Background
Gestational trophoblastic disease (GTD) refers to a group of rare tumors originating in the syncytiotrophoblast, cytotrophoblast or intermediate trophoblast of the placenta. Epitheloid Trophoblastic Tumor (ETT) and Placental Site Trophoblastic Tumor (PSTT) are malignant forms of GTD that both originate in the intermediate trophoblast. Their benign counterparts are respectively placental site nodule (PSN) and exaggerated placental site reaction (EPSR). PSN can present with abnormal vaginal blood loss, amenorrhea or as an incidental finding in postpartum endometrium sampling¹. A minority of these PSNs have an atypical appearance for which a new entity called Atypical Placental Site Nodule (APSN) is suggested. To the best of our knowledge, only one cohort of patients with APSN has been described in literature by Kaur et al., consisting of twenty-one registered cases between 2005-2013 at the Charing Cross Gestational Trophoblastic Disease Centre of which three (14%) progressed to or co-existed with GTN².
Histological diagnosis of APSN should be considered when a PSN lesion displays increased cellularity, mild atypia and larger lesion size. An index of the marker of proliferation Ki-67 between 8 and 10-12% is indicative for APSN, while a Ki-67 index below 8% corresponds to PSN and above 12% to ETT³. APSN is not acknowledged by the World Health Organization since no consensus on the histological definition has been reached yet.
Due to its rarity, the clinical significance of APSN is not well known and therefore recommendations on treatment and follow-up are lacking. However, it is important to learn more about the risk of ETT or PSTT development, as these malignant forms of GTD are less responsive to chemotherapy and have a lower overall survival after 5 and 10 years of respectively 80% and 75%⁴. Prognostic factors for reduced overall survival in ETT and PSTT were also determined by Froeling et al. The hazard ratio (HR) in the group of patients with >48 months from antecedent pregnancy to start of treatment was 14.57 (95% CI 4.17–50.96, p < 0.001), which highlights the importance of avoiding delays in treatment⁴.
In addition, the incidence and outcome of pregnancy following the diagnosis of APSN are unknown, which makes it difficult to counsel patients. Knowledge of the course of pregnancy and its effect on APSN is necessary to better understand this entity. In this case-report, we describe a woman with two pregnancies after the diagnosis of APSN, which was considered fully resected by hysteroscopy prior to these pregnancies. After fulfilling her child wish a hysterectomy was performed and a clinically and radiologically undetected persistent APSN was found in the final hysterectomy specimen. We have written permission from our patient to publish her case.