Primary uterine nongestational placental site trophoblastic tumor as a distinct entity

Uterine placental site trophoblastic tumors (PSTTs) are rare trophoblastic neoplasms, presumed to be of gestational origin. Herein, using a comprehensive morphologic, immunohistochemical, and molecular approach, we describe 5 cases of primary uterine nongestational PSTTs. The median age at presentation was 32 years (range 25 to 45). All tumors were initially expected to be of gestational origin as all were located in the uterus and all patients had a history of pregnancy (5/5, 100%). The median size of the primary uterine tumors was 6.3 cm (range 4.8 to 7.5). Three patients (3/5, 60%) had metastatic disease at presentation or revealed during initial workup (1/5 [20%] patients with lymph node metastasis only and 2/5 [40%] with distant metastases). All tumors showed similar histopathologic and immunohistochemical features to those of gestational PSTTs. The tumor cells expressed hPL in 5/5 (100%) tumors, hCG in 5/5 (100%; focal in all tumors), and GATA3 in 5/5 (100%). However, short tandem repeat (STR) genotyping did not identify any nonpatient alleles in the tumors, indicating a nongestational origin. The median progression-free survival was 18 months (range: 0 to 85) and 2/5 (40%) patients died from disease, highlighting the potential poor prognosis of this nongestational tumor. Thus, in the same way as gestational and nongestational choriocarcinomas are recognized as different entities, nongestational PSTTs could be viewed as a distinct entity from their gestational counterparts, although further investigation and more cases are needed. Furthermore, we propose recommendations for diagnosing and staging of nongestational PSTTs to improve patient stratification and management.