Gynecologic tumors and symptoms in childhood and adolescence; 10-years' experience

lnt J Gynecol Obstet, 1994, 45: 221-234

221

International Federation of Gynecology and Obstetrics

Gynecologic tumors and symptoms in childhood and adolescence; 1O-years’ experience A. Imai, T. Furui

and T. Tamaya

Department of Obstetrics and Gynecology, Gifu University School of Medicine, Tsukasamachi. Gifu (Japan)

(Received December 8th, 1993) (Revised and accepted March 25th, 1994)

Abstract OBJECTIVES: The advancement of diagnostic imaging evaluations and the earlier occurrence of secondary sexual development prompted us to review our recent experience with genital tract tumors in children. METHODS: We analyzed data for 1938 patients aged less than 18 years who were referred to Gifu University School of Medicineaffiliated Hospitals for the years 1984 through 1993. RESULTS: Of the patients, 145 underwent surgical treatment. Vaginal tumor was seen in 5 patients; 1 endodermal sinus tumor, I sarcoma botryoides and 3 Gartner’s duct cysts. Two patients with malignant tumor presented only with bloody vaginal discharge; recurrent abdominal pain due to vaginal obstruction was noted in 1 patient with the cyst. Ten had benign tumors in the vulva, presenting with a genital mass. Of 114 ovarian tumors, 3 were diagnosed by antenatal ultrasonographic examinations. Fifty-five had germ cell tumors, 33 had epithelial tumors, and 18 had stromal tumors. The most common symptom was abdominal pain and approximately one-third of girls who complained of abdominal pain had an ovarian tumor. Precocious puberty was noted in 4 girls with stromal tumor. Two of the 23 malignant tumors developed in the vagina and the others originated in the ovary. In 19patients unilateral salpingo-oophorectomy or local excision was done in an attempt for reproductive organ con0020-72921948.07.00 0 1994 International Federation of Gynecology and Obstetrics

Printed and Published in Ireland

servation; 4 cases of advanced stage disease were treated with hysterectomy and/or bilateral salpingo-oophorectomy. Only 3 of the 23 patients with malignant tumor died within 4 years and others are free from disease. CONCLVSIONS: Genital symptoms, even common, alert us to the posibility of a genital tract tumor. The prompt and precise detection of either benign or malignant tumors in children may lead to cure and preservation of fertility with conservative surgery.

Keywords: Genital tumors in girls; Malignant ovarian tumors; Germ cell tumors. Introduction In girls, genital tract tumors should be considered as an underlying cause of genital symptoms or signs, even common disorders such as a fetid or bloody discharge, abdominal pain or enlargement, or premature sexual maturation [l-3]. Despite their rarity, all varieties are seen in children and adolescents, and the incidence of malignant or premalignant degeneration of neoplasms is higher than in adult women [3,4]. Clinical signs and type of tumor often differ from those in adults. The alarming symptom, therefore, requires a prompt and careful investigation. Until recently, one-fourth to a half of all Article

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to the Department of Obstetrics and Gynecology, Gifu University School of Medicineaffiliated Hospitals’ during the period 1984- 1993. We also included clinical records of the Nagara National Children’s Hospital, an integral part of the facilities of Gifu University School of Medicine. The subjects fell into four groups: young children (early childhood, age up to 6 years), older children (late childhood, age 7-10 years), young adolescents (early puberty, age 1 l- 14 years), and adolescents (late puberty, age 15 years and over). The date of complaints, diagnoses and

childhood genital tumors eluded diagnosis before exploratory laparotomy was performed [l-4]. However, diagnostic imaging evaluations like ultrasonography (US) or magnetic resonance imaging (MRI) have now come to be an accepted procedure in the well child examination [5-71, permitting early detection of genital disorders including tumors. As a result there is now more appropriate management than earlier literature on the genital tumors. We therefore attempted to analyze the clinical and pathologic findings of the last lo-years’ experience of treating genital tumors at Gifu University Medical Center and affiliated Hospitals.

‘Gifu University Medical Center, Gifu Municipal Hospital, Gifu Prefectural Gifu and Gero Hospitals, Takayama Red Cross Hospital, Tokai Central Hospital, Chuno General Hospital, Gihoku General Hospital, Tajimi Municipal Hospital, Hashima Municipal Hospital, Gujo Central Hospital, and Matsunami General Hospital.

Materials and methods Our study included registrations for all patients aged less than 18 who were referred

Table 1. Primary complaints for 1938 patients younger than I8 years.

Age

0

Total no.

I 2 3 4 5 6

I4 15 30 36 33 30 28

7 8 9 IO II I2

31 38 30 42 53 15

13 14 15 I6 I7 I8

103 I34 169 254 349 474 I938

Abnormal external genitalia

Abdominal pain, distention

II

3

4 I

Vaginal discharge, itching

Vaginal bleeding

Premature breast development

Menstrual problems”

26 37 43 51 54 77

I7 I5 I2 39 50 54

I9 I6 I7 23 26 27

374

360

201

2 2

25

4 3

I I2 24

3 6 4 9 I6 20

32 54 82 I25 I91 282

65

803

“Including secondary amenorrhea, hypermenorrhea, dysmenorrhea and abnormal menstrual bleeding. blncluding prenatal diagnosis of ovarian cyst, anemia. genital mass, galactorrhea, hematuria and hypertrichosis. Int J Gynecol Obstet 45

Othersb

3 I

5 I3 I9 22 21 8 I3 II I4 I7 I5 I5

62

Primary amenorrhea

I 3

Gynecologic

patient’s characteristics were routinely checked, whenever possible, against hospital records, and amended whenever necessary. Of a total of 1938 cases, 145 were submitted to surgical treatment (excluding repairs for genital injuries). Microscopic sections of all specimens were reviewed. The tumors obtained were classified into three main categories: germ cell tumors, stromal tumors and epithelial tumors. The germ cell tumors were subdivided into live groups in line with the dysgerWHO classification: teratoma, minoma, endodermal sinus tumor (yolk sac tumor), embryonal carcinoma, and choriocarcinema. The teratomas were classified according to the type of tissue present: mature (adult) type, consisting of well differentiated tissue only; and immature (malignant) type, containing one or more malignant germ cell components (dysgerminoma, endodermal sinus tumor, embryonal carcinoma, or choriocarcinoma) in addition to benign or embryonic tissue. Staging was according to the International Federation of Gynecology and Obstetrics (FIGO) criteria. Results

Table 1 summarizes primary complaints for 1938 patients reviewed. The patients ranged in age from 1 day to 18 years. The ages of patients were distributed equally in the early and late childhood, the largest group being adolescents over 15. Such difference in the patient distribution between children and adolescents seems to account for the number of menstruation-related complaints (primary amenorrhea and menstrual problems), and abdomnal pain and distention. There was no signilicant difference in the incidence of other sympchildhood and early toms throughout puberty. Of those patients, 145 underwent surgical treatment; Table 2 demonstrates their pathological diagnoses. Abdominal pain was the most common complaint for ovarian tumors. Of the 374 patients who complained of abdominal pain and distention, 119 were

lumors

in girls

229

clinically diagnosed as having ovarian tumors, 2 with extrauterine pregnancies and 2 with intraperitoneal bleeding. Of the patients whose clinical presentation suggested ovarian tumor, exploratory laparotomy revealed acute appendicitis in 2 and no positive finding in 3. Of the 114 patients with ovarian tumors, 33 presented with torsion of the tumor and fallopian tube. All of these patients had a history of nausea or vomiting and some had fever. Vaginal bleeding and premature breast development were other presenting symptoms in the ovarian stromal tumors. Vaginal bleeding results from a local lesion of the genital tract or precocious puberty. The tumors of the genital tract causing vaginal bleeding were vaginal endodermal sinus tumor in 1 patient, vaginal sarcoma botryoides, and Gartner’s duct cyst (Table 2). Both patients with malignant tumors presented with bloody vaginal discharge alone. A patient with a large Gartner’s duct cyst, causing obstruction of the vagina and accumulation of secretions, reported recurrent pelvic pain. Of the 23 patients with stromal tumors of the ovary, 9 experienced vaginal bleeding and/or premenarcheal breast development. Figure 1 demonstrates the distribution of the origin site of ovarian tumor by age. The epithelial tumors occurred only in patients more than 10 years of age, while germ cell tumors developed frequently throughout early childhood to adolescence. The stromal tumors also had a tendency to arise in older patients, except 1 case of juvenile granulosa cell tumor in a 2-year old girl and 3 fetal follicular cysts. Table 3 summarizes our experiences with 23 children with genital tract malignant tumors. Two developed in the vagina and the others originated in the ovary. Discussion

The major problems that occur in pediatric and adolescent gynecology are well divided into four major categories: (i) infections, (ii) endocrine disorders and intersex problems,

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Table 2.

Pathological diagnoses and primary complaints of 145 patients who underwent surgical treatment.

Type of tumor

No. of cases

Complaints Abdominal pain, distention

Vulva

Condyloma Hemangioma Lipoma Fibromatosis Bartholin’s duct cyst

Vaginal bleeding

Genital mass

IO 3

1 2

I 3

Vagina

Endodermal sinus tumor Gartner’s duct cyst Sarcoma botryoides Ovary Germ cell tumors

Teratoma (mature) (immature) Dysgerminoma Embryonal carcinoma Endodermal sinus tumor

I

114 58 43 5 I

1

Epithelial tumors

2 33

Cystadenoma Cystadenocarcinoma Sex cor#stromal tumors Follicularilutein cyst Juvenile granulosa cell tumor Theta cell tumor

30 3 23 l9h 2 2

Others

I6 7 2 2 2 3

Hemato- and pyosalpinx Ovarian bleeding Tubal pregnancy Appendicitis No positive finding Total

145

43 5’ 18 le 2 30 3 16d

I” 1”

I

6’ 2

I

I”

;‘, 3b 124

6

IO

“Associated with premature breast development. bLaparotomy as clinical diagnosis of ovarian cyst. CAssociated with imperforate hymen in one case. dAssociated with premature breast development in five cases. ‘Associated with vaginal bleeding. ‘Associated with vaginal bleeding in one case. gAssociated with premature breast development. hlncluding three cases of prenatal diagnosis.

(iii) anomalies, and (iv) tumors. Although tumors are the less frequently seen group, they should be considered in the different diagnosis because of the high incidence of potential malignancy in genital tumors than in Int J Gynecol Obstet 45

adult. We reviewed 145 patients who required surgical treatment, of which 114 had ovarian tumor and 15 were of vulva and vagina disease. Malignant lesions in the lower genital tract

Gynecologic

Table 3. Case No.

Our experiences Age (years)

of malignant

genital

Diagnosis

tumors

in girls

231

tract tumors.

(stage)”

Therapyb

Follow-upc

Vagina

I

6 months

EST

2

2

Sarcoma

botryoides

3 4

IO II

Immature

teratoma

5 6 7 8

17 3 18 16

9 10

14 I8

11 12 13 14

13 13 16 8

15 16 17 18

I5 I2 I2 2

(lC) (IA) Embryonal carcinoma (IA) Juvenile granulosa cell tumor

19 20

IO 13

(IA) (IA) EST (IIA)

21 22 23

18 12 9

H & partial vaginectomy, Wide local excision. C

C

NED, 2 years NED, 7 years

Ovary

(IA) Malignant

(IA)

teratoma

(D) (IIB)

(EC) (HA) (EST)(IA) Mutinous cystadenocarcinoma (IA) (IA) (IA) Dysgerminoma (IIIA)

NED. NED, NED, DFD. NED, NED,

8 5 7 4 2 2

years years years years years years

U. C u. c U U

NED, NED, NED, DFD, DFD, NED, NED, NED, NED, NED.

3 9 4 I 2 6 5 6 2 2

years years years years years years years years years years

U U. C. Radiation U U U

NED, NED, NED, NED, NED.

4 9 6 6 2

years years years years years

U, Omentectomy B. C U. C u. c U

(IA)

U, C U B, C U, C u. c

(HA) (IA)

(BA) Theta cell tumor

u, c u. c

(IA)

(IA)

& H. C

“D, dysgerminoma; EST, endodermal sinus tumor; EC, embryonal carcinoma. bU, B, unilateral, bilateral salpingo-oophorectomy; H, hysterectomy; C, chemotherapy. CNED, no evidence of disease; DFD, dead from disease.

usually bleed early in their development [4,8-lo], while benign tumors seldom cause bleeding. One of our patients with endoderma1 sinus tumor of the vagina and one with sarcoma botryoides developed bright red spotting on her diaper only, and cytologic examination of vaginal smear was negative. As noted in previous studies, sarcoma botyoides [8,11,12], adenocarcinoma [ 131and endodermal sinus tumor [ 14- 171of the vagina occur in children under the age of 10. These tumors are often not palpable per rectum and not detected in cytology. These carry a dismal prognosis, demanding a prompt and precise location and extent of the lesion. Thus, careful examinations such as vaginoscopy under anesthesia, US or MRI may be the mainstays of evaluation to exclude the

presence of tumors, foreign bodies, or other local causes of bleeding. We have reported the accuracy of MRI in the evaluation of the lesion of the case with vaginal endodermal sinus tumor before surgical treatment [ 171. Vaginal bleeding was most often associated with vulvovaginitis in our series, but, during childhood, should always alert us to the possibility of a genital tumor. An alternative suspected source of vaginal bleeding may be from the endometrium as a manifestation of precocious puberty. Hormonally active ovarian tumors may cause irregular vaginal bleeding that is heavy at times. One patient with juvenile granulosa cell tumor [18] and one with theta cell tumor in our series presented with vaginal bleeding resulting from precocious puberty. When the Article

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Imai et al.

Epithelial Tumors Stromal Tumors Germ Cell Tumors

I

1

2

3

4

5

6

7

8 Aw

9

10 11 12 13 14 15

16 17 18

(wars)

Fig. 1. Age distribution and incidence of ovarian tumors in 106 patients.

bleeding appears to have come from the endometrial cavity, the following evaluation may be required: (i) determination of serum estradiol, (ii) US or MRI of the pelvis to rule out the presence of a gonadal or adrenal tumor, and (iii) MRI or CT of the brain to evaluate the central nervous system. Most benign tumors of the lower genital tract in children are unilocular cyctic remnants of the mesonephric (Gartner’s) duct; these are usually asymptomatic [3]. In one of our cases, large cyst may have blocked the vagina and caused recurrent abdominal pain rather than local symptoms. The ovary is the most frequent site of tumor formation in the child, but they comprise not more than 1% of all new growths in the child [ 19,201. Approximately 75% of our ovarian tumors were benign, 20% were malignant, and 5% had an endocrine function. The latter, of course, are potentially (pre)malignant. PreIntJ

Gynecol Obster 45

vious literatures compiled several large series of ovarian tumors in children and found 20 to 35% to be malignant [5,21-241. In children with ovarian neoplasm, the frequency of germ cell tumors varies from 67 to 85 %. In our current series, the incidence was approximately 50%. The stromal tumors were seen in 15% incidence; a lo- 12% incidence has been reported by others [25]. The epithelial tumors occurred only in the older patients who were lo-18 years of age; approximately one-third of ovarian tumors in the adolescents being of epithelial cell origin. In adults, they are the most common ovarian neoplasms (80%) [26]. Over 90% of the patients with ovarian tumor complained of abdominal pain and/or distension. Ovarian tumor was found in approximately 30% of the patients who developed abdominal pain. Acute symptoms of severe pain, peritoneal irritation, or intraabdominal hemorrhage resulting from a

Gynecologic tumors in girls

tumor accident (torsion, rupture, perforation) may lead to an erroneous diagnosis of appendicitis, intussusception, or volvulus. At least one-fourth of all childhood ovarian tumors were believed to elude diagnosis until exploratory lapatotomy was performed. Appendicitis is the most frequent misdiagnosis in these patients [25,27]. In our series, even when the mass was palpable and thereby ovarian tumor was preoperative diagnosis, 2 revealed acute appendicitis and 3 had no positive findings. US is now the standard approach as the first step in the workup of abdominal masses. Ovarian tumors can easily be diagnosed by US alone, although MRI or CT is needed for further evaluation. The diagnostic procedure can give us a new advance to delineate accurate extent and location of the children’s pelvic lesion. In children with malignant tumors of the genital tract, many long survivors have been treated with a multimodal approach, usually combining operative excision with radiation therapy and/or systemic chemotherapy. The surgery recommended for a malignant ovarian tumor is bilateral salpingo-oophorectomy and hysterectomy [23,28]. The only exception to radical surgery is stage IA tumors. Recently, however, some groups reported diseasefree patients beyond 5 years treated with chemotherapy and less extensive surgery in young children where fertility is of importance [ 14,151. The survival rate at 5 years was 86% in the patients treated postoperatively with combination chemotherapy [20,29]. In our series, 19 of 21 patients, unilateral salpingo-oophorectomy was performed in an attempt for reproductive organ conservation, 3 cases of advanced diseases were treated with and/or bilateral salpingohysterectomy oophorectomy. Only 3 died within 4 years and others are free from disease. In conclusion, the presenting symptoms and signs of genital tract tumor were similar to those reported in other series. However, our experience suggests that a prompt and precise detection of either benign or malignant tumors Gan lead to both cure and preser-

vation of fertility with conservative whenever possible.

233

surgery

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Address for reprinb: A. Imni Department of Obstetrics and Gynecology Cifu University Schuol of Medicine Tsukasamacki Gifu 500, Japan