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

Gestational trophoblastic neoplasia: Epidemiology, clinical features, diagnosis, staging, and risk stratification

Authors
Ross S Berkowitz, MD
Donald Peter Goldstein, MD
Neil S Horowitz, MD
Section Editors
Barbara Goff, MD
Don S Dizon, MD, FACP
Deputy Editors
Sandy J Falk, MD, FACOG
Sadhna R Vora, MD

INTRODUCTION

Gestational trophoblastic neoplasia (GTN) refers to a group of malignant neoplasms that consist of abnormal proliferation of trophoblastic tissue, and may follow a hydatiform mole or a nonmolar pregnancy. GTN is comprised of the following histologic types:

Invasive mole

Choriocarcinoma

Placental site trophoblastic tumor (PSTT)

Epithelioid trophoblastic tumor (ETT)

                                           

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: Nov 2016. | This topic last updated: Mon Jan 05 00:00:00 GMT+00:00 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.
References
Top
  1. Brewer JI, Eckman TR, Dolkart RE, et al. Gestational trophoblastic disease. A comparative study of the results of therapy in patients with invasive mole and with choriocarcinoma. Am J Obstet Gynecol 1971; 109:335.
  2. Goldstein DP, Berkowitz RS. Current management of gestational trophoblastic neoplasia. Hematol Oncol Clin North Am 2012; 26:111.
  3. Hertig AT, Mansell H. Tumors of the female sex organs. Part 1. Hydatidiform mole and choriocarcinoma. In: Atlas of Tumor Pathology (1st series), Armed Forces Institute of Pathology, Washington, DC 1956. Fascicle 33.
  4. Ngan S, Seckl MJ. Gestational trophoblastic neoplasia management: an update. Curr Opin Oncol 2007; 19:486.
  5. Brinton LA, Bracken MB, Connelly RR. Choriocarcinoma incidence in the United States. Am J Epidemiol 1986; 123:1094.
  6. Smith HO. Gestational trophoblastic disease epidemiology and trends. Clin Obstet Gynecol 2003; 46:541.
  7. Altieri A, Franceschi S, Ferlay J, et al. Epidemiology and aetiology of gestational trophoblastic diseases. Lancet Oncol 2003; 4:670.
  8. Moodley M, Tunkyi K, Moodley J. Gestational trophoblastic syndrome: an audit of 112 patients. A South African experience. Int J Gynecol Cancer 2003; 13:234.
  9. Messerli ML, Lilienfeld AM, Parmley T, et al. Risk factors for gestational trophoblastic neoplasia. Am J Obstet Gynecol 1985; 153:294.
  10. Berkowitz RS, Cramer DW, Bernstein MR, et al. Risk factors for complete molar pregnancy from a case-control study. Am J Obstet Gynecol 1985; 152:1016.
  11. Goldstein DP, Berkowitz RS. Gestational Trophoblastic Neoplasms: Clinical Principles of Diagnosis and Management, WB Saunders, Philadelphia 1982.
  12. Soto-Wright V, Bernstein M, Goldstein DP, Berkowitz RS. The changing clinical presentation of complete molar pregnancy. Obstet Gynecol 1995; 86:775.
  13. Berkowitz RS, Goldstein DP. Clinical practice. Molar pregnancy. N Engl J Med 2009; 360:1639.
  14. Berkowitz RS, Goldstein DP. Gestational trophoblastic diseases. In: Principles and Practice of Gynecologic Oncology, 3rd ed, Hoskins WJ, Perez CA, Young RD (Eds), Williams and Wilkins, Philadelphia 2000. p.1127.
  15. Seckl MJ, Sebire NJ, Berkowitz RS. Gestational trophoblastic disease. Lancet 2010; 376:717.
  16. Feltmate CM, Genest DR, Wise L, et al. Placental site trophoblastic tumor: a 17-year experience at the New England Trophoblastic Disease Center. Gynecol Oncol 2001; 82:415.
  17. Berkowitz RS, Goldstein DP. Chorionic tumors. N Engl J Med 1996; 335:1740.
  18. Lurain JR. Gestational trophoblastic disease I: epidemiology, pathology, clinical presentation and diagnosis of gestational trophoblastic disease, and management of hydatidiform mole. Am J Obstet Gynecol 2010; 203:531.
  19. Osborne R, Dodge J. Gestational trophoblastic neoplasia. Obstet Gynecol Clin North Am 2012; 39:195.
  20. Fox H, Sebire NJ. Pathology of the placenta, 3rd ed, Elsevier, Philadelphia 2007.
  21. Baergen RN, Rutgers JL, Young RH, et al. Placental site trophoblastic tumor: A study of 55 cases and review of the literature emphasizing factors of prognostic significance. Gynecol Oncol 2006; 100:511.
  22. Hassadia A, Gillespie A, Tidy J, et al. Placental site trophoblastic tumour: clinical features and management. Gynecol Oncol 2005; 99:603.
  23. Lan C, Li Y, He J, Liu J. Placental site trophoblastic tumor: lymphatic spread and possible target markers. Gynecol Oncol 2010; 116:430.
  24. Shih IM, Kurman RJ. Epithelioid trophoblastic tumor: a neoplasm distinct from choriocarcinoma and placental site trophoblastic tumor simulating carcinoma. Am J Surg Pathol 1998; 22:1393.
  25. Allison KH, Love JE, Garcia RL. Epithelioid trophoblastic tumor: review of a rare neoplasm of the chorionic-type intermediate trophoblast. Arch Pathol Lab Med 2006; 130:1875.
  26. Zhang X, Lü W, Lü B. Epithelioid trophoblastic tumor: an outcome-based literature review of 78 reported cases. Int J Gynecol Cancer 2013; 23:1334.
  27. Mao TL, Seidman JD, Kurman RJ, Shih IeM. Cyclin E and p16 immunoreactivity in epithelioid trophoblastic tumor--an aid in differential diagnosis. Am J Surg Pathol 2006; 30:1105.
  28. Bamberger AM, Aupers S, Milde-Langosch K, Löning T. Expression pattern of the cell cycle promoter cyclin e in benign extravillous trophoblast and gestational trophoblastic lesions: correlation with expression of Ki-67. Int J Gynecol Pathol 2003; 22:156.
  29. Berkowitz RS, Goldstein DP. Pathogenesis of gestational trophoblastic neoplasms. Pathobiol Annu 1981; 11:391.
  30. Berkowitz RS, Goldstein DP. Current management of gestational trophoblastic diseases. Gynecol Oncol 2009; 112:654.
  31. Berkowitz RS, Goldstein DP, Bernstein MR. Natural history of partial molar pregnancy. Obstet Gynecol 1985; 66:677.
  32. Rajatanavin R, Chuahirun S, Chailurkit L, et al. Virilization associated with choriocarcinoma. J Endocrinol Invest 1995; 18:653.
  33. Dhillon T, Palmieri C, Sebire NJ, et al. Value of whole body 18FDG-PET to identify the active site of gestational trophoblastic neoplasia. J Reprod Med 2006; 51:879.
  34. Garner EI, Meyerovitz M, Goldstein DP, Berkowitz RS. Successful term pregnancy after selective arterial embolization of symptomatic arteriovenous malformation in the setting of gestational trophoblastic tumor. Gynecol Oncol 2003; 88:69.
  35. Lim AK, Agarwal R, Seckl MJ, et al. Embolization of bleeding residual uterine vascular malformations in patients with treated gestational trophoblastic tumors. Radiology 2002; 222:640.
  36. Bakri YN, Berkowitz RS, Khan J, et al. Pulmonary metastases of gestational trophoblastic tumor. Risk factors for early respiratory failure. J Reprod Med 1994; 39:175.
  37. Bagshawe KD, Noble MI. Cardio-respiratory aspects of trophoblastic tumours. Q J Med 1966; 35:39.
  38. Jones WB, Wagner-Reiss KM, Lewis JL Jr. Intracerebral choriocarcinoma. Gynecol Oncol 1990; 38:234.
  39. Hongzhao S, Baozhen W. Brain metastasis in choriocarcinoma and malignant mole: an analysis of 98 cases. Chin Med J (Engl) 1979; 92:164.
  40. Bakri Y, Berkowitz RS, Goldstein DP, et al. Brain metastases of gestational trophoblastic tumor. J Reprod Med 1994; 39:179.
  41. Athanassiou A, Begent RH, Newlands ES, et al. Central nervous system metastases of choriocarcinoma. 23 years' experience at Charing Cross Hospital. Cancer 1983; 52:1728.
  42. Liu TL, Deppe G, Chang QT, Tan TT. Cerebral metastatic choriocarcinoma in the People's Republic of China. Gynecol Oncol 1983; 15:166.
  43. Bakri YN, Subhi J, Amer M, et al. Liver metastases of gestational trophoblastic tumor. Gynecol Oncol 1993; 48:110.
  44. Schmid P, Nagai Y, Agarwal R, et al. Prognostic markers and long-term outcome of placental-site trophoblastic tumours: a retrospective observational study. Lancet 2009; 374:48.
  45. Hoekstra AV, Keh P, Lurain JR. Placental site trophoblastic tumor: a review of 7 cases and their implications for prognosis and treatment. J Reprod Med 2004; 49:447.
  46. Papadopoulos AJ, Foskett M, Seckl MJ, et al. Twenty-five years' clinical experience with placental site trophoblastic tumors. J Reprod Med 2002; 47:460.
  47. Cole LA, Khanlian SA, Muller CY, et al. Gestational trophoblastic diseases: 3. Human chorionic gonadotropin-free beta-subunit, a reliable marker of placental site trophoblastic tumors. Gynecol Oncol 2006; 102:160.
  48. Kohorn EI. What we know about low-level hCG: definition, classification and management. J Reprod Med 2004; 49:433.
  49. Zhou Q, Lei XY, Xie Q, Cardoza JD. Sonographic and Doppler imaging in the diagnosis and treatment of gestational trophoblastic disease: a 12-year experience. J Ultrasound Med 2005; 24:15.
  50. Okumura M, Fushida K, Rezende WW, et al. Sonographic appearance of gestational trophoblastic disease evolving into epithelioid trophoblastic tumor. Ultrasound Obstet Gynecol 2010; 36:249.
  51. Gamer EI, Garrett A, Goldstein DP, Berkowitz RS. Significance of chest computed tomography findings in the evaluation and treatment of persistent gestational trophoblastic neoplasia. J Reprod Med 2004; 49:411.
  52. Ngan HY, Chan FL, Au VW, et al. Clinical outcome of micrometastasis in the lung in stage IA persistent gestational trophoblastic disease. Gynecol Oncol 1998; 70:192.
  53. Sung HC, Wu PC, Hu MH, Su HT. Roentgenologic manifestations of pulmonary metastases in choriocarcinoma and invasive mole. Am J Obstet Gynecol 1982; 142:89.
  54. BAGSHAWE KD, GARNETT ES. RADIOLOGICAL CHANGES IN THE LUNGS OF PATIENTS WITH TROPHOBLASTIC TUMOURS. Br J Radiol 1963; 36:673.
  55. EVANS KT, COCKSHOTT WP, HENDRICKSEPDE V. PULMONARY CHANGES IN MALIGNANT TROPHOBLASTIC DISEASE. Br J Radiol 1965; 38:161.
  56. Libshitz HI, Baber CE, Hammond CB. The pulmonary metastases of choriocarcinoma. Obstet Gynecol 1977; 49:412.
  57. Bakri Y, al-Hawashim N, Berkowitz R. CSF/serum beta-hCG ratio in patients with brain metastases of gestational trophoblastic tumor. J Reprod Med 2000; 45:94.
  58. Bagshawe KD, Harland S. Immunodiagnosis and monitoring of gonadotrophin-producing metastases in the central nervous system. Cancer 1976; 38:112.
  59. Kohorn EI. The new FIGO 2000 staging and risk factor scoring system for gestational trophoblastic disease: description and critical assessment. Int J Gynecol Cancer 2001; 11:73.
  60. Kohorn EI. Negotiating a staging and risk factor scoring system for gestational trophoblastic neoplasia. A progress report. J Reprod Med 2002; 47:445.
  61. Ngan HY, Bender H, Benedet JL, et al. Gestational trophoblastic neoplasia, FIGO 2000 staging and classification. Int J Gynaecol Obstet 2003; 83 Suppl 1:175.
  62. Harvey RA, Mitchell HD, Stenman UH, et al. Differences in total human chorionic gonadotropin immunoassay analytical specificity and ability to measure human chorionic gonadotropin in gestational trophoblastic disease and germ cell tumors. J Reprod Med 2010; 55:285.
  63. Braunstein GD, Vaitukaitis JL, Carbone PP, Ross GT. Ectopic production of human chorionic gonadotrophin by neoplasms. Ann Intern Med 1973; 78:39.
  64. Mutch DG, Soper JT, Baker ME, et al. Role of computed axial tomography of the chest in staging patients with nonmetastatic gestational trophoblastic disease. Obstet Gynecol 1986; 68:348.
  65. Berkowitz RS, Birnholz J, Goldstein DP, Bernstein MR. Pelvic ultrasonography and the management of gestational trophoblastic disease. Gynecol Oncol 1983; 15:403.
  66. Kohorn EI, McCarthy SM, Taylor KJ. Nonmetastatic gestational trophoblastic neoplasia. Role of ultrasonography and magnetic resonance imaging. J Reprod Med 1998; 43:14.
  67. Kohorn EI. Imaging practices in the diagnosis and management of gestational trophoblastic disease: an assessment. J Reprod Med 2012; 57:207.
  68. Mangili G, Spagnolo D, Valsecchi L, Maggi R. Transvaginal ultrasonography in persistent trophoblastic tumor. Am J Obstet Gynecol 1993; 169:1218.
  69. Dobkin GR, Berkowitz RS, Goldstein DP, et al. Duplex ultrasonography for persistent gestational trophoblastic tumor. J Reprod Med 1991; 36:14.
  70. Long MG, Boultbee JE, Begent RH, et al. Preliminary Doppler studies on the uterine artery and myometrium in trophoblastic tumours requiring chemotherapy. Br J Obstet Gynaecol 1990; 97:686.
  71. FIGO Committee on Gynecologic Oncology. Current FIGO staging for cancer of the vagina, fallopian tube, ovary, and gestational trophoblastic neoplasia. Int J Gynaecol Obstet 2009; 105:3.
  72. Pecorelli S, Benedet JL, Creasman WT, Shepherd JH. FIGO staging of gynecologic cancer. 1994-1997 FIGO Committee on Gynecologic Oncology. International Federation of Gynecology and Obstetrics. Int J Gynaecol Obstet 1999; 64:5.
  73. Goldstein DP, Zanten-Przybysz IV, Bernstein MR, Berkowitz RS. Revised FIGO staging system for gestational trophoblastic tumors. Recommendations regarding therapy. J Reprod Med 1998; 43:37.
  74. World Health Organization Scientific Group on Gestational Trophoblastic Disease. WHO Tech Rep Ser 1983; 692:1.
  75. Lurain JR. Treatment of gestational trophoblastic tumors. Curr Treat Options Oncol 2002; 3:113.
  76. Gordon AN, Gershenson DM, Copeland LJ, et al. High-risk metastatic gestational trophoblastic disease: further stratification into two clinical entities. Gynecol Oncol 1989; 34:54.
  77. Mortakis AE, Braga CA. "Poor prognosis" metastatic gestational trophoblastic disease: the prognostic significance of the scoring system in predicting chemotherapy failures. Obstet Gynecol 1990; 76:272.
  78. Dubuc-Lissoir J, Zweizig S, Schlaerth JB, Morrow CP. Metastatic gestational trophoblastic disease: a comparison of prognostic classification systems. Gynecol Oncol 1992; 45:40.
  79. DuBeshter B, Berkowitz RS, Goldstein DP, et al. Metastatic gestational trophoblastic disease: experience at the New England Trophoblastic Disease Center, 1965 to 1985. Obstet Gynecol 1987; 69:390.
  80. Sita-Lumsden A, Short D, Lindsay I, et al. Treatment outcomes for 618 women with gestational trophoblastic tumours following a molar pregnancy at the Charing Cross Hospital, 2000-2009. Br J Cancer 2012; 107:1810.
  81. McNeish IA, Strickland S, Holden L, et al. Low-risk persistent gestational trophoblastic disease: outcome after initial treatment with low-dose methotrexate and folinic acid from 1992 to 2000. J Clin Oncol 2002; 20:1838.
  82. You B, Harvey R, Henin E, et al. Early prediction of treatment resistance in low-risk gestational trophoblastic neoplasia using population kinetic modelling of hCG measurements. Br J Cancer 2013; 108:1810.