Influence of Tumor Site and Histology on Long-Term Survival in 193 Children with Extracranial Germ Cell Tumors

Abstract

Aims: Although germ cell tumors (GCT) supposedly share the same cell type of origin, their clinical course differs considerably depending on tumor site and histology. The aim of this work was to study long-term survival stratified for tumor site and tumor histology. Materials and Methods: The medical records of 193 consecutive infants and children with extracranial GCT were studied. The GCT arose in the following anatomical sites: sacrococcygeal (n = 70), ovary (n = 66), testis (n = 20), retroperitoneum (n = 12), neck (n = 8), mediastinum (n = 7), and miscellaneous (n = 10). Histological analysis revealed 152 teratomas (mature: 115, immature: 37), 27 yolk sac tumors, 8 mixed tumors, 2 dysgerminomas, 2 gonadoblastomas, 1 choriocarcinoma and 1 embryonal carcinoma. Results: Overall survival (OS) for the whole patient group was 0.91 ± 0.02, and event-free survival (EFS) was 0.88 ± 0.02 at ten years. Patients with gonadal GCT had a higher probability of OS than those with extragonadal GCT (p = 0.029). Patients with cervical and mediastinal tumors had a lower probability of EFS than those with gonadal, retroperitoneal or sacrococcygeal GCT (p = 0.018). Patients with choriocarcinoma, embryonal carcinoma, immature teratoma, yolk sac tumor and mixed GCT had a lower probability of EFS than patients with mature teratoma or gonadoblastoma (p < 0.001). Conclusions: Mortality in children with extracranial germ cell tumors is not only dictated by malignant histology, but also, as in the case of mature teratomas, by occurrence at certain sites.

Key words

germ cell tumor - teratoma - childhood cancer - survival

References

• 1 Anteby E Y, Yagel S. Route of delivery of fetuses with structural anomalies.  Eur J Obstet Gynecol Reprod Biol. 2003;  106 5-9
• 2 Bezuidenhout J, Schneider J W, Hugo F, Wessels G. Teratomas in infancy and childhood at Tygerberg hospital, South Africa, 1973 to 1992.  Arch Pathol Lab Med. 1997;  121 499-502
• 3 Billmire D F, Grosfeld J L. Teratomas in childhood: analysis of 142 cases.  J Pediatr Surg. 1986;  21 548-551
• 4 Billmire D, Vinocur C, Rescorla F, Cushing B, London W, Schlatter M, Davis M, Giller R, Lauer S, Olson T. Outcome and staging evaluation in malignant germ cell tumors of the ovary in children and adolescents: an intergroup study.  J Pediatr Surg. 2004;  39 424-429
• 5 De Backer A, Madern G C, van de Ven C P, Tibboel D, Hazebroek F W. Strategy for the management of newborns with cervical teratoma.  J Perinat Med. 2004;  32 500-508
• 6 De Backer A, Madern G C, Hazebroek F W. Retroperitoneal germ cell tumors: a clinical study of 12 patients.  J Pediatr Surg. 2005;  40 1475-1481
• 7 De Backer A, Hakvoort-Cammel F G, Oosterhuis J W, Hazebroek F W. Mediastinal germ cell tumors in children: clinical aspects and outcome in 7 patients.  Eur J Pediatr Surg. 2006;  16 318-322
• 8 De Backer A, Madern G C, Hakvoort-Cammel F G, Haentjens P, Oosterhuis J W, Hazebroek F W. Study of the factors associated with recurrence in children with sacrococcygeal teratoma.  J Pediatr Surg. 2006;  41 173-181
• 9 De Backer A, Madern G C, Oosterhuis J W, Hakvoort-Cammel F G, Hazebroek F W. Ovarian germ cell tumors: a clinical study of 66 patients.  Pediatr Blood Cancer. 2006;  46 459-464
• 10 De Backer A, Madern G C, Wolffenbuttel K, Oosterhuis J W, Hakvoort-Cammel F G, Hazebroek F W. Testicular germ cell tumors in children: management and outcome in a series of 20 patients.  J Pediatr Urol. 2006;  2 197-201
• 11 Derikx J PM, De Backer A, van Der Schoot L, Aronson D C, de Langen Z J, van den Hoonaard T L, Bax N MA, van der Staak F, van Heurn L WE. Factors associated with recurrence and metastatic disease in sacrococcygeal teratoma: results in the Netherlands (1970 - 2003).  Br J Surg. 2006;  93 1543-1548
• 12 Göbel U, Schneider D T, Calaminus G, Haas R J, Schmidt P, Harms D. Germ cell tumors in childhood and adolescence.  Ann Oncol. 2000;  11 263-271
• 13 Göbel U, Schneider D T, Calaminus G, Jürgens H, Spaar H J, Sternschulte W, Waag K, Harms D. Multimodal treatment of malignant sacrococcygeal germ cell tumors: a prospective analysis of 66 patients of the German cooperative protocols MAKEI 83/86 and 89.  J Clin Oncol. 2001;  19 1943-1950
• 14 Hirose S, Farmer D L, Lee H, Nobuhara K K, Harrsion M R. The ex utero intrapartum treatment procedure: looking back at the EXIT.  J Pediatr Surg. 2004;  39 375-380
• 15 Isaacs H. Perinatal (fetal and neonatal) germ cell tumors.  J Pediatr Surg. 2004;  39 1003-1013
• 16 Lo Curto M, Lumia F, Alaggio R, Cecchetto G, Almasio P, Indolfi P, Siracusa F, Bagnulo S, De Bernardi B, De Laurentis T, Di Cataldo A, Tamaro P. Malignant germ cell tumors in childhood: results of the first Italian cooperative study group “TCG 91”.  Med Pediatr Oncol. 2003;  41 417-425
• 17 Marsden H B, Birch J M, Swindell R. Germ cell tumours of childhood: a review of 137 cases.  J Clin Pathol. 1981;  34 879-883
• 18 Mostofi F K, Sobin L H. Histopathological typing of testis tumors. Geneva; World Health Organization 1993
• 19 Norris H J, Zirkin H J, Benson W L. Immature (malignant) teratoma of the ovary. A clinical and pathologic study of 58 cases.  Cancer. 1976;  37 2359-2372
• 20 Oosterhuis J W, Looijenga H J. Testicular germ-cell tumours in a broader perspective.  Nat Rev Cancer. 2005;  5 210-222
• 21 Palmer R D, Nicholson J C, Hale J P. Management of germ cell tumours in childhood.  Current Paediatrics. 2003;  13 213-220
• 22 Pinkerton C R. Malignant germ cell tumours in childhood.  Eur J Cancer. 1997;  33 895-902
• 23 Reedijk A MJ, Janssen-Heijnen M LG, Louwman M WJ, Snepvangers Y, Hofhuis W JD, Coebergh J WW. Increasing incidence and improved survival of cancer in children and young adults in Southern Netherlands, 1973 - 1999.  Eur J Cancer. 2005;  41 760-769
• 24 Rescorla F J. Germ cell tumors.  Sem Pediatr Surg. 1997;  6 29-37
• 25 Schneider D T, Calaminus G, Koch S, Teske C, Schmidt P, Haas R J, Harms D, Göbel U. Epidemiologic analysis of 1442 children and adolescents registered in the German germ cell tumor protocols.  Pediatr Blood Cancer. 2004;  42 169-175
• 26 Serov S F, Scully R E, Sobin L H. Histological typing of ovarian tumors. International histological classification of tumors, no. 9. Geneva; World Health Organization 1973
• 27 Suita S, Shono K, Tajiri T, Takamatsu T, Mizote H, Nagasaki A, Inomata Y, Hara T, Okamura J, Miyazaki S, Kawakami K, Eguchi H, Tsuneyoshi M. Malignant germ cell tumors: clinical characteristics, treatment and outcome. A report from the study group for pediatric solid malignant tumors in the Kyushu area, Japan.  J Pediatr Surg. 2002;  37 1703-1706
• 28 Tapper D, Lack E E. Teratomas in infancy and childhood. A 54-year experience at the children's hospital medical center.  Ann Surg. 1983;  198 398-410