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.