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Prepubertal Testicular and Paratesticular Tumors
Article Last Updated: Nov 1, 2007
AUTHOR AND EDITOR INFORMATION
Section 1 of 11  
Author: Christopher S Cooper, MD, FACS, FAAP, Associate Professor of Urology, Director of Pediatric Urology, University of Iowa, Children's Hospital of Iowa; Associate Dean for Student Affairs and Curriculum, University of Iowa Carver College of Medicine
Christopher S Cooper is a member of the following medical societies: Alpha Omega Alpha, American Academy of Pediatrics, American College of Surgeons, American Medical Association, American Urological Association, International Children's Continence Society, Phi Beta Kappa, Society for Basic Urologic Research, Society for Fetal Urology, and Society for Pediatric Urology
Coauthor(s):
Brian L Gallagher, MD, Staff Physician, Department of Urology, University of Iowa Hospitals and Clinics
Editors: Bartley G Cilento, Jr, MD, Instructor, Department of Surgery, Division of Urology, Children's Hospital of Boston and Harvard Medical School; Mary L Windle, PharmD, Adjunct Assistant Professor, University of Nebraska Medical Center College of Pharmacy, Pharmacy Editor, eMedicine.com, Inc; Harry P Koo, MD, Chairman of Urology Division and Director of Pediatric Urology, Virginia Commonwealth University; Professor of Surgery, VCU School of Medicine, Medical College of Virginia; Director of Urology, Children's Hospital of Richmond; Daniel Rauch, MD, FAAP, Director, Pediatric Hospitalist Program, Associate Professor, Department of Pediatrics, New York University School of Medicine; Marc Cendron, MD, Associate Professor of Surgery, Harvard School of Medicine; Consulting Staff, Department of Urological Surgery, Children's Hospital Boston
Author and Editor Disclosure
Synonyms and related keywords:
prepubertal testicular tumor, paratesticular tumor, cancer, neoplasms, yolk sac tumor, yolk-sac tumor teratoma, teratocarcinoma, seminoma, gonadal stromal tumor, juvenile granulosa cell tumor, juvenile granulosa-cell tumor, Leydig cell tumor, Leydig-cell tumor, Sertoli cell tumor, Sertoli-cell tumor, pediatric prepubertal testicular tumor, germ-cell tumor, embryonal carcinoma, teratoma, testis tumor, gynecomastia, congenital adrenal hyperplasia, gonadoblastoma, leukemia, lymphoma, rhabdomyosarcoma
Background
Testicular tumors account for 2% of all pediatric tumors, with an incidence of 0.05-2 per 100,000 children. A bimodal age distribution is observed; one peak occurs in the first 2 years of life, and the second occurs in young adulthood. Pediatric prepubertal testicular tumors are dramatically different from adult neoplasms. Germ-cell tumors account for only 60-77% of testicular tumors in children but account for 95% of testicular tumors in adults. Adult germ-cell tumors with malignant potential, such as seminoma and embryonal carcinoma, are not present in prepubertal patients. Teratomas, which are uniformly benign in children, are often malignant in adults. The most common germ-cell tumors are teratomas and yolk-sac tumors, which account for about 65% of testis tumors. Some series report that teratomas, which most believe are vastly underreported because of their benign nature, may account for almost 50% of prepubertal testicular tumors. However, in tumor registries yolk-sac tumors are more common than teratomas, which may reflect a reporting bias.1, 2 Gonadal stromal tumors are significantly less frequent than germ-cell tumors (ie, tumors of non–germ-cell origin) and primarily include juvenile granulosa-cell tumors, Leydig-cell tumors, and Sertoli-cell tumors.
The vast majority of yolk-sac tumors in children (85%) present as clinical stage I disease, compared with 35% in adults. Alpha-fetoprotein (AFP) can be used as a reliable marker because levels are increased in more than 90% of yolk-sac tumors and because the yolk sac is extremely sensitive to chemotherapy. Therefore, patients can be safely managed with observation after orchiectomy followed by chemotherapy for recurrent tumors. Retroperitoneal lymph node dissection is limited to those children with persistent retroperitoneal lymphadenopathy or increased serum tumor markers after orchiectomy and chemotherapy.
Prepubertal teratomas account for 30% of testicular germ-cell tumors in children and are uniformly benign. Although 80-90% of adult teratomas are found to contain carcinoma in situ elsewhere in that testis, this is not true in prepubertal boys with teratoma. Histology is often pure with diploid DNA content containing all 3 embryological germ layers (ectoderm, mesoderm, and endoderm). Testis-sparing surgery with frozen section is a reasonable consideration for this and other benign prepubertal tumors. No follow-up is recommended for prepubertal teratomas, whereas postpubertal patients should be followed as adults.
Epidermoid cysts are benign tumors of epithelial origin. They are often firm and well-defined, with a central hypoechoic region or mixed internal echogenicity surrounded by an echogenic rim on ultrasonography. These tumors are benign and, following tumor enucleation, do not require follow-up.
Seminomas and mixed germ-cell tumors are extremely rare in prepubertal children. Most believe that seminomas should be managed as in adults and mixed germ cell tumors should be treated based on the most malignant subtype.
Sertoli-cell tumors are the most common gonadal stromal tumors in prepubertal children. These tumors tend to appear as painless masses in boys younger than 6 months and produce no endocrinologic effects; however, 14% of patients present with gynecomastia. All reported lesions in children less than 5 years of age have been benign. Therefore, children younger than 5 are adequately treated with orchiectomy and do not require metastatic evaluation. Older children should undergo chest radiography and abdominal CT scanning to rule out metastases. Metastases are treated with a combination of radiotherapy, chemotherapy, and retroperitoneal lymph node dissection. Large-cell calcifying Sertoli-cell tumor is a variant with large amounts of cytoplasm and calcification. One-third of patients with this tumor have associated genetic abnormalities; however, these tumors are universally benign.
Leydig-cell tumors are the second most common gonadal stromal tumors in children and are also benign. These tumors most often occur in boys aged 5-10 years, and the synthesis of testosterone may produce precocious puberty, gynecomastia, and elevated levels of 17-ketosteroids. Leydig-cell tumors must be differentiated from hyperplastic nodules that develop in boys with poorly controlled congenital adrenal hyperplasia (CAH).
Juvenile granulosa-cell tumors account for 27% of all neonatal testicular tumors and commonly appear as cystic, painless testicular masses. They almost exclusively appear in the first year of life and most appear by age 6 months. They can be associated with anomalies of the Y chromosome, mosaicism, and ambiguous genitalia. These tumors are hormonally inactive and benign.
Gonadoblastoma occurs in association with disorders of sexual development (intersex). About 80% of cases involve phenotypic females with intra-abdominal testes or streak gonads. The putative gonadoblastoma gene is on the Y chromosome, and the tumor almost always develops in a child with a Y chromosome. The streak gonads in patients with mixed gonadal dysgenesis often develop gonadoblastomas. The incidence peaks at puberty, and early gonadectomy is recommended in patients at risk for gonadoblastoma. Metastatic spread of a gonadoblastoma occurs in 10% of patients. These tumors may elevate serum levels of beta-human chorionic gonadotropin (beta-HCG).
Cystic dysplasia of the testis is a benign lesion that is often associated with ipsilateral renal agenesis or dysplasia. This association, along with a characteristic ultrasonographic appearance (ie, hypoechoic lesions), permits preoperative diagnosis and possible treatment with testicular-sparing surgery.
Leukemia and lymphoma are the most common malignancies to affect the testis secondarily and account for 2-5% of all testis tumors; most present bilaterally. Because the blood-testis barrier may protect the intratesticular cells, the testis may be the site of residual tumor in children after therapy.
Paratesticular structures can give rise to various benign (lipoma, leiomyoma, hemangioma, or fibroma) and malignant tumors; however, these are extremely rare. Rhabdomyosarcoma is the most common malignant tumor (17%) and may arise from the distal spermatic cord and appear as a scrotal mass or hydrocele. These tumors have a bimodal distribution and occur in boys aged 3-4 months and in teenagers. As many as 70% of patients have involvement of the retroperitoneal lymph nodes at presentation. These tumors are highly aggressive and spread via the blood, lymphatics, or direct extension to the lungs, the cortical bone, or to the bone marrow in 20% of patients at the time of diagnosis. Radical inguinal orchiectomy followed by retroperitoneal lymph node dissection is recommended for all children older than 10 years, and in those younger than 10 years with retroperitoneal disease. Those with positive lymph nodes are treated with multimodal therapy (chemotherapy and radiation).
Pathophysiology
The testes are the affected organs.
Frequency
United States
Testicular tumors account for approximately 1-2% of all pediatric solid tumors. The incidence is 0.05-2 per 100,000 children. Although benign tumors are more common in prepubertal patients than in postpubertal patients, yolk-sac tumors have been more commonly reported in some series and tumor registries. The true incidence of benign tumors, such as teratomas, may be less than what is reported because of reporting bias.
International
The worldwide incidence is similar to that of the United States.
Mortality/Morbidity
One death occurs per every 10 million cases per year.
Race
The frequency in African-Americans and Asians may be less than that in whites although worldwide data is not available.
Sex
Testicular tumors occur in boys and men.
Age
The incidence of pediatric testicular tumors peaks in children aged 2-4 years. Most yolk-sac tumors occur in children younger than 2 years.
History
- About 85% of children with testicular tumors present with painless scrotal swelling. A few present with a hydrocele, scrotal pain, or a history of trauma, any of which probably alerts the child to the presence of a painless and enlarged testicle.
- A hard mass may be palpable on physical examination. However, normal physical findings are not sufficient to exclude a tumor.
- About 10-25% of patients with malignant tumors present with a hydrocele.
Physical
Physical examination usually reveals a painless scrotal swelling with a hard mass or associated hydrocele. Some hormonally active tumors may appear in association with precocious puberty or gynecomastia.
Causes
The cause is unknown. An association with prenatal exposure to diethylstilbestrol (DES) has been postulated but not demonstrated.
Hydrocele and Hernia in Children
Varicocele in Adolescents
Other Problems to be Considered
Epididymitis
Testicular torsion
Lab Studies
- Obtain a serum AFP level before treating a testicular mass.
- AFP levels are elevated in 80% of patients with yolk-sac carcinomas and serve as a tumor marker.
- The half-life of AFP is about 5 days, and levels should return to normal (<20 ng/mL) within 1 month after complete removal of the tumor.
- AFP levels are normally elevated in neonates (approximately 50,000 ng/mL) and drops to 10,000 ng/mL by age 2 weeks and to 300 ng/mL by age 2 months; therefore, age-specific values should be used.
- Persistently elevated AFP levels after surgery suggest tumor metastases or recurrence.
- Liver dysfunction can also cause false-positive elevations of AFP levels.
- Serum testosterone levels may be elevated in Leydig-cell tumors.
- Gonadoblastoma may elevate levels of beta-HCG.
Imaging Studies
- Ultrasonography is helpful in evaluating the testicle and in distinguishing an extratesticular mass from an intratesticular mass (see Media files 1-2).
- Chest radiography should be performed because 20% of yolk-sac tumors occur with metastases to the lung.
- Patients with rhabdomyosarcomas require chest radiography, abdominal-pelvic CT scanning, bone scanning, and bone-marrow aspiration.
Procedures
- The type of testicular tumor is diagnosed after inguinal orchiectomy or after an inguinal approach to testicular-sparing surgery is used.
- When preoperative AFP levels are normal and the suspicion for a benign lesion (eg, cystic dysplasia, teratoma) is high, the tumor is excised from the testis by using an inguinal approach. Intraoperative histologic confirmation of a benign lesion permits testicular-sparing surgery.
Histologic Findings
Histologic evaluation of the yolk-sac tumor demonstrates eosinophilic periodic acid-Schiff (PAS)–positive inclusions in the cytoplasm of clear cells that consist of AFP and Schiller-Duval bodies. Teratomas and teratocarcinomas contain elements derived from more than one of the 3 germ tissues: endoderm, mesoderm, and ectoderm. These tumors are often cystic, and tissues such as skin, hair, bone, and even teeth may be present. Although they contain areas of poorly differentiated cells with a malignant appearance, teratomas are consistently benign in children younger than 2 years. About 90% of paratesticular rhabdomyosarcomas demonstrate a favorable embryonal pattern on histology.
Staging
The intergroup staging system for testicular germ cell tumors is as follows: - Stage I - Limited to the testis and completely resected
- Stage II - Removed by transscrotal orchiectomy, involvement of scrotum or spermatic cord, persistently elevated markers
- Stage III - Retroperitoneal lymph node involvement (≤2 cm, no visceral or extra-abdominal involvement)
- Stage IV - Distant metastases
Medical Care
Current chemotherapeutic regimens for yolk-sac tumors are platinum-based protocols. Common agents include etoposide, bleomycin, and cisplatin. Most often, a pediatric oncologist enrolls patients who require chemotherapy into a multigroup research protocol. The protocols vary depending on the particular trial.
Surgical Care
- The treatment for yolk-sac tumors is inguinal orchiectomy and close surveillance.
- The tumor usually spreads to the lungs.
- Follow-up should include monthly tests of serum AFP levels, chest radiography every 2 months for 2 years, and CT scanning or MRI of the retroperitoneum every 3 months for the first year and then biannually.
- Because spread to the retroperitoneal lymph nodes is uncommon, routine prophylactic dissection of the nodes is not performed.
- Chemotherapy is administered in patients with radiographic evidence of metastatic disease or persistently elevated serum AFP levels.
- The use of combination chemotherapy with cisplatin, etoposide, and bleomycin has been an effective treatment for metastatic disease, with a survival rate approaching 90%.
- More than 99% of all patients with yolk-sac tumors are expected to survive.
- Chemotherapy is recommended in all patients with yolk-sac tumors and stage II disease.
- In boys with persistently elevated levels of tumor markers after chemotherapy, dissection of the retroperitoneal lymph node may be required.
- Boys with stage III or IV germ-cell tumors are treated with chemotherapy.
- If elevated marker levels or retroperitoneal disease persists, biopsy or resection of residual tumor is performed.
- Prepubertal testicular teratomas, Leydig-cell tumors, and Sertoli-cell tumors are benign, and orchiectomy or testicular-sparing surgery with complete excision is curative.
- Stage II or higher teratocarcinomas require treatment with cisplatin, bleomycin, and vinblastine.
- Treatment of gonadoblastoma involves removal of the gonad. Streak gonads are routinely removed because of the risk of malignant degeneration.
- Seminoma is rare before puberty and is managed as in the adult.
- Juvenile granulosa-cell tumor is managed by inguinal orchiectomy and follow-up chest radiography for 1 year.
- Juvenile granulosa-cell tumors rarely metastasize.
- Testicular-sparing surgery has not been routinely recommended, although a case report described a 5-year recurrence-free survival rate after testicular-sparing surgery for granulosa-cell tumor.
- Perform radical inguinal orchiectomy to treat paratesticular rhabdomyosarcoma.
- If the scrotum is involved, hemiscrotectomy should be performed, with adjuvant chemotherapy.
- All children with rhabdomyosarcoma require vincristine, Adriamycin and dactinomycin (VAC) chemotherapy or treatment with a combination of these drugs.
- Patients with evidence of metastatic disease may require radiation therapy.
- Routine dissection of the retroperitoneal lymph nodes is recommended for all patients aged 10 years or older (regardless of the imaging results) and for patients younger than 10 years whose images show retroperitoneal disease.
- Children younger than 10 years have a survival rate of nearly 95%. Children older than 10 years have a worse prognosis and an increased risk for involvement of the retroperitoneal lymph nodes; therefore, an aggressive approach with dissection of the retroperitoneal lymph nodes is recommended.
- Routine dissection of the retroperitoneal lymph nodes is not performed to manage prepubertal testicular tumors. The incidence of metastases to the retroperitoneal lymph nodes is lower for these tumors than for postpubertal testicular tumors. However, the prognosis of children older than 10 years who have rhabdomyosarcoma is poor; modified retroperitoneal lymph node dissection is now recommended for these patients.
Consultations
Consult a pediatric oncologist if chemotherapy is to be administered; consult radiation oncologists for external-beam irradiation as indicated.
Consult with a pediatric oncologist regarding chemotherapy for most current regimen and dosing (see Treatment).
Further Outpatient Care
- The type of tumor determines the need for further evaluation and follow-up care (see Surgical Care).
Complications
- Treatment-related complications include known short- and long-term effects of surgery, chemotherapy, and external-beam irradiation.
- The effects include risk of infertility, hemorrhagic cystitis, and subsequent development of secondary malignancy.
- Children should be counseled regarding these risks before treatment.
- Long-term follow-up care is required.
Prognosis
- The prognosis for patients with benign testicular lesions is excellent.
- Even for patients with metastatic yolk-sac tumor, survival with chemotherapy is approximately 90%.
- Patients with rhabdomyosarcoma have an overall survival rate of more than 70% when treated with multimodal therapy. Poor prognostic indicators include alveolar histology, age older than 7 years, unresectable retroperitoneal disease, and distant metastatic disease.
Patient Education
Medical/Legal Pitfalls
Special Concerns
- Because some testicular tumors appear in association with a hydrocele, the physician must consider ultrasonography if a hydrocele prevents physical examination of the testicle.
| Media file 1:
Ultrasonogram revealing cystic dysplasia of the testicle. |
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Media type: Ultrasound
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| Media file 2:
Ultrasonogram in an infant revealing a heterogeneous intratesticular mass that proved to be a juvenile granulosa-cell tumor. |
 | View Full Size Image | |
Media type: Ultrasound
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Prepubertal Testicular and Paratesticular Tumors excerpt Article Last Updated: Nov 1, 2007
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