Skip to main content

Diagnosis and Management of Gestational Trophoblastic Neoplasia

  • Chapter
  • First Online:
International Manual of Oncology Practice

Abstract

Gestational trophoblastic neoplasia (GTN) is the term used for an uncommon group of diseases that originate in the placenta and have the potential to locally invade the uterus and metastasize. The histological entities included in this group are: partial (PHM) and complete hydatidiform mole (CHM), invasive mole (IM), choriocarcinoma (CCA), placental site trophoblastic tumor (PSTT) and epithelioid trophoblastic tumor (ETT).

This is a preview of subscription content, log in via an institution to check access.

Access this chapter

Chapter
USD 29.95
Price excludes VAT (USA)
  • Available as PDF
  • Read on any device
  • Instant download
  • Own it forever
eBook
USD 149.00
Price excludes VAT (USA)
  • Available as EPUB and PDF
  • Read on any device
  • Instant download
  • Own it forever
Softcover Book
USD 199.99
Price excludes VAT (USA)
  • Compact, lightweight edition
  • Dispatched in 3 to 5 business days
  • Free shipping worldwide - see info
Hardcover Book
USD 199.99
Price excludes VAT (USA)
  • Durable hardcover edition
  • Dispatched in 3 to 5 business days
  • Free shipping worldwide - see info

Tax calculation will be finalised at checkout

Purchases are for personal use only

Institutional subscriptions

References

  1. Hertz R, Lewis JL Jr, Lipsett MB (1961) Five years experience with the chemotherapy of metastatic choriocarcinoma and related trophoblastic tumors in women. Am J Obstet Gynecol 82:631–640

    Article  CAS  PubMed  Google Scholar 

  2. Brewer JL, Eckman TR, Dolkart RE et al (1971) Gestational trophoblastic disease. A comparative study of the results of therapy in patients with invasive mole and with choriocarcinoma. Am J Obstet Gynecol 109:335–340

    Article  CAS  PubMed  Google Scholar 

  3. Goldstein DP, Berkowitz RS (2012) Current management of gestational trophoblastic neoplasia. Hematol Oncol Clin North Am 26:111–113

    Article  PubMed  Google Scholar 

  4. Bracken MB (1987) Incidence and aetiology of hydatidiform mole: an epidemiologic review. Br J Obstet Gynecol 94:1123–1135

    Article  CAS  Google Scholar 

  5. Palmer JR (1994) Advances in the epidemiology of gestational trophoblastic disease. J Reprod Med 39:155–162

    CAS  PubMed  Google Scholar 

  6. Atrash HK, Hogue CJR, Grimes DA (1986) Epidemiology of hydatidiform mole during early gestation. Am J Obstet Gynecol 154:906–909

    Article  CAS  PubMed  Google Scholar 

  7. Bagshawe KD, Dent J, Webb J (1986) Hydatidiform mole in England and Wales 1973–83. Lancet 2:673–677

    Article  CAS  PubMed  Google Scholar 

  8. Takeuchi S (1987) Incidence of gestational trophoblastic disease by regional registration in Japan. Hum Reprod 2:729–734

    Article  CAS  PubMed  Google Scholar 

  9. Smith HO (2003) Gestational trophoblastic disease epidemiology and trends. Clin Obstet Gynecol 46:541–556

    Article  PubMed  Google Scholar 

  10. Parazzini F, Mangili G, LaVecchia C et al (1991) Risk factors for gestational trophoblastic disease:a separate analysis of complete and partial hydatidiform moles. Obstet Gynecol 78:1039–1045

    CAS  PubMed  Google Scholar 

  11. Sebire NJ, Foskett M, Fisher RA et al (2002) Risk of partial and complete molar pregnancy in relation to maternal age. Br J Obstet Gynaecol 109:99–102

    Article  CAS  Google Scholar 

  12. Berkowitz RS, Cramer DW, Bernstein MR et al (1985) Risk factors for complete molar pregnancy from a case-control study. Am J Obstet Gynecol 152:1016–1020

    Article  CAS  PubMed  Google Scholar 

  13. Parazzini F, LaVecchia C, Mangili G et al (1988) Dietary factors and risk of trophoblastic disease. Am J Obstet Gynecol 158:93–99

    Article  CAS  PubMed  Google Scholar 

  14. Brinton LA, Bracken MB, Connelly RR (1986) Choriocarcinoma incidence in the United States. Am J Epidemiol 123:1094–1100

    Article  CAS  PubMed  Google Scholar 

  15. Smith HO, Qualls CR, Prarie BA et al (2003) Trends in gestational choriocarcinoma: a 27-year perspective. Obstet Gynecol 102:978–987

    PubMed  Google Scholar 

  16. Hertig AT, Mansell H (1956) Tumors of the female sex organs. Part 1. Hydatidiform mole and choriocarcinoma. In: Atlas of tumor pathology (1st series), Fascicle 33. Armed Forces Institute of Pathology, Washington, DC

    Google Scholar 

  17. Kajii T, Ohama K (1977) Androgenetic origin of hydatidiform mole. Nature 268:633–634

    Article  CAS  PubMed  Google Scholar 

  18. Yamashita K, Wake N, Araki T et al (1979) Human lymphocyte antigen expression in hydatidiform mole: androgenesis following fertilization by a haploid sperm. Am J Obstet Gynecol 135:597–605

    Article  CAS  PubMed  Google Scholar 

  19. Fisher RA, Newlands ES (1998) Gestational trophobastic disease: molecular and genetic studies. J Reprod Med 434:81–97

    Google Scholar 

  20. Azuma C, Saji F, Tukugawa Y et al (1991) Application of gene amplification by polymerase chain reaction by genetic analysis of molar mitochondiial DNA: the detection of anuclear empty ovum as the cause of complete mole. Gynecol Oncol 40:29–33

    Article  CAS  PubMed  Google Scholar 

  21. Szulman AE, Surti U (1978) The syndromes of hydatidiform mole I. Cytogenetic and morphologic correlations. Am J Obstet Gynecol 131:665–771

    Article  CAS  PubMed  Google Scholar 

  22. Lawler SD, Fisher RA, Dent J (1991) A prospective genetic study of complete and partial hydatidiform moles. Am J Obstet Gynecol 164:1270–1277

    Article  CAS  PubMed  Google Scholar 

  23. Lage JM, Mark SD, Roberts D et al (1992) A flow cytometric study of 137 fresh hydropic placentas: correlation between types of hydatidiform moles and nuclear DNA ploidy. Obstet Gynecol 79:403–410

    Article  CAS  PubMed  Google Scholar 

  24. Fox H, Sebire NJ (2007) Pathology of the placenta, 3rd edn. Elsevier, Philadelphia

    Google Scholar 

  25. Baergen RN, Rutgers JL, Young RH et al (2006) Placental site trophoblastic tumor: a study of 55 cases and review of the literature emphasizing factors of prognostic significance. Gynecol Oncol 100:511–520

    Article  PubMed  Google Scholar 

  26. Cole LA, Khanlian SA, Muller CY et al (2006) Gestational trophoblastic diseases: 3. Human chorionic gonadotropin-free beta-subunit:a reliable marker of placental site trophoblastic tumors. Gynecol Oncol 102:160–164

    Article  CAS  PubMed  Google Scholar 

  27. Shih IM, Kurman RJ (1998) Epithelioid trophoblastic tumor: a neoplasm distinct from choriocarcinoma and placental site trophoblastic tumour simulating carcinoma. Am J Surg Pathol 22:1393–1403

    Article  CAS  PubMed  Google Scholar 

  28. Allison KH, Love JE, Garcia RL (2006) Epithelioid trophoblastic tumor: review of a rare neoplasm of the chorionic-type intermediate trophoblast. Arch Pathol Lab Med 130:1875–1877

    PubMed  Google Scholar 

  29. Berkowitz RS, Goldstein DP (2009) Molar pregnancy. N Engl J Med 360:1639–1645

    Article  CAS  PubMed  Google Scholar 

  30. Cole LA, Kohorn EI (2006) The need for an hCG assay that appropriately detects trophoblastic disease and other hCG-producing tumors. J Reprod Med 51:793–811

    CAS  PubMed  Google Scholar 

  31. Cole LA, Sasaki Y, Muller CY (2007) Normal production of human chorionic gonadotropin in menopause. N Engl J Med 356:1184–1186

    Article  CAS  PubMed  Google Scholar 

  32. Lurain JR (2010) Gestational trophoblastic disease. II: classification and management of gestational trophoblastic neoplasia. Am J Obstet Gynecol 203:11–18

    Article  Google Scholar 

  33. Betel C, Atri M, Arenson A-M et al (2006) Sonographic diagnosis of gestational trophoblastic disease and comparison with retained products of conception. J Ultrasound Med 25:985–993

    Article  PubMed  Google Scholar 

  34. Garner EIO, Garrett A, Goldstein DP, Berkowitz RS (2004) Significance of chest computed tomography findings in the evaluation and treatment of persistent gestational trophoblastic neoplasia. J Reprod Med 49:411–414

    Google Scholar 

  35. Bagshawe KD, Harland S (1976) Immunodiagnosis and monitoring of gonadotropin-producing metastases in the central nervous system. Cancer 38:112–118

    Article  CAS  PubMed  Google Scholar 

  36. Bakri YN, Al-Hawashim N, Berkowitz RS (2000) Cerebrospinal fluid/serum beta subunit human chorionic gonadotropin ratio in patients with brain metastases of gestational trophoblastic tumor. J Reprod Med 45:94–96

    CAS  PubMed  Google Scholar 

  37. Dhillon T, Palmieri C, Sebire NJ et al (2006) Value of whole body 18 FDG-PET to identify the active site of gestational trophoblastic neoplasia. J Reprod Med 51:879–887

    PubMed  Google Scholar 

  38. Kohorn EI (2002) Negotiating a staging and risk factor scoring system for gestational trophoblastic neoplasia. A progress report. J Reprod Med 47:445–450

    PubMed  Google Scholar 

  39. Goldstein DP, Zanten-Przybysz BMR, Berkowitz RS (1998) Revised FIGO staging system for gestational trophoblastic tumors; recommendations regarding therapy. J Reprod Med 43:37–43

    CAS  PubMed  Google Scholar 

  40. Lurain JR (2003) Pharmacotherapy of gestational trophoblastic disease. Expert Opin Pharmacother 4:1–13

    Article  Google Scholar 

  41. Van Trommel NE, Massuger LFAHG, Verheijen RHM et al (2005) The curative effect of a second curettage in persistent trophoblastic disease: a retrospective cohort study. Gynecol Oncol 99:6–13

    Article  PubMed  Google Scholar 

  42. Garner EIO, Feltmate CM, Goldstein DP, Berkowitz RS (2005) The curative effect of a second curettage in persistent trophoblastic disaese: a retrospective cohort study. Gynecol Oncol 99:3–5

    Article  PubMed  Google Scholar 

  43. Alazzam M, Tidy JA, Hancock BW et al (2009) First line chemotherapy in low risk gestational trophoblastic neoplasia. Cochrane Database Syst Rev 21(1):CD007102

    Google Scholar 

  44. Kohorn EI (2002) Is lack of response to single-agent chemotherapy in gestational trophoblastic disease associated with dose scheduling or chemotherapy resistance? Gynecol Oncol 85:36–39

    Article  CAS  PubMed  Google Scholar 

  45. Berkowitz RS, Goldstein DP, Bernstein MR (1990) Methotrexate infusion with folinic acid in primary therapy of nonmetastatic trophoblastic tumors. Gynecol Oncol 36:56–59

    Article  CAS  PubMed  Google Scholar 

  46. Lybol C, Sweep FC, Harvey R et al (2012) Relapse rates after two versus three consolidation courses of methotrexate in the treatment of low-risk gestational trophoblastic neoplasia. Gynecol Oncol 125:576–579

    Article  CAS  PubMed  Google Scholar 

  47. McGrath S, Short D, Harvey R (2010) The management and outcome of women with post-hydatidiform mole ‘low-risk’ gestational trophoblastic neoplasia, but hCG levels in excess of 100,000 IU/L. Br J Cancer 102:810–814

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  48. Feltmate CM, Genest DR, Goldstein DP, Berkowitz RS (2002) Advances in the understanding of placental site trophoblastic tumor. J Reprod Med 47:337–341

    PubMed  Google Scholar 

  49. Palmer JE, Macdonald M, Wells M et al (2008) Epithelioid trophoblastic tumor: a review of the literature. J Reprod Med 53:465–475

    CAS  PubMed  Google Scholar 

  50. Papadopoulos AJ, Foskett M, Seckl MJ et al (2002) Twenty-five years’ clinical experience with placental site trophoblastic tumors. J Reprod Med 47:460–464

    PubMed  Google Scholar 

  51. Hassaida A, Gillespie A, Tidy J (2005) Placental site trophoblastic tumor: clinical features and management. Gynecol Oncol 99:603–607

    Article  Google Scholar 

  52. Schmid P, Nagai Y, Agarwal R et al (2009) Prognostic markers and long-term outcome of placental-site trophoblastic tumors: a retrospective observational study. Lancet 374:48–55

    Article  CAS  PubMed  Google Scholar 

  53. Pfeffer PE, Sebire N, Lindsay I et al (2007) Fertility-sparing partial hysterectomy for placental-site trophoblastic tumour. Lancet Oncol 8:744–746

    Article  PubMed  Google Scholar 

  54. Leiserowitz GS, Webb MJ (1996) Treatment of placental site trophoblastic tumor with hysterotomy and uterine reconstruction. Obstet Gynecol 88:696–699

    Article  CAS  PubMed  Google Scholar 

  55. Bower M, Newlands ES, Holden L et al (1997) EMA/CO for high-risk gestational trophoblastic tumors: results from a cohort of 272 patients. J Clin Oncol 15:2636–2643

    Article  CAS  PubMed  Google Scholar 

  56. Lurain JR, Singh DK, Schink JC (2006) Primary treatment of metastatic high-risk gestational trophoblastic neoplasia with EMA-CO chemotherapy. J Reprod Med 51:767–772

    PubMed  Google Scholar 

  57. Turan T, Karacay O, Tulunay G et al (2006) Results with EMA/CO (etoposide, ethotrexate, actinomycin D, cyclophosphamide, vincristine) chemotherapy in gestational trophoblastic neoplasia. Int J Gynecol Oncol 16:1432–1438

    Article  CAS  Google Scholar 

  58. Lu WG, Ye F, Shen YM et al (2008) EMA-CO chemotherapy for high-risk gestational trophoblastic neoplasia: a clinical analysis of 54 patients. Int J Gynecol Oncol 18:357–362

    Article  Google Scholar 

  59. Lurain JR, Nejad B (2005) Secondary chemotherapy for high-risk gestational trophoblastic neoplasia. Gynecol Oncol 97:618–623

    Article  CAS  PubMed  Google Scholar 

  60. Mao Y, Wan X, Lu W et al (2007) Relapsed or refractory gestational trophoblastic neoplasia treated with etoposide and cisplatin/etoposide, methotrexate, and actinomycin D (EP-EMA) regimen. Int J Gynecol Oncol 98:44–47

    CAS  Google Scholar 

  61. Newlands ES, Mulholland PJ, Holden L et al (2000) Etoposide and cisplatin/etoposide, methotrexate and actinomycin D (EMA) for patients with high-risk gestational trophoblastic tumors refractory to EMA/cyclophosphamide and vincristine and patients presenting with metastastic placental site tumors. J Clin Oncol 18:854–859

    Article  CAS  PubMed  Google Scholar 

  62. Powles Y, Savage PM, Stebbins J et al (2007) A comparison of patients with relapsed and chemo-refractory gestational trophoblastic neoplasia. Br J Cancer 96:732–737

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  63. Mutch DG, Soper JT, Babcock CJ et al (1990) Recurrent gestational trophoblastic disease. Experience of the Southeastern Regional Trophoblastic Disease Center. Cancer 66:978–982

    Article  CAS  PubMed  Google Scholar 

  64. Seckl MJ, Sebire NJ, Berkowitz S (2010) Gestational trophoblastic disease. Lancet 375:717–729

    Article  Google Scholar 

  65. Alifrangis C, Agarwal R, Short D et al (2013) EMA/CO for high-risk gestational trophoblastic neoplasia: good outcomes with induction low-dose etoposide-cisplatin and genetic analysis. J Clin Oncol 31(2):280–286

    Article  CAS  PubMed  Google Scholar 

  66. Newlands ES, Holden L, Seckl MJ et al (2002) Management of brain metastases in patients with high risk gestational trophoblastic tumors. J Reprod Med 47:465–471

    CAS  PubMed  Google Scholar 

  67. Soper JT (2003) Role of surgery and radiation therapy in the management of gestational trophoblastic disease. Best Pract Res Clin Obstet Gynecol 17:943–958

    Article  Google Scholar 

  68. Rustin GJS, Newlands ES, Lutz JM et al (1996) Combination but not single-agent methotrexate chemotherapy for gestational trophoblastic tumors increases the incidence of second tumors. J Clin Oncol 14:2769–2773

    Article  CAS  PubMed  Google Scholar 

  69. Savage PM, Cook R, O’Nions J, et al (2014) The effects of chemotherapy treatment for gestational trophoblastic tumours on second tumour risk and early menopause. XVII World Congress on Gestational Trophoblastic Diseases; 71–2(Abstract)

    Google Scholar 

  70. Giacalone PL, Benos P, Donnadio D, Laffargue F (1995) High-dose chemotherapy with autologous bone marrow transplantation for refractory metastatic gestational trophoblastic disease. Gynecol Oncol 58:383–385

    Article  CAS  PubMed  Google Scholar 

  71. Van Besien K, Verschraegen C, Mehra R et al (1997) Complete remission of refractory gestational trophoblastic disease with brain metastases treated with multicycle ifosfamide, carboplatin, and etoposide (ICE) and stem cell rescue. Gynecol Oncol 65:366–369

    Article  PubMed  Google Scholar 

  72. Cole LA, Muller CY (2010) Hyperglycosylated hCG in the management of quiescent and chemorefractory gestational trophoblastic diseases. Gynecol Oncol 116:3–9

    Article  CAS  PubMed  Google Scholar 

  73. Kohorn EI (2004) What we know about low-level hCG: definition, classification and management. J Reprod Med 49:433–437

    PubMed  Google Scholar 

  74. Hancock BW (2006) hCG measurement in gestational trophoblastic neoplasia: a critical appraisal. J Reprod Med 51:859–860

    PubMed  Google Scholar 

  75. Hwang D, Hancock BW (2004) Management of persistent, unexplained, low-level human chorionic gonadotropin elevation: a report of 5 cases. J Reprod Med 49:559–562

    PubMed  Google Scholar 

  76. Khanlian SA, Cole LA (2006) Management of gestational trophoblastic disease and other cases with low serum levels of human chorionic gonadotropin. J Reprod Med 51:812–818

    CAS  PubMed  Google Scholar 

  77. Kim JH, Park DC, Bae SN et al (1998) Subsequent reproductive experience after treatment for gestational trophoblastic disease. Gynecol Oncol 71:108–112

    Article  CAS  PubMed  Google Scholar 

  78. Ayhan A, Ergeneli MH, Yuce K et al (1990) Pregnancy after chemotherapy for gestational trophoblastic disease. J Reprod Med 35:522–524

    CAS  PubMed  Google Scholar 

  79. Amir MF (1999) Return of fertility after successful chemotherapy treatment for gestational trophoblastic tumors. Int J Fertil Womens Med 44:146–149

    Google Scholar 

  80. Vargas R, Barroilhet L, Esselen K et al (2014) Subsequent pregnancy outcomes in patients with molar pregnancy and persistent gestational trophoblastic neoplasia: updated results. J Reprod Med 59:188–194

    PubMed  Google Scholar 

  81. Woolas RP, Bower M, Newlands ES et al (1998) Influence of chemotherapy for gestational trophoblastic disease on subsequent pregnancy outcome. Br J Obstet Gynecol 105:1032–1035. 9:1326–1327

    Article  CAS  Google Scholar 

  82. Matsui H, Iitsuka Y, Suzuka K et al (2004) Early pregnancy outcomes after chemotherapy for gestational trophoblastic tumor. J Reprod Med 49:531–534

    PubMed  Google Scholar 

  83. Blagden SP, Foskett MA, Fisher RA et al (2002) The effect of early pregnancy following chemotherapy on disease relapse and foetal outcome in women treated for gestational trophoblastic tumours. Br J Cancer 86:26–30

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  84. Wenzel L, Berkowitz RS, Newlands E et al (2002) Quality of life after gestational trophoblastic disease. J Reprod Med 47:387–394

    PubMed  Google Scholar 

  85. Horowitz NS, Wenzel LB (2009) Psychosocial consequences of gestational trophoblastic disease. In: Hancock BW, Seckl MJ, Berkowitz RS (eds) Gestational trophoblastic disease, 3rd edn. L Cole, Sheffield, pp 460–469

    Google Scholar 

Download references

Author information

Authors and Affiliations

Authors

Corresponding author

Correspondence to Donald Peter Goldstein .

Editor information

Editors and Affiliations

Rights and permissions

Reprints and permissions

Copyright information

© 2019 Springer Nature Switzerland AG

About this chapter

Check for updates. Verify currency and authenticity via CrossMark

Cite this chapter

Goldstein, D.P., Berkowitz, R.S., Horowitz, N.S. (2019). Diagnosis and Management of Gestational Trophoblastic Neoplasia. In: De Mello, R., Mountzios, G., Tavares, Á. (eds) International Manual of Oncology Practice. Springer, Cham. https://doi.org/10.1007/978-3-030-16245-0_25

Download citation

Publish with us

Policies and ethics