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.