Rare Tumors In Children and Adolescents pp 205-211

Part of the Pediatric Oncology book series (PEDIATRICO) | Cite as

Mediastinal Germ Cell Tumors

  • Dominik T. Schneider
  • Giovanni Cecchetto
  • Thomas A. Olson
Chapter

Abstract

The general aspects of germ cell tumors common to all germ cell tumors occurring at different sites are discussed in the chapters of gonadal germ cell tumors (see Chap. 39). In the thorax, germ cell tumors almost exclusively develop in midline locations, mostly in the anterior mediastinum. Therefore, it has been debated whether such extragonadal germ cell tumors, in particular teratomas may originate from midline somatic stem cells. On the other hand, there is molecular evidence that both gonadal and extragonadal germ cell tumors indeed originate from primordial germ cells at different stages of development. Thus, the examination of the epigenetic control of genomic imprinting reveals a methylation pattern that is characteristic of primordial germ cells during and shortly after their migration during early embryonal development (Schneider et al. 2001b; Bussey et al. 2001). In addition, this methylation pattern distinguishes germ cell tumors from other embryonal tumors with presumed stem cell origin such as nephroblastoma (Sievers et al. 2005), thus substantiating the hypothesis of their specific germ cell origin.

References

  1. Afifi HY, Bosl GJ, Burt ME (1997) Mediastinal growing teratoma syndrome. Ann Thorac Surg 64:359–362PubMedCrossRefGoogle Scholar
  2. Billmire D, Vinocur C, Rescorla F, Colombani P, Cushing B, Hawkins E, London WB, Giller R, Lauer S (2001) Malignant mediastinal germ cell tumors: an intergroup study. J Pediatr Surg 36:18–24PubMedCrossRefGoogle Scholar
  3. Blohm ME, Vesterling-Hörner D, Calaminus G, Göbel U (1998) Alpha 1-fetoprotein (AFP) reference values in infants up to 2 years of age. Pediatr Hematol Oncol 15:135–142PubMedCrossRefGoogle Scholar
  4. Bokemeyer C, Nichols CR, Droz JP, Schmoll HJ, Horwich A, Gerl A, Fossa SD, Beyer J, Pont J, Kanz L, Einhorn L, Hartmann JT (2002) Extragonadal germ cell tumors of the mediastinum and retroperitoneum: results from an international analysis. J Clin Oncol 20:1864–1873PubMedCrossRefGoogle Scholar
  5. Bokemeyer C, Schleucher N, Metzner B, Thomas M, Rick O, Schmoll HJ, Kollmannsberger C, Boehlke I, Kanz L, Hartmann JT (2003) First-line sequential high-dose VIP chemotherapy with autologous transplantation for patients with primary mediastinal nonseminomatous germ cell tumours: a prospective trial. Br J Cancer 89:29–35PubMedCrossRefGoogle Scholar
  6. Bussey KJ, Lawce HJ, Himoe E, Shu XO, Heerema NA, Perlman EJ, Olson SB, Magenis RE (2001) SNRPN methylation patterns in germ cell tumors as a reflection of primordial germ cell development. Genes Chromosomes Cancer 32:342–352PubMedCrossRefGoogle Scholar
  7. Calaminus G, Schneider DT, Weissbach L, Schönberger S, Okpanyi V, Leuschner I, Poremba C, Göbel U (2009) Survival after an antiangiogenetic therapy and surgery in a wide spread growing teratoma originating from a testicular mixed malignant germ cell tumor. Klin Padiatr 221:136–140PubMedCrossRefGoogle Scholar
  8. Chaganti RS, Houldsworth J (1998) The cytogenetic theory of the pathogenesis of human adult male germ cell tumors. APMIS 106:80–83; discussion 83–84PubMedCrossRefGoogle Scholar
  9. Chaganti RS, Ladanyi M, Samaniego F, Offit K, Reuter VE, Jhanwar SC, Bosl GJ (1989) Leukemic differentiation of a mediastinal germ cell tumor. Genes Chromosomes Cancer 1:83–87PubMedCrossRefGoogle Scholar
  10. Cushing B, Giller R, Cullen JW, Marina NM, Lauer SJ, Olson TA, Rogers PC, Colombani P, Rescorla F, Billmire DF, Vinocur CD, Hawkins EP, Davis MM, Perlman EJ, London WB, Castleberry RP (2004) Randomized comparison of combination chemotherapy with etoposide, bleomycin, and either high-dose or standard-dose cisplatin in children and adolescents with high-risk malignant germ cell tumors: a pediatric intergroup study – Pediatric Oncology Group 9049 and Children’s Cancer Group 8882. J Clin Oncol 22:2691–2700PubMedCrossRefGoogle Scholar
  11. De SM, Bokemeyer C, Becherer A, Stoiber F, Oechsle K, Kletter K, Dohmen BM, Dittrich C, Pont J (2001) Predictive impact of 2-18fluoro-2-deoxy-D-glucose positron emission tomography for residual postchemotherapy masses in patients with bulky seminoma. J Clin Oncol 19:3740–3744Google Scholar
  12. Donadio AC, Motzer RJ, Bajorin DF, Kantoff PW, Sheinfeld J, Houldsworth J, Chaganti RSK, Bosl GJ (2003) Chemotherapy for teratoma with malignant transformation. J Clin Oncol 21:4285–4291PubMedCrossRefGoogle Scholar
  13. Fizazi K, Culine S, Droz JP, Kramar A, Theodore C, Ruffie P, Le CT (1998) Primary mediastinal nonseminomatous germ cell tumors: results of modern therapy including cisplatin-based chemotherapy. J Clin Oncol 16:725–732PubMedGoogle Scholar
  14. Frazier AL, Rumcheva P, Olson T, Giller R, Cushing B, Cullen J, Marina N, London WB (2008) Application of the adult international germ cell classification system to pediatric malignant non-seminomatous germ cell tumors: a report from the Children’s Oncology Group. Pediatr Blood Cancer 50:746–751PubMedCrossRefGoogle Scholar
  15. Ganjoo KN, Rieger KM, Kesler KA, Sharma M, Heilman DK, Einhorn LH (2000) Results of modern therapy for patients with mediastinal nonseminomatous germ cell tumors. Cancer 88:1051–1056PubMedCrossRefGoogle Scholar
  16. Gobbi D, Rubino M, Chiandetti L, Zanon GF, Cecchetto G (2007) Neonatal intrapericardial teratoma: a challenge for the pediatric surgeon. J Pediatr Surg 42:E3–E6PubMedCrossRefGoogle Scholar
  17. Göbel U, Schneider DT, Teske C, Schönberger S, Calaminus G (2010) Brain metastases in children and adolescents with extracranial germ cell tumor - data of the MAHO/MAKEI-registry. Klin Pädiatr 222:140–144PubMedCrossRefGoogle Scholar
  18. Goel D, Prayaga AK, Sundaram C, Raghunadharao D, Rajappa SJ, Rammurti S, Rao TM, Kumar RV (2008) Utility of fine needle aspiration cytology in mediastinal lesions: a clinicopathologic study of 1617 cases from a single institution. Acta Cytol 52:404–411PubMedCrossRefGoogle Scholar
  19. Grosfeld JL, Skinner MA, Rescorla FJ, West KW, Scherer LR III (1994) Mediastinal tumors in children: experience with 196 cases. Ann Surg Oncol 1:121–127PubMedCrossRefGoogle Scholar
  20. Group, IGCCC (1997) International Germ Cell Consensus Classification: a prognostic factor- based staging system for metastatic germ cell cancers. International Germ Cell Cancer Collaborative Group. J Clin Oncol 15:594–603Google Scholar
  21. Hainsworth JD (2002) Diagnosis, staging, and clinical characteristics of the patient with mediastinal germ cell carcinoma. Chest Surg Clin N Am 12:665–672PubMedCrossRefGoogle Scholar
  22. Hartmann JT, Nichols CR, Droz JP, Horwich A, Gerl A, Fossa SD, Beyer J, Pont J, Fizazi K, Einhorn L, Kanz L, Bokemeyer C (2000) Hematologic disorders associated with primary mediastinal nonseminomatous germ cell tumors. J Natl Cancer Inst 92:54–61PubMedCrossRefGoogle Scholar
  23. Kaplan SS, Bornstein SG, Christopherson WA, Surti U (1991) Associated leukemia and mixed germ cell tumor in a patient with gonadal dysgenesis. Int J Gynaecol Obstet 35:83–88PubMedCrossRefGoogle Scholar
  24. Koo CH, Reifel J, Kogut N, Cove JK, Rappaport H (1992) True histiocytic malignancy associated with a malignant teratoma in a patient with 46XY gonadal dysgenesis. Am J Surg Pathol 16:175–183PubMedCrossRefGoogle Scholar
  25. Logothetis CJ, Samuels ML, Trindade A, Johnson DE (1982) The growing teratoma syndrome. Cancer 50:1629–1635PubMedCrossRefGoogle Scholar
  26. Mann JR, Raafat F, Robinson K, Imeson J, Gornall P, Sokal M, Gray E, McKeever P, Hale J, Bailey S, Oakhill A (2000) 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 18:3809–3818PubMedGoogle Scholar
  27. Mayer F, Stoop H, Scheffer GL, Scheper R, Oosterhuis JW, Looijenga LH, Bokemeyer C (2003) Molecular determinants of treatment response in human germ cell tumors. Clin Cancer Res 9:767–773PubMedGoogle Scholar
  28. Motzer RJ, Amsterdam A, Prieto V, Sheinfeld J, Murty VV, Mazumdar M, Bosl GJ, Chaganti RS, Reuter VE (1998) Teratoma with malignant transformation: diverse malignant histologies arising in men with germ cell tumors. J Urol 159:133–138PubMedCrossRefGoogle Scholar
  29. Nichols CR, Heerema NA, Palmer C, Loehrer PJ Sr, Williams SD, Einhorn LH (1987) Klinefelter’s syndrome associated with mediastinal germ cell neoplasms. J Clin Oncol 5:1290–1294PubMedGoogle Scholar
  30. Nichols CR, Roth BJ, Heerema N, Griep J, Tricot G (1990) Hematologic neoplasia associated with primary mediastinal germ- cell tumors. N Engl J Med 322:1425–1429PubMedCrossRefGoogle Scholar
  31. Olak J (1996) Parasternal mediastinotomy (Chamberlain procedure). Chest Surg Clin N Am 6:31–40PubMedGoogle Scholar
  32. Oosterhuis JW, Van den Berg E, de Jong B, Timens W, Castedo SM, Rammeloo RH, Sleijfer DT (1991) Mediastinal germ cell tumor with secondary nongerm cell malignancy, and extensive hematopoietic activity. Pathology, DNA-ploidy, and karyotyping. Cancer Genet Cytogenet 54:183–195PubMedCrossRefGoogle Scholar
  33. Orazi A, Neiman RS, Ulbright TM, Heerema NA, John K, Nichols CR (1993) Hematopoietic precursor cells within the yolk sac tumor component are the source of secondary hematopoietic malignancies in patients with mediastinal germ cell tumors. Cancer 71:3873–3881PubMedCrossRefGoogle Scholar
  34. Postovsky S, Epelbaum M, Ben Itzhak O, Beck D, Ben Arush MW (2004) Growing teratoma syndrome treated by interferon alpha-2beta: case report and literature review. Pediatr Hematol Oncol 21:9–16PubMedGoogle Scholar
  35. Priola SM, Priola AM, Cardinale L, Perotto F, Fava C (2006) The anterior mediastinum: anatomy and imaging procedures. Radiol Med 111:295–311PubMedCrossRefGoogle Scholar
  36. Schmoll HJ, Kollmannsberger C, Metzner B, Hartmann JT, Schleucher N, Schoffski P, Schleicher J, Rick O, Beyer J, Hossfeld D, Kanz L, Berdel WE, Andreesen R, Bokemeyer C (2003) Long-term results of first-line sequential high-dose etoposide, ifosfamide, and cisplatin chemotherapy plus autologous stem cell support for patients with advanced metastatic germ cell cancer: an extended phase I/II study of the German Testicular Cancer Study Group. J Clin Oncol 21:4083–4091PubMedCrossRefGoogle Scholar
  37. Schneider DT, Calaminus G, Reinhard H, Gutjahr P, Kremens B, Harms D, Göbel U (2000) Primary mediastinal germ cell tumors in children and adolescents: results of the German cooperative protocols MAKEI 83/86, 89, and 96. J Clin Oncol 18:832–839PubMedGoogle Scholar
  38. Schneider DT, Calaminus G, Göbel U (2001a) Diagnostic value of alpha_1_-fetoprotein and human chorionic gonadotropic hormone in infancy and childhood. Pediatr Hematol Oncol 18:11–26PubMedCrossRefGoogle Scholar
  39. Schneider DT, Schuster AE, Fritsch MK, Hu J, Olson T, Lauer S, Göbel U, Perlman EJ (2001b) Multipoint imprinting analysis indicates a common precursor cell for gonadal and nongonadal pediatric germ cell tumors. Cancer Res 61:7268–7276PubMedGoogle Scholar
  40. Schneider DT, Perlman EJ, Harms D, Fritsch MK, Calaminus G, Göbel U (2002a) Mediastinal germ cell tumors (MGCT) in children and adolescents: age correlates with histological differentiation, genetic profiles and clinical outcome. In: Harnden P, Joffe JK, Jones WG (eds) Germ cell tumours V(26). Springer, London, pp 127–128Google Scholar
  41. Schneider DT, Schuster AE, Fritsch MK, Calaminus G, Göbel U, Harms D, Lauer S, Olson T, Perlman EJ (2002b) Genetic analysis of mediastinal nonseminomatous germ cell tumors in children and adolescents. Genes Chromosomes Cancer 34:115–125PubMedCrossRefGoogle Scholar
  42. Schneider DT, Calaminus G, Koch S, Teske C, Schmidt P, Haas RJ, Harms D, Göbel U (2004) Epidemiologic analysis of 1,442 children and adolescents registered in the German germ cell tumor protocols. Pediatr Blood Cancer 42:169–175PubMedCrossRefGoogle Scholar
  43. Shamberger RC, Holzman RS, Griscom NT, Tarbell NJ, Weinstein HJ (1991) CT quantitation of tracheal cross-sectional area as a guide to the surgical and anesthetic management of children with anterior mediastinal masses. J Pediatr Surg 26:138–142PubMedCrossRefGoogle Scholar
  44. Sievers S, Alemazkour K, Zahn S, Perlman EJ, Gillis AJ, Looijenga L, Göbel U, Schneider DT (2005) IGF2/H19 imprinting analysis with the methylation-sensitive single nucleotide primer extension method in human germ cell tumors reflects their origin from different stages of primordial germ cell development. Genes Chromosomes Cancer 44:256–264PubMedCrossRefGoogle Scholar
  45. Van den Belt-Dusebout AW, Nuver J, de Wit R, Gietema JA, ten Bokkel Huinink WW, Rodrigus PTR, Schimmel EC, Aleman BMP, van Leeuwen FE (2006) Long-term risk of cardiovascular disease in 5-year survivors of testicular cancer. J Clin Oncol 24:467–475PubMedCrossRefGoogle Scholar

Copyright information

© Springer-Verlag Berlin Heidelberg 2012

Authors and Affiliations

  • Dominik T. Schneider
    • 1
  • Giovanni Cecchetto
    • 2
  • Thomas A. Olson
    • 3
  1. 1.Klinik für Kinder- und JugendmedizinClinic of PediatricsDortmundGermany
  2. 2.Department of Pediatrics, Pediatric SurgeryUniversity of PaduaPaduaItaly
  3. 3.Division Pediatric Hematology/OncologyChildren’s Healthcare of Atlanta at EglestonAtlantaUSA

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