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  • Print publication year: 2018
  • Online publication date: February 2018

36 - Ovarian Germ Cell Tumors

from Section 5 - Gynecologic Oncology

Summary

Introduction

Ovarian germ cell tumors (OGCTs) arise from primordial germ cells and may exhibit a broad spectrum of histologic differentiation and pathologic behavior (1). They comprise approximately 20–25 percent of ovarian neoplasms and account for less than 5 percent of ovarian malignancies (2–4). These tumors principally occur during adolescence and early adulthood, accounting for the majority of ovarian tumors in this age group (5). Significant improvements in the management of OGCTs have been achieved allowing a large portion of women to retain reproductive potential with excellent clinical outcomes. The pathology, clinical presentation, staging, treatment, and prognosis of malignant OGCTs will be reviewed in this chapter.

Pathology

The WHO classifies OGCTs into three main categories as shown in Box 36.1. These categories include primitive germ cell tumors, biphasic or triphasic teratomas, and monodermal teratoma or somatic-type tumors associated with dermoid cysts. Dysgerminoma, immature teratoma, yolk sac tumors, and mixed germ cell tumors account for 90 percent of cases of malignant OGCT (6).

Box 36.1 WHO Classification for Ovarian Germ Cell Tumors

Primitive germ cell tumors

Dysgerminoma

Yolk sac (endodermal sinus) tumor

Embryonal tumor

Choriocarcinoma

Mixed

Biphasic/triphasic teratoma

Mature teratoma

Immature teratoma

Monodermal teratoma/somatic-type tumors arising from mature teratoma

Struma ovarii

Carcinoid

Neuroectodermal-type tumors

Sebaceous tumors

Other (squamous cell carcinoma)

Dysgerminoma

Dysgerminomas account for approximately 30–40 percent of malignant OGCTs (6,7). Though most dysgerminomas arise in patients with a normal karyotype, it is the most frequent ovarian neoplasm in patients with gonadal dysgenesis (8–10). Approximately 5–10 percent of these tumors develop in association with gonadoblastomas, which is most common in phenotypic females who have a Y chromosome including patients with pure gonadal dysgenesis (46, XY), mixed gonadal dysgenesis (45X, 46, XY), or complete androgen insensitivity (46, XY), but can also be found in patients with Turner syndrome (45, X; 45 X/46XX; 45X/46XY) (8,9,11).

On gross examination, dysgerminomas tend to be large, firm, lobulated masses with a cream to pale-tan color (12,13). Areas of hemorrhage, necrosis, or cystic degeneration may be present (7). While the vast majority are unilateral, approximately 10 percent are bilateral on gross examination and another 10 percent have microscopic involvement of the contralateral ovary (10,12,13).

1. Blaustein, A, Kurman, RJ. Blaustein's Pathology of the Female Genital Tract. 6th ed. New York: Springer; 2011. xv, 1246pp.
2. Talerman, A. Germ cell tumors of the ovary. Curr Opin Obstet Gynecol. 1997;9(1):44–7.
3. Low, JJ, Ilancheran, A, Ng, JS. Malignant ovarian germ-cell tumours. Best Pract Res Clin Obstet Gynaecol. 2012;26(3):347–55.
4. Gershenson, DM. Management of early ovarian cancer: germ cell and sex cord-stromal tumors. Gynecol Oncol. 1994;55(3 Pt 2):S62–72.
5. Norris, HJ, Jensen, RD. Relative frequency of ovarian neoplasms in children and adolescents. Cancer. 1972;30(3):713–9.
6. Smith, HO, Berwick, M, Verschraegen, CF. Incidence and survival rates for female malignant germ cell tumors. Obstet Gynecol. 2006;107(5):1075–85.
7. Kurman, RJ, International Agency for Research on Cancer, World Health Organization. WHO Classification of Tumours of Female Reproductive Organs. 4th ed. Lyon: International Agency for Research on Cancer; 2014. 307 pp.
8. Lin, KY, Bryant, S, Miller, DS, Kehoe, SM, Richardson, DL, Lea, JS. Malignant ovarian germ cell tumor: role of surgical staging and gonadal dysgenesis. Gynecol Oncol. 2014;134(1):84–9.
9. Scully, RE. Gonadoblastoma: a review of 74 cases. Cancer. 1970;25(6):1340–56.
10. Matei, DE, Michael, H, Riussell, AH, Gershenson, DM. Ovarian germ cell tumors. In: Barakat, RR, Markman, M, Randall, ME, eds. Principles and Practice of Gynecologic Oncology, 5th ed. Baltimore, MD: Lippincott Williams & Wilkins; 2009. p. 837–54.
11. Schellhas, HF. Malignant potential of the dysgenetic gonad. Part 1. Obstet Gynecol. 1974;44(2):298–309.
12. Young, RH. Ovarian tumors and tumor-like lesions in the first three decades. Sem Diag Pathol. 2014;31(5):382–426.
13. Kurman, RJ, Norris, HJ. Malignant germ cell tumors of the ovary. Hum Pathol. 1977;8(5):551–64.
14. Sever, M, Jones, TD, Roth, LM et al. Expression of CD117 (c-kit) receptor in dysgerminoma of the ovary: diagnostic and therapeutic implications. Mod Pathol. 2005;18(11):1411–16.
15. Cheng, L, Thomas, A, Roth, LM, Zheng, W, Michael, H, Karim, FW. OCT4: a novel biomarker for dysgerminoma of the ovary. Am J Surg Pathol. 2004;28(10):1341–6.
16. Hoei-Hansen, CE, Kraggerud, SM, Abeler, VM, Kaern, J, Meyts, E Rajpert-De, Lothe, RA. Ovarian dysgerminomas are characterised by frequent KIT mutations and abundant expression of pluripotency markers. Mol Cancer. 2007;6:12.
17. Nogales, FF, Preda, O, Nicolae, A. Yolk sac tumours revisited. A review of their many faces and names. Histopath. 2012;60(7):1023–33.
18. Kurman, RJ, Norris, HJ. Endodermal sinus tumor of the ovary: a clinical and pathologic analysis of 71 cases. Cancer. 1976;38(6):2404–19.
19. McCluggage, WG, Young, RH. Immunohistochemistry as a diagnostic aid in the evaluation of ovarian tumors. Semin Diagn Pathol. 2005;22(1):3–32.
20. Ramalingam, P, Malpica, A, Silva, EG, Gershenson, DM, Liu, JL, Deavers, MT. The use of cytokeratin 7 and EMA in differentiating ovarian yolk sac tumors from endometrioid and clear cell carcinomas. Am J Surg Pathol. 2004;28(11):1499–1505.
21. Kurman, RJ, Norris, HJ. Embryonal carcinoma of the ovary: a clinicopathologic entity distinct from endodermal sinus tumor resembling embryonal carcinoma of the adult testis. Cancer. 1976;38(6):2420–33.
22. Kurman, RJ, Norris, HJ. Malignant mixed germ cell tumors of the ovary: a clinical and pathologic analysis of 30 cases. Obstet Gynecol. 1976;48(5):579–89.
23. Doss, N, Jr., Forney, JP, Vellios, F, Nalick, RH. Covert bilaterality of mature ovarian teratomas. Obstet Gynecol. 1977;50(6):651–3.
24. Ayhan, A, Aksu, T, Develioglu, O, Tuncer, ZS, Ayhan, A. Complications and bilaterality of mature ovarian teratomas (clinicopathological evaluation of 286 cases). Aust N Z J Obstet Gynaecol. 1991;31(1):83–5.
25. Rim, SY, Kim, SM, Choi, HS. Malignant transformation of ovarian mature cystic teratoma. Int J Gynecol Cancer. 2006;16(1):140–4.
26. Westhoff, C, Pike, M, Vessey, M. Benign ovarian teratomas: a population-based case-control study. Br J Cancer. 1988;58(1):93–8.
27. Santos, L Dos, Mok, E, Iasonos, A et al. Squamous cell carcinoma arising in mature cystic teratoma of the ovary: a case series and review of the literature. Gynecol Oncol. 2007;105(2):321–4.
28. Norris, HJ, Zirkin, HJ, Benson, WL. Immature (malignant) teratoma of the ovary: a clinical and pathologic study of 58 cases. Cancer. 1976;37(5):2359–72.
29. O'Connor, DM, Norris, HJ. The influence of grade on the outcome of stage I ovarian immature (malignant) teratomas and the reproducibility of grading. Int J Gynecol Pathol. 1994;13(4):283–9.
30. Backer, A De, Madern, GC, Oosterhuis, JW, Hakvoort-Cammel, FG, Hazebroek, FW. Ovarian germ cell tumors in children: a clinical study of 66 patients. Pediatr Blood Cancer. 2006;46(4):459–64.
31. Gershenson, DM, Junco, G Del, Copeland, LJ, Rutledge, FN. Mixed germ cell tumors of the ovary. Obstet Gynecol. 1984;64(2):200–206.
32. Tangjitgamol, S, Hanprasertpong, J, Manusirivithaya, S, Wootipoom, V, Thavaramara, T, Buhachat, R. Malignant ovarian germ cell tumors: clinico-pathological presentation and survival outcomes. Acta Obstet Gynecol Scand. 2010;89(2):182–9.
33. Yang, C, Wang, S, Li, CC, Zhang, J, Kong, XR, Ouyang, J. Ovarian germ cell tumors in children: a 20-year retrospective study in a single institution. Eur J Gynaecol Oncol. 2011;32(3):289–92.
34. Panteli, C, Curry, J, Kiely, E et al. Ovarian germ cell tumours: a 17-year study in a single unit. Eur J Pediatr Surg. 2009;19(2):96–100.
35. Asadourian, LA, Taylor, HB. Dysgerminoma. An analysis of 105 cases. Obstet Gynecol. 1969;33(3):370–9.
36. Kodama, M, Grubbs, BH, Blake, EA et al. Feto-maternal outcomes of pregnancy complicated by ovarian malignant germ cell tumor: a systematic review of literature. Eur J Obstet Gynecol Repr Bio. 2014;181:145–56.
37. Pectasides, D, Pectasides, E, Kassanos, D. Germ cell tumors of the ovary. Cancer Treat Rev. 2008;34(5):427–41.
38. Sekiya, S, Seki, K, Nagai, Y. Rise of serum CA 125 in patients with pure ovarian yolk sac tumors. Int J Gynaecol Obstet. 1997;58(3):323–4.
39. Levato, F, Martinello, R, Campobasso, C, Porto, S. LDH and LDH isoenzymes in ovarian dysgerminoma. Eur J Gynaecol Oncol. 1995;16(3):212–5.
40. Schwartz, PE, Morris, JM. Serum lactic dehydrogenase: a tumor marker for dysgerminoma. Obstet Gynecol. 1988;72(3 Pt 2):511–5.
41. Gershenson, DM, Junco, G Del, Herson, J, Rutledge, FN. Endodermal sinus tumor of the ovary: the M. D. Anderson experience. Obstet Gynecol. 1983;61(2):194–202.
42. Talerman, A, Haije, WG, Baggerman, L. Serum alphafetoprotein (AFP) in diagnosis and management of endodermal sinus (yolk sac) tumor and mixed germ cell tumor of the ovary. Cancer. 1978;41(1):272–8.
43. Kawai, M, Furuhashi, Y, Kano, T et al. Alpha-fetoprotein in malignant germ cell tumors of the ovary. Gynecol Oncol. 1990;39(2):160–6.
44. Konishi, I, Fujii, S, Okamura, H, Sakahara, H, Endo, K, Torizuka, K, et al. Analysis of serum CA125, CEA, AFP, LDH levels and LDH isoenzymes in patients with ovarian tumors: correlation between tumor markers and histological types of ovarian tumors. Nihon Sanka Fujinka Gakkai Zasshi. 1986;38(6):827–36.
45. Prat, J, Oncology FCoG. FIGO's staging classification for cancer of the ovary, fallopian tube, and peritoneum: abridged republication. J Gynecol Oncol. 2015;26(2):87–9.
46. Gershenson, DM. Management of ovarian germ cell tumors. J Clin Oncol. 2007;25(20):2938–43.
47. Gershenson, DM. Fertility-sparing surgery for malignancies in women. J Natl Cancer Inst Monogr. 2005(34):43–7.
48. Low, JJ, Perrin, LC, Crandon, AJ, Hacker, NF. Conservative surgery to preserve ovarian function in patients with malignant ovarian germ cell tumors. A review of 74 cases. Cancer. 2000;89(2):391–8.
49. Schwartz, PE, Chambers, SK, Chambers, JT, Kohorn, E, McIntosh, S. Ovarian germ cell malignancies: the Yale University experience. Gynecol Oncol. 1992;45(1):26–31.
50. Perrin, LC, Low, J, Nicklin, JL, Ward, BG, Crandon, AJ. Fertility and ovarian function after conservative surgery for germ cell tumours of the ovary. Aust N Z J Obstet Gynaecol. 1999;39(2):243–5.
51. Slayton, RE, Park, RC, Silverberg, SG, Shingleton, H, Creasman, WT, Blessing, JA. Vincristine, dactinomycin, and cyclophosphamide in the treatment of malignant germ cell tumors of the ovary. A Gynecologic Oncology Group Study (a final report). Cancer. 1985;56(2):243–8.
52. Billmire, D, Vinocur, C, Rescorla, F et al. Outcome and staging evaluation in malignant germ cell tumors of the ovary in children and adolescents: an intergroup study. J Pediatr Surg. 2004;39(3):424–9 (9).
53. Ertas, IE, Taskin, S, Goklu, R et al. Long-term oncological and reproductive outcomes of fertility-sparing cytoreductive surgery in females aged 25 years and younger with malignant ovarian germ cell tumors. J Obstet Gynaecol Res. 2014;40(3):797–805.
54. Park, JY, Kim, DY, Suh, DS et al. Outcomes of pediatric and adolescent girls with malignant ovarian germ cell tumors. Gynecol Oncol. 2015;137(3):418–22.
55. Yoo, SC, Kim, WY, Yoon, JH, Chang, SJ, Chang, KH, Ryu, HS. Young girls with malignant ovarian germ cell tumors can undergo normal menarche and menstruation after fertility-preserving surgery and adjuvant chemotherapy. Acta Obstet Gynecol Scand. 2010;89(1):126–30.
56. Billmire, DF. Malignant germ cell tumors in childhood. Semin Pediatr Surg. 2006;15(1):30–6.
57. Williams, SD, Blessing, JA, Moore, DH, Homesley, HD, Adcock, L. Cisplatin, vinblastine, and bleomycin in advanced and recurrent ovarian germ-cell tumors. A trial of the Gynecologic Oncology Group. Ann Int Med. 1989;111(1):22–7.
58. Bafna, UD, Umadevi, K, Kumaran, C, Nagarathna, DS, Shashikala, P, Tanseem, R. Germ cell tumors of the ovary: is there a role for aggressive cytoreductive surgery for nondysgerminomatous tumors? Int J Gynecol Cancer. 2001;11(4):300–304.
59. Williams, SD, Blessing, JA, DiSaia, PJ, Major, FJ, Ball, HG III, Liao, SY. Second-look laparotomy in ovarian germ cell tumors: the Gynecologic Oncology Group experience. Gynecol Oncol. 1994;52(3):287–91.
60. Gershenson, DM. Chemotherapy of ovarian germ cell tumors and sex cord stromal tumors. Semin Surg Oncol. 1994;10(4):290–8.
61. Billmire, DF, Cullen, JW, Rescorla, FJ et al. Surveillance after initial surgery for pediatric and adolescent girls with stage I ovarian germ cell tumors: report from the Children's Oncology Group. J Clin Oncol. 2014;32(5):465–70.
62. Dark, GG, Bower, M, Newlands, ES, Paradinas, F, Rustin, GJ. Surveillance policy for stage I ovarian germ cell tumors. J Clin Oncol. 1997;15(2):620–4.
63. Patterson, DM, Murugaesu, N, Holden, L, Seckl, MJ, Rustin, GJ. A review of the close surveillance policy for stage I female germ cell tumors of the ovary and other sites. Int J Gynecol Cancer. 2008;18(1):43–50.
64. Mangili, G, Sigismondi, C, Lorusso, D, Pignata, S. Surveillance policy for stage IA malignant ovarian germ cell tumors in children and young adults. J Clin Oncol. 2014;32(25):2814–5.
65. Gershenson, DM, Morris, M, Cangir, A et al. Treatment of malignant germ cell tumors of the ovary with bleomycin, etoposide, and cisplatin. J Clin Oncol. 1990;8(4):715–20.
66. Williams, S, Blessing, JA, Liao, SY, Ball, H, Hanjani, P. Adjuvant therapy of ovarian germ cell tumors with cisplatin, etoposide, and bleomycin: a trial of the Gynecologic Oncology Group. J Clin Oncol. 1994;12(4):701–6.
67. 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. 2000;18(22):3809–18.
68. Doi, M, Okamoto, Y, Yamauchi, M, Naitou, H, Shinozaki, K. Bleomycin-induced pulmonary fibrosis after tumor lysis syndrome in a case of advanced yolk sac tumor treated with bleomycin, etoposide and cisplatin (BEP) chemotherapy. Int J Clin Oncol. 2012;17(5):528–31.
69. O'Sullivan, JM, Huddart, RA, Norman, AR, Nicholls, J, Dearnaley, DP, Horwich, A. Predicting the risk of bleomycin lung toxicity in patients with germ-cell tumours. Ann Oncol. 2003;14(1):91–6.
70. Usman, M, Faruqui, ZS, Din, N ud, Zahid, KF. Bleomycin induced pulmonary toxicity in patients with germ cell tumours. J Ayub Med Coll Abbottabad. 2010;22(3):35–7.
71. Buskirk, SJ, Schray, MF, Podratz, KC et al. Ovarian dysgerminoma: a retrospective analysis of results of treatment, sites of treatment failure, and radiosensitivity. Mayo Clin Proc. 1987;62(12):1149–57.
72. Mangili, G, Sigismondi, C, Gadducci, A et al. Outcome and risk factors for recurrence in malignant ovarian germ cell tumors: a MITO-9 retrospective study. Int J Gynecol Cancer. 2011;21(8):1414–21.
73. Murugaesu, N, Schmid, P, Dancey, G et al. Malignant ovarian germ cell tumors: identification of novel prognostic markers and long-term outcome after multimodality treatment. J Clin Oncol: Offic J Am Soc Clin Oncol. 2006;24(30):4862–6.
74. Solheim, O, Gershenson, DM, Trope, CG et al. Prognostic factors in malignant ovarian germ cell tumours (the surveillance, epidemiology and end results experience 1978–2010). Euro J Cancer. 2014;50(11):1942–50.
75. Weinberg, LE, Lurain, JR, Singh, DK, Schink, JC. Survival and reproductive outcomes in women treated for malignant ovarian germ cell tumors. Gynecol Oncol. 2011;121(2):285–9.
76. Loren, AW, Mangu, PB, Beck, LN et al. Fertility preservation for patients with cancer: American Society of Clinical Oncology clinical practice guideline update. J Clin Oncol. 2013;31(19):2500–2510.
77. Simone, CG, Markham, MJ, Dizon, DS. Chemotherapy in ovarian germ cell tumors: a systematic review. Gynecol Oncol. 2016;141(3):602–607.