy and by laparotomy. Am J Obstet Gynecol 1995; 173:769-71. 7. Bollen N, Camus M, Tournaye H, Demur& L, Devroey P. Laparoscopic removal of benign mature teratoma. Hum Reprod 1992;7:1429-32. 8. Nezhat C, Winer WK, Nezhat F. Laparoscopic removal of dermoid cysts. Obstet Gynecol 1989;73:278-80. 9. Reich H, McGlynn F, Sekel L, Taylor P. Laparoscopic management of ovarian dermoid cysts. J Reprod Med 1992;37: 640-4. 10. Chapron C, Dubuisson JB, Samouth N, Foulot H, Aubriot Fertility

and Sterility@

11.

12.

13.

14.

IX, Amsquer Y, et al. Treatment of ovarian dermoid cysts. Place and modalities of operative laparoscopy. Surg Endosc 1994;8:1092-5. Scully RE, Mark EJ, McNeely WF, McNeely BU. Case records of the Massachusetts General Hospital. N Engl J Med 1995; 332:1631-6. Toaff R, Toaff ME, Peyser MR. Infertility following wedge resection of the ovaries. Am J Obstet Gynecol 1974; 124:926. Weinstein D, Polishuk WZ. The role of wedge resection of the ovary as a cause for mechanical sterility. Surg Gynecol Obstet 1975; 141:417-g. Tulandi T, Collins JA, Burrows E, Jarrell JF, McInnes RA, Wrixon W, et al. Treatment-dependent and treatment-independent pregnancy among women with periadnexal adhesions. Am J Obstet Gynecol 1990; 162354-7.

Vol. 68, No. 3, September 1997

15. Blackwell WJ, Dockerty MB, Masson JC, Mussey RD. Dermoid cysts of the ovary: their clinical and pathologic significance. Am J Obstet Gynecol 1946;51:151-72. 16. Comerci JT, Licciardi F, Bergh PA, Gregori C, Breen JL. Mature cystic teratoma: a clinicopathological evaluation of 517 cases and review of the literature. Obstet Gynecol 1994; 84:22-g. 17. Stamp GH, McConnell EM. Malignancy arising in cystic ovarian teratomas: a report of 24 cases. Br J Obstet Gynaecol 1983;90:671-5. 18. Chadha S, Schaberg A. Malignant transformation in benign cystic teratomas: dermoids of the ovary. Eur J Obstet Gynecol Reprod Biol 1988;29:329-38. 19. Currie JL. Malignant tumors of the uterine corpus. In: Thompson JD, Rock JA, editors. Te Linde’s operative gynecology. 7th ed. Philadelphia: Lippincott, 1992:1253-g.

Caspi et al.

Expectant

management

of dermoid

cysts

505