This treatment information summary on childhood (pediatric) extracranial germ cell tumors is an overview of the etiology, histologic classification, current treatment strategies, and prognosis for these patients. (Refer to the PDQ summary on Childhood Brain Tumors Treatment for more information regarding the management of patients with intracranial germ cell tumors.) The National Cancer Institute created the PDQ database to increase the availability of new treatment information and its use in treating patients. Information and references from the most recently published literature are included after review by pediatric oncology specialists.

In general, cancer in children and adolescents is rare. Children and adolescents with cancer should be referred to medical centers that have a multidisciplinary team of cancer specialists with experience treating the cancers that occur during childhood and adolescence. This multidisciplinary team incorporates the skills of the primary care physician, pediatric surgical subspecialists, radiation oncologist, pediatric hematologist/oncologist, rehabilitation specialists, pediatric nurse specialists, social workers, and others in order to ensure that children receive treatment, supportive care, and rehabilitation that will achieve optimal survival and quality of life. Guidelines for pediatric cancer centers and their role in the treatment of pediatric patients with cancer have been outlined by the American Academy of Pediatrics.[1] At these pediatric cancer centers, clinical trials are available for most of the types of cancer that occur in children and adolescents, and the opportunity to participate in these trials is offered to most patients/families. Clinical trials for children and adolescents with cancer are generally designed to compare potentially better therapy with therapy that is currently accepted as standard. The majority of the progress made in identifying curative therapies for childhood cancers has been achieved through clinical trials. Information about ongoing clinical trials is available from the NCI Cancer.gov Web site.

Childhood extracranial germ cell tumors are rare in children younger than 15 years, accounting for only 2% to 3% of cancer cases in this age group.[2] Extracranial germ cell tumors (particularly testicular germ cell tumors) are much more common among patients 15 to 19 years, representing approximately 14% of cancer diagnoses. The distribution of extracranial germ cell tumors by 5 year age group and by gender is shown in Table 1 below.

The germ cell tumors that arise in younger children have different biological characteristics from those that arise in adolescents and young adults. Biologically distinctive subtypes of germ cell tumors include the following:

• Testicular germ cell tumors of early childhood: These germ cell tumors commonly present with yolk sac tumor (endodermal sinus tumor) histology and are generally diploid or tetraploid and lack the isochromosome of the short arm of chromosome 12 that is characteristic of testicular cancer in young adults.[3-6] Deletions of chromosomes 1p, 4q, and 6q, and gains of chromosomes 1q, 3, and 20q are reported as recurring chromosomal abnormalities for this group of tumors.[5-7] Treatment for young boys with testicular germ cell tumors is summarized later in this document.



• Testicular germ cell tumors of the adolescent and young adult male: These tumors typically possess an isochromosome of the short arm of chromosome 12 [8-12] and are aneuploid.[3,11] Testicular cancer is broadly divided into seminomatous and nonseminomatous tumors, which is important for treatment planning because seminomas are more sensitive to radiation therapy. (Refer to the PDQ summary on Testicular Cancer Treatment for more information.)



• Extragonadal, extracranial germ cell tumors: These tumors typically present during early childhood. The majority of these tumors are benign teratomas occurring in the sacrococcygeal region, and hence they are not reported by SEER areas.[13,14] Malignant yolk sac tumor histology occurs in a minority of these tumors, however, with cytogenetic abnormalities similar to those observed for tumors occurring in the testes of young males.[4-7] Treatment for young children with nongonadal, noncentral nervous system germ cell tumors is also summarized in this document.



• Extragonadal, extracranial germ cell tumors of older children and adults: The most common primary sites for these tumors occur within the mediastinum.[15] Mediastinal germ cell tumors in children less than 8 years old share the same genetic gains and losses as sacrococcygeal and testicular tumors in young children.[16-18] The gain in chromosome 12p has been reported in mediastinal tumors in children 8 years and older.[18] Treatment for children with these extragonadal, extracranial germ cell tumors is summarized in this document.



• Ovarian germ cell tumors: These tumors occur primarily in adolescents and young adults. They show greater biological diversity than do germ cell tumors arising in the testes, and include benign mature teratomas, immature teratomas, and malignant germ cell tumors (dysgerminomas, yolk sac tumors, and mixed germ cell tumors). The latter, like their testicular counterparts, commonly show increased copies of the short arm of chromosome 12.[12] Treatment for girls and adolescents with ovarian malignant germ cell tumors is summarized elsewhere. (Refer to the PDQ summary on Ovarian Germ Cell Tumor Treatment for more information.)

These germ cell tumors originate in pluripotent germ cells,[19] are composed of elements from at least 1 of the 3 embryonic germ layers, and usually contain tissues foreign to the anatomic site of origin. In general, germ cell tumors encompass a variety of histologic diagnoses including teratomas and malignant germ cell tumors. The teratomas can be further classified as mature or immature and can be either pure or a component of a mixed malignant germ cell tumor.

Childhood extracranial germ cell tumors most commonly arise in midline extragonadal sites (including but not limited to the retroperitoneum, sacrococcygeal area, mediastinum, and neck), but can also occur at gonadal sites in either the ovaries or testes. Their typical midline location hypothetically relates to the deposition of primordial germ cells along their migration pathway from the hind gut-yolk sac region into the embryonic genital ridge.[19] The signs and symptoms produced by these tumors will vary according to their anatomic location. Generally, sacrococcygeal tumors can cause constipation and urinary retention, testicular tumors usually present as painless swelling or a mass, while ovarian tumors tend to cause increasing abdominal girth and pain.

Very little is known about the potential genetic or environmental factors associated with childhood extracranial germ cell tumors. Patients with Klinefelter’s syndrome, however,[20-22] appear to be at increased risk for mediastinal germ cell tumors, while patients with Swyer’s syndrome appear at increased risk for gonadoblastomas and germinomas.[23,24]

Primary site [25] and the stage of disease [25-27] appear to be the most important prognostic factors identified in patients with childhood extracranial germ cell tumors. The search for other factors (i.e., biologic or genetic) which could have an impact on outcome is ongoing. The appropriate therapy for patients with these tumors is discussed in detail in the treatment information section of this summary.

References

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3. Oosterhuis JW, Castedo SM, de Jong B, et al.: Ploidy of primary germ cell tumors of the testis. Pathogenetic and clinical relevance. Lab Invest 60 (1): 14-21, 1989.  [PUBMED Abstract]
   
   
4. Silver SA, Wiley JM, Perlman EJ: DNA ploidy analysis of pediatric germ cell tumors. Mod Pathol 7 (9): 951-6, 1994.  [PUBMED Abstract]
   
   
5. Perlman EJ, Cushing B, Hawkins E, et al.: Cytogenetic analysis of childhood endodermal sinus tumors: a Pediatric Oncology Group study. Pediatr Pathol 14 (4): 695-708, 1994 Jul-Aug.  [PUBMED Abstract]
   
   
6. Schneider DT, Schuster AE, Fritsch MK, et al.: Genetic analysis of childhood germ cell tumors with comparative genomic hybridization. Klin Padiatr 213 (4): 204-11, 2001 Jul-Aug.  [PUBMED Abstract]
   
   
7. Perlman EJ, Valentine MB, Griffin CA, et al.: Deletion of 1p36 in childhood endodermal sinus tumors by two-color fluorescence in situ hybridization: a pediatric oncology group study. Genes Chromosomes Cancer 16 (1): 15-20, 1996.  [PUBMED Abstract]
   
   
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9. Bosl GJ, Ilson DH, Rodriguez E, et al.: Clinical relevance of the i(12p) marker chromosome in germ cell tumors. J Natl Cancer Inst 86 (5): 349-55, 1994.  [PUBMED Abstract]
   
   
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11. van Echten J, Oosterhuis JW, Looijenga LH, et al.: No recurrent structural abnormalities apart from i(12p) in primary germ cell tumors of the adult testis. Genes Chromosomes Cancer 14 (2): 133-44, 1995.  [PUBMED Abstract]
    
    
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19. Dehner LP: Gonadal and extragonadal germ cell neoplasia of childhood. Hum Pathol 14 (6): 493-511, 1983.  [PUBMED Abstract]
    
    
20. Dexeus FH, Logothetis CJ, Chong C, et al.: Genetic abnormalities in men with germ cell tumors. J Urol 140 (1): 80-4, 1988.  [PUBMED Abstract]
    
    
21. Nichols CR, Heerema NA, Palmer C, et al.: Klinefelter's syndrome associated with mediastinal germ cell neoplasms. J Clin Oncol 5 (8): 1290-4, 1987.  [PUBMED Abstract]
    
    
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23. Coutin AS, Hamy A, Fondevilla M, et al.: [Pure 46XY gonadal dysgenesis] J Gynecol Obstet Biol Reprod (Paris) 25 (8): 792-6, 1996.  [PUBMED Abstract]
    
    
24. Amice V, Amice J, Bercovici JP, et al.: Gonadal tumor and H-Y antigen in 46,XY pure gonadal dysgenesis. Cancer 57 (7): 1313-7, 1986.  [PUBMED Abstract]
    
    
25. Ablin AR, Krailo MD, Ramsay NK, et al.: Results of treatment of malignant germ cell tumors in 93 children: a report from the Childrens Cancer Study Group. J Clin Oncol 9 (10): 1782-92, 1991.  [PUBMED Abstract]
    
    
26. Mann JR, Pearson D, Barrett A, et al.: Results of the United Kingdom Children's Cancer Study Group's malignant germ cell tumor studies. Cancer 63 (9): 1657-67, 1989.  [PUBMED Abstract]
    
    
27. Marina N, Fontanesi J, Kun L, et al.: Treatment of childhood germ cell tumors. Review of the St. Jude experience from 1979 to 1988. Cancer 70 (10): 2568-75, 1992.  [PUBMED Abstract]
    
    

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