Original ArticlesChronic Intervillositis of Unknown Etiology Development of a Grading and Scoring System That Is Strongly Associated With Poor Perinatal OutcomesSauvestre, Fanny MD*,†; Mattuizzi, Aurélien MD†,‡; Sentilhes, Loïc MD, PhD‡; Poingt, Marion MD§; Blanco, Patrick MD, PhD†,∥; Houssin, Clémence MD‡; Carles, Dominique MD*; Pelluard, Fanny MD*,¶; Andre, Gwenaëlle MD*; Lazaro, Estibaliz MD, PhD†,#Author Information *Fœtopathology Unit, Department of Pathology ‡Department of Obstetrics and Gynecology ∥Immunology and Immunogenetics Laboratory, Bordeaux University Hospital, Pellegrin Hospital §Department of Obstetrics and Gynecology, Bordeaux Nord Polyclinic †CNRS-UMR 5164 ImmunoConcEpT ¶INSERM UMR1053, Bordeaux Research in Translational Oncology, BaRITOn, Bordeaux University, Bordeaux #Internal Medicine Department, Bordeaux University Hospital, Pessac, France The English in this document has been checked by at least 2 professional editors, both native speakers of English. For a certificate, please see: www.textcheck.com/certificate/oNmWLF. Conflicts of Interest and Source of Funding: The authors have disclosed that they have no significant relationships with, or financial interest in, any commercial companies pertaining to this article. Correspondence: Fanny Sauvestre, MD, Fœtopathology Unit, Department of Pathology, Bordeaux University Hospital, Pellegrin Hospital, Place Amélie Raba Leon, 33076 Bordeaux Cedex, France (e-mail: [email protected]). The American Journal of Surgical Pathology: October 2020 - Volume 44 - Issue 10 - p 1367-1373 doi: 10.1097/PAS.0000000000001549 Buy Metrics Abstract Chronic intervillositis of unknown etiology (CIUE) is a rare placental disease characterized by intervillous infiltration of maternal macrophages and associated with poor pregnancy outcomes and a high risk of recurrence in subsequent pregnancies. Its pathophysiology remains unclear and prognostic factors have not yet been established. In addition, clear relationships between the histologic extent of lesions and the severity of perinatal outcomes have not been demonstrated. Our objectives were to validate a CIUE classification system based on the gradation of macrophagic infiltration of the intervillous space, and to attempt to correlate these results with perinatal outcomes. For this multicenter retrospective study, 3 pathologists reviewed all cases diagnosed with “intervillositis” between 1997 and 2018. Confirmed CIUE cases were semiquantitatively graded based on the percentage of macrophagic infiltrate in the intervillous space: grade 1 (5% to 10%), grade 2 (10% to 50%), and grade 3 (>50%). Multiple pregnancies and pregnancies with medical follow-up completed outside of the study centers were excluded. In total, 122 cases of CIUE in 102 patients were included in the study. Microscopic classification based on one criterion was easy to perform, and interobserver correlation was good. Grade 3 infiltration was strongly associated with poor perinatal outcomes and fetal growth restriction (P<0.0001). After delivery, only 16.1% of newborns from the grade 3 CIUE group were alive, compared with 59% from the grade 2 and 86.5% from the grade 1 group (P=0.0002). Recurrence risk was associated with CIUE gradation of the index case (P=0.004), with 95% of recurrent CIUE cases being from patients with grades 2 and 3 CIUE. In this study, conducted with the largest CIUE cohort to date, a classification based only on the degree of macrophagic infiltration of the intervillous space was validated, and this classification was shown to be strongly associated with poor perinatal outcomes and risk of recurrence. Copyright © 2020 Wolters Kluwer Health, Inc. All rights reserved.