Official reprint from UpToDate®
www.uptodate.com ©2016 UpToDate®

Extragonadal germ cell tumors involving the mediastinum and retroperitoneum

Philip W Kantoff, MD
Section Editor
William K Oh, MD
Deputy Editors
Michael E Ross, MD
Helen Hollingsworth, MD


Germ cell tumors (GCTs) are classified as extragonadal if there is no evidence of a primary tumor in the testes or ovaries [1]. Extragonadal GCTs typically arise in midline locations, and specific sites vary with age. In adults, the most common sites, in order of frequency, are the anterior mediastinum, retroperitoneum, and the pineal and suprasellar regions. In infants and young children, sacrococcygeal and intracranial GCTs are most common. (See "Uncommon brain tumors" and "Sacrococcygeal germ cell tumors" and "Intracranial germ cell tumors".)

Histologically, extragonadal GCTs are classified as seminomas (termed dysgerminomas in women), nonseminomatous GCTs (termed nondysgerminomas in women), mature teratomas, and immature teratomas [1]. (See "Pathology of mediastinal tumors".)

Seminomas and dysgerminomas must be distinguished from nonseminomatous and nondysgerminomatous GCTs because of the differences in prognosis and treatment. In children, these tumors are often referred to as germinomas and nongerminomas.

The nonseminomatous tumors, like the nondysgerminomas and nongerminomas, include yolk sac tumors, choriocarcinomas, embryonal carcinomas, teratomas, and mixed tumors that contain more than one cell line.

Mature teratomas of the mediastinum generally behave in a benign manner, unlike testicular GCTs where there is no clear prognostic distinction between mature and immature teratoma. In adults, immature teratomas of the mediastinum can be aggressive tumors similar to other nonseminomas and have a poor prognosis, whereas in prepubertal children, immature elements in a teratoma are not associated with malignant behavior [2,3]. (See "Pathology of mediastinal tumors".)


Subscribers log in here

To continue reading this article, you must log in with your personal, hospital, or group practice subscription. For more information or to purchase a personal subscription, click below on the option that best describes you:
Literature review current through: Sep 2016. | This topic last updated: Sep 10, 2015.
The content on the UpToDate website is not intended nor recommended as a substitute for medical advice, diagnosis, or treatment. Always seek the advice of your own physician or other qualified health care professional regarding any medical questions or conditions. The use of this website is governed by the UpToDate Terms of Use ©2016 UpToDate, Inc.
  1. Wick MR, Perlman EJ, Orazi A, Muller-Hermelink HK. Germ cell tumours of the mediastinum. In: Tumours of the Lung, Pleura, Thymus and Heart, Travis WD, Brambilla E, Muller-Hermelink HK, Harris CC. (Eds).
  2. Marina N, London WB, Frazier AL, et al. Prognostic factors in children with extragonadal malignant germ cell tumors: a pediatric intergroup study. J Clin Oncol 2006; 24:2544.
  3. McKenney JK, Heerema-McKenney A, Rouse RV. Extragonadal germ cell tumors: a review with emphasis on pathologic features, clinical prognostic variables, and differential diagnostic considerations. Adv Anat Pathol 2007; 14:69.
  4. Glenn OA, Barkovich AJ. Intracranial germ cell tumors: a comprehensive review of proposed embryologic derivation. Pediatr Neurosurg 1996; 24:242.
  5. Chaganti RS, Houldsworth J. Genetics and biology of adult human male germ cell tumors. Cancer Res 2000; 60:1475.
  6. Hailemariam S, Engeler DS, Bannwart F, Amin MB. Primary mediastinal germ cell tumor with intratubular germ cell neoplasia of the testis--further support for germ cell origin of these tumors: a case report. Cancer 1997; 79:1031.
  7. Chaganti RS, Rodriguez E, Mathew S. Origin of adult male mediastinal germ-cell tumours. Lancet 1994; 343:1130.
  8. Daugaard G, Rørth M, von der Maase H, Skakkebaek NE. Management of extragonadal germ-cell tumors and the significance of bilateral testicular biopsies. Ann Oncol 1992; 3:283.
  9. Schmoll HJ, Souchon R, Krege S, et al. European consensus on diagnosis and treatment of germ cell cancer: a report of the European Germ Cell Cancer Consensus Group (EGCCCG). Ann Oncol 2004; 15:1377.
  10. Hartmann JT, Fossa SD, Nichols CR, et al. Incidence of metachronous testicular cancer in patients with extragonadal germ cell tumors. J Natl Cancer Inst 2001; 93:1733.
  11. Chen CK, Chang YL, Jou ST, et al. Treatment of mediastinal immature teratoma in a child with precocious puberty and Klinefelter's syndrome. Ann Thorac Surg 2006; 82:1906.
  12. Phowthongkum P. The second case of de novo intracranial germinoma association with Klinefelter's syndrome. Surg Neurol 2006; 66:332; author reply 332.
  13. Aguirre D, Nieto K, Lazos M, et al. Extragonadal germ cell tumors are often associated with Klinefelter syndrome. Hum Pathol 2006; 37:477.
  14. Völkl TM, Langer T, Aigner T, et al. Klinefelter syndrome and mediastinal germ cell tumors. Am J Med Genet A 2006; 140:471.
  15. Böhle A, Studer UE, Sonntag RW, Scheidegger JR. Primary or secondary extragonadal germ cell tumors? J Urol 1986; 135:939.
  16. McAleer JJ, Nicholls J, Horwich A. Does extragonadal presentation impart a worse prognosis to abdominal germ-cell tumours? Eur J Cancer 1992; 28A:825.
  17. Comiter CV, Renshaw AA, Benson CB, Loughlin KR. Burned-out primary testicular cancer: sonographic and pathological characteristics. J Urol 1996; 156:85.
  18. Balzer BL, Ulbright TM. Spontaneous regression of testicular germ cell tumors: an analysis of 42 cases. Am J Surg Pathol 2006; 30:858.
  19. Hainsworth JD, Johnson DH, Greco FA. Cisplatin-based combination chemotherapy in the treatment of poorly differentiated carcinoma and poorly differentiated adenocarcinoma of unknown primary site: results of a 12-year experience. J Clin Oncol 1992; 10:912.
  20. Currow DC, Findlay M, Cox K, Harnett PR. Elevated germ cell markers in carcinoma of uncertain primary site do not predict response to platinum based chemotherapy. Eur J Cancer 1996; 32A:2357.
  21. Pavlidis N, Kalef-Ezra J, Briassoulis E, et al. Evaluation of six tumor markers in patients with carcinoma of unknown primary. Med Pediatr Oncol 1994; 22:162.
  22. Yonemori K, Ando M, Shibata T, et al. Tumor-marker analysis and verification of prognostic models in patients with cancer of unknown primary, receiving platinum-based combination chemotherapy. J Cancer Res Clin Oncol 2006; 132:635.
  23. Motzer RJ, Rodriguez E, Reuter VE, et al. Molecular and cytogenetic studies in the diagnosis of patients with poorly differentiated carcinomas of unknown primary site. J Clin Oncol 1995; 13:274.
  24. Bokemeyer C, Nichols CR, Droz JP, et al. Extragonadal germ cell tumors of the mediastinum and retroperitoneum: results from an international analysis. J Clin Oncol 2002; 20:1864.
  25. Cameron RB, Loehrer PJ, Thomas CR. Neoplasms of the mediastinum. In: Cancer: Principles and Practice of Oncology, DeVita VT, Hellman S, Rosenber SA (Eds), Lippincott Williams & Wilkins, New York 2001.
  26. Lewis BD, Hurt RD, Payne WS, et al. Benign teratomas of the mediastinum. J Thorac Cardiovasc Surg 1983; 86:727.
  27. Adebonojo SA, Nicola ML. Teratoid tumors of the mediastinum. Am Surg 1976; 42:361.
  28. Gunes S, Varon J, Walsh G. Mediastinal teratoma presenting as massive hemoptysis in an adult. J Emerg Med 1997; 15:313.
  29. Polansky SM, Barwick KW, Ravin CE. Primary mediastinal seminoma. AJR Am J Roentgenol 1979; 132:17.
  30. Moeller KH, Rosado-de-Christenson ML, Templeton PA. Mediastinal mature teratoma: imaging features. AJR Am J Roentgenol 1997; 169:985.
  31. Dulmet EM, Macchiarini P, Suc B, Verley JM. Germ cell tumors of the mediastinum. A 30-year experience. Cancer 1993; 72:1894.
  32. Takeda S, Miyoshi S, Ohta M, et al. Primary germ cell tumors in the mediastinum: a 50-year experience at a single Japanese institution. Cancer 2003; 97:367.
  33. Feo CF, Chironi G, Porcu A, et al. Videothoracoscopic removal of a mediastinal teratoma. Am Surg 1997; 63:459.
  34. Arai K, Ohta S, Suzuki M, Suzuki H. Primary immature mediastinal teratoma in adulthood. Eur J Surg Oncol 1997; 23:64.
  35. Donadio AC, Motzer RJ, Bajorin DF, et al. Chemotherapy for teratoma with malignant transformation. J Clin Oncol 2003; 21:4285.
  36. Moran CA, Suster S, Przygodzki RM, Koss MN. Primary germ cell tumors of the mediastinum: II. Mediastinal seminomas--a clinicopathologic and immunohistochemical study of 120 cases. Cancer 1997; 80:691.
  37. 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 1997; 15:594.
  38. Bokemeyer C, Droz JP, Horwich A, et al. Extragonadal seminoma: an international multicenter analysis of prognostic factors and long term treatment outcome. Cancer 2001; 91:1394.
  39. Samuels ML, Johnson DE, Holoye PY, Lanzotti VJ. Large-dose bleomycin therapy and pulmonary toxicity. A possible role of prior radiotherapy. JAMA 1976; 235:1117.
  40. Horwich A, Paluchowska B, Norman A, et al. Residual mass following chemotherapy of seminoma. Ann Oncol 1997; 8:37.
  41. Duchesne GM, Stenning SP, Aass N, et al. Radiotherapy after chemotherapy for metastatic seminoma--a diminishing role. MRC Testicular Tumour Working Party. Eur J Cancer 1997; 33:829.
  42. Schultz SM, Einhorn LH, Conces DJ Jr, et al. Management of postchemotherapy residual mass in patients with advanced seminoma: Indiana University experience. J Clin Oncol 1989; 7:1497.
  43. Motzer R, Bosl G, Heelan R, et al. Residual mass: an indication for further therapy in patients with advanced seminoma following systemic chemotherapy. J Clin Oncol 1987; 5:1064.
  44. Puc HS, Heelan R, Mazumdar M, et al. Management of residual mass in advanced seminoma: results and recommendations from the Memorial Sloan-Kettering Cancer Center. J Clin Oncol 1996; 14:454.
  45. De Santis M, Bokemeyer C, Becherer A, et al. Predictive impact of 2-18fluoro-2-deoxy-D-glucose positron emission tomography for residual postchemotherapy masses in patients with bulky seminoma. J Clin Oncol 2001; 19:3740.
  46. Hinz S, Schrader M, Kempkensteffen C, et al. The role of positron emission tomography in the evaluation of residual masses after chemotherapy for advanced stage seminoma. J Urol 2008; 179:936.
  47. Hainsworth JD, Greco FA. Extragonadal germ cell tumors and unrecognized germ cell tumors. Semin Oncol 1992; 19:119.
  48. Jain KK, Bosl GJ, Bains MS, et al. The treatment of extragonadal seminoma. J Clin Oncol 1984; 2:820.
  49. Hartmann JT, Nichols CR, Droz JP, et al. Hematologic disorders associated with primary mediastinal nonseminomatous germ cell tumors. J Natl Cancer Inst 2000; 92:54.
  50. Moran CA, Suster S, Koss MN. Primary germ cell tumors of the mediastinum: III. Yolk sac tumor, embryonal carcinoma, choriocarcinoma, and combined nonteratomatous germ cell tumors of the mediastinum--a clinicopathologic and immunohistochemical study of 64 cases. Cancer 1997; 80:699.
  51. Knapp RH, Hurt RD, Payne WS, et al. Malignant germ cell tumors of the mediastinum. J Thorac Cardiovasc Surg 1985; 89:82.
  52. Fizazi K, Culine S, Droz JP, et al. Primary mediastinal nonseminomatous germ cell tumors: results of modern therapy including cisplatin-based chemotherapy. J Clin Oncol 1998; 16:725.
  53. Fizazi K, Pagliaro LC, Flechon A, et al. A phase III trial of personalized chemotherapy based on serum tumor decline in poor-prognosis germ-cell tumors: Results of GETUG 13. J Clin Oncol 31, 2013 (suppl; abstr LBA4500).
  54. Kesler KA, Rieger KM, Hammoud ZT, et al. A 25-year single institution experience with surgery for primary mediastinal nonseminomatous germ cell tumors. Ann Thorac Surg 2008; 85:371.
  55. Vuky J, Bains M, Bacik J, et al. Role of postchemotherapy adjunctive surgery in the management of patients with nonseminoma arising from the mediastinum. J Clin Oncol 2001; 19:682.
  56. Radaideh SM, Cook VC, Kesler KA, Einhorn LH. Outcome following resection for patients with primary mediastinal nonseminomatous germ-cell tumors and rising serum tumor markers post-chemotherapy. Ann Oncol 2010; 21:804.
  57. Ganjoo KN, Rieger KM, Kesler KA, et al. Results of modern therapy for patients with mediastinal nonseminomatous germ cell tumors. Cancer 2000; 88:1051.
  58. Schneider BP, Kesler KA, Brooks JA, et al. Outcome of patients with residual germ cell or non-germ cell malignancy after resection of primary mediastinal nonseminomatous germ cell cancer. J Clin Oncol 2004; 22:1195.
  59. Hidalgo M, Paz-Ares L, Rivera F, et al. Mediastinal non-seminomatous germ cell tumours (MNSGCT) treated with cisplatin-based combination chemotherapy. Ann Oncol 1997; 8:555.
  60. Broun ER, Nichols CR, Einhorn LH, Tricot GJ. Salvage therapy with high-dose chemotherapy and autologous bone marrow support in the treatment of primary nonseminomatous mediastinal germ cell tumors. Cancer 1991; 68:1513.
  61. Saxman SB, Nichols CR, Einhorn LH. Salvage chemotherapy in patients with extragonadal nonseminomatous germ cell tumors: the Indiana University experience. J Clin Oncol 1994; 12:1390.
  62. Hartmann JT, Einhorn L, Nichols CR, et al. Second-line chemotherapy in patients with relapsed extragonadal nonseminomatous germ cell tumors: results of an international multicenter analysis. J Clin Oncol 2001; 19:1641.
  63. Nichols CR, Roth BJ, Heerema N, et al. Hematologic neoplasia associated with primary mediastinal germ-cell tumors. N Engl J Med 1990; 322:1425.
  64. Ladanyi M, Samaniego F, Reuter VE, et al. Cytogenetic and immunohistochemical evidence for the germ cell origin of a subset of acute leukemias associated with mediastinal germ cell tumors. J Natl Cancer Inst 1990; 82:221.
  65. Orazi A, Neiman RS, Ulbright TM, et al. Hematopoietic precursor cells within the yolk sac tumor component are the source of secondary hematopoietic malignancies in patients with mediastinal germ cell tumors. Cancer 1993; 71:3873.
  66. Hartmann JT, Nichols CR, Droz JP, et al. The relative risk of second nongerminal malignancies in patients with extragonadal germ cell tumors. Cancer 2000; 88:2629.
  67. Motzer RJ, Amsterdam A, Prieto V, et al. Teratoma with malignant transformation: diverse malignant histologies arising in men with germ cell tumors. J Urol 1998; 159:133.
  68. Ehrlich Y, Beck SD, Ulbright TM, et al. Outcome analysis of patients with transformed teratoma to primitive neuroectodermal tumor. Ann Oncol 2010; 21:1846.
  69. Gatcombe HG, Assikis V, Kooby D, Johnstone PA. Primary retroperitoneal teratomas: a review of the literature. J Surg Oncol 2004; 86:107.
  70. Yoon SS, Tanabe KK, Warshaw AL. Adult primary retroperitoneal teratoma. Surgery 2005; 137:663.
  71. Huang JC, Shin JS, Huang YT, et al. Primary retroperitoneal teratoma in an adult. J Chin Med Assoc 2003; 66:497.