Surgically treated adnexal masses in infancy, childhood, and adolescence

Surgically treated adnexal masses in infancy, childhood, and adolescence jo T. Van Winter, MD, Patricia S. Simmons, MD, and Karl C. Podratz, MD, PhD Rochester, Minnesota OBJECTIVE: We retrospectively evaluated the clinical presentation and histopathologic findings of benign and malignant adnexal masses in infants, children, and adolescents. STUDY DESIGN: Between 1955 and 1992, 486 patients (aged 7 days through 20 years) with adnexal masses were surgically evaluated. RESULTS: Of 521 adnexal masses, 92% were benign, including 335 nonneoplastic and 144 of 186 (77%) neoplastic lesions. The frequency of ovarian malignancies correlated inversely with patient age. Germ cell, stromal, and epithe(ial malignancies accounted for 40%, 21%, and 33%, respeGtively, of the 42 cancers. Nonconcordance between preoperative and postoperative diagnoses was noted in 94 oases. The most common preoperative diagnosis necessitating reassignment was acute appendicitis. During the last decade of this study, ultrasonography and computed tomography missed no malignancies. CONCLUSION: Physicians who care for young girls must be familiar with the differential diagnosis of adnexal masses to advise conservative management when appropriate and surgical intervention when necessary. (AM J OBSTETGYNECOL1994;170:1780-9.)

Key words: Adnexal mass, ovarian cyst, ovarian neoplasm

Ovarian and adnexal masses are rare during childhood and, with the exception o f benign cysts, are uncommon during adolescence. ~* A compilation '~ of studies conducted f r o m 1940 to 1975 reported that 35% of all ovarian neoplasms occurring in childhood and adolescence were malignant. In girls aged -<9 years, approximately 80% of the ovarian neoplasms were malignant?' 4 T h e r e f o r e the presence of an adnexal mass in a y o u n g girl is a serious concern because of the increased potential for malignancy if the mass is a neoplasm. Careful assessment and deliberation are then required so that a decision regarding possible surgical intervention can be made. Most studies of ovarian cancer in the literatnre are of adults. These data must not be applied uniformly to the pediatric population because the spectrum of disease differs. For instance, 60% to 85% o f ovarian neoplasms in the pediatric and y o u n g e r adolescent age groups are of germ cell origin, ~' '~ whereas in adults germ cell tumors account for only 20% of ovarian neoplasms." Conversely, epithelial neoplasms in adults account for 67% to 80% of ovarian neoplasms, compared with 15% to 25% in childrela and younger adolescents?' ~' ~ From the Departments of Obstetrics and Gynecology and Pediatric and Adolescent Medicine, Mayo Clinic and Mayo Foundation. Presented at the Sixty-first Annual Meeting of The Central Association of Obstetricians a~zd Gynecologists, White Sulphur Springs, West Virginia, October 28-30, 1995. Reprint requests:J.T. Van Winter MD, Mayo Clinic, 200 First St. SW, Rochester, MN 55905. Copyright © 1994 by Mosby-Year Book, inc. 0002-9378/94 $3.00 + 0 6/6/55189 1780

Because there is a paucity o f data on the presentation and outcome of children and adolescents with adnexal masses, an outcome analysis was initiated to assess these variables. The aim was to analyze the age-specific presentation, type and distribution of adnexal masses, and corresponding patient outcome in surgically evaluated infants, children, and adolescents at the Mayo Clinic from 1955 to 1992. Considering that during a significant portion of the 37-year interval sophisticated imaging and laparoscopy were not available, this study represents a reasonable assessment of the clinical manifestation o f adnexal masses and frequencies of various histologic subtypes. Material and methods

From 1955 to 1992, 486 consecutive local and referred patients from infancy through age 20 years with primary adnexal masses or recurrent or persistent ovarian cancer were surgically evaluated at the Mayo Clinic. Local patients were from Rochester, Minnesota, and adjacent counties; referred patients were from all other locations. All data in this retrospective study were obtained from the Mayo Clinic medical, surgical, and pathology records. These records were identified tl~rough computer search for adnexal tissue removed during any type of operation. Patients with karyotypes other than 46,XX were excluded, as were patients with ovarian cancer referred for radiation therapy or chemotherapy only. Stage, histologic findings, and tumor grade dictated the introduction of adjuvant radiation therapy, which was used primarily for metastatic or

Volume 170, Number 6 AmJ Obstet Gynecol

recurrent dysgerminoma. Chemotherapy before 1975 consisted of single alkylating agents for epithelial cancers. Thereafter, epithelial cell cancers were predominantly treated with cyclophosphamide and cisplatin. Chemotherapy for germ cell tumors during this later time interval included combinations of the following agents: actinomycin D (Cosmegen), doxorubicin (Adriamycin), Neomycin (Blenoxane), vinblastine, vincristine, etoposide (V-P-16), cisplatin, and cyclophosphamide. Variables analyzed included patient age at surgical diagnosis, preoperative symptoms, physical findings and clinical diagnoses, histologic characteristics of the adnexal mass(es), and survival status of ovarian cancer patients. Tumor markers were not analyzed because they were not measured in the majority of patients during the early years of this study. Adnexal surgical procedures consisted of cystectomy, oophorectomy, cyst aspiration or biopsy, and salpingectomy. The frequencies of these procedures were 63%, 22%, 13%, and 2%, respectively. In addition, 3% of patients underwent hysterectomy. Surgeons performing the operations were from the Divisions of Gynecologic, Pediatric, and General Surgery. Histologic features of neoplasms were determined by Mayo Clinic pathologists using Broders' grading criteria. Hematoxylin and eosin sections were supplemented with special stains when necessary. The number of patients who had imaging studies before operation increased during this study. From 1955 through 1966, 26 patients (32.5%) had abdominal or chest radiographs (or both), During this interval, 67.5% of patients had no preoperative imaging performed. From 1967 through 1979, 63 patients (37%) had abdominal or chest radiographs (or both), 18 patients (11%) had sonograms, and 3 patients (2%) had computed tomographic scans. Fifty percent of patients had no preoperative imaging. From 1980 through 1991, 64 patients (27%) had abdominal or chest radiographs (or both), 138 patients (58%) had ultrasonograms, and 15 patients (6%) had computed tomographic scans. Only 9% of patients had no preoperative imaging during this last interval. The category of nonneoplastic adnexal masses and ovarian enlargements included simple and fhnctional cysts, endornetriotic implants, polycystic ovaries, ectopic pregnancies, and inflammatory masses. The neoplasm category included benign and malignant epithelial, germ cell, and stromal tumors. Borderline tumors and grade 1 cystadenocarcinomas were combined in this study for convenience in presentation. Although cystadenofibromas contained some stromal elements, they were classified as epithelial neoplasms because of the predominant epithelial component. Immature teratomas in this stndy referred to neoplasms containing derivatives of one or more germ

Van Winter, Simmons, and Podratz 1781

Table I. Symptoms at initial presentation Symptom

Patients (No.)

Pain* Masst Menstrual irregularity;t Dysmenorrhea Amenon'hea, primary Amenorrhea, secondary Increased abdominal girth Urinary complaints§ Hirsutism Premature sexual development

271 151 71 50 12 35 34 16 13 6

*Mass was secondarily discovered in 150 of these patients. tWithout accompanyingpain. SMetrorrhagia, menorrhagia, oligomenorrhea. §Frequency, dysuria, suprapubic pressure. cell layers but excluded neoplasms containing embryonal carcinoma, endodermal sinus tumor, or dysgerminoma. Neoplasms containing granulosa elements were classified as granulosa cell tumors, whether theca ceils were or were not present, because of the metastatic potential of the granulosa component. Neoplasms containing both granulosa cells and primitive dysgerminoma cells were placed in a separate category known as gonadobIastoma. Data analysis consisted of descriptive techniques, which included two-way tables. Results

During the time interval 1955 to 1992, 486 patients (258 local, 228 referred) with 521 adnexal masses were surgically evaluated at the Mayo Clinic. The patients ranged in age from 7 days through 20 years. Presenting symptoms are listed in Table I. Abdominal or pelvic pain was the most fi'equent symptom, followed by a palpable mass. Less frequent symptoms included menstrual irregularities, dysmenorrhea, amenorrhea, increased abdominal girth, urinary complaints, hirsutism, and premature sexual development. Urinary frequency and increased abdominal girth were associated with larger masses but had no correlation with type of cyst or neoplasm. Primary amenorrhea was the presenting complaint in 20% of patients with polycystic ovarian syndrome. Secondary amenorrhea occurred in both patients with masculinizing tumors, as well as the patients with ectopic pregnancies. Hirsutism was present in both patients with Sertoli-Leydig cell tumors and in 62.5% of patients with polycystic ovarian syndrome. Premature sexual development occurred in one prepubertal patient with a luteinized follicular cyst, one prepubertal patient with a granulosa cell tumor, and one prepubertal patient with an embryonal cell cancer. Histologic assessment demonstrated that 92% of all adnexal masses were benign, including 335 nonneoplas-

1782

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June 199,[ Am J Obstet Gynecol

T a b l e II. Stratification a n d frequency distribution o f adnexal masses according to age

Age ofpatient at diagnosis O-lOyr Mass Nonneoplastic Simple or follicular cyst Corpus luteum cyst Other~ Neoplastic Benign Malignant Germ cell Stromal Epithelial Gonadoblastoma

No.

_..

Subtotal*[Total (%) (%)

11-15yr No.

0-20 yr

16-20 yr

Subtotal'[Total (%) (%)

No.

Subtotal* (%)

Total (%)

9 0 0

60 -

2 -

26 16 3

33 21 4

5 3 0.6

82 127 72

19 30 17

16 24 14

4 2 1 1 0 0

27 13

0.8 0.4

22 11 7 2 1 1

28 14

4 2

118 29 9 6 13 1

28 7

23 6

TOTAL

No.

%

335 117 143 75 186 144 42 17 9 14 2 521

64 23 28 14 36 28 8 3 2 3 1

*Subtotal percentage within each age category. tEndometrioma, polycystic ovary syndrome, pelvic inflammatory disease, ectopic pregnancy.

tic a n d 144 o f 186 neoplastic (77%) lesions (Table II). T h e frequency of o v a r i a n malignancies correlated inversely with patient age; 14% of all masses (n = 93) and 33% o f neoplastic masses (n = 39) were malignant in patients y o u n g e r t h a n age 16 years. In patients aged 16 t h r o u g h 20 years, 7% o f a t l masses (n = 428) a n d 20% of neoplastic masses (~z = 147) were malignant. T a b l e II displays the classification a n d the distribution freqnency of t h e various adnexal masses according to p a t i e n t a g e at diagnosis. Nonneoplastic lesions acc o u n t e d for 64% o f all surgically excised masses; of these, 78% were e i t h e r simple o r functional cysts. T h e p a t i e n t ' s age at diagnosis o f the functional or simple cysts r a n g e d ti'om 7 days t h r o u g h 20 years. These cysts v a r i e d from 5 to 25 cm, b u t the majority were between 6 a n d t 1 cm. T o r s i o n of a simple or follicular cyst was e n c o u n t e r e d in 26 patients, 16 of whom were a g e d -< 15 years. All patients with torsion e x p e r i e n c e d acute or i n t e r m i t t e n t pain associated with an adnexal mass. O o p h o r e c t o m y was p e r f o r m e d in 7 patients (aged -< 12 years) with simple or follicular ovarian cysts in the earlier years o f the study. T h e diagnosis was not known before histologic evaluation. T h e remaining 22% o f the n o n n e o p l a s t i c adnexal masses were sequelae of endometriosis, polycystic ovarian syndrome, ectopic pregnancy, a n d inflammatory processes. T h e y o u n g e s t age at p r e s e n t a t i o n of a patient with endometriosis was 15 years (menarche at age 13 years). D y s m e n o r r h e a was the m o s t c o m m o n pres e n t i n g symptom, a l t h o u g h this c o m p l a i n t occurred in only 50% o f patients with endometriosis. Polycystic ovarian syndrome o c c u r r e d in 16 patients, the youngest of w h o m was age 14 years. T h e r e were six ectopic pregnancies, and in eight additional patients a leaking corpus l u t e u m a c c o m p a n y i n g a n intrauterine preg-

nancy was misdiagnosed as an ectopic pregnancy. Most of these occurred before the use of ultrasonography, particularly transvaginal ultrasonography. In addition, 14 patients h a d an inflammatory adnexal mass. The majority of masses were the result of pelvic inflammatory disease; however, in two cases the right tuboovarian abscess was thought to be the result of an abscessed appendix. In recent years ultrasonography has been an excellent predictor of the presence of a simple cyst in young children, and no malignancy or benign n e o p l a s m in our study was seen as a simple cyst on sonogram o r computed tomographic scan. I n fact, concordance between all preoperative diagnoses and final histologic diagnoses has improved greatly with the aid of m o d e r n imaging techniques (Table III). From 1955 t h r o u g h 1966, abdominal r a d i o g r a p h s correctly diagnosed 80% of d e r m o i d cysts because of the presence of calcifications. However, no corpus luteum cyst was diagnosed preoperatively by radiographs during this time. From 1967 through 1979, ultrasonographic imaging had a 72% concordance rate between preoperative diagnosis and postoperative category of mass. Several corpus luteum cysts were misdiagnosed preoperatively as tumors because of the cystic and solid a p p e a r a n c e on sonograms. F r o m 1980 through 1991, both sonograms and c o m p u t e d tomographic scans h a d an approxlnaately 90% concordance rate between preoperative diagnosis and postoperative type of cyst or category of mass. No malignancies were missed on either sonogram or c o m p u t e d tomographic scan during this intela, al. Of the 186 neoplasms, 144 (77%)were benign (Table [I), T h e patients' ages r a n g e d from 2 through 20 years, and 94% of benign neoplasms occurred in patients > 12 years old. The most c o m m o n presenting symptom in

Van Winter, Simmons, and Podratz 1783

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Am,] Obstet Gynecol

Table I I I . Accuracy of imaging diagnosis*

Technique 1955-1966 Radiograph 1967-1979 Radiograph Sonogram Computed tomographic scan 1980-1991 Radiograph Sonogram Computed tomogxaphic scan

Total patients (No.)

1

[ I

Patients with hnaging (No.)

Accurate diagnosis (~)

80

26

46

169

84

54 72 75

237

216

57 90 90

*Radiographic accuracy defined as identification of a pelvic mass or ovarian dermoid cyst. Sonogram or scan accuracy defined as identification of an ovarian cyst (simple or complex) or ovarian neoplasm. patients with benign neoplasms was abdominal or pelvic pain, which appeared to be unrelated to the size of the neoplasm. The smallest (3 cm) and largest (30 cm) neoplasms were dermoids (a fibroma and two cystadenemas were also 30 cm). Bilaterality was noted in 10 patients with benign neoplasms; 6 patients had bilateral dermoids (approximately 9% of all dermoids), 3 patients had bilateral cystadenomas, and 1 patient had bilateral fibromas (Table IV). Of the neoplastic adnexal masses, 42 (23%) were malignant (Table II). These included 17 germ cell tumors, 9 sex cord-stromal tumors, 2 gonadoblastomas, and 14 epithelial carcinomas (Table II). The age range at diagnosis for patients with malignant neoplasms was from 2 through 20 years. Importantly, no epithelial cancers were found in patients aged < 15 years. Pain was again the most common symptom and appeared independent of neoplasm size. The majority of malignancies were larger than 10 cm, and no epithelial malignancy was < 8 crn. One patient with a grade 1 cystadenocarcinoma had bilateral involvement at initial presentation. T h e stage of the malignant process at diagnosis and the subsequent deaths attributed to the neoplasms are summarized in Table IV. Overall, the survival reflected the early diagnosis, and the only three deaths were in a patient with a metastatic granulosa cell tumor (diagnosed in 1963), a patient with an endodermal sinus tumor (1980), and a patient with an immature teratoma (1981). T h e metastatic granulosa cell tumor was unique in that it was the only stromal tmnor not confined to the ovary. The two malignant germ cell neoplasms leading to death of the patients were stage III, grade 3 and grade 4 minors at diagnosis. More recently, aggressive chemotherapy has resulted in the salvage of all patients with germ cell tumors, even those in whom high-grade neoplasms have spread beyond the ovaries. All epithelial cancers were grade 1, and 86% were stage I. No deaths occurred after conservative surgical management. One of the more striking observations in this series

was the level of nonconcordance between preoperative and postoperative diagnoses. Ninety-four preoperative diagnoses were inaccurate (Table V). Most of these discrepancies occurred before the widespread use of modern imaging techniques. T h e most c o m m o n misdiagnosis was acute appendicitis; the most common diagnosis at operation was a leaking or ruptured corpus luteum cyst and a normal appendix. In addition, 16 patients operated on for a nongynecologic reason underwent cystectomy for benign adnexal cysts or ovarian neoplasms (or both). Comment

Most reports of childhood ovarian neoplasms refer to individual case reports or to small groups of patients. When such reports are combined into a single larger series, misinterpretation is possible because the groups are frequently not comparable. In one series 3 nonneoplastic enlargements were reported in combination with benign neoplasms, thus making accurate interpretation of the results difficult. The current outcome analyses were derived from a single series of patients aged < 20 years who had adnexal masses removed at the Mayo Clinic between 1955 and 1992. Considering the ready availability and ease of application o f sophisticated pelvic imaging, knowledge of the frequency distribution of various histologic features encountered with adnexal masses beforc puberty and during the perimenarchal and later adolescent years would be beneficial. This should provide additional information to both the primary care physician and the diagnostic imager, thereby facilitating the differential diagnoses and determination of appropriate medical management in infants, children, and adolescents. No infants in the current study had an ovarian malignancy. Adnexal masses consisted of simple or follicular cysts and presented as abdominal masses. This finding is consistent with the literaturc. ~0.,~ Before the use of ultrasonography in our study, laparotomy resulted in cystectomy or oophorectomy. However; it is

1784 Van Winter, Simmons, and Podratz

June 1994 Am J Obstet Gynecol

Table IV. Benign a n d malignant ovarian neoplasms (N = 186): Frequency distribution, bilaterality, and stage (when applicable) according to histologic classification* Neoplasms Histotogic type

Germ cell Benigaa$ Malignant Dysgerminoma Immature teratoma Endodermal sinus tumor Embryonal cell carcinoma Gonadoblastoma§ Stromal Benignll Malignant Granulosa cell Sertoli-Leydig Epithelial Benign¶ Malignant#

No.

86 69 17 12 2 2 1 2 22 13 9 7 2 76 62 14

stage %

Bilateral f" (No.)

46 37 9

6 6 0

1 12 7 5

0 ] 1 0

41 33 8

4 3 1

.. II-III

I

Cancer deaths (No.)

6 4 1 0 1 2

11 8 1 2 0 0

2

8 6 2

1 1 0

1 1

12

2

0

l 1 0

*Different neoplasms in opposite ovaries were counted as two separate neoplasms. ?Bilateral neoplasms (same type) counted as one neoplasm. $Cystic teratoma (dermoid cyst). §Gonadoblastoma contains malignant germ cell and stromal cell components. UFibroma (thecoma). ¶Cystadenoma and cystadenofibroma. #All borderline or grade 1 cystadenocarcinoma.

now recognized that these unilocular cysts usually regress in 3 to 6 months. Close observation, cyst aspiration u n d e r ultrasonographic guidance, or laparoscopic excision is r e c o m m e n d e d . ~ ° ~ The potential risk associated with observation is ovarian torsion, and this must be discussed with the infant's parents or caregiver. In children aged -< 10 years, 33% of the neoplasms were malignant. T h e observed frequency of cancer in this group was considerably less than in two other studies, which reported 59% "~ and 82% 14 malignancy rates a m o n g neoplasms in the first decade of life. This discrepancy may result from the small number of y o u n g e r children in our study; also, the other studies might have had m o r e patients referred with malignancies. A wide variety o f symptoms caused by ovarian cysts and neoplasms occurred in this age group. Therefore abdominal palpation and bimanual rectoabdominal examination are important in any child who has nonspecific abdominal or pelvic complaints. T h e finding of a unilocular cyst on sonogram in this age ga'oup allows consideration of conservation managemerit. ~ In contrast, the finding of a solid component in an adnexal mass of a prepubertal child mandates operative or histologic assessment (or both). Modern imaging techniques have enabled the surgeon to objectively select patients requiring operative assessment, thereby avoiding unnecessary cystectomies and, particularly, unnecessary oophorectomies in these young patients.

Comparisons of neoplasms within patient age groups showed a malignancy frequency of 33% for ages 0 through 15 years compared with 20% for the 16through 20-year group (Table II). Furthermore, epithelial neoplasms occurred only in the second decade o f life; no epithelial malignancy occurred before age 15 years. In contrast to the epithelial tumors, neoplasms o f germ cell origin commonly occurred in the first decade of life and composed 83% of neoplasms. During the second decade the frequency of germ cell neoplasms decreased to 45%. There were also differences in the distribution o f neoplasms between younger and older adolescents. I n adolescents < 15 years old, the frequency of epithelial neoplasms was 15% and the frequency of germ cell neoplasms was 70%. These frequencies in younger adolescents were similar to those in two large series in the literature except for a greater percentage of stromal neoplasms in the Mayo Clinic series (Table VI). In adolescents aged -> 15 years, the frequency of epithelial neoplasms was 46% and the frequency of germ cell neoplasms was 43%. Management of an adnexal mass during childhood and adolescence depends on the age of the patient and the characteristics of the mass at presentation. Neoplastic masses were identified with an accuracy of 90% by sonogram or computed tomogTaphic scan in the recent years o f this study. It is anticipated that with continued

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Van Winter, Simmons, and Podratz 1785

Table V. Assessment of cases exhibiting nonconcordance between preoperative and pathologic diagnoses Preoperative diagnosis

Patients (No.)

Ovarian hl.stologic diagnosis

Patients (No.)

Acute appendicitis or appendiceal abscess

54

Leaking or ruptured corpus luteum or benign cyst Ovarian torsion Endometriosis Corpus luteum or simple cyst Corpus luteum cyst (intrauterine pregnancy) Corpus luteum or other benign ovarian cyst Endometrioma Benign ovarian cyst Tuboovarian abscess Appendiceal abscess Leaking corpus luteum cyst Cystadenoma Benign ovarian cyst Polycystic ovarian syndrome Simple cyst Cystadenoma Cystadenocarcinoma, grade 1, stage I

46

Pelvic inflammatory disease

8

Ectopic pregnancy Dermoid cyst

9 9

Endometriosis

3

Torsion

2

Ovarian malignancy

6

Neuroblastoma Liposarcoma Benign ovarian cyst

1 1 1

8 2 6 9 7 2 2 1 1 1 1 4 1 1 1 1

Table VI. Frequency of ovarian neoplasms according to histologic features in patients < 15 years old Type

Mayo series (n = 20) (%)

AFIP series* (n = 150) (%)

Germ cell Stromal Epithelial Miscellaneous

70 15 15 0

71 6 19 4

I

] I

Groeber seriesi (n = 220) (%) 80 8 7 5

AFIP, Armed Forces Institute of Pathology. *Data from Non'is and Jensen. ~ tData from Groeber. ~s

technologic advances in equipment and enhanced practitioner expertise, imaging resolution will continue to improve and yield even higher levels of precision. Magnetic resonance imaging has also shown improved accuracy in defining the structure of adnexal masses? 7 In addition, Doppler flow studies ~s (in older adolescents) have assisted in delineating benign from malignant neoplasms. Management of benign neoplasms usually involves cystectomy alone unless the involved ovary is replaced by the neoplasm. Bivalving of the opposite ovary was done in the earlier years of this study, particularly in patients with dermoid cysts. This routine practice is no longer recommended because it potentially leads to peritubal and periovarian adhesions. '~ Alternatively, bivalving can be replaced with careful palpation and evaluation of the opposite ovary, with biopsy limited to questionable lesions. If an ovarian malignancy is suspected in a patient whose condition is stable, she may benefit from surgical assessment at a referral center. Frozen-section histologic analysis at the initial operation is mandatory. Familiarity with the natural history of the neoplasm

allows appropriate operative management, including conservation of endocrine and reproductive function whenever possible. After operation, adjuvant chemotherapy (if appropriate) is begun with careful follow-up, This is essential because there may be recurrences many years later, especially with epithelial tumors of low malignant potential and granulosa cell minors. The most common and often most frustrating problem faced by physicians who care for adolescents is the management of functional cysts. In this study corpus luteum cysts represented 28% of all surgically excised masses. Many of these cystectomies were performed before ultrasonographic imaging or in the early years of ultrasonographic imaging when the cystic and apparently solid components of corpus luteum cysts were misdiagnosed as tumors. These functional cysts often were associated with menstrual abnormalities and a tender 5 to 6 cm palpable mass (78% of corpus luteum cysts in this study were -< 6 cm and none were larger than 8 em). Occasionally, corpus luteum cysts rupture and cause a hemoperitoneum or undergo torsion; these situations obviously require immediate surgical intervention. The majority of patients with a corpus luteum

1786 Van Winter, Simmons, and Podratz

cyst can be obsewed or, preferably, receive a monophasic contraceptive pill (50 ~g ethinyl estradiol). Although corpus luteum cysts appear in patients ingesting low-dose oral contraceptives (6 patients in our study using low-dose oral contraceptives had symptomatic corpus luteum cysts), there is at least some evidence '~° to suggest that the use of oral contraceptives aids in suppression of gonadotropin stimulation, When oral contraceptives are contraindicated, another option is intramuscular injection of Depo-Provera (medroxyprogesterone acetate), If the cyst persists through three pill cycles or begins to enlarge, operative intervention is required. The surgical procedure should be conservative, with presetwation of as much ovarian tissue as possible. Often the operation can be perfbrmed through the laparoscope with microsurgical techniques, if possible, to decrease periovarian adhesions. There is the potential risk that the "cyst" undergoing attempted suppression is actually an epithelial malignancy. In only one of the older adolescent patients was a carcinoma thought to be a benign cyst on ultrasonographic imaging in tim earlier years o1' this study, The "cyst" was detected 2 months beR)re operative intervention, The histologic diagnosis at operation was a stage 1, grade 1 cystadenocarcinoma, Therefore attempting to suppress the adnexal mass tbr a limited mnount of time should not alter the 100% survival rate noted in adolescent patients with borderline tumors or grade 1 cystadenocarcinomas. In summmT, the current study analyzed the outcomes of 486 young patients (infancy through age 20 years) with adnexal masses who underwent surgical management at the Mayo Clinic between 1955 and 1992. Presenting symptoms, preoperative evaluation, histologic diagnosis, and survival were assessed and correlated at presentation. This type of knowledge is necessary for all physicians who evaluate young female patients with abdominopelvic pain or adnexal masses (or both). REFERENCES

1, Ehren IM, Mahour GH, Isaacs H Jr. Benign and malignant ovarian tumors in children and adolescents: a review of 63 cases. Am J Snrg 1984;147:339-44. 2, Breen .]L, Maxson WS. Ovarian tumors in children and adolescents, Clin Obstet Gynecol 1977;20',607-23. 3, Norris HJ, Jensen RD, Relative li'equency of ovarian neoplasms in children and adolescents, Cancer 1972;30:713-9. 4. Lampkin BC, Wong KY, Kallnyak KA, et al. Solid malignancies in children and adolescents, Surg Clin North Am 1985;68:1351-86. 5. Westfall CT, Andrassy RI. Giant ovarian cyst: case report and review of differential diagnosis in adolescents. Clin Pediatr 1982;21:228-30. 6. Ein SH, DarteJMM, Stephens CA, Cystic and solid ovarian tumors in children: a 44-year review. J Pediatr Sm'g 1970; 5:148-56. 7, Adelman S, Benson CD, Hertzler JH. Surgical lesions of tlm ovary in infancy and childhood. Surg Gynecol Obstet 1975;141:219-22.

June 1994 Am ,] ()bstet (;ynec01

8. Bower R], Adkins .JC. Surgical ovarian lesions in children. Am Surg 1981;47:474-8, 9, Golladay ES, Mollitt DL, Ovarian masses in the child and adolescent. South Med J 1983;76:954-7, 961, 10. Starceski PJ,, Lee PA, Sieber WK, Bilateral owwimi pathology in infancy: assessment of pubertal and gonadal function. Adolesc Pediatr Gynecol 1988; l: 199-202. 11. Emans SJH, Goldstein DP, Pediau'ic and adolescent gynecology, 3rd ed. Boston: Little Brown, 1990:11l, 164, 179,294, 298, 12. Lack EE, Goldstein DP, Primm7 ovarian minors in childhood and adolescence. Curr Probl Ohstet Gynecol 1984; 8',I. 13, Kennedy AW, Ovarian neoplasms in childhood and adolescence, Semin Reprod Endocrinol 1988;6:79-90, 14. Haefner HK, Roberts JA, Schmidt RW, The university experience o[' clink:al and patln)logical lindings of ovm'ian neoplasms in children and adolescents. Adolesc Pediatr Gynecol 1992;5:182-6. 15. Milhu' DlVl, Blake JM, Stringer I)A, Hara H, Babiak C. Prepubertal ovarian cyst formalion: live years' experience. Obstel Gynecol 199"t;8t :,134-8. 16. Groeher WR. ()wu'ian tumors during inl,mcy and childhood. AMJ Oilsrl,:T C;VNI,'.¢,OL1963;86:1027-35. 17. Fedelc L, t)orta M, Briosclfi I), Arcaini I., Can¢liani GB. Magnetic resonance evaluation of gynecologic masses in adolescents. Adolesc Pediatr (;ynecol 199(I;3:8."t-8. 18, Fleischer AC, Rodgers WH, Rao BK, et al. Assessment of ovarian tumor vascuhu'ity witl~ transwtginal color Doppler sonography. J Uhl'aSotlI|d Med 1991; 10:563-8. 19, March CM, Mishell DR Jr. Induction of ovulation, In: Mishell DR Jr, l)awtjan V, eds. Infertility, contraception and reproductive endocrinology. 2nd ed. Oradcll, New Jersey: Medical Econonfics Books, 1986;389-411, 20. 8peroff L. Fmlclional owu'ian cysts and or;tl conwacepfives. Obstet Gynecol Clin Alert 1992;9:5. Discussion

DR. ASGtlaRAFSARI,West Bloomfield, Michigan. Masses originating in the ovary in children and adolescent patients can be clinically challenging problems for the gynecologist in terms of not only diagnosis but also management of the aftereffects and consequences, Familiarity with symptoms and distribution of signs, utilization of ultrasonography by means of color flow-directed Doppler measurements, ~ computed tomographic scan, magnetic resonance imaging, and particularly early laparoscopy should afford the opportunity to diagnose the ovarian tumors earlier, so this in turn can avoid organ removal or impairment of future reproductive potential and endocrine function. Actually, any ovarian neoplasm occurring in an adult can be found in children and adolescents. It is estimated that <5% of lesions occur in this age group. Nevertheless ovarian neoplasms are the most common form of gynecologic neoplasm for this age. When a physician encounters a child with pelvic or abdominal pain and detects a pelvic or abdominal mass, an early diagnosis of the origin of the mass and the plan of immediate management, with emphasis on longterm effects on possible r e c m ' r e n c e s , endocrine function, and future fertility, as well as potential malignancy, should be evaluated and the family should be counseled. Reviewing this retrospective outcome analysis by Van Winter et al. in regard to this subject matter is impres-

Volume 170, Number 6 AmJ Obstel (;vnec(~l

sire in terms of sheer number of cases. Additionally, the authors have tried to give us an insight into the prognostic possibility of the pathologic entities of the tumors. FIowevm, their findings confirm the earlier impressions of many other authors in terms of magnitude of symptoms, primarily pain, and then detection of a mass. A precise description of pain in terms of acuteness or chronicity is of paramount importance. In a study of 112 patients, both children and adolescents, by Wolfman and Kreutner, 'a 89% of patients with acute pain had identifiable pelvic abnormality whereas 27% of those with chronic pain had a normal result of laparoscopic examittation. In differential diagnosis of pain, discerning the type of pain may help to decide on a possible immediate need [br surgical intervention. Indeed, an acute colicky pain is probably the only striking sign of torskm, as has been dearly pointed out by the authors. If the adnexal area is to be preserved, the diagnosis must be made early and emergency laparoscopy and appropriate rneasures must be undertaken. It is noteworthy that torsion was encountered in only 5% of all cases and in 22% of simple or follicular cysts (26 patients, 16 of whom were ~ 15 years old); this means 16 out of 35 patients or 46%. This is a significant percentage that the clinician must take into consideration in an older age-segregated group of children, A nonconcordance diagnosis was encountered in 94 out of d86 patients, and another 16 patients were operated on for a nongynecologic condition and were detected to have adnexal masses, with an incidence of > 20%, reflecting that the most common diagnosis was acute appendicitis. More accurate and prompt diagnosis can be made with more widespread use of laparoscopy. In terms of suggested close observation, which has been advocated in patients with simple or functional cysts, this should depend not only on the patient's age and characteristics of the mass but also on severity of symptoms, duration of pain, and other developing signs. A follow-up sonogram should be obtained, and careful attention should be gwen to the changes on Doppler flow studies (i.e., conversion of an echo-free enlarged cyst to a more echogenic solid variety). Furthermore, ultrasonography guided ovarian cyst aspiration must not be regarded as a management of choice. The study of 41 aspirations by Lipitz et al? has shown a recurrence rate of 54% under ultrasonographic guidance and 30% via laparoscopy over a 36-monlh Follow-up. Moreover, because of the uncertainty of a diagnosis of torsion and the potential irreversibility of the process if a timely diagnosis has not been established, potential pregnancy achievement may be compromised because of possible hemorrhage, infarction, rupture, and postoperative adhesion fbrmation, should the adnexal area need to be extirpated subsequently. In this situation a laparoscopic microsurgieal ovarian cystectomy and subcortical closure are more advantageous. REFERENCES

1. Timor-Tritsch IE, Lerner JP, Monteagudo A, and Santos R. Transvaginal ultrasonographic characterization of ovarian

Van Winter, Simmons, and Podratz 1787

masses by means of color flow-directed Doppler measurements and a morphotogic scoring system. AM J O~s'r~'v GvnEcoL 1993;168:909-i3. 2. Wolfman WL, Kreutner K. Laparoscopy in children and adolescents. J Adolesc Health Care 1984;5:261-5. 3. Lipitz S, Seidman DS, Menszer J, et al. Recurrence rates after fluid aspiration from sonographically benign appearing ovarian cysts. J Reprod Med 1992;37:845-8. DR. SUSANM. Mou, Kansas City, Missouri. Local and referred cases have been combined for analysis. This combined sample may not be representative of a general pediatric population. Cases that were referred to the Mayo Clinic, rather than being managed in the patient's home town, may have been more complex or may have had some other high-risk factors prompting referral, Nevertheless, a large series of adnexal masses was reviewed; thus this article represents a significant addition to the literature on adnexal masses in children. The 37 years required to accrue the 486 patients indicates that adnexal masses in female children are uncommon. I would ask the authors if there was any difference in the histologic characteristics found in referred patients as compared with local patients? Another limitation of the study is that only patients with adnexal masses who required surgery were included. Histologic characteristics provide an exact diagnosis for each patient in the study. The authors conclude that knowledge of the frequency of distribution of various histologic entities encountered with adnexal masses before puberty, perimenarchally, and in later adolescence will help the diagnostic imager and primary care physician. This concept is not supported by the article because patients who did not require surgical intervention are not represented. A question that must be asked in future studies is the following: How many adnexal masses were observed and resolved without therapy? Also, the risk of ovarian torsion while a cystic adnexal mass is observed is mentioned but not quantified. This is a risk physicians need to quantify to be better able to counsel caregivers. Other studies, such as the study of Millar et al., ~ suggest consideration of conservative management, whereas Merritt" proposed a rapid and precise diagnosis to allow early intervention when torsion may occur. Van Winter et al. cannot really address the issue of management because only patients who underwent operation are described. If the histologic findings alone are considered, more, rather than fewer, operations could be advocated by a prinaary physician who does not carefully read the tables in this article and realize 13% of adnexal masses removed are malignant in children aged 0 to 10. Similarly, in children aged 11 to 15, 1,1% of adnexal masses are malignant. it is not 13% and 14% of all adnexal masses in these respective age groups. At the Children's Mercy Hospital in Kansas City, Missouri, we frequently have patients refen-ed from outside physicians for evaluation of adnexal masses found incidentally on ultrasonography, computed tomographic scan, or magnetic resonance imaging. Not all of these patients acmaUy require surgical intervention. Diagnostic imaging of the prepubertal and peripubertal female pelvis is just beginning

1788 Van Winter, Simmons, and Podratz

to answer questions as to what is normal and what is abnormal in this young age group. I a m impressed by the high correlation between c o m p u t e d tomographic scan, uItrasonography, and surgical histologic findings described in this article during the last few years of the study; however, cystic masses will represent a clinical challenge. T h e authors did a nice j o b of stratifying by age the incidence of histologic entities. I p r o p o s e that an alternate stratification could have been by pubertal status, because age at puberty varies so widely, and the clinician's response to adnexal masses is influenced more with pubertal status than with chronologic age. Did the authors have knowledge o f pubertal status from their chart review, and why did they choose to present the data by age rather than pubertal status? Risk behaviors in adolescents are changing. More adolescents are sexually active now than when this study b e g a n in 1955. I suspect that incidences of ectopic pregnancy and pelvic inflammatory disease first seen as adnexal masses are on the increase, especially in the age group 16 to 20 years. This article thoroughly reviews what has h a p p e n e d over 37 years at the Mayo Clinic. An interesting study in the 1990s would be prospective, multi-centered based research into how pediatric adnexal masses are first seen, diagnosed, and treated with our current imaging techniques, hormonal assays, and laparoscopic surgical techniques. REFERENCES

I. Millar DM, Blake JM, Stringer DA, Hara H, Babiak C. Prepubertal ovarian cyst formation: 5 Years' experience. Obstet Gynecol 1993;81:434-8. 2. Merritt DF. Torsion of the uterine adnexa: a review. Adolesc Pediatr Gynecol 1991;4:3-13. DR. SUSANF. POKORNY, Houston, Texas. One o f the comments was that in the last decade the use of ultrasonography and similar techniques has changed management. I would ask the authors if m a n a g e m e n t also has changed in terms of whether the child is managed by a pediatric surgical specialist or by a gynecologic specialist. DR. JAPER 1~. MAORINA,Scottsdale, Arizona. I n regard to the suppression of functional ovarian cysts, there is indeed a prospective randomized study published in Fertility and Sterility. It divided the groups into those that received oral contraceptives and those that didn't; and it made no difference in the percentage of patients with regression and those without. DR. M~LVINV. GERBIE, Chicago, Illinois. I didn't see any reference to parovarian cysts. In adolescents these cysts should be considered in the differential diagnosis of an acute abdomen. Dm I_aNgJ. M~RC~R, Chicago, Illinois. I was somewhat surprised by the distribution of masses in that in a referral center such as the Mayo Clinic there was no mention of uterine anomalies and presentation of uterine anomalies, such as uterus unicornis and others. Was this a matter of the nature by which you did your computer search through the records or do you not see these in Minnesota?

June [994 Am J Obstet Gynecol

Second, I see no mention of infectious masses, such as tuboovarian abscesses. Were they excluded by the nature o f the search? Last, I reiterate what was said by the second reviewer, about the timing of pubescence rather than the chronologic timing being important. In many o f these young w o m e n multicystic ovaries develop and are a matter o f hypersensitivity to follicle-stimulating hormone or in some cases reflect an abnormality of thyroid function. I was surprised by the young age of your patients with polycysfic ovaries. Indeed, were these actually polycystic ovaries or a different clinical entity o f multicystic ovaries, and would it not be beneficial to review these pathologic conditions again to make sure that histologic differences are present? Multicystic ovaries is a self-limiting disease process not requiring surgical intervention but rather reflecting an immaturity of the ovarian hypothalamic system as opposed to polycystic ovaries, which as we know is an ongoing process. Dx. VAN WrNTER (Closing). With respect to acute and chronic pain in children, especially small children, sometimes it is difficult to differentiate unless the pain is acute e n o u g h to have peritoneal signs. Many times you have to depend on the information supplied by the child's caregiver, and sometimes this information is inadequate or inaccurate. Most o f the time when a child is referred to us, there is already a diagnosis o f an adnexal mass through the use of an imaging technique; but if any of you are primarily seeing children, there certainly are a lot o f other masses in the pelvis that are more c o m m o n in the young child. The differential diagnosis includes masses causing acute pain such as intussusception, urachaI cysts, mesenteric cysts, pelvic cysts, duplication of the bowel, a n d liver cysts. Fortunately, when we see these children, we most often have the diagnosis of an ovarian or adnexal mass made for us. As far as the concern of torsion, yes, it is a significant concern; and I think that a lot of caregivers would go ahead with diagnostic laparoscopy and whatever surgical procedure is then necessary to avoid this potential complication. However, one has to balance all the factors; and in considering that with general anesthesia the potential risk of death is about half a percent, other factors including cost need to be weighed. That is an individual decision only the surgeon can make at the time o f assessment as to whether to obverve this cyst in an infant or prepubertal child or go ahead with diagnostic laparoscopy. I appreciate the comment on the treatment o f recurrent cysts with ultrasonography-guided aspiration o r even possibly laparoscopie excision, but again the potential benefits of that treatment must be balanced with the cost and risks of general anesthesia, as well as the possibility the cyst may resolve on its own. As far as the comments about the patients referred to the Mayo Clinic and the difference in histologic diagnoses, there were 258 local patients and 228 referred

Volume 170, Number 6 Am J Obstet Gyrlecol

patients. The referred patients did constitute a higher proportion with neoplasms and cancers. However, when you look at any type of a population, if you are to garner enough neoplasms for a meaningful analysis, you are usually looking at a fairly high percentage of a referral-based population that is not really representative of the general population. Most other studies in the literature on neoplasms simply reflect that all the patients are referred, which would potentially make their data less representative of the general population than ours is. Again, I agree that pubertal status is very important; and that certainly is a valid constructive criticism in respect to girls with endometriosis and polycystic ovarian syndrome. The timing of menarche is part of our data, and I can certainly look at that and possibly make the article more informative to the reader by reassessing that aspect. I agree that cystic masses have continued to be a challenge on ultrasonography. Fortunately, in the last 10 years of the study, ultrasonography or computed tomographic scan missed no neoplasms or malignancies. In the earlier years of the study, ultrasonography misdiagnosed many corpus luteum cysts as "tumors" because of the solid components. Improvement in equipment and imaging techniques, including Doppler flow studies, as well as improvement in the learning curve by persons analyzing the images, has helped improve the assessment of cystic masses in terms of etiology. When the question of probable diagnosis has been resolved, the decision to operate or observe is obviously made more easily. With regard to some of the questions, I certainly agree that ultrasonography has become an extremely

Van Winter, Simmons, and Podratz 1789

important tool in the diagnosis of ovarian cysts, simple cysts, and neoplasms, particularly in the neonatal and prepubertal age groups. As far as uterine anomalies are concerned, they weren't accessed in our computer search unless they were specifically associated with an adnexal mass. We do, in fact, have uterine anomalies in children and young adults that are evaluated at the Mayo Clinic; and we certainly appreciate this comment. Again, as far as the difference between polycystic ovary syndrome and multicystic ovaries, I appreciate that comment; and we can certainly again review the histologic diagnosis. However, I did look at the outcome of several of the adolescents with polycystic ovary syndrome or "disease," which is really an interesting terminology because it appears to represent some entity on a continuum of chronic anovulation. Many of the adolescents in our study with the diagnosis of polycystic ovary syndrome eventually had fertility problems, menstrual irregularities, hirsutism, and some level of insulin resistance. Rarely, cancer of the endometrium developed. For these reasons I believe that the majority of adolescents in this study had polycystic ovary syndrome, not benign multicystic ovaries. As far as Dr. Magrina's comment on ovarian suppression, I appreciate the fact that a randomized, prospective study showed no difference. Anecdotally, however, I really think that it does seem to make a difference; until we have more prospective, randomized studies, I believe that using oral contraceptives helps to suppress gonadotropins and therefore aids in preventing formation of new cysts. Therefore the existing cyst is easier to follow up for resolution, persistence, or enlargement.