Sachiko Minamiguchi

B cells play a critical role in tumor immunity, with their presence associated with improved prognosis in various cancers, including endometrial cancer (EC). However, the nature of the B-cell response within the tumor microenvironment (TME) remains incompletely understood. In this study, we conducted single-cell analyses of B cells and CD4+ T cells in the TME of EC. We found that the TME of EC harbored abundant plasmablasts and plasma cells (PCs), which were rare in normal endometria. PCs primarily expressed either IgG or IgA, and a high abundance of IgG in TME was associated with better overall survival. B-cell receptor (BCR) repertoire analysis revealed a clonal expansion of IgG+ B cells, coinciding with an increased presence of T follicular helper (Tfh) cells in the TME. Notably, Tfh cells shared T-cell receptor clones with cycling CD4+ T cells, indicating local proliferation. BCR repertoire analysis also suggested that IgG+ PCs differentiate from IFN-responding B cells and double-negative B cells in the TME. Additionally, recombinant oligoclonal IgG antibodies were found to recognize antigens expressed by tumor cells as well as normal endometrial cells. Collectively, our study shows that the clonal expansion of IgG+ B cells, along with the Tfh cell response, is associated with a better outcome in EC.

ABSTRACT Background Subamniotic or subchorionic hematoma (SAH/SCH) is associated with diverse pregnancy outcomes. The clinical implications of accompanying oligohydramnios and hemorrhagic amniotic fluid on MRI remain unclear. Purpose To investigate the importance of oligohydramnios and hemorrhagic amniotic fluid on placental MRI for SAH/SCH in risk stratification. Study Type Retrospective. Population Seventy‐one singleton pregnancies with SAH/SCH identified on placental MRI performed during the second or third trimesters, from 2016 to 2023. Field Strength/Sequence 1.5 T, Fat‐saturated T1‐weighted gradient echo and half‐Fourier‐acquired single‐shot turbo spin echo sequences. Assessment Cases were classified into three groups: Groups A (oligohydramnios and hemorrhagic amniotic fluid), B (either oligohydramnios or hemorrhagic amniotic fluid), and C (SAH or SCH only). Groups B and C were subclassified as B‐1 (oligohydramnios), B‐2 (hemorrhagic amniotic fluid), C‐1 (detected hematoma on ultrasound before MRI), and C‐2 (incidentally detected hematoma on MRI). Unfavorable obstetric outcome (abortion or birth before 34 gestational weeks) and neonatal outcome (duration of neonatal intensive care unit [NICU] stay) were compared. Statistical Tests Fisher's exact test, Kruskal–Wallis test, Mann–Whitney U test, and Kaplan–Meier analysis with Log‐rank test. Significance was determined at p  < 0.05. Results Unfavorable obstetric outcomes were significantly higher in Group A (11/12, 91.7%) than groups B (6/17, 35.3%) and C (9/42, 21.4%). Significant differences were found among the five subclassified groups, most notably between B‐1 and B‐2. The median duration of NICU stay was 87, 30.5, 0, 25, and 8 days in Groups A ( n  = 12), B‐1 ( n  = 5), B‐2 ( n  = 12), C‐1 ( n  = 11), and C‐2 ( n  = 31), respectively. Group A showed the worst neonatal outcomes. Data Conclusion MRI findings of oligohydramnios and/or hemorrhagic amniotic fluid in pregnancies with SAH/SCH are associated with adverse obstetric and neonatal outcomes, supporting risk stratification. Evidence Level 4. Technical Efficacy Stage 5.

To explore the clinicopathological features and origin of mesonephric-like adenocarcinomas (MLAs), 83 cases diagnosed or suspected to be MLAs were collected from various institutions in Japan. We clearly classified 78 as MLAs (uterus: 47, ovary: 31) and 5 as non-MLAs (all ovary) based on our morphological and immunohistochemical criteria. In uterine MLAs (uMLAs), lymphovascular space invasion was an independent prognostic factor for progression-free survival (PFS) (P = 0.03). Patients with uMLAs had significantly shorter PFS and overall survival (OS) than those diagnosed with endometrial endometrioid carcinomas (EECs) (P < 0.0001 and P < 0.001, respectively) and comparable PFS and OS to those with copy number-high tumors. PFS and OS of ovarian MLAs (oMLAs) were similar to those of ovarian endometrioid carcinomas (OECs) overall but worse for patients with stage II-IV. Endometriosis was observed with oMLAs as often as with OECs (94% vs 93%, respectively). Adenomyosis was more frequently observed with uMLAs than with EECs (62% vs 28%, respectively, P = 0.0005). Six uMLAs were confined to the myometrium and adjacent to adenomyosis. In an analysis of molecularly speculated origin, among 29 oMLAs harboring a KRAS hotspot mutation, 23 (79%) instances of endometriosis in the background had the same mutation. Among 36 uMLAs carrying the KRAS hotspot mutation, common mutations were observed in 12 (33%) instances of adjacent adenomyosis (12/21 [67%] of adenomyosis). These findings suggest a histogenetic link between MLAs and ectopic endometrium, implicating both ovarian endometriosis and adenomyosis in MLA pathogenesis, with potential clinical significance.