Impact of atypical extra-villous trophoblast foci on the natural history and management of post-molar gestational trophoblastic neoplasia
Approximately 15% to 20% of complete hydatidiform moles progress to post-molar gestational trophoblastic neoplasia. The presence of atypical extra-villous trophoblast foci, described in complete hydatidiform moles, has been associated with an increased risk of developing post-molar gestational trophoblastic neoplasia. The primary objective of this study was to evaluate the predictive value of atypical extra-villous trophoblast foci for treatment response in post-molar gestational trophoblastic neoplasia. Secondary objectives were to assess the clinical impact of these foci on disease characteristics, the International Federation of Gynecology and Obstetrics (FIGO) score, disease stage, and human chorionic gonadotropin (hCG) kinetics. A retrospective multi-center study was conducted by the Belgian Gestational Trophoblastic Diseases Registry (French-speaking center) between January 2017 and December 2022. All cases of complete hydatidiform mole were centrally reviewed by expert pathologists specialized in placental pathology from 3 university hospitals. Post-molar gestational trophoblastic neoplasia was diagnosed according to FIGO 2000 criteria. Clinical features were compared according to the presence or absence of atypical trophoblast foci. Among 216 patients diagnosed with complete hydatidiform mole, 56 (26%) developed post-molar gestational trophoblastic neoplasia. Atypical extra-villous trophoblast foci were identified in 38 of 56 (68%) cases. Baseline demographic characteristics, including age, were comparable between the 2 groups. Patients with atypical foci more frequently had FIGO scores ≥6 (p =.044) and pulmonary metastases (18.4% vs 5.6%). All patients requiring multi-agent chemotherapy belonged to the atypical foci group (p =.073). Pre-treatment hCG nadir levels were higher, and hCG slopes steeper in the atypical group (p =.0027 and p =.0052). Post-molar gestational trophoblastic neoplasia arising from complete hydatidiform moles with atypical extra-villous trophoblast foci is more frequently associated with an unfavorable prognosis and the need for multi-agent chemotherapy than disease arising from moles without atypical foci.