Elsevier

The Lancet

Volume 356, Issue 9223, 1 July 2000, Pages 36-39
The Lancet

Early Report
Choriocarcinoma and partial hydatidiform moles

https://doi.org/10.1016/S0140-6736(00)02432-6Get rights and content

Summary

Background

Partial hydatidiform moles (PMs) rarely require chemotherapy and have never previously been proven to transform into choriocarcinoma, the most malignant form of gestational trophoblastic disease (GTD). Consequently, some have questioned whether women with PMs need human chorionic gonadotropin (hCG) follow-up. Here, we investigate whether PMs can transform into choriocarcinomas.

Methods

Patients with a PM who developed a subsequent choriocarcinoma were identified from our GTD database. The histology of both PM and ensuing choriocarcinoma was reviewed and flow cytometry used to verify the triploid status of the PMs. To determine whether the choriocarcinoma arose from the PM, DNA from the PM and choriocarcinoma in each patient was compared using microsatellite polymorphisms.

Findings

Of the 3000 patients with PM, 15 required chemotherapy for persisting GTD. This was identified as choriocarcinoma in three cases. In one patient, the local pathologist could not differentiate between a PM or a hydropic abortion and neither central histological review nor hCG follow-up were obtained. This patient nearly died before the diagnosis of choriocarcinoma was made. Fortunately, the local pathologists correctly diagnosed PM in the two other patients who were then registered for hCG follow-up. Some months later, the hCG was rising and repeat uterine evacuation revealed choriocarcinoma. The PM was confirmed to be triploid in all three cases and genetic analysis showed that the subsequent choriocarcinomas contained identical single maternal and two paternal alleles at several independent loci.

Interpretation

Our results show that PMs can transform into choriocarcinoma. All patients with suspected PM should be reviewed centrally and, if confirmed, need hCG follow-up.

Introduction

Gestational trophoblastic disease comprises a spectrum of disorders from the benign hydatidiform mole (complete and partial) through to the malignant invasive mole, choriocarcinoma, and the rare placental site/epithelioid trophoblastic tumour.1 Complete hydatidiform moles (CM) occur in about one per 1000 pregnancies and partial hydatidiform moles (PM) in three per 1000 pregnancies.2 They can be distinguished histologically and genetically; CMs are diploid and nearly always androgenetic in origin, whereas PMs are triploid consisting of one maternal and two paternal sets of chromosomes.3

Both CMs and PMs secrete human chorionic gonadotropin (hCG), but their distinct histological and genetic identities lead to important differences in clinical behaviour. Thus, after termination of a molar pregnancy, the risk of developing malignant disease, simply detected by a plateau or rising serum or urine concentration of human chorionic gonadotropin (hCG), is 15% for a CM and only 0·5% for a PM.4 Moreover, whereas the tumour resulting from CM or PM is usually an invasive mole, choriocarcinoma can arise in up to 3% of CMs but has never been proven to arise after a PM. Clinically, invasive moles grow more slowly and metastasise less rapidly than the highly malignant choriocarcinomas.

Because of the small chance of developing an invasive mole after a PM, and the fact that such patients are not considered to be at risk of choriocarcinoma, some centres recommend discontinuing hCG follow-up at an earlier stage than for CMs. Indeed, one major centre has advocated discontinuing all hCG follow-ups on PMs. However, if PMs can transform into choriocarcinomas this would represent a potentially dangerous decision because a highly malignant tumour would go undetected until widespread metastatic disease was present. This could increase the risk of unnecessary deaths in women of childbearing age.

Section snippets

Patients

The Charing Cross Hospital gestational trophoblastic disease (GTD) database was searched to identify all patients who had been treated for PM between 1980 and 2000. The diagnosis of PM was confirmed by central review and in most cases by flow cytometry. Choriocarcinoma subsequently developed in five of 15 patients with PM. Suitable material was available for genetic analysis in three cases.

Flow cytometry

One 30 μm section of formalin-fixed paraffin-embedded tissue from each patient was dewaxed by immersion in

Patient 1

A 27-year-old woman presented to her local gynaecologist with bleeding per vaginem after 7 weeks of amenorrhoea. 9 years previously she had had a spontaneous abortion and subsequently two term deliveries of healthy boys, now aged 5 years and 6 years. A pregnancy test was positive, the serum hCG was 35 600 IU/L, and ultrasonography of the pelvis showed a sac but no viable fetus. She continued to bleed per vaginem and ultrasonography 14 days later showed retained products. A dilatation and

Discussion

Although most women with choriocarcinoma can be expected to be successfully treated with modern chemotherapy, more than 10% of patients with high-risk disease die.7 Commonly, this is because of delayed diagnosis in women who are not enrolled in hCG follow-up. Our results show that PMs can progress to choriocarcinoma. Moreover, in the patients who need treatment after a PM, the risk that a PM will develop into choriocarcinoma seems to be at least 20% (3 of 15 PMs treated in our centre during the

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