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Childhood Extracranial Germ Cell Tumors Treatment (PDQ®): Treatment - Health Professional Information [NCI] - Histologic Classification of Childhood Extracranial GCTs

Childhood extracranial germ cell tumors (GCTs) comprise a variety of histologic diagnoses and can be broadly classified into mature or immature teratomas and malignant GCTs.

Mature Teratomas

Mature teratomas usually occur in the ovary or at extragonadal locations and are the most common histological subtype of childhood GCT.[1,2,3] These teratomas usually contain well-differentiated tissues from the ectodermal, mesodermal, and endodermal germ cell layers, and any tissue type may be found within the tumor. Mature teratomas are benign, though some mature and immature teratomas may secrete enzymes or hormones, including insulin, growth hormone, androgens, prolactin, and vasopressin.[4,5,6]

Immature Teratomas

Immature teratomas contain tissues from all three germ cell layers, but immature tissues, primarily neuroepithelial, are also present. Immature teratomas are graded from 0 to 3 based on the amount of immature neural tissue found in the tumor specimen.[7] Tumors of higher grade are more likely to have foci of yolk sac tumor.[8] Immature teratomas occur primarily in young children at extragonadal sites and in the ovaries of girls near the age of puberty, but there is no correlation between tumor grade and patient age.[8,9]

Malignant GCTs

GCTs contain frankly malignant tissues of germ cell origin, and rarely, tissues of somatic origin. Isolated malignant elements may constitute a small fraction of a predominantly mature or immature teratoma.[9,10] Malignant germ cell elements of children, adolescents, and young adults can broadly be classified by location (see Tables 2 and 3).

Table 2. Histology of Malignant Germ Cell Tumors in Young Childrena

Malignant Germ Cell ElementsLocation
E = extragonadal; O = ovarian; T = testicular.
a Modified from Perlman et al.[11]
Yolk sac tumorE, O, T
Dysgerminoma (rare in young children)O

Table 3. Histology of Malignant Germ Cell Tumors in Adolescents and Young Adultsa

Malignant Germ Cell ElementsLocation
E = extragonadal; O = ovarian; T = testicular.
a Modified from Perlman et al.[11]
Yolk sac tumorE, O, T
ChoriocarcinomaE, O, T
Embryonal carcinomaT
Mixed germ cell tumorsE, O

Yolk sac tumors produce alpha-fetoprotein (AFP), while germinomas (seminomas and dysgerminomas), and especially choriocarcinomas, produce beta-human chorionic gonadotropin, resulting in elevated serum levels of these substances. Most children with malignant GCTs will have a component of yolk sac tumor and have elevations of AFP,[12,13] which is serially monitored during treatment to help assess response to therapy.[9,10,12]

Adolescents and young adults present with more germinomas (testicular and mediastinal seminomas in males and ovarian dysgerminomas in females). These tumors are usually treated with chemotherapy. They are also sensitive to radiation therapy, but radiation is rarely recommended. Radiation therapy and surgery for the patient with brain metastases may provide palliation and occasionally, long-term survival.[14][Level of evidence: 3iiiA]


  1. Göbel U, Calaminus G, Engert J, et al.: Teratomas in infancy and childhood. Med Pediatr Oncol 31 (1): 8-15, 1998.
  2. Rescorla FJ: Pediatric germ cell tumors. Semin Surg Oncol 16 (2): 144-58, 1999.
  3. Harms D, Zahn S, Göbel U, et al.: Pathology and molecular biology of teratomas in childhood and adolescence. Klin Padiatr 218 (6): 296-302, 2006 Nov-Dec.
  4. Tomlinson MW, Alaverdian AA, Alaverdian V: Testosterone-producing benign cystic teratoma with virilism. A case report. J Reprod Med 41 (12): 924-6, 1996.
  5. Lam SK, Cheung LP: Inappropriate ADH secretion due to immature ovarian teratoma. Aust N Z J Obstet Gynaecol 36 (1): 104-5, 1996.
  6. Kallis P, Treasure T, Holmes SJ, et al.: Exocrine pancreatic function in mediastinal teratomata: an aid to preoperative diagnosis? Ann Thorac Surg 54 (4): 741-3, 1992.
  7. Norris HJ, Zirkin HJ, Benson WL: Immature (malignant) teratoma of the ovary: a clinical and pathologic study of 58 cases. Cancer 37 (5): 2359-72, 1976.
  8. Heifetz SA, Cushing B, Giller R, et al.: Immature teratomas in children: pathologic considerations: a report from the combined Pediatric Oncology Group/Children's Cancer Group. Am J Surg Pathol 22 (9): 1115-24, 1998.
  9. Marina NM, Cushing B, Giller R, et al.: Complete surgical excision is effective treatment for children with immature teratomas with or without malignant elements: A Pediatric Oncology Group/Children's Cancer Group Intergroup Study. J Clin Oncol 17 (7): 2137-43, 1999.
  10. Göbel U, Calaminus G, Schneider DT, et al.: The malignant potential of teratomas in infancy and childhood: the MAKEI experiences in non-testicular teratoma and implications for a new protocol. Klin Padiatr 218 (6): 309-14, 2006 Nov-Dec.
  11. Perlman EJ, Hawkins EP: Pediatric germ cell tumors: protocol update for pathologists. Pediatr Dev Pathol 1 (4): 328-35, 1998 Jul-Aug.
  12. Mann JR, Raafat F, Robinson K, et al.: The United Kingdom Children's Cancer Study Group's second germ cell tumor study: carboplatin, etoposide, and bleomycin are effective treatment for children with malignant extracranial germ cell tumors, with acceptable toxicity. J Clin Oncol 18 (22): 3809-18, 2000.
  13. 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.
  14. Göbel U, Schneider DT, Teske C, et al.: Brain metastases in children and adolescents with extracranial germ cell tumor - data of the MAHO/MAKEI-registry. Klin Padiatr 222 (3): 140-4, 2010.

WebMD Public Information from the National Cancer Institute

Last Updated: February 25, 2014
This information is not intended to replace the advice of a doctor. Healthwise disclaims any liability for the decisions you make based on this information.
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