Gestational trophoblastic disease

She bled at ten weeks, the scan was reported as a missed miscarriage, and the registrar evacuated her and sent the tissue. Histology came back five days later as partial mole. The fellowship question is not whether you can name the tumour — it is whether you closed the loop: registered her, plotted the hCG, and named the surveillance that protects the next pregnancy. Gestational trophoblastic disease is one of oncology's curable success stories, and it stays curable only when the surveillance is not lost between the scan and the letter.^[1][19]

Overview and definition — the spectrum that turns on hCG

Gestational trophoblastic disease encompasses the premalignant disorders — complete and partial hydatidiform mole — and the malignant forms, collectively termed gestational trophoblastic neoplasia: invasive mole, choriocarcinoma, and the rare placental-site and epithelioid trophoblastic tumours. Improvement in management and centralised follow-up mean overall cure rates now exceed 98 per cent with fertility retention.^[1]

• Hydatidiform mole is the premalignant lesion — trophoblastic proliferation with swollen villi. Most never progresses.^[1]
• Gestational trophoblastic neoplasia is the disease that needs chemotherapy or excision because hCG persists or metastases appear. The commonest antecedent is a molar pregnancy, but choriocarcinoma can follow any pregnancy — term, abortion, or ectopic.^[3][19]
• The unifying principle: trophoblast makes human chorionic gonadotropin, so hCG is simultaneously the tumour marker that tracks every form of the disease and the hormone that drives its complications.^[1]

References19ShowHide

1. [1]Seckl MJ, Sebire NJ, Berkowitz RS Gestational trophoblastic disease Lancet, 2010.PMID 20673583
2. [2]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.PMID 11285037
3. [3]Ngan HYS, Seckl MJ, Berkowitz RS, Xiang Y, Golfier F, Sekharan PK, Braga A, Garrett A Diagnosis and management of gestational trophoblastic disease: 2025 update Int J Gynaecol Obstet, 2025.PMID 40631439
4. [4]Sebire NJ Recurrent GTD and GTD coexisting with normal twin pregnancy Best Pract Res Clin Obstet Gynaecol, 2021.PMID 33451920
5. [5]Fisher RA, Hodges MD, Rees HC, Sebire NJ, Seckl MJ, Newlands ES, Genest DR, Castrillon DH The maternally transcribed gene p57(KIP2) (CDNK1C) is abnormally expressed in both androgenetic and biparental complete hydatidiform moles Hum Mol Genet, 2002.PMID 12471053
6. [6]Genest DR, Dorfman DM, Castrillon DH Ploidy and imprinting in hydatidiform moles. Complementary use of flow cytometry and immunohistochemistry of the imprinted gene product p57KIP2 to assist molar classification J Reprod Med, 2002.PMID 12063872
7. [7]Albright BB, Shorter JM, Mastroyannis SA, Ko EM, Schreiber CA, Sonalkar S Gestational Trophoblastic Neoplasia After Human Chorionic Gonadotropin Normalization Following Molar Pregnancy: A Systematic Review and Meta-analysis Obstet Gynecol, 2020.PMID 31809433
8. [8]Sebire NJ, Foskett M, Short D, Savage P, Stewart W, Thomson M, Seckl MJ Shortened duration of human chorionic gonadotrophin surveillance following complete or partial hydatidiform mole: evidence for revised protocol of a UK regional trophoblastic disease unit BJOG, 2007.PMID 17516969
9. [9]Agarwal R, Teoh S, Short D, Harvey R, Savage PM, Seckl MJ Chemotherapy and human chorionic gonadotropin concentrations 6 months after uterine evacuation of molar pregnancy: a retrospective cohort study Lancet, 2012.PMID 22130490
10. [10]McNeish IA, Strickland S, Holden L, Rustin GJ, Foskett M, Seckl MJ, Newlands ES 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.PMID 11919242
11. [11]Alifrangis C, Agarwal R, Short D, Fisher RA, Sebire NJ, Harvey R, Savage PM, Seckl MJ EMA/CO for high-risk gestational trophoblastic neoplasia: good outcomes with induction low-dose etoposide-cisplatin and genetic analysis J Clin Oncol, 2013.PMID 23233709
12. [12]Bolis G, Bonazzi C, Landoni F, Mangili G, Vergadoro F, Zanaboni F, Mangioni C EMA/CO regimen in high-risk gestational trophoblastic tumor (GTT) Gynecol Oncol, 1988.PMID 2846414
13. [13]Braga A, Paiva G, Ghorani E, Freitas F, Velarde LGC, Kaur B, Unsworth N, Lozano-Kuehne J, Dos Santos Esteves APV, Rezende Filho J, Amim J Jr, Aguiar X, Sarwar N, Elias KM, Horowitz NS, Berkowitz RS, Seckl MJ Predictors for single-agent resistance in FIGO score 5 or 6 gestational trophoblastic neoplasia: a multicentre, retrospective, cohort study Lancet Oncol, 2021.PMID 34181884
14. [14]Agarwal R, Harding V, Short D, Fisher RA, Sebire NJ, Harvey R, Patel D, Savage PM, Lim AK, Seckl MJ Uterine artery pulsatility index: a predictor of methotrexate resistance in gestational trophoblastic neoplasia Br J Cancer, 2012.PMID 22374461
15. [15]Schmid P, Nagai Y, Agarwal R, Hancock B, Savage PM, Sebire NJ, Lindsay I, Wells M, Fisher RA, Short D, Newlands ES, Wischnewsky MB, Seckl MJ Prognostic markers and long-term outcome of placental-site trophoblastic tumours: a retrospective observational study Lancet, 2009.PMID 19552948
16. [16]Papadopoulos AJ, Foskett M, Seckl MJ, McNeish I, Paradinas FJ, Rees H, Newlands ES Twenty-five years' clinical experience with placental site trophoblastic tumors J Reprod Med, 2002.PMID 12092014
17. [17]Burkett WC, Soper JT A Review of Current Management of Placental Site Trophoblastic Tumor and Epithelioid Trophoblastic Tumor Obstet Gynecol Surv, 2022.PMID 35201361
18. [18]Ghorani E, Kaur B, Fisher RA, Short D, Joneborg U, Carlson JW, Akarca A, Marafioti T, Quezada SA, Sarwar N, Seckl MJ Pembrolizumab is effective for drug-resistant gestational trophoblastic neoplasia Lancet, 2017.PMID 29185430
19. [19]Soper JT Gestational Trophoblastic Disease: Current Evaluation and Management Obstet Gynecol, 2021.PMID 33416290