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DOI: 10.1055/s-2003-44644
Georg Thieme Verlag Stuttgart · New York
Villöse und nicht villöse gestationsbedingte Trophoblasterkrankungen - eine Übersicht
Gestational Trophoblastic Disease - a ReviewPublikationsverlauf
Eingang Manuskript: 23. Oktober 2002
Eingang revidiertes Manuskript: 5. März 2003
Akzeptiert: 12. März 2003
Publikationsdatum:
26. November 2003 (online)
Zusammenfassung
Gestationsbedingte Trophoblasterkrankungen (GTD) sind selten und stellen aufgrund ihrer klinikopathologischen Besonderheiten eine große Herausforderung für Pathologen und Kliniker dar. Die Blasenmole und die Partialmole als Formen der villösen GTD sind aufgrund ihres differenten Risikos für eine persistierende Erkrankung und ihres zytogenetischen Hintergrundes streng zu trennen. Die häufigste Form der nicht villösen GTD ist das Chorionkarzinom. Die notwendige Chemotherapie erfolgt in strenger Korrelation zum WHO-Prognosescore. Als weitere Entitäten sind in den vergangenen Jahren der Plazentabettknoten und die hyperplastische Implantationsstelle abgegrenzt worden, die keiner weiteren Therapie bedürfen und im Allgemeinen Zufallsbefunde darstellen. Zu den Tumoren, die vom intermediären Trophoblasten ausgehen, zählen der Plazentabetttumor und der jüngst beschriebene epitheloide Trophoblasttumor. Beide zeigen in der Majorität einen benignen Verlauf, sollten jedoch, ähnlich wie die Blasenmole und das Chorionkarzinom, mit sequenziellen HCG-Bestimmungen überwacht werden. Die Prognose der GTD hängt in entscheidendem Maße vom rechtzeitigen Beginn der adäquaten Therapie ab, was einer engen Kooperation zwischen Pathologen und Gynäkologen bedarf. Angestrebt werden sollte die Zentralisation der betroffenen Patientinnen in spezialisierten Einrichtungen.
Abstract
Gestational trophoblastic disease (GTD) comprises a spectrum of uncommon and unique clinical and pathologic entities. The process of GTD is now better understood and new entities such as placental-site trophoblastic tumor (PSST) and epitheloid trophoblastic tumor have been morphologically defined. Complete hydatiform mole, a form of the villous type of GTD, has to be distinguished from partial mole because of the different cytogenetic composition and risk for persistent disease. Choriocarcinoma is the most frequent form of nonvillous GTD. Both PSST and epitheloid trophoblastic tumor derive from the intermediate trophoblastic cells and usually have a benign course. Optimal treatment requires a precise morphologic classification and close cooperation between the pathologist and the clinician. All patients treated for GTD require long-term monitoring of serum hCG. Patients with GTD should be registered, and possibly treated, at specialized centers.
Schlüsselwörter
Chorionkarzinom - hyperplastische Implantationsstelle - Plazentabetttumor - Trophoblast - maligne - Trophoblasterkrankung - Schwangerschaft - gestationsbedingt
Key words
Trophoblast - gestational - trophoblastic disease - placental site trophoblastic tumor - placental site nodule - epitheloid trophoblastic tumor - choriocarcinoma - malignant - treatment - placenta
Literatur
- 1 Baergen R N. Gestational choriocarcinoma. Gen Diagn Pathol. 1997; 143 127-141
- 2 Baergen R N, Rutgers J L. Trophoblastic lesions of the placental site. Gen Diagn Pathol. 1997; 143 143-158
- 3 Bagshawe K D. Risk and prognostic factors in trophoblastic neoplasia. Cancer. 1976; 38 1173-1235
- 4 Bagshawe K D, Dent J, Newlands E S, Begent R H, Rustin G J. The role of low-dose methotrexate and folinic acid in gestational trophoblastic tumors. Brit J Obstet Gynaecol. 1989; 96 795-802
- 5 Berkowitz R S, Goldstein D P. Gestational trophoblastic disease. Cancer. 1995; 76: (Suppl 10) 2079-2085
- 6 Bilek K, Horn L C, Abu Hmeidan F, Pretzsch G. Gestationsbedingte Trophoblasterkrankungen - Ergebnisse der Jahre 1976 - 1992. Geburtsh Frauenheilk. 1994; 54 519-523
- 7 Bischoff P, Martelli M. Current topic: Proteolysis in the penetration phase of the implantation process. Placenta. 1992; 13 17-24
- 8 Bower M, Paradinas F J, Fisher R A, Nicholson S K, Rustin G J, Begent R H, Bagshawe K D, Newlands E S. Placental site trophoblastic tumor: Molecular analysis and clinical experience. Clin Cancer Res. 1996; 2 897-902
- 9 Brackertz M. Zur Genetik der Blasenmolen. Geburtsh Frauenheilk. 1983; 43 461-468
- 10 Chang Y L, Chang T C, Hsueh S. Prognostic factors and treatment for placental site trophoblastic tumor: Report of 3 cases and analysis of 88 cases. Gynecol Oncol. 1999; 73 216-222
- 11 Cheung A N, Shen D H, Khoo U S, Chiu M P, Tim V P, Chung L P, Ngan Ny. Immunohistochemical and mutational analysis of p53 tumor suppressor gene in gestational trophoblastic disease: Correlation with mdm2, proliferation index and clinicopathologic parameters. Int J Gynecol Cancer. 1999; 9 123-130
- 12 Davis G A, Survit E A, Garay J P, Fortier J J. Sex assignment in gestational trophoblastic neoplasia. Am J Obstet Gynecol. 1984; 148 722-725
- 13 Denny L A, Dehaeck K, Nevin J, Soeters R, van Wuk A L, Megevand E, Block B. Placental site trophoblastic tumor: Three case reports and literature review. Gynecol Oncol. 1995; 59 300-303
- 14 DiCintio E, Parazzini F, Rosa C, Chatenoud L, Benzi G. The epidemiology of gestational trophoblastic disease. Gen Diagn Pathol. 1997; 143 103-108
- 15 Dobson L S, Lorigan P C, Coleman R E, Hancock B W. Persistent gestational trophoblastic disease: Results of MEA (methotrexate, etoposide and dactinomycine) as first-line chemotherapy in high risk disease and EA (etoposide and dactinomycine) as second-line therapy for low risk disease. Brit J Cancer. 2000; 82 1547-1552
- 16 Faulk W P, Coulam C B, McIntyre J A. The role of trophoblast antigens in repetitive spontaneous abortions. Semin Reprod Immunol. 1989; 7 180-187
- 17 Fine C, Bundy A L, Berkowitz R S. Sonographic diagnosis of partial hydatidiform mole. Obstet Gynecol. 1989; 73 414-420
- 18 Fisher R A, Khatoon R, Paradinas F J, Roberts A P, Newlands E S. Repetitive complete hydatidiform mole can be biparental in origin and either male or female. Hum Reprod. 2000; 15 594-598
- 19 Florio P, Severi F M, Cobellis L, Danero S, Bomé A, Luisi S, Petraglia F. Serum activin A and inhibin A. New clinical markers for hydatidiform mole. Cancer. 2002; 94 2618-2622
- 20 Fox H, Laurini R N. Intraplacental choriocarcinoma: A report of two cases. J Clin Pathol. 1988; 41 1085-1088
- 21 Fox H. Differential diagnosis of hydatidiform mole. Gen Diagn Pathol. 1997; 143 117-125
- 22 Fulop V, Mok S C, Gati I, Berowitz R S. Recent advances in molecular biology of gestational trophoblastic disease. A review. J Reprod Med. 2002; 47 369-379
- 23 Genest D R. Partial hydatidiform mole: Clinicopathologic features, differential diagnosis, ploidy and molecular studies and gold standards for diagnosis. Int J Gynecol Pathol. 2001; 20 315-322
- 24 Goldstein D P, Berkowitz R S. Current management of complete and partial molar pregnancy. J Reprod Med. 1994; 39 139-146
- 25 Hamazaki S, Nakamoto S, Okino T. Epitheloid trophoblastic tumor: Morphological and immunohistochemical study of three lesions. Hum Pathol. 1999; 30 1321-1327
- 26 Hammond C B, Borchert L G, Tyrey L. Treatment of metastatic trophoblastic disease: Good and poor prognosis. Am J Obstet Gynecol. 1973; 115 451-457
- 27 Herbst H, Horn L C, Löning T. Trophoblasterkrankungen und Trophoblasttumoren. Pathologe. 1999; 20 72-81
- 28 Horn L C, Bilek K, Nenning H. Postpartal gestational choriocarcinoma initially misdiagnosed as squamous cell cancer of the uterine cervix. Gen Diagn Pathol. 1997; 143 191-196
- 29 Horn L C, Bilek K, Pretzsch G, Baier D. Chorionkarzinom bei tubarer Extrauteringravidität. Geburtsh Frauenheilk. 1994; 54 375-377
- 30 Horn L C, Bilek K. Histologic classification and staging of gestational trophoblastic disease. Gen Diagn Pathol. 1997; 143 87-101
- 31 Horn L C, Emmrich P, Bilek K, Bruder E. Der frühe plazentare Trophoblast: II. Tumorförmige Störungen der trophoblastären Entwicklung. Zentralbl Gynäkol. 1996; 118 591-597
- 32 Horn L C, Rosenkranz M, Bilek K. Wertigkeit der Plazentahistologie für die Erkennung genetisch bedingter Aborte. Z Geburtsh Perinatol. 1991; 195 47-53
- 33 Horn L C. Genetisch bedingte Frühaborte. Gynäkol Prax. 1993; 17 21-32
- 34 Huettner P C, Gersell D J. Placental site nodule: A clinicopathologic study of 38 cases. Int J Gynecol Pathol. 1994; 13 191-198
- 35 Janni W, Hantschmann P, Rehbock J, Braun S, Locmüller E, Kindermann G. Successful treatment of malignant placental site trophoblastic tumor with combined cytostatic-surgical approach: Case report and review of literature. Gynecol Oncol. 1999; 75 164-169
- 36 Janni W, Hantschmann P, Rehbock J, Kindermann. Malignant placental site trophoblastic tumor - a rare gestational trophoblastic malignancy. Geburtsh Frauenheilk. 2000; 60 302-307
-
37 Kaufmann P.
Control of normal trophoblast invasion in the human placenta. Hauptmann S et al. Surgical Pathology Update. Berlin; ABW 2001: 161-165 - 38 Kashimura Y, Kashimura M, Masamichi K, Sugimori H, Tsukamoto N, Matsuyama T, Matsukama K, Kamora T, Saito T, Kawano H, Nose R. Prophylactic chemotherapy for hydatidiform mole. Cancer. 1986; 58 624-629
- 39 Kendall Gollmore A R, Newlands E. Chemotherapy for trophoblastic disease: Current standards. Curr Opin Obstet Gynecol. 2002; 14 33-38
- 40 Kim J H, Park D C, Bae S N, Namkoong S E, Kim S J. Subsequent reproductive experience after treatment for gestational trophoblastic disease. Gynecol Oncol. 1998; 71 108-112
- 41 Kim S J, Bae S N, Kim J H, Kim C J, Han K T, Chung J K, Lee J M. Epidemiology and time trends of gestational trophoblastic disease in Korea. Int J Gynaecol Obstet. 1998; 60 (Suppl 1) S33-38
- 42 Kohorn E I. The new FIGO 2000 staging and risk factor scoring system for gestational trophoblastic disease: Description and critical assessment. Int J Gynecol Cancer. 2001; 11 73-77
- 43 Klare P, Buchmann E. Erstmanifestation eines Chorionkarzinoms bei einer 24-jährigen Patientin in Form einer Hemiparese. Zentralbl Gynäkol. 1997; 119 282-283
- 44 Kurman R J, Scully R E, Norris H J. Trophoblastic pseudotumor of the uterus: An exaggerated form of “syncytial endometritis” simulating a malignant tumor. Cancer. 1976; 38 1214-1226
- 45 Kurman R J. The morphology, biology and pathology of the intermediate trophoblast: A look back to the present. Hum Pathol. 1991; 22 847-855
- 46 Lan Z, Hongzaho S, Xiuyu Y, Yang X. Pregnancy outcomes of patients who conceived within 1 year after chemotherapy for gestational trophoblastic tumor: A clinical report of 22 patients. Gynecol Oncol. 2001; 83 146-148
- 47 Lage J M, Bagg A, Berchem G J. Gestational trophoblastic disease. Curr Opin Obstet Gynecol. 1996; 8 79-82
- 48 Lage J M, Sheikh S S. Genetic aspects of gestational trophoblastic disease: A general overview with emphasis on new approaches in determining genetic composition. Gen Diagn Pathol. 1997; 143 109-115
- 49 Liotta L A, Rao C N, Wewer U M. Biochemical interactions of tumor cells with the basement membrane. Am Rev Biochem. 1986; 55 1037-1057
- 50 Lorigan P C, Sharma S, Bright N, Coleman R E, Hancock B W. Characteristics of women with recurrent molar pregnancies. Gynecol Oncol. 2000; 78 288-292
- 51 Lurain J R. Treatment of gestational trophoblastic tumors. Curr Treat Options Oncol. 2002; 3 113-124
- 52 Marchand F I. Ueber die sogenannten „decidualen“ Geschwülste im Anschluß an normale Geburt, Abort, Blasenmole und Extrauterinschwangerschaft. Monatsschr Geburtsh Gynaekol. 1895; 1 513-563
- 53 McNeish I A, Strickland S, Holden L, Rustin G J, Foskett M, Seckl M J, Newlands E S. Low-risk peristent gestational trophoblastic disaese: Outcome after initial treatment with low-dose methotrexate and folinic acid from 1992 to 2000. J Clin Oncol. 2002; 20 1838-1844
- 54 Messerli M L, Parmley T, Woodruff J L, Lilienfeld A M, Bevilacqua L, Rosenheim N B. Inter- and intrapathologist variability in the diagnosis of gestational trophoblastic neoplasia. Obstet Gynecol. 1987; 69 622-626
- 55 Motzer R J, Cooper K, Geller N L, Bajorin R F, Dimitrovsky R, Herr H, Morse M, Fair W, Sogani P, Russo P. The role of ifosfamid and cisplatin-based chemotherapy as salvage therapy for patients with refractory germ cell tumors. Cancer. 1990; 66 2476-2481
- 56 Newlands E S, Mulholland P J, Holden L, Seckl M J, Rustin G J. Etoposide and cisplatin/etoposide, methotrexate and actinomycin D (EMA) chemotherapy for patients with high-risk gestational trophoblastic tumors refractory to EMA/cyclophosphamide and vincristine chemotherapy and patients representing with metastatic placental site trophoblastic tumors. J Clin Oncol. 2000; 18 854-859
- 57 Ngan H YS, Odicino F, Maisonneuve P, Beller U, Benedt J L, Heintz A PM, Pecorelli S, Siderei M, Creasman W T. Gestational trophoblastic disease. J Epidemiol Biostat. 2001; 6 177-184
- 58 Olvera M, Harris S, Amezuca C A, McCourty A, Rezk S, Koo C, Felix J C, Brynes R K. Immunohistochemical expression of cell cycle proteins E2 F-1, Cdk-2, cyclin E, p27(kip 1) and Ki-67 in normal placenta and gestational trophoblastic disease. Mod Pathol. 2001; 14 1036-1042
- 59 Papadopoulos A J, Foskett M, Seckl M J, McNeish I, Paradinas F J, Rees H, Newlands E S. Twenty-five year's clinical experience with placental site trophoblastic tumors. J Reprod Med. 2002; 47 460-464
- 60 Rice L W, Lage J M, Berkowitz R S, Goldstein D P, Bernstein M R. Repetitive complete and partial hydatidiform mole. Obstet Gynecol. 1989; 74 217-219
- 61 Ringertz N. Hydatidiform mole, invasive mole and choriocarcinoma in Sweden 1958 - 1965. Acta Obstet Gynecol Scand. 1970; 49 195-203
- 62 Rinne K, Shahabi S, Cole L. Following metastatic placental site trophoblastic tumor with urine β-core fragment. Gynecol Oncol. 1999; 74 302-303
- 63 Roberts J P, Lurain J R. Treatment of low-risk metastatic gestational trophoblastic tumors with single-agent chemotherapy. Am J Obstet Gynecol. 1996; 174 1917-1923
- 64 Rutgers J L, Baergen R N, Young R H, Scully R E. Placental site trophoblastic tumor: Clinicopathologic study of 64 cases. Mod Pathol. 1995; 8 96A
- 65 Scully R E, Bonfiglio T A, Kurman R J, Silverberg S G, Wilkinson E J. WHO-Histological Typing of Female Genital Tract Tumours. Berlin, Heidelberg, New York, London, Paris, Tokyo, Hong Kong, Barcelona, Budapest; Springer 1994
- 66 Seckl M J, Fisher R A, Salerno G, Rees H, Paradinas F J, Foskett M, Newlands E S. Choriocarcinoma and partial hydatidiform moles. Lancet. 2000; 356 1443-1444
- 67 Seckl M J, Newlands E S. Treatment of gestational trophoblastic disease. Gen Diagn Pathol. 1997; 143 159-171
- 68 Shih I M, Kurman R J. Epitheloid trophoblastic tumor - a neoplasm distinct from choriocarcinoma and placental site trophoblastic tumor simulating carcinoma. Am J Surg Pathol. 1998; 22 1393-1403
- 69 Shih I M, Kurman R J. The pathology of the intermediate trophoblastic tumors and tumorlike lesions. Int J Gynecol Pathol. 2001; 20 31-47
- 70 Shih I M, Kurman R J. Molecular basis of gestational trophoblastic diseases. Curr Mol Med. 2002; 2 1-12
- 71 Shih I M, Seidman J D, Kurman R J. Placental site nodule and characterisation of distinctive types of intermediate trophoblast. Hum Pathol. 1999; 30 687-694
- 72 Silverberg S G, Kurman R J. Tumors of the Uterine Corpus and Gestational Trophoblastic Disease. Atlas of Tumor Pathology. Washington, D. C.; Armed Forces Institute of Pathology 1992: 219-286
- 73 Szulman A E. Syndromes of hydatidiform moles. Partial versus complete. J Reprod Med. 1984; 29 788-791
- 74 Vaccarello L, Apte S M, Diaz P T, Lewandowski G S, Copeland L J. Respiratory failure from metastatic choriocarcinoma: A survivor of mechanical ventilation. Gynecol Oncol. 1997; 67 111-114
- 75 Vassilakos P, Riotton G, Kajii T. Hydatidiform mole: Two entities. A morphologic and cytogenetic study with some clinical considerations. Am J Obstet Gynecol. 1977; 127 167-170
- 76 Wallace D C, Surti U, Adams C W, Szulman A E. Complete moles have paternal chromosomes but maternal mitochondrial DNA. Hum Genet. 1982; 61 145-147
- 77 World Health Organisation Scientific Group on Gestational Trophoblastic Disease .Technical report Series No. 692. Geneva; WHO 1983
- 78 Wittekind C, Meyer H J, Bootz F. TNM-Klassifikation maligner Tumoren. 6. Aufl. Berlin, Heidelberg, New York; Springer 2002
- 79 Yang X, Zhang Z, Jia C, Li J, Yin L, Jiang S. The relationship between expression of c-ras, c-erbB-2, nm23 and p53 gene products and development of trophoblastic tumor and their predictive significance for the malignant transformation of complete hydatidiform mole. Gynecol Oncol. 2002; 85 438-444
- 80 Yen S, MacMahon B. Epidemiologic features of trophoblastic disease. Am J Obstet Gynecol. 1968; 101 126-132
- 81 Young R H, Kurman R J, Scully R E. Placental site nodules and plaques: A clinicopathologic analysis of 20 cases. Am J Surg Pathol. 1990; 14 1001-1009
OA PD Dr. med. L.-C. Horn
Institut für Pathologie
Universität Leipzig
Liebigstraße 26
04103 Leipzig
eMail: hornl@medizin.uni-leipzig.de