PDF herunterladen
Geburtshilfe Frauenheilkd 2015; 75(10): 1043-1050
DOI: 10.1055/s-0035-1558054
Review
GebFra Science
Georg Thieme Verlag KG Stuttgart · New York

Gestational Trophoblastic Disorders: An Update in 2015

Trophoblasterkrankungen: ein Update für 2015
F. T. Stevens
1   Department of Obstetrics and Gynecology, Heinrich Heine University Medical Center, Düsseldorf
,
N. Katzorke
1   Department of Obstetrics and Gynecology, Heinrich Heine University Medical Center, Düsseldorf
,
C. Tempfer
2   Department of Obstetrics and Gynecology, Ruhr University Bochum, Bochum
,
U. Kreimer
1   Department of Obstetrics and Gynecology, Heinrich Heine University Medical Center, Düsseldorf
,
G. I. Bizjak
1   Department of Obstetrics and Gynecology, Heinrich Heine University Medical Center, Düsseldorf
,
M. C. Fleisch
1   Department of Obstetrics and Gynecology, Heinrich Heine University Medical Center, Düsseldorf
,
T. N. Fehm
1   Department of Obstetrics and Gynecology, Heinrich Heine University Medical Center, Düsseldorf
› Institutsangaben
Weitere Informationen

Publikationsverlauf

received 12. Mai 2015
revised 03. August 2015

accepted 08. August 2015

Publikationsdatum:
02. November 2015 (online)

Auch verfügbar auf
   Lizenzen und Reprints

Abstract

Gestational trophoblastic diseases (GTD) are a group of pregnancy-related disorders representing rare human tumours. They encompass premalignant disorders including complete (CHM), partial hydatidiform mole (PHM), exaggerated placental site (EPS), and placental-site nodule (PSN) as well as malignant disorders (also known as “gestational trophoblastic neoplasia [GTN]”) including invasive mole, choriocarcinoma (CC), placenta-site trophoblastic tumour (PSTT), and epitheloid trophoblastic tumours (ETT) (Fig. 1). Originally, GTD develop from abnormal proliferation of trophoblastic tissue and form botryoid arranged vesicles. Premalignant moles are usually treated by suction curettage while persistent and recurrent moles and malignant forms require systemic therapy with methotrexate or combination chemotherapy consisting of etoposide, actimomycin D, methotrexate, vincristine, and cyclophosphamide (EMA-CO). β-human chorion gonadotropin (β-hCG) plays a crucial role in diagnosis and monitoring therapeutic effects. Since the definitive diagnosis cannot be obtained by histology in most cases, persistent or recurrent disease is diagnosed by elevated or persistent serum levels of β-hCG. While curing rates are described to be as high as 98 %, GTD may initially present, recur, or end up as a metastasising systemic disease. This underlines the importance of a regular and consistent follow-up after treatment.

Zusammenfassung

Gestationsbedingte Trophoblasterkrankungen (GTE) gehören zu der Gruppe seltener menschlicher Tumoren, die im Rahmen einer Schwangerschaft entstehen. Diese Gruppe umfasst prämaligne Veränderungen wie Blasenmole und Partialmole, hyperplastische Implantationsstelle des Plazentabetts (exaggerated placental site, EPS) und Plazentabettknötchen (placental site nodule, PSN) sowie maligne Erkrankungen (auch gestationsbedingte Trophoblastneoplasien [GTN] genannt) wie invasive Molen, Chorionkarzinom, Plazentabetttumor (placental site trophoblastic tumor, PSTT) und epitheloider Trophoblasttumor (ETT) (Abb. 1). Die Entstehung von GTE ist durch die abnorme Proliferation von Trophoblastzellen gekennzeichnet, die traubenförmig angeordnete Bläschen bilden. Prämaligne Molen werden zumeist mit Saugkürettage therapiert. Die Behandlung persistierender und rezidivierender Molen sowie maligner Formen besteht aus einer systemischen Therapie mit Methotrexat oder einer Kombinationschemotherapie aus Etoposid, Actinomycin-D, Methotrexat, Vincristin, und Cyclophosphamid (EMA-CO). β-humanes Choriongonadotropin (β-hCG) spielt eine wichtige Rolle bei der Diagnose und Kontrolle der Therapie. Da eine histologische Untersuchung in den meisten Fällen keine endgültige Diagnose liefert, beruht die Diagnose von Persistenz und Rezidiv auf erhöhten (persistierenden) Serumkonzentrationen von β-hCG. Obwohl die in der Literatur angegebenen Heilungsraten hoch sind mit bis zu 98 %, können GTE nach dem ersten Auftreten rekurrieren oder in eine systemische Erkrankung mit Metastasierung übergehen. Dies unterstreicht die Bedeutung einer regelmäßigen und konsequenten Nachsorge.

Key words

gestational trophoblastic disease - hydatidiform moles - molar pregnancy - gestational neoplasia - human chorion gonadotropin

Schlüsselwörter

gestationsbedingte Trophoblasterkrankung - Blasenmole - molare Schwangerschaft - gestationsbedingte Neoplasie - humanes Choriongonadotropin
 

  • References

  • 1 Seckl MJ, Sebire NJ, Berkowitz RS. Gestational trophoblastic disease. Lancet 2010; 376: 717-729
    CrossrefPubMedGoogle Scholar
  • 2 Palmer JR. Advances in the epidemiology of gestational trophoblastic disease. J Reprod Med 1994; 39: 155-162
    PubMedGoogle Scholar
  • 3 Ngan S, Seckl MJ. Gestational trophoblastic neoplasia management: an update. Curr Opin Oncol 2007; 19: 486-491
    CrossrefPubMedGoogle Scholar
  • 4 Seckl MJ, Fisher RA, Salerno G et al. Choriocarcinoma and partial hydatidiform moles. Lancet 2000; 356: 36-39
    CrossrefPubMedGoogle Scholar
  • 5 Fisher RA, Lawler SD, Povey S et al. Genetically homozygous choriocarcinoma following pregnancy with hydatidiform mole. Br J Cancer 1988; 58: 788-792
    CrossrefPubMedGoogle Scholar
  • 6 Kajii T, Ohama K. Androgenetic origin of hydatidiform mole. Nature 1977; 268: 633-634
    CrossrefPubMedGoogle Scholar
  • 7 Yamashita K, Ishikawa M, Shimizu T et al. HLA antigens in husband-wife pairs with trophoblastic tumour. Gynecol Oncol 1981; 12: 68-74
    CrossrefPubMedGoogle Scholar
  • 8 Fisher RA, Newlands ES. Gestational trophoblastic disease. Molecular and genetic studies. J Reprod Med 1998; 43: 87-97
    PubMedGoogle Scholar
  • 9 Pattillo RA, Sasaki S, Katayama KP et al. Genesis of 46,XY hydatidiform mole. Am J Obstet Gynecol 1981; 141: 104-105
    CrossrefPubMedGoogle Scholar
  • 10 Azuma C, Saji F, Tokugawa Y et al. Application of gene amplification by polymerase chain reaction to genetic analysis of molar mitochondrial DNA: the detection of anuclear empty ovum as the cause of complete mole. Gynecol Oncol 1991; 40: 29-33
    CrossrefPubMedGoogle Scholar
  • 11 Fisher RA, Hodges MD, Newlands ES. Familial recurrent hydatidiform mole: a review. J Reprod Med 2004; 49: 595-601
    PubMedGoogle Scholar
  • 12 Murdoch S, Djuric U, Mazhar B et al. Mutations in NALP7 cause recurrent hydatidiform moles and reproductive wastage in humans. Nat Genet 2006; 38: 300-302
    CrossrefPubMedGoogle Scholar
  • 13 Judson H, Hayward BE, Sheridan E et al. A global disorder of imprinting in the human female germ line. Nature 2002; 416: 539-542
    CrossrefPubMedGoogle Scholar
  • 14 Fisher RA, Hodges MD, Rees HC et al. The maternally transcribed gene p 57(KIP2) (CDNK1C) is abnormally expressed in both androgenetic and biparental complete hydatidiform moles. Hum Mol Genet 2002; 11: 3267-3272
    CrossrefPubMedGoogle Scholar
  • 15 Kinoshita T, Wang Y, Hasegawa M et al. PYPAF3, a PYRIN-containing APAF-1-like protein, is a feedback regulator of caspase-1-dependent interleukin-1beta secretion. J Biol Chem 2005; 280: 21720-21725
    CrossrefPubMedGoogle Scholar
  • 16 Szulman AE, Surti U. The syndromes of hydatidiform mole. I. Cytogenetic and morphologic correlations. Am J Obstet Gynecol 1978; 131: 665-671
    CrossrefPubMedGoogle Scholar
  • 17 Lawler SD, Fisher RA, Dent J. A prospective genetic study of complete and partial hydatidiform moles. Am J Obstet Gynecol 1991; 164: 1270-1277
    CrossrefPubMedGoogle Scholar
  • 18 Lage JM, Mark SD, Roberts DJ et al. A flow cytometric study of 137 fresh hydropic placentas: correlation between types of hydatidiform moles and nuclear DNA ploidy. Obstet Gynecol 1992; 79: 403-410
    CrossrefPubMedGoogle Scholar
  • 19 Seckl MJ, Sebire NJ, Fisher RA et al. Gestational trophoblastic disease: ESMO Clinical Practice Guidelines for diagnosis, treatment and follow-up. Ann Oncol 2013; 24 (Suppl. 06) vi39-vi50
    PubMedGoogle Scholar
  • 20 Sebire NJ, Makrydimas G, Agnantis NJ et al. Updated diagnostic criteria for partial and complete hydatidiform moles in early pregnancy. Anticancer Res 2003; 23 (2C) 1723-1728
    PubMedGoogle Scholar
  • 21 Sebire NJ, Fisher RA, Rees HC. Histopathological diagnosis of partial and complete hydatidiform mole in the first trimester of pregnancy. Pediatr Dev Pathol 2003; 6: 69-77
    CrossrefPubMedGoogle Scholar
  • 22 Sebire NJ, Seckl MJ. Gestational trophoblastic disease: current management of hydatidiform mole. BMJ 2008; 337: a1193
    CrossrefPubMedGoogle Scholar
  • 23 Fisher RA, Newlands ES. Rapid diagnosis and classification of hydatidiform moles with polymerase chain reaction. Am J Obstet Gynecol 1993; 168: 563-569
    CrossrefPubMedGoogle Scholar
  • 24 Makrydimas G, Sebire NJ, Thornton SE et al. Complete hydatidiform mole and normal live birth: a novel case of confined placental mosaicism: case report. Hum Reprod 2002; 17: 2459-2463
    CrossrefPubMedGoogle Scholar
  • 25 Osada H. A complete hydatidiform mole coexisting with a normal fetus was confirmed by Variable Number Tandem Repeat (VNTR) polymorphism analysis using polymerase chain reaction. Gynecol Oncol 1995; 56: 90-93
    CrossrefPubMedGoogle Scholar
  • 26 Ozalp SS, Oge T. Gestational trophoblastic diseases in Turkey. J Reprod Med 2013; 58: 67-71
    PubMedGoogle Scholar
  • 27 Arima T, Imamura T, Amada S et al. Genetic origin of malignant trophoblastic neoplasms. Cancer Genet Cytogenet 1994; 73: 95-102
    CrossrefPubMedGoogle Scholar
  • 28 Fisher RA, Savage PM, MacDermott C et al. The impact of molecular genetic diagnosis on the management of women with hCG-producing malignancies. Gynecol Oncol 2007; 107: 413-419
    CrossrefPubMedGoogle Scholar
  • 29 Baergen RN, Rutgers JL, Young RH et al. Placental site trophoblastic tumour: A study of 55 cases and review of the literature emphasizing factors of prognostic significance. Gynecol Oncol 2006; 100: 511-520
    CrossrefPubMedGoogle Scholar
  • 30 Shih IM, Kurman RJ. Epithelioid trophoblastic tumour: a neoplasm distinct from choriocarcinoma and placental site trophoblastic tumour simulating carcinoma. Am J Surg Pathol 1998; 22: 1393-1403
    CrossrefPubMedGoogle Scholar
  • 31 Hou JL, Wan XR, Xiang Y et al. Changes of clinical features in hydatidiform mole: analysis of 113 cases. J Reprod Med 2008; 53: 629-633
    PubMedGoogle Scholar
  • 32 Fowler DJ, Lindsay I, Seckl MJ et al. Histomorphometric features of hydatidiform moles in early pregnancy: relationship to detectability by ultrasound examination. Ultrasound Obstet Gynecol 2007; 29: 76-80
    CrossrefPubMedGoogle Scholar
  • 33 Fowler DJ, Lindsay I, Seckl MJ et al. Routine pre-evacuation ultrasound diagnosis of hydatidiform mole: experience of more than 1000 cases from a regional referral center. Ultrasound Obstet Gynecol 2006; 27: 56-60
    PubMedGoogle Scholar
  • 34 Seckl MJ, Gillmore R, Foskett M et al. Routine terminations of pregnancy–should we screen for gestational trophoblastic neoplasia?. Lancet 2004; 364: 705-707
    CrossrefPubMedGoogle Scholar
  • 35 Berkowitz RS, Goldstein DP. Chorionic tumours. N Engl J Med 1996; 335: 1740-1748
    CrossrefPubMedGoogle Scholar
  • 36 Xia ZF, Song HZ, Tang MY. Risk of malignancy and prognosis using a provisional scoring system in hydatidiform mole. Chin Med J (Engl) 1980; 93: 605-612
    PubMedGoogle Scholar
  • 37 Sebire NJ, Foskett M, Paradinas FJ et al. Outcome of twin pregnancies with complete hydatidiform mole and healthy co-twin. Lancet 2002; 359: 2165-2166
    CrossrefPubMedGoogle Scholar
  • 38 Hancock BW, Nazir K, Everard JE. Persistent gestational trophoblastic neoplasia after partial hydatidiform mole incidence and outcome. J Reprod Med 2006; 51: 764-766
    PubMedGoogle Scholar
  • 39 Tse KY, Chan KKL, Tam KF et al. Current management of gestational trophoblastic disease. Obstet Gynaecol Reprod Med 2015; 25: 12-21
    CrossrefPubMedGoogle Scholar
  • 40 Kohorn EI. Negotiating a staging and risk factor scoring system for gestational trophoblastic neoplasia. A progress report. J Reprod Med 2002; 47: 445-450
    PubMedGoogle Scholar
  • 41 Froeling FE, Seckl MJ. Gestational trophoblastic tumours. Curr Oncol Rep 2014; 16: 408
    CrossrefPubMedGoogle Scholar
  • 42 Agarwal R, Strickland S, McNeish IA et al. Doppler ultrasonography of the uterine artery and the response to chemotherapy in patients with gestational trophoblastic tumours. Clin Cancer Res 2002; 8: 1142-1147
    PubMedGoogle Scholar
  • 43 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: 1838-1844
    CrossrefPubMedGoogle Scholar
  • 44 Garrett AP, Garner EO, Goldstein DP et al. Methotrexate infusion and folinic acid as primary therapy for nonmetastatic and low-risk metastatic gestational trophoblastic tumours. 15 years of experience. J Reprod Med 2002; 47: 355-362
    PubMedGoogle Scholar
  • 45 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: 1810-1814
    CrossrefPubMedGoogle Scholar
  • 46 Lybol C, Sweep FC, Harvey R et al. Relapse rates after two versus three consolidation courses of methotrexate in the treatment of low-risk gestational trophoblastic neoplasia. Gynecol Oncol 2012; 125: 576-579
    CrossrefPubMedGoogle Scholar
  • 47 Lurain JR. Treatment of gestational trophoblastic tumours. Curr Treat Options Oncol 2002; 3: 113-124
    CrossrefPubMedGoogle Scholar
  • 48 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: 48-55
    CrossrefPubMedGoogle Scholar
  • 49 Woolas RP, Bower M, Newlands ES et al. Influence of chemotherapy for gestational trophoblastic disease on subsequent pregnancy outcome. Br J Obstet Gynaecol 1998; 105: 1032-1035
    CrossrefPubMedGoogle Scholar
  • 50 Kohorn EI. Worldwide survey of the results of treating gestational trophoblastic disease. J Reprod Med 2014; 59: 145-153
    PubMedGoogle Scholar