Pediatric Seminoma

Updated: Sep 16, 2022
  • Author: Arnold C Paulino, MD; Chief Editor: Cameron K Tebbi, MD  more...
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Overview

Practice Essentials

Testicular tumors in children are rare, accounting for only 1-2% of all solid tumors in this age group. [1]  The annual incidence of testicular tumors in children is 0.5 to 2.0 per 100.000, with the majority occurring in less than two years of age. [2]  In both children and adults, the vast majority of testis tumors arise from germ cells. Seminoma is a type of testicular germ cell tumor that is believed to originate from the germinal epithelium of the seminiferous tubules. These tumors have been shown to have dramatic sensitivity to both radiotherapy and cytotoxic chemotherapy. In most patients with testicular tumors (including seminoma), the disease is readily cured with minimal long-term morbidity. The management of childhood seminoma is similar to that of adult seminoma.

Signs and symptoms

The most common presenting symptom in a patient with a seminoma is a painless testicular mass. Other symptoms can include testicular pain or heaviness.

See Presentation for more detail.

Diagnosis

Laboratory studies

Measurements of alpha-fetoprotein (AFP), human chorionic gonadotropin (beta-hCG), and lactate dehydrogenase (LDH) are important in the management of patients with testicular tumors. 

Imaging studies

Plain chest radiography and CT scanning of the abdomen and pelvis are the most important radiologic investigations in determining the extent of disease in patients with seminoma.

See Workup for more detail.

Management

After orchiectomy, adjuvant moderate-dose pelvic and/or para-aortic radiotherapy remains the standard treatment for patients with early-stage seminoma (stage I, IIA, or IIB). However, patients who have more advanced disease (stage IIC, III, IV) have a high risk of systemic relapse if treated with surgery and radiation alone, and the standard treatment for these patients is combination chemotherapy.

See Treatment and Medication for more detail.

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Pathophysiology

Germ cell tumors account for 95% of testicular tumors and include seminomas, teratomas, choriocarcinomas, and mixed tumors. Seminomas comprise approximately 50% of all germ cell tumors. Seminomas are generally believed to arise from the germinal epithelium of the seminiferous tubules because "seminoma cells" are morphologically similar to spermatogonia and also because seminomas are frequently found within the seminiferous tubules in early stages.

Most researchers believe that seminomas can arise from any or all of the spermatocytic elements because undifferentiated seminomas can resemble primordial germ cells, spermatogonia, or spermatocytes. Unlike the nonseminomatous germ cell tumors, pure seminoma tends to remain localized or tends to involve only lymph nodes. Seminoma is confined to the testis in 85% of patients at presentation. It initially spreads to draining lymph nodes in the retroperitoneum and then spreads proximally to involve the next echelon of draining lymphatics in the mediastinum and supraclavicular fossa. Seminoma can spread hematogenously to involve lung parenchyma, bone, liver, or brain (ie, stage IV). Less than 5% of patients present with stage III or stage IV disease. [3]

 

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Etiology

The cause of germ cell tumors is unknown. Familial clustering has been observed.

Prior testicular cancer is a major risk factor for a contralateral malignancy. The cumulative risk 25 years after original diagnosis is 3.6% for patients with seminoma.

Cryptorchidism especially when bilateral, is a predisposing factor in the development of germ cell tumors arising from the testis. In fact, 7-10% of testis tumors occur in association with cryptorchidism. [4]  Orchiopexy performed before puberty reduces the risk of germ cell tumors and improves the ability to observe the testis. [5]  However, 25% of the cancers found in association with cryptorchidism occur in the contralateral, normally descended testis, which suggests that a developmental defect is responsible for both the maldescent and the tumor. The risk of an individual with cryptorchidism developing testicular cancer is directly related to the degree of maldescent. The risk is 1 in 20 if the testis is intra-abdominal and is 1 in 80 if it is within the inguinal canal. Hypospadias and hydrocele are other genitourinary anomalies that have been associated with testicular cancers.

Presence of chromosomal abnormalities including del(1p36), i(12p), loss of chromosomes 11,13 and 18; gain in chromosomes 7, 8 or X.  In germ cell tumors, deletions of chromosomes 1p, 4q, and 6q and gains of chromosomes 1q, 3, and 20q have been reported.

Klinefelter syndrome is associated with the development of mediastinal germ cell tumors. [6]

Human immunodeficiency virus (HIV) infection may be associated with an increased risk of germ cell tumors. Other possible associations include mumps, orchitis, history of testicular trauma, immunosuppression after organ transplant, and prior vasectomy. [5]

A Children's Oncology Group study suggests that maternal vitamin supplementation may reduce the risk of pediatric germ cell tumors in their offspring. [7]

No clear association between seminoma or other testicular germ cell tumors and previous exposure to diethylstilbestrol has been identified.

A meta-analysis by Bräuner et al showed that maternal exposure to environmental endocrine-disrupting chemicals was associated with a higher risk of testicular cancer, including seminomas, in male offspring. In addition, high exposure during pregnancy to grouped organochlorines and organohalogens was related to a higher risk of both seminomas and nonseminomas in the offspring. [8]

Testicular teratomas and malignant testicular germ cell tumors (GCTs) are seen in early childhood. These are often composed of pure yolk sac tumor which are also called endodermal sinus.

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Epidemiology

United States statistics

Germ cell tumors are the most common solid tumor in men aged 15-35 years. [4] The worldwide incidence has more than doubled over the past 40 years, and approximately 7500 cases are diagnosed annually in the United States. Seminomas account for nearly 50% of these cases.

International statistics

Among children in Saudi Arabia, seminomas are the most common testicular cancer, representing 39% of all cases in those aged 1-14 years. [9]

Race-, sex-, and age-related demographics

Geographic distribution of testicular cancer widely varies, with the highest rates among North American whites, Scandinavians, and Western Europeans. The lowest rates occur among Asians, Africans, Puerto Ricans, and North American Blacks. Recent data show a White-to-Black incidence ratio of approximately 5:1, and a report from the US military showed a relative White-to-Black incidence ratio of 40:1.

In children and adolescents, the pattern of racial distribution for testicular cancer is different. A review of the Surveillance, Epidemiology, and End Results (SEER) data from 1973-2000 reported that Asians and Pacific Islanders had the highest incidence of testicular cancer at 7.6 per million, whereas American Indians and Alaskan Natives had an incidence of 1.4 per million children. The rates for Caucasian and African American children were the same at 5.1 per million. [10]

Seminomas arise from the male testicle.

As noted above, germ cell tumors are the most common solid tumors in men aged 15-35 years. Seminoma (the most common germ cell tumor) occurs most commonly in the fourth decade of life. Children represent only 2-5% of all patients with testicular cancer. Seminoma is considered a postpubertal tumor, although it has been reported in a patient as young as 8 years.

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Prognosis

Prognosis depends on several factors including stage of the disease and decline in tumor marker (ie, alpha feto protein and beta-hCG) in response to therapy.

  • Early-stage seminoma: Relapse occurs in approximately 4% of patients with stage I and 10% of patients with stage IIA or stage IIB seminoma. Subsequent treatment with chemotherapy cures more than 90% of patients whose disease relapses after radiotherapy. Therefore, approximately 99% of patients with early-stage seminoma are cured.

  • Advanced seminoma: With the development of effective cytotoxic chemotherapy, many patients with advanced (70-80%), recurrent (50-60%), or even metastatic (20-30%) seminomas are cured of their disease. Further studies of alternative chemotherapy regimens and high-dose regimens with stem cell support are ongoing.

  • A combined study of five US trials and two UK trials for malignant extracranial GCTs merged by the Malignant Germ Cell Tumor International Collaborative (MaGIC) is available. For this collaboration, data from 519 young patients, incorporating age at diagnosis, stage, and site of primary tumor, pretreatment AFP level and histology were combined. Of these, patients aged 11 years and older with stages III to IV extragonadal disease or ovarian stage IV disease had a less than 70% likelihood of long-term disease-free survival. This ranged from 40% (extragonadal stage IV) to 67% (ovarian stage IV). AFP levels and histologies, other than pure yolk sac were found to be negative factors, but did not achieve statistical significance at the 0.05 level. [11]

Morbidity/mortality

With advances in radiologic staging, serum tumor marker surveillance, and platinum-based chemotherapy for advanced disease, overall survival (ie, cure) rates for patients with seminoma have increased to more than 90%. Nearly 100% of patients with stage I testicular seminoma are cured. Potential adverse effects/morbidity related to therapy for this malignancy are discussed below; in general, morbidity includes infertility, second cancers, chemotherapy-related nausea and vomiting, nephrotoxicity, and cardiovascular toxicity or peptic ulcer disease from mediastinal or retroperitoneal irradiation, if this is used, respectively.

Complications

Patients treated with orchiectomy and adjuvant radiotherapy are at increased risk for subfertility, even though the contralateral testis is not located directly within the radiotherapy field. [12]  Scrotal shielding during radiation treatments reduces the dose of scattered radiation and should be employed routinely.

Second malignancies have been reported following orchiectomy and postoperative adjuvant radiotherapy for seminoma. [13]  Although such malignancies are uncommon, the actuarial risk increases with time from diagnosis; second cancer sites have included the rectum, small intestine, stomach, and bladder.

Potential long-term complications of cisplatin/etoposide chemotherapy include loss of high-frequency hearing, nephrotoxicity, hypomagnesemia/Raynaud phenomenon, subfertility, and acute nonlymphocytic leukemia.

Although cardiovascular toxicity has been reported following treatment of seminoma with orchiectomy and adjuvant radiotherapy, it was associated with the use of radiotherapy fields that treated the mediastinum and supraclavicular fossae. These fields are no longer routinely treated because the incidence of recurrence in these areas is low for patients with stage I, stage IIA, or stage IIB disease.

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Patient Education

Patients diagnosed with testicular seminoma have an increased risk of developing a contralateral testis tumor. These patients should be taught methods of testicular self-examination. This form of screening should be performed monthly so that a second primary tumor can be identified at the earliest possible stage.

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