Published: 2021-08-27

Classification and etiologies of gestational trophoblastic disease

Nadia D. Younis, Fatimah H. Juwayd, Mohammed A. Aljawi, Fai T. Althoini, Fatema H. Alsaffaf, Ahmed M. B. Samman, Khuzama A. Alghasham, Alia N. Ismail, Norah A. Aljaloud, Shahad H. Bakhashwain, Hessa K. Almuhaisen


Various forms of trophoblastic diseases were reported in the literature, including complete and partial of hydatidiform moles, gestational choriocarcinomas, placental-site and epitheloid trophoblastic tumors. Among patients who suffer from hydatidiform mole, gestational trophoblastic neoplasia can be easily diagnosed by using the levels of the human chorionic gonadotropin (hCG). Therefore, complex investigations are not usually necessary in measuring the levels of hCG, physical examination and assessments. In addition, patients’ medical history can help the attending physicians to draw an adequate treatment plan for patients with gestational trophoblastic neoplasia. However, Pelvic Doppler ultrasonography might also be used for additional assessments, including the presence or absence of pregnancy, measurement of the uterine volume and size. Additionally, it determines the vasculature and spread of the neoplasm within the pelvic region. Furthermore, genetic analysis can be used to differentiate between the types of the disease. Moreover, among the reported staging and classification systems, the international federation of gynecology and obstetrics (FIGO) seems to be the best efficacious modality for the determination of the prognosis of the various types of the disease to properly choose the best treatment modality.


Gestational trophoblastic disease, Hydatidiform mole, Prognosis, Staging, Classification

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Seckl MJ, Sebire NJ, Berkowitz RS. Gestational trophoblastic disease. Lancet. 2010;376(9742):717-29.

Hui P. Gestational Trophoblastic Tumors: A Timely Review of Diagnostic Pathology. Arch Pathol Lab Med. 2019;143(1):65-74.

Lurain JR. Gestational trophoblastic disease I: epidemiology, pathology, clinical presentation and diagnosis of gestational trophoblastic disease, and management of hydatidiform mole. Am J Obstetr Gynecol. 2010;203(6):531-9.

Kajii T, Ohama K. Androgenetic origin of hydatidiform mole. Nature. 1977;268(5621):633-4.

Yamashita K, Ishikawa M, Shimizu T, Kuroda M. HLA antigens in husband-wife pairs with trophoblastic tumor. Gynecol Oncol. 1981;12(1):68-74.

Fisher RA, Newlands ES. Gestational trophoblastic disease. Molecular and genetic studies. J Reprod Med. 1998;43(1):87-97.

Hashan MR, Ghozy S, El-Qushayri AE, Pial RH, Hossain MA, Al Kibria GM. Association of dengue disease severity and blood group: A systematic review and meta-analysis. Rev Med Virol. 2021;31(1):1-9.

El-Qushayri AE, Ghozy S, Abbas AS. Hyperimmunoglobulin therapy for the prevention and treatment of congenital cytomegalovirus: a systematic review and meta-analysis. Expert Rev Anti Infect Ther. 2020:1-9.

Pattillo RA, Sasaki S, Katayama KP, Roesler M, Mattingly RF. Genesis of 46,XY hydatidiform mole. American journal of obstetrics and gynecology. 1981;141(1):104-5.

Azuma C, Saji F, Tokugawa Y. 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(1):29-33.

Fisher RA, Hodges MD, Newlands ES. Familial recurrent hydatidiform mole: a review. J Reprod Med. 2004;49(8):595-601.

Moglabey YB, Kircheisen R, Seoud M, El Mogharbel N, Van den Veyver I, Slim R. Genetic mapping of a maternal locus responsible for familial hydatidiform moles. Human molecular genetics. 1999;8(4):667-71.

Murdoch S, Djuric U, Mazhar B. Mutations in NALP7 cause recurrent hydatidiform moles and reproductive wastage in humans. Nature genetics. 2006;38(3):300-2.

Kou YC, Shao L, Peng HH. A recurrent intragenic genomic duplication, other novel mutations in NLRP7 and imprinting defects in recurrent biparental hydatidiform moles. Molecular human reproduction. 2008;14(1):33-40.

Wang CM, Dixon PH, Decordova S. Identification of 13 novel NLRP7 mutations in 20 families with recurrent hydatidiform mole; missense mutations cluster in the leucine-rich region. J Med Genetics. 2009;46(8):569-75.

Deveault C, Qian JH, Chebaro W. NLRP7 mutations in women with diploid androgenetic and triploid moles: a proposed mechanism for mole formation. Human Molecular Genetics. 2009;18(5):888-97.

Lawler SD, Fisher RA, Dent J. A prospective genetic study of complete and partial hydatidiform moles. American journal of obstetrics and gynecology. 1991;164(5):1270-7.

Szulman AE, Surti U. The syndromes of hydatidiform mole. I. Cytogenetic and morphologic correlations. Am J Obstet Gynecol. 1978;131(6):665-71.

Lage JM, Mark SD, Roberts DJ, Goldstein DP, Bernstein MR, Berkowitz RS. A flow cytometric study of 137 fresh hydropic placentas: correlation between types of hydatidiform moles and nuclear DNA ploidy. Obstetrics and gynecology. 1992;79(3):403-10.

Genest DR, Ruiz RE, Weremowicz S, Berkowitz RS, Goldstein DP, Dorfman DM. Do nontriploid partial hydatidiform moles exist? A histologic and flow cytometric reevaluation of nontriploid specimens. J Reprod Med. 2002;47(5):363-8.

Hancock BW. Staging and classification of gestational trophoblastic disease. Best Practice & Res Clin Obstetr Gynaecol. 2003;17(6):869-83.

Agarwal R, Strickland S, McNeish IA. Doppler ultrasonography of the uterine artery and the response to chemotherapy in patients with gestational trophoblastic tumors. Clinical cancer research: an official journal of the Am Association Cancer Res. 2002;8(5):1142-7.

Lin LH, Polizio R, Fushida K, Francisco RPV. Imaging in Gestational Trophoblastic Disease. Seminars Ultrasound CT MR. 2019;40(4):332-49.

Berkowitz RS, Goldstein DP. Current management of gestational trophoblastic diseases. Gynecol Oncol. 2009;112(3):654-62.

Ngan HY, Chan FL, Au VW, Cheng DK, Ng TY, Wong LC. Clinical outcome of micrometastasis in the lung in stage IA persistent gestational trophoblastic disease. Gynecol Oncol. 1998;70(2):192-4.

Darby S, Jolley I, Pennington S, Hancock BW. Does chest CT matter in the staging of GTN? Gynecol Oncol. 2009;112(1):155-60.

Kohorn EI. Negotiating a staging and risk factor scoring system for gestational trophoblastic neoplasia. A progress report. J Reprod Med. 2002;47(6):445-50.

Pezeshki M, Hancock BW, Silcocks P. The role of repeat uterine evacuation in the management of persistent gestational trophoblastic disease. Gynecol Oncol. 2004;95(3):423-9.

van Trommel NE, Massuger LF, Verheijen RH, Sweep FC, Thomas CM. The curative effect of a second curettage in persistent trophoblastic disease: a retrospective cohort survey. Gynecol Oncol. 2005;99(1):6-13.

Lawrie TA, Alazzam M, Tidy J, Hancock BW, Osborne R. First-line chemotherapy in low-risk gestational trophoblastic neoplasia. The Cochrane Database Systematic Rev. 2016;6:CD007102.

McNeish IA, Strickland S, Holden L. Low-risk persistent gestational trophoblastic disease: outcome after initial treatment with low-dose methotrexate and folinic acid from 1992 to 2000. Journal of clinical oncology : official journal of the American Society of Clinical Oncology. 2002;20(7):1838-44.

Berkowitz RS, Goldstein DP, Bernstein MR. Ten year's experience with methotrexate and folinic acid as primary therapy for gestational trophoblastic disease. Gynecol Oncol. 1986;23(1):111-8.

McGrath S, Short D, Harvey R, Schmid P, Savage PM, Seckl MJ. 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(-1). Br J Cancer. 2010;102(5):810-4.

Bagshawe KD, Lawler SD, Paradinas FJ, Dent J, Brown P, Boxer GM. Gestational trophoblastic tumours following initial diagnosis of partial hydatidiform mole. Lancet. 1990;335(8697):1074-6.

Newlands ES, Holden L, Seckl MJ, McNeish I, Strickland S, Rustin GJ. Management of brain metastases in patients with high-risk gestational trophoblastic tumors. J Reprod Med. 2002;47(6):465-71.

Seckl MJ, Rustin GJ, Newlands ES, Gwyther SJ, Bomanji J. Pulmonary embolism, pulmonary hypertension, and choriocarcinoma. Lancet. 1991;338(8778):1313-5.

Athanassiou A, Begent RH, Newlands ES, Parker D, Rustin GJ, Bagshawe KD. Central nervous system metastases of choriocarcinoma. 23 years' experience at Charing Cross Hospital. Cancer. 1983;52(9):1728-35.

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(3):413-9.

Patten DK, Lindsay I, Fisher R, Sebire N, Savage PM, Seckl MJ. Gestational choriocarcinoma mimicking a uterine adenocarcinoma. J Clin Oncol. 2008;26(31):5126-7.

Smith DB, O'Reilly SM, Newlands ES. Current approaches to diagnosis and treatment of gestational trophoblastic disease. Current Opinion Obstet Gynecol. 1993;5(1):84-91.

Smith DB, Holden L, Newlands ES, Bagshawe KD. Correlation between clinical staging (FIGO) and prognostic groups with gestational trophoblastic disease. Br J Obstet Gynaecol. 1993;100(2):157-10.

Feltmate CM, Genest DR, Goldstein DP, Berkowitz RS. Advances in the understanding of placental site trophoblastic tumor. J Reprod Med. 2002;47(5):337-41.

Papadopoulos AJ, Foskett M, Seckl MJ. Twenty-five years' clinical experience with placental site trophoblastic tumors. J Reprod Med. 2002;47(6):460-4.

Palmieri C, Fisher RA, Sebire NJ, et al. Placental site trophoblastic tumour arising from a partial hydatidiform mole. Lancet. 2005;366(9486):688.

Schmid P, Nagai Y, Agarwal R. Prognostic markers and long-term outcome of placental-site trophoblastic tumours: a retrospective observational study. Lancet. 2009;374(9683):48-55.

Cole LA, Khanlian SA, Muller CY, Giddings A, Kohorn E, Berkowitz R. Gestational trophoblastic diseases: 3. Human chorionic gonadotropin-free beta-subunit, a reliable marker of placental site trophoblastic tumors. Gynecol Oncol. 2006;102(2):160-4.

Harvey RA, Pursglove HD, Schmid P, Savage PM, Mitchell HD, Seckl MJ. Human chorionic gonadotropin free beta-subunit measurement as a marker of placental site trophoblastic tumors. J Reprod Med. 2008;53(8):643-8.

Newlands ES, Bower M, Fisher RA, Paradinas FJ. Management of placental site trophoblastic tumors. J Reprod Med. 1998;43(1):53-9.

Horn L-C, Einenkel J, Hoehn AK. Classification and Morphology of Gestational Trophoblastic Disease. Current Obstet Gynecol Reports. 2014;3(1):44-54.