Advanced gestational trophoblastic neoplasm favoring placental site trophoblastic tumor, presenting with multiple metastases to the lung, pancreas, and liver as initial manifestations: a diagnosis-oriented case report

Abstract Placental site trophoblastic tumor (PSTT) is a rare subtype of gestational trophoblastic neoplasia (GTN), originating from intermediate trophoblasts at the implantation site. Its clinical presentations are often atypical, leading to misdiagnosis and delayed diagnosis, and the clinical management of advanced metastatic cases is extremely challenging. This article reports a highly challenging case of stage IV GTN favoring PSTT. A 33-year-old female presented with menstrual irregularities and progressively elevated serum β-HCG more than 3 years after a spontaneous vaginal delivery. Imaging revealed lesions predominantly distributed in the lungs, liver, and pancreas, while gynecological imaging showed only intrauterine calcification foci without a definite uterine mass. The diagnostic process involved multiple biopsies and pathological consultations with discordant results. Ultimately, targeted next-generation sequencing showing tumor variants shared with the spouse’s germline and absent from the patient’s own germline strongly supported a gestational origin, and the morphological and immunohistochemical profile (scattered HPL/β-hCG positivity, p63 negativity) favored PSTT as the most consistent subtype, although definitive subtyping was limited by the incomplete immunohistochemical panel. The patient subsequently received seven courses of EMA-EP chemotherapy; serum β-hCG normalized during treatment, and restaging 18 F-FDG PET/CT showed marked regression of the metastatic lesions without abnormal FDG uptake. This case highlights the clinical pitfall of PSTT presenting with atypical metastatic lesions as the initial manifestation and no definite uterine mass detected on imaging. Its delayed onset, elevated β-HCG levels, and multi-organ involvement significantly distinguish it from typical PSTT. This report emphasizes that in young women with postpartum elevated β-HCG and multi-organ lesions but negative uterine imaging, clinicians should maintain a high index of suspicion for PSTT and may use HPL immunohistochemistry and, when morphology is inconclusive, molecular testing as diagnostic adjuncts. This article provides an important reference for enhancing clinicians’ awareness of the atypical presentations and metastatic patterns of this rare tumor.