Metastatic trophoblastic disease after an initial diagnosis of partial hydatidiform mole: genotyping and chromosome in situ hybridization analysis.

BACKGROUND: Hydatidiform mole (HM) is classified into partial (PHM) and complete (CHM) subtypes according to histopathologic and genetic criteria. Traditionally, it is believed that PHM carries a better prognosis and rarely develops metastasis. However, making a distinction between PHM and CHM using histologic criteria alone may be difficult. METHODS: The authors used fluorescent microsatellite genotyping following laser-capture microdissection and chromosome in situ hybridization (CISH) to perform a genetic analysis of six patients with histologically diagnosed PHM who subsequently developed metastatic gestational trophoblastic neoplasia. RESULTS: Patients ranged in age from 25 years to 44 years (mean, 33.2 years). The gestational age of the molar pregnancies varied from 6 weeks to 20 weeks. All six patients had pulmonary metastases, with additional liver metastasis in two patients. Among the six patients with histologically diagnosed PHM, it was found that four patients had a diploid karyotype and no maternal alleles; thus, their neoplasms actually were CHM. Maternal genome was detected in the remaining two patients consistent with a biparental origin, and these patients had a triploid karyotype. CISH findings in all patients correlated with the genotyping findings. Triploid HM had maternally derived alleles, whereas diploid HMs were purely androgenetic. CONCLUSIONS: In the current study, which may be the largest series of genetically analyzed metastatic PHMs to date, the difficulty of histologic distinction between PHM and CHM was confirmed. Molecular analysis may help to refine the classification of HM. Although the current findings support the belief that most aggressive trophoblastic diseases are derived from CHM, a small number of PHMs do progress to metastatic disease. Thus, the current study reaffirmed that all patients with HM should be followed closely irrespective of histologic subclassification.

Analysis of gestational trophoblastic disease by genotyping and chromosome in situ hybridization.

Hydatidiform mole is classified into partial and complete subtypes according to histopathological and genetic criteria. Distinction between the two by histology alone may be difficult. Genetically, a complete mole is diploid without maternal contribution, whereas a partial mole is triploid with a maternal chromosome complement. To assess the accuracy of histological diagnosis by correlating with the genetic composition, we performed fluorescent microsatellite genotyping to detect the presence or absence of maternal genome in a hydatidiform mole and carried out chromosome in situ hybridization to analyze the ploidy. For genotyping analysis, paraffin sections of 36 complete and nine partial moles, diagnosed according to histological criteria, were microdissected and DNA was separately extracted from the decidua and molar villi. Six pairs of primers that flank polymorphic microsatellite repeat sequences on five different chromosomes were used. In all, 34 cases, including 31 complete moles and three partial moles diagnosed histologically, showed no maternal contribution by genotyping; thus these could be genetically considered as complete mole. The other 11 cases (five complete moles and six partial moles previously diagnosed by histology) showed the presence of maternal contribution and were genetically diagnosed as partial moles. The genotyping results correlated with histological evaluation in 88% (37/45) of hydatidiform mole and correlated with chromosome in situ hybridization findings in all the cases, that is, triploid hydatidiform moles had maternal-derived alleles, while diploid hydatidiform moles were purely androgenetic. Compared with genetic diagnosis, histological evaluation was more reliable for the diagnosis of a complete mole (91%, 31/34) than that of a partial mole (55%, 6/11) (P=0.0033). Seven complete moles and three partial moles diagnosed genetically developed gestational trophoblastic neoplasia. To conclude, genotyping and chromosome in situ hybridization can provide reliable adjunct to histology for the classification of a hydatidiform mole, especially in cases with difficult histological evaluation and early gestational age. As a partial mole still carries a risk of developing gestational trophoblastic neoplasia, follow-up is considered necessary for both complete and partial moles.