Clinical features of testicular tumors in children

Authors


Yoichi Arai, Department of Urology, Tohoku University School of Medicine, 1-1 Seiryo-Machi, Aoba-ku, Sendai 980-8574, Japan. Email: yarai@uro.med.tohoku.ac.jp

Abstract

Aim:  Testicular tumors are not common pediatric solid tumors, especially in Asian children. There have been few reviews of cases in Japan to date. We present the clinical features of 14 pediatric testicular tumor patients.

Methods:  Clinical features of 14 testicular tumor patients, such as chief complaints, age at diagnosis, pathology, stages, treatments and prognosis, were examined from medical records. Two patients had their semen tested at adolescence.

Results:  Of the 14 prepubescent patients, 12 (85.7%) patients were diagnosed before 3 years of age. Ten cases (71.4%) were diagnosed as yolk sac tumors, three (21.4%) as mature teratomas and one case as an epidermoid cyst. Nine cases (90.0%) among the 10 cases of yolk sac tumor were diagnosed as stage I and one case was stage IV. One stage I yolk sac tumor patient developed lung metastasis later. Eventually, two yolk sac tumor patients died, despite chemotherapy. While all the cases with a diagnosis before 2 years of age survived, 67% (2/3) of cases with a diagnosis after the age of 2 died of tumors. Semen analysis in two patients showed normospermia.

Conclusion:  In the present study, the most common testicular tumors were yolk sac tumors and the patients diagnosed before 2 years of age showed favorable results. Age could be a relapse risk factor in yolk sac tumors. Guidelines for handling testicular tumors in children is not yet well established in Japan. An organized system seems necessary to gather and accumulate the results of the cases in Japan in order to develop better guidelines for treatment.

Introduction

Testicular tumors are uncommon in childhood, especially among black and Asian children, accounting for 1% to 2% of all pediatric solid tumors.1 In Japan, there have been few reviews of cases to date.2,3 We have examined 14 patients with testicular tumors before puberty, who were treated at the Tohoku University School of Medicine Hospital, Sendai, Japan over the last 27 years and have evaluated the results.

Methods

Between March 1975 and March 2002, 240 testicular tumor patients were treated at the Tohoku University School of Medicine Hospital. Among them, 14 cases (5.8%) were prepubescent. The age at diagnosis ranged from 8 months to 10 years old (median, 1 year old). Clinical features, such as chief complaints, age at diagnosis, pathology, stages, treatments and prognosis were examined retrospectively. The stage of the disease was determined according to the staging system used by the Children's Oncology Group.1 The survival rate was calculated according to the Kaplan-Meyer method. Two of the patients had their semen tested, according to their wishes at adolescence.

Results

The 14 cases are summarized in Table 1. The chief complaint was painless scrotal swelling in all cases, except case 1, who claimed concomitant testicular torsion.

Table 1.  List of 14 cases with testicular tumor before puberty
CaseAgeSideSurgery/other treatmentsPathologyMetastasis/stageOutcome (period)
  1. E, epidermoid cyst; Chemo, chemotherapy; Lt, left; m, months; Rad, radiation therapy; Rt, right; T, mature teratoma; y, years; YST, yolk sac tumor.

 1 1yRtHigh orchiectomy/noneTnone/IAlive (5y 7m)
 2 8mLtHigh orchiectomy/noneTnone/IUnknown
 3 9mRtHigh orchiectomy/Chemo and RadYSTnone/IAlive (24y)
 4 1yRtHigh orchiectomy/noneYSTnone/IAlive (22y)
 5 6yRtHigh orchiectomy/noneTnone/IUnknown
 6 3yLtHigh orchiectomy/ChemoYSTlung/IVDied (1y 5m)
 7 3yLtHigh orchiectomy/noneYSTnone/IAlive (19y)
 8  9mRtHigh orchiectomy/noneYSTnone/IAlive (19y)
 9 2yLtHigh orchiectomy/noneYSTnone/IAlive (5y)
10 3yRtHigh orchiectomy/noneYSTnone/I
lung/IV
Died (5y)
11 1yRtHigh orchiectomy/noneYSTnone/IAlive (8y)
12 9mLtHigh orchiectomy/noneYSTnone/IAlive (7y)
13 1yLtHigh orchiectomy/noneYSTnone/IAlive (5y)
1410yRtHigh orchiectomy/noneEnone/IAlive (1m)

Of the 14 cases, 12 (85.7%) were diagnosed before the age of 3 years. Pathologically, 10 cases (71.4%) were diagnosed as yolk sac tumors, three (21.4%) as mature teratoma and one case as an epidermoid cyst.

Nine cases (90.0%) among the 10 cases of yolk sac tumor were diagnosed as stage I and serum α-fetoproteins (AFP) declined according to the estimated half-value period after high orchiectomy. One of the stage I patients (case 10) developed lung metastasis later and died of the tumor 5 years after the initial treatment. Because this patient failed to report to hospital after initial treatment, we were unable to reveal the details of the case after initial treatment. One patient with stage IV yolk sac tumor (case 6) received postoperative chemotherapy of one course VAC (Vincristine, Actinomycin D, Cyclophosphamide) and one course PVB (Cisplatinum, Vinblastine, Bleomycin), but the patient died despite the chemotherapy. Overall, two patients with yolk sac tumors (20.0%) died of the disease (Fig. 1). While all the cases under the age of 2 survived, 66.7% (2/3) of the cases over the age of 2 died of their tumors.

Figure 1.

Survival curve of infantile yolk sac tumors (Kaplan-Meyer method).

The initial operation was high orchiectomy in all cases, even in mature teratomas and epidermoid cysts. Routine retroperitoneal lymphnode dissection (RPLND) was not performed in any of the cases. Routine adjuvant chemotherapy or radiotherapy was not performed in any stage I case, except case 3. Case 3 received adjuvant radiotherapy and chemotherapy in the Pediatric Surgery Department.

The follow-up period for all patients varied from 1 month to 22 years. Two patients (cases 3 and 4) wished to have their semen tested. Their semen showed normospermia, although case 3 received postoperative radiotherapy and chemotherapy, as already described.

Discussion

Testicular tumors in children are now better described in Campbell's Urology, Eighth Edition,1 but there have been few reviews of cases in Japan to date.2,3 We reviewed 14 cases of testicular tumor before puberty and evaluated our results compared with previous reports.1–3

The most common chief complaint was painless scrotal swelling. Kay R reported that among 327 prepubertal testicular tumors, 87% showed mass as a presenting symptom.4 In this present study, one case showed scrotal swelling since birth. It is not clear whether the tumor had already developed before birth or, if there had been concomitant hydrocele testis upon birth.

In most cases, tumor onset was before age 3. In general, testicular tumors have two peak periods of onset, after birth and after puberty.5 Since there are also two peaks of serum testosterone level, at birth and at puberty, testosterone could contribute to developing testicular tumor.6,7

Pathologically the most frequent tumors were yolk sac tumors, which did not necessarily show favorable prognosis. This agrees with previous reports.2,3 The second most frequent tumors were mature teratoma and all of them, except unknown cases, experienced favorable results after initial treatment.

Initial operation was high orchiectomy in all cases, but when mature teratoma or epidermoid cyst is suspected by ultrasonography and serum AFP is within normal range, testis-sparing surgery could have been taken into consideration1 although there had not been enough results of patients with testis-sparing operation.2,3,8 and it should be noted that in cases of mature teratoma before 8 months old, serum AFP may be elevated phisiologically.9 Most recently Kay et al. has advocated a surgical approach that allows for testis sparing surgery for all potentially benign tumors.9 Pre-pubescent mature teratoma have a benign clinical course, in contrast to the clinical behavior of teratomas in adults, which have the propensity to metastasize.1

It is now accepted that routine chemotherapy, radiotherapy and RPLND are not required in pediatric yolk sac tumors stage I patients.1 Although case 10 relapsed and died of lung metastasis 5 years later, we cannot stress the necessity of adjuvant chemotherapy, because this case failed to continue treatment at our hospital, which could have resulted in failure to detect the relapse of AFP. It is very important to make parents understand the necessity of close follow-up after the initial treatment. Chest radiography, CT or MRI of the retroperitoneum is recommended monthly for three months, again three months later, and then every subsequent six months until 36 months after treatmant.1

Because the disease is rare, there is not yet a standard protocol of chemotherapy against advanced stages. Connolly JA et al. contend that all children except stage I should be treated with combination chemotherapy using VAC or PVB for a year and 58% of these patients will be salvaged.10

As for overall prognosis, Kay et al. has recently reported that, among 112 cases of yolk sac tumor, 12.5% died of the disease.9 In this study, among 10 prepubescent cases of yolk sac tumor, two (20%) died of tumor and both of them were age 3. Among the eight cured patients of stage I yolk sac tumor, seven patients were under age 2, and most under age 1. According to the report by Terai A et al.2 among 4 cases of stage I yolk sac tumor, 3 were under age 2 and among 3 cases of higher stage, 2 were over age 2. Age may be an important prognostic variable with infantile yolk sac tumors.11 Children older than age 2 appear to be at greater risk of tumor progression.10 The relapse–free survival rate for patients under 1 years of age was 78% and it fell to 24% for patients older than 2.12 Kay reported that according to the results of 207 cases of prepubescent yolk sac tumors, there was no statistically significant difference of prognosis between the children under the age of 2 and those over the age of 2; however, he also suggested a slightly higher trend for metastatic disease in children who presented after the age of 2. Adjuvant chemotherapy could be one option for the possible high risk group.

As far as we know, there has been no report of semen analysis of patients who underwent high orchiectomy in childhood. Two cases of yolk sac tumors (cases 3 and 4) had their semen tested at adolescence. Both showed normspermia, although case 3 underwent adjuvant chemotherapy and radiation therapy. Case 4 also showed normal gonadotropin/endocrine data (data not shown). Further investigation is encouraged to evaluate the future paternity of the infantile testicular tumors patients.

Because of the rarity of testicular tumors in children, guidelines for treatment are not yet well established in Japan. The pathogenesis is poorly understood along with that of adult testicular tumors. Kay reported 327 cases with prepubescent testicular tumors over 12 years by mailing all members of the Section on Urology and the American Academy of Pediatrics encouraging all members to enroll, entering the data into the computerized database and presenting the results yearly at the annual meeting.4 An organized system seems necessary to gather and accumulate the results of the cases in Japan to develop better guidelines for treatment.

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