Extragonadal Germ Cell Tumors
- Author: Kush Sachdeva, MD; Chief Editor: Jules E Harris, MD, FACP, FRCPC more...
Extragonadal germinal cell syndromes are rare tumors that predominantly affect young males. Literature suggests that the only known risk factor for extragonadal germ cell tumors (EGCTs) is Klinefelter syndrome (47XXY), which is associated with mediastinal nonseminomatous germ cell tumors.[1, 2] They are characterized by their location on the midline from the pineal gland to the coccyx. In extragonadal germ cell tumors, no evidence of a primary malignancy is present in either the testes or ovaries by radiologic imaging or physical examination. Extragonadal germ cell tumors produce a rich symptomatology and may reach large volumes if they arise in silent areas. Histologically, they mirror their gonadal counterparts with which they share the same chemosensitivity and radiosensitivity. Modern approaches to diagnosis and treatment can result in high rates of long-term survival and even cure.
Controversy remains regarding the origin of extragonadal germ cell tumors (EGGCTs). These tumors can be found anywhere on the midline, particularly the retroperitoneum, the anterior mediastinum, the sacrococcyx, and the pineal gland. Other less common sites include the orbit, suprasellar area, palate, thyroid, submandibular region, anterior abdominal wall, stomach, liver, vagina, and prostate. The classic theory suggests that germ cell tumors (GCTs) in these areas are derived from local transformation of primordial germ cells misplaced during embryogenesis.
A recent alternative theory suggests that primary mediastinal presentations represent reverse migration of occult carcinoma in situ (CIS) lesions in the gonad; hence, they may be gonadal in origin. According to this theory, the differences in phenotypes expressed by mediastinal germ cell tumors (MGCTs) and gonadal germ cell tumors may be explained by differences in the cellular environment between the gonad and the anterior mediastinum. Some retroperitoneal extragonadal germ cell tumors may represent metastases from a testicular cancer, with subsequent spontaneous necrosis of the primary tumour.
To explain the origin of occult carcinoma in situ cells, 2 models have been proposed. The first suggests that fetal gonocytes whose development into spermatogonia is blocked may undergo abnormal cell division and then invasive growth mediated by postnatal and pubertal gonadotrophin stimulation. The second model postulates that the most likely target cell for transformation is the zygotene-pachytene spermatocyte. During this stage of germ cell development, aberrant chromatid exchange events associated with crossing over can occur. Normally, these cells are eliminated by apoptosis. In occasional cells, this crossing over may lead to increased 12p copy number and overexpression of cyclin D2. The cell carrying this abnormality is relatively protected against apoptotic death because of the oncogenic effect of CCND2, leading to re-initiation of cell cycle and genomic instability.
Malignant transformation of germ cells is the result of a multistep process of genetic changes. One of the earliest events is the increased copy number of 12p, either as 1 or more copies of i(12p) or as tandem duplications of chromosome arm 12p. This abnormality is found in occult carcinoma in situ lesions as well as more advanced disease. Further studies indicate that the CCND2 gene is present at chromosome band 12p13 and CCND2 is overexpressed in most GCTs, including CIS. Amplification of CCND2 activates cdk4/6, allowing the cell to progress through the G1-S checkpoint.
Hematologic malignancies are frequently associated with mediastinal germ cell tumors. Embryologically, hematopoietic stem cells arise in the yolk sac. Highly differentiated yolk-sac tumors make up 30% of mediastinal germ cell tumors, providing a possible basis for this association.
The balance of the p53-mdm2 interaction has been shown to be disrupted in intracranial germ cell tumors (ICGCTs). mdm2 sequesters p53 and inhibits its function as G1-S checkpoint controller and apoptosis inducer. In normal cells, mdm2 availability is controlled by ARF, the product of the p14ARF gene located on INK4a/ARF locus, which binds with mdm2 and induces its degradation. Mutation of ARF, reported in 71% of intracranial germ cell tumors, results in mdm2 accumulation and functional impairment of p53. This abnormality was reported in 90% of seminomatous and 55% of nonseminomatous intracranial germ cell tumors (NS-ICGCTs) examined.
Extra-gonadal germ cell tumors (EGGCTs) represent 5-10% of all germ cell tumor (GCTs).
In Norway, a recent study by Dueland et al estimated the incidence of extra-gonadal germ cell tumor (EGGCTs) at 0.5 per 100,000 population per year. This represents about 2% of the number of testicular cancers reported for the same period. Intracranial germ cell tumors (ICGCTs) represent 0.3-3.4% of primary intracranial tumors in Western countries and 2.1-12.7% in Japan. In Germany, Rusner et al studied more than 16,000 patients with malignant GCTs from 1998-2008. They concluded that differences in age-specific and age-standardized incidence rates may be the result of different etiologies.
For patients receiving intensive chemotherapy, 5-year survival rates of 40-65% have been reported. Extragonadal seminomas carry the best survival rates. Mortality due to the treatment may be seen in as many as 12% of patients with nonseminomatous extragonadal germ cell tumors (NS-EGGCTs).
Seminomas account for 30-40% of these tumors, and nonseminomatous germ cell tumors (NS-GCTs) account for 60-70%. Nonseminomatous germ cell tumors include yolk-sac tumors, embryonal carcinomas, choriocarcinomas, teratomas, and nonteratomatous combined germ cell tumors.
The most common site of extragonadal germ cell tumors (EGGCTs) is the mediastinum (50-70%) followed by the retroperitoneum (30-40%), the pineal gland (5%), and the sacrococcygeal area (less than 5%).
Pathology of postchemotherapy residual masses reveals necrosis in 24%, teratoma in 45%, sarcoma in 5%, and viable germ cell cancer in 26%. However, the smaller the residual mass, the lower the chance that it harbors viable tumor cells.
In children, benign and malignant extragonadal germ cell tumors (EGGCTs) occur equally in males and females. In adults, only benign extragonadal germ cell tumors (teratomas) occur at equal frequency in both sexes; more than 90% of malignant extragonadal germ cell tumors occur in males.
Extragonadal germinal cell syndromes are rare tumors that predominantly affect young males.
Hasle H, Mellemgaard A, Nielsen J, et al. Cancer incidence in men with Klinefelter syndrome. Br J Cancer. 1995 Feb. 71(2):416-20. [Medline].
Hasle H, Jacobsen BB, Asschenfeldt P, et al. Mediastinal germ cell tumour associated with Klinefelter syndrome. A report of case and review of the literature. Eur J Pediatr. 1992 Oct. 151(10):735-9. [Medline].
Bosl GJ, Ilson DH, Rodriguez E, et al. Clinical relevance of the i(12p) marker chromosome in germ cell tumors. J Natl Cancer Inst. 1994 Mar 2. 86(5):349-55. [Medline].
Hartmann JT, Nichols CR, Droz JP, et al. Hematologic disorders associated with primary mediastinal nonseminomatous germ cell tumors. J Natl Cancer Inst. 2000 Jan 5. 92(1):54-61. [Medline].
Iwato M, Tachibana O, Tohma Y, et al. Alterations of the INK4a/ARF locus in human intracranial germ cell tumors. Cancer Res. 2000 Apr 15. 60(8):2113-5. [Medline].
Dueland S, Stenwig AE, Heilo A, et al. Treatment and outcome of patients with extragonadal germ cell tumours--the Norwegian Radium Hospital's experience 1979-94. Br J Cancer. 1998. 77(2):329-35. [Medline].
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 Jan 15. 97(2):367-76. [Medline].
Rusner C, Trabert B, Katalinic A, Kieschke J, Emrich K, Stang A. Incidence patterns and trends of malignant gonadal and extragonadal germ cell tumors in Germany, 1998-2008. Cancer Epidemiol. 2013 Aug. 37(4):370-3. [Medline].
Albany C, Einhorn LH. Extragonadal germ cell tumors: clinical presentation and management. Curr Opin Oncol. 2013 May. 25(3):261-5. [Medline].
Ganslandt O, Buchfelder M, Grabenbauer GG. Primary spinal germinoma in a patient with concomitant Klinefelter's syndrome. Br J Neurosurg. 2000 Jun. 14(3):252-5. [Medline].
Albers P, Bender H, Yilmaz H, et al. Positron emission tomography in the clinical staging of patients with Stage I and II testicular germ cell tumors. Urology. 1999 Apr. 53(4):808-11. [Medline].
Cremerius U, Effert PJ, Adam G, et al. FDG PET for detection and therapy control of metastatic germ cell tumor. J Nucl Med. 1998 May. 39(5):815-22. [Medline].
Stephens AW, Gonin R, Hutchins GD, et al. Positron emission tomography evaluation of residual radiographic abnormalities in postchemotherapy germ cell tumor patients. J Clin Oncol. 1996 May. 14(5):1637-41. [Medline].
De Santis M, Becherer A, Bokemeyer C, et al. 2-18fluoro-deoxy-D-glucose positron emission tomography is a reliable predictor for viable tumor in postchemotherapy seminoma: an update of the prospective multicentric SEMPET trial. J Clin Oncol. 2004 Mar 15. 22(6):1034-9. [Medline].
Womeldorph CM, Zalupski MM, Knoepp SM, Soltani M, Elmunzer BJ. Retroperitoneal germ cell tumor diagnosed by endoscopic ultrasound-guided fine needle aspiration. World J Gastrointest Oncol. 2010 Dec 15. 2(12):443-5. [Medline]. [Full Text].
Cao D, Liu A, Wang F, Allan RW, Mei K, Peng Y, et al. RNA-binding protein LIN28 is a marker for primary extragonadal germ cell tumors: an immunohistochemical study of 131 cases. Mod Pathol. 2011 Feb. 24(2):288-96. [Medline].
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 Feb. 16(2):725-32. [Medline].
Samuels ML, Johnson DE, Holoye PY, et al. Large-dose bleomycin therapy and pulmonary toxicity. A possible role of prior radiotherapy. JAMA. 1976 Mar 15. 235(11):1117-20. [Medline].
Walsh GL, Taylor GD, Nesbitt JC, et al. Intensive chemotherapy and radical resections for primary nonseminomatous mediastinal germ cell tumors. Ann Thorac Surg. 2000 Feb. 69(2):337-43; discussion 343-4. [Medline].
Saxman SB, Nichols CR, Einhorn LH. Salvage chemotherapy in patients with extragonadal nonseminomatous germ cell tumors: the Indiana University experience. J Clin Oncol. 1994 Jul. 12(7):1390-3. [Medline].
Calaminus G, Bamberg M, Baranzelli MC, et al. Intracranial germ cell tumors: a comprehensive update of the European data. Neuropediatrics. 1994 Feb. 25(1):26-32. [Medline].
Balmaceda C, Heller G, Rosenblum M, et al. Chemotherapy without irradiation--a novel approach for newly diagnosed CNS germ cell tumors: results of an international cooperative trial. The First International Central Nervous System Germ Cell Tumor Study. J Clin Oncol. 1996 Nov. 14(11):2908-15. [Medline].
Pectasides D, Aravantinos G, Visvikis A, et al. Platinum-based chemotherapy of primary extragonadal germ cell tumours: the Hellenic Cooperative Oncology Group experience. Oncology. 1999 Jul. 57(1):1-9. [Medline].
Nichols CR, Fox EP. Extragonadal and pediatric germ cell tumors. Hematol Oncol Clin North Am. 1991 Dec. 5(6):1189-209. [Medline].
Andre F, Fizazi K, Culine S, et al. The growing teratoma syndrome: results of therapy and long-term follow-up of 33 patients. Eur J Cancer. 2000 Jul. 36(11):1389-94. [Medline].
Gunes S, Varon J, Walsh G. Mediastinal teratoma presenting as massive hemoptysis in an adult. J Emerg Med. 1997 May-Jun. 15(3):313-6. [Medline].
Weijl NI, Rutten MF, Zwinderman AH, et al. Thromboembolic events during chemotherapy for germ cell cancer: a cohort study and review of the literature. J Clin Oncol. 2000 May. 18(10):2169-78. [Medline].
International Germ Cell Cancer Collaborative Group. International Germ Cell Consensus Classification: a prognostic factor- based staging system for metastatic germ cell cancers. J Clin Oncol. 1997 Feb. 15(2):594-603. [Medline].
Ganjoo KN, Rieger KM, Kesler KA, et al. Results of modern therapy for patients with mediastinal nonseminomatous germ cell tumors. Cancer. 2000 Mar 1. 88(5):1051-6. [Medline].
Abeloff MD, Armitage JO, Niederhuber J, et al. Clinical Oncology. 4nd ed. New York: Churchill Livingstone; 2008.
Adebonojo SA, Nicola ML. Teratoid tumors of the mediastinum. Am Surg. 1976 May. 42(5):361-5. [Medline].
Arai K, Ohta S, Suzuki M, et al. Primary immature mediastinal teratoma in adulthood. Eur J Surg Oncol. 1997 Feb. 23(1):64-7. [Medline].
Baranzelli MC, Patte C, Bouffet E, et al. Nonmetastatic intracranial germinoma: the experience of the French Society of Pediatric Oncology. Cancer. 1997 Nov 1. 80(9):1792-7. [Medline].
Bokemeyer C, Droz JP, Horwich A, et al. Extragonadal seminoma: an international multicenter analysis of prognostic factors and long term treatment outcome. Cancer. 2001 Apr 1. 91(7):1394-401. [Medline].
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 Apr 1. 20(7):1864-73. [Medline].
Broun ER, Nichols CR, Einhorn LH, et al. Salvage therapy with high-dose chemotherapy and autologous bone marrow support in the treatment of primary nonseminomatous mediastinal germ cell tumors. Cancer. 1991 Oct 1. 68(7):1513-5. [Medline].
Böhle A, Studer UE, Sonntag RW, et al. Primary or secondary extragonadal germ cell tumors?. J Urol. 1986 May. 135(5):939-43. [Medline].
Chaganti RS, Houldsworth J. Genetics and biology of adult human male germ cell tumors. Cancer Res. 2000 Mar 15. 60(6):1475-82. [Medline].
Chaganti RS, Rodriguez E, Mathew S. Origin of adult male mediastinal germ-cell tumours. Lancet. 1994 May 7. 343(8906):1130-2. [Medline].
Cheng L. Establishing a germ cell origin for metastatic tumors using OCT4 immunohistochemistry. Cancer. 2004 Nov 1. 101(9):2006-10. [Medline].
Christmas TJ, Doherty AP, Rustin GJ, et al. Primary retroperitoneal germ cell tumours: excision via a thoracoabdominal extraperitoneal approach. Br J Surg. 1997 Jul. 84(7):1022-5. [Medline].
Comiter CV, Renshaw AA, Benson CB, et al. Burned-out primary testicular cancer: sonographic and pathological characteristics. J Urol. 1996 Jul. 156(1):85-8. [Medline].
Crossen JR, Garwood D, Glatstein E, et al. Neurobehavioral sequelae of cranial irradiation in adults: a review of radiation-induced encephalopathy. J Clin Oncol. 1994 Mar. 12(3):627-42. [Medline].
Daugaard G, Rorth M, von der Maase H, et al. Management of extragonadal germ-cell tumors and the significance of bilateral testicular biopsies. Ann Oncol. 1992 Apr. 3(4):283-9. [Medline].
Davis RD Jr, Oldham HN Jr, Sabiston DC Jr. Primary cysts and neoplasms of the mediastinum: recent changes in clinical presentation, methods of diagnosis, management, and results. Ann Thorac Surg. 1987 Sep. 44(3):229-37. [Medline].
DeVita VT, Lawrence T,S Rosenberg SA, eds. Cancer, Principles and Practice of Oncology. 8th ed. Philadelphia: Lippincott, Williams & Wilkins; 2008.
Donadio AC, Motzer RJ, Bajorin DF, et al. Chemotherapy for teratoma with malignant transformation. J Clin Oncol. 2003 Dec 1. 21(23):4285-91. [Medline].
Droz JP, Horwich A. Extragonadal Germ Cell Tumors. Comprehensive Textbook of Genitourinary Oncology, Vogelzang, NJ, Scardino, PT, Shipley, WU, Doffey, DS (Eds). Second Edition. New York: Lippincott Williams and Wilkins; 2005.
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 May. 33(6):829-35. [Medline].
Duffner PK, Cohen ME, Thomas PR, et al. The long-term effects of cranial irradiation on the central nervous system. Cancer. 1985 Oct 1. 56(7 Suppl):1841-6. [Medline].
Dulmet EM, Macchiarini P, Suc B, et al. Germ cell tumors of the mediastinum. A 30-year experience. Cancer. 1993 Sep 15. 72(6):1894-901. [Medline].
Einhorn LH, Williams SD, Loehrer PJ, et al. Evaluation of optimal duration of chemotherapy in favorable-prognosis disseminated germ cell tumors: a Southeastern Cancer Study Group protocol. J Clin Oncol. 1989 Mar. 7(3):387-91. [Medline].
Feo CF, Chironi G, Porcu A, et al. Videothoracoscopic removal of a mediastinal teratoma. Am Surg. 1997 May. 63(5):459-61. [Medline].
Glenn OA, Barkovich AJ. Intracranial germ cell tumors: a comprehensive review of proposed embryologic derivation. Pediatr Neurosurg. 1996. 24(5):242-51. [Medline].
Gordon MS, Battiato LA, Finch D, et al. Dramatic response of teratoma-associated non--germ-cell cancer with all-trans retinoic acid in a patient with nonseminomatous germ cell tumor. Am J Clin Oncol. 2001 Jun. 24(3):269-71. [Medline].
Hailemariam S, Engeler DS, Bannwart F, et al. 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 Mar 1. 79(5):1031-6. [Medline].
Hainsworth JD, Greco FA. Extragonadal germ cell tumors and unrecognized germ cell tumors. Semin Oncol. 1992 Apr. 19(2):119-27. [Medline].
Hainsworth JD, Greco FA. Poorly differentiated carcinoma and germ cell tumors. Hematol Oncol Clin North Am. 1991 Dec. 5(6):1223-31. [Medline].
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 Mar 15. 19(6):1641-8. [Medline].
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 Nov 21. 93(22):1733-8. [Medline].
Hartmann JT, Nichols CR, Droz JP, et al. Prognostic variables for response and outcome in patients with extragonadal germ-cell tumors. Ann Oncol. 2002 Jul. 13(7):1017-28. [Medline].
Hartmann JT, Nichols CR, Droz JP, et al. The relative risk of second nongerminal malignancies in patients with extragonadal germ cell tumors. Cancer. 2000 Jun 1. 88(11):2629-35. [Medline].
Heinonen K, Rao PN, Slack JL, et al. Isochromosome 12p in two cases of acute myeloid leukaemia without evidence of germ cell tumour. Br J Haematol. 1996 Jun. 93(3):677-80. [Medline].
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 Jun. 8(6):555-9. [Medline].
Hooda BS, Finlay JL. Recent advances in the diagnosis and treatment of central nervous system germ-cell tumours. Curr Opin Neurol. 1999 Dec. 12(6):693-6. [Medline].
Horton Z, Schlatter M, Schultz S. Pediatric germ cell tumors. Surg Oncol. 2007 Nov. 16(3):205-13. [Medline].
Horwich A, Paluchowska B, Norman A, et al. Residual mass following chemotherapy of seminoma. Ann Oncol. 1997 Jan. 8(1):37-40. [Medline].
Iczkowski KA, Butler SL, Shanks JH, et al. Trials of new germ cell immunohistochemical stains in 93 extragonadal and metastatic germ cell tumors. Hum Pathol. 2008 Feb. 39(2):275-81. [Medline].
Jacob R, Ramadas K, Jyothirmayi R, et al. Extragonadal germ-cell tumors: a ten-year experience. Am J Clin Oncol. 1998 Apr. 21(2):198-202. [Medline].
Knapp RH, Hurt RD, Payne WS, et al. Malignant germ cell tumors of the mediastinum. J Thorac Cardiovasc Surg. 1985 Jan. 89(1):82-9. [Medline].
Knappe UJ, Bentele K, Horstmann M, et al. Treatment and long-term outcome of pineal nongerminomatous germ cell tumors. Pediatr Neurosurg. 1998 May. 28(5):241-5. [Medline].
Kumano M, Miyake H, Hara I, et al. First-line high-dose chemotherapy combined with peripheral blood stem cell transplantation for patients with advanced extragonadal germ cell tumors. Int J Urol. 2007 Apr. 14(4):336-8. [Medline].
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 Feb 7. 82(3):221-7. [Medline].
Lewis BD, Hurt RD, Payne WS, et al. Benign teratomas of the mediastinum. J Thorac Cardiovasc Surg. 1983 Nov. 86(5):727-31. [Medline].
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 Jun 1. 24(16):2544-8. [Medline].
McAleer JJ, Nicholls J, Horwich A. Does extragonadal presentation impart a worse prognosis to abdominal germ-cell tumours?. Eur J Cancer. 1992. 28A(4-5):825-8. [Medline].
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 Mar. 14(2):69-92. [Medline].
Medical Economics Staff. Physician Desk Reference. 54th ed. Medical Economics Company; 2000.
Merchant TE, Sherwood SH, Mulhern RK, et al. CNS germinoma: disease control and long-term functional outcome for 12 children treated with craniospinal irradiation. Int J Radiat Oncol Biol Phys. 2000 Mar 15. 46(5):1171-6. [Medline].
Moeller KH, Rosado-de-Christenson ML, Templeton PA. Mediastinal mature teratoma: imaging features. AJR Am J Roentgenol. 1997 Oct. 169(4):985-90. [Medline].
Moran CA, Suster S. Primary germ cell tumors of the mediastinum: I. Analysis of 322 cases with special emphasis on teratomatous lesions and a proposal for histopathologic classification and clinical staging. Cancer. 1997 Aug 15. 80(4):681-90. [Medline].
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 Aug 15. 80(4):699-707. [Medline].
Moran CA, Suster S, Przygodzki RM, et al. Primary germ cell tumors of the mediastinum: II. Mediastinal seminomas--a clinicopathologic and immunohistochemical study of 120 cases. Cancer. 1997 Aug 15. 80(4):691-8. [Medline].
Mordecai D, Shaw RJ, Fisher PG, et al. Case study: suprasellar germinoma presenting with psychotic and obsessive-compulsive symptoms. J Am Acad Child Adolesc Psychiatry. 2000 Jan. 39(1):116-9. [Medline].
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 Jul. 5(7):1064-70. [Medline].
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 Jan. 159(1):133-8. [Medline].
Motzer RJ, Rodriguez E, Reuter VE, et al. Genetic analysis as an aid in diagnosis for patients with midline carcinomas of uncertain histologies. J Natl Cancer Inst. 1991 Mar 6. 83(5):341-6. [Medline].
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 Jan. 13(1):274-82. [Medline].
Nichols CR, Roth BJ, Heerema N, et al. Hematologic neoplasia associated with primary mediastinal germ-cell tumors. N Engl J Med. 1990 May 17. 322(20):1425-9. [Medline].
Oosterhuis JW, Stoop H, Honecker F, et al. Why human extragonadal germ cell tumours occur in the midline of the body: old concepts, new perspectives. Int J Androl. 2007 Aug. 30(4):256-63; discussion 263-4. [Medline].
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 Jun 15. 71(12):3873-81. [Medline].
Parada D, Pena KB, Moreira O, et al. Extragonadal retroperitoneal germ cell tumor: primary versus metastases?. Arch Esp Urol. 2007 Jul-Aug. 60(6):713-9. [Medline].
Pectasides D, Valavanis C, Nikolaou M, et al. Molecular markers in extragonadal germ cell tumours: a matched case-control study. Histopathology. 2007 Feb. 50(3):394-6. [Medline].
Perry MC, ed. The Chemotherapy Source Book. 3rd ed. Philadelphia: Lippincott Williams & Wilkins; 2001.
Polansky SM, Barwick KW, Ravin CE. Primary mediastinal seminoma. AJR Am J Roentgenol. 1979 Jan. 132(1):17-21. [Medline].
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 Feb. 14(2):454-60. [Medline].
Rescorla FJ. Pediatric germ cell tumors. Semin Surg Oncol. 1999 Mar. 16(2):144-58. [Medline].
Richardson RL, Schoumacher RA, Fer MF, et al. The unrecognized extragonadal germ cell cancer syndrome. Ann Intern Med. 1981 Feb. 94(2):181-6. [Medline].
Rothman J, Greenberg RE, Jaffe WI. Nonseminomatous germ cell tumor of the testis 9 years after a germ cell tumor of the pineal gland: case report and review of the literature. Can J Urol. 2008 Jun. 15(3):4122-4. [Medline].
Sawamura Y, Ikeda JL, Tada M, et al. Salvage therapy for recurrent germinomas in the central nervous system. Br J Neurosurg. 1999 Aug. 13(4):376-81. [Medline].
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 Sep. 15(9):1377-99. [Medline].
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 Apr 1. 22(7):1195-200. [Medline].
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 Oct. 7(10):1497-503. [Medline].
Shivdasani, RA,, Kantoff, PW. Extragonadal germ cell tumors. Raghavan, D, Scher, HI, Leibel, SA, Lange, P (Eds). Principles and Practice of Genitourinary Oncology. Lippincott-Raven: Philadelphia; 1997.
Uchiyama M, Kantoff PW, Kaplan WD. Gallium-67-citrate imaging in extragonadal and gonadal seminomas: relationship to radiologic findings. J Nucl Med. 1994 Oct. 35(10):1624-30. [Medline].
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 Feb 1. 19(3):682-8. [Medline].