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Byline: Raymond W. Redline (1), Ilana Ariel (2), Rebecca N. Baergen (3), Derek J. deSa (4), Frederick T. Kraus (5), Drucilla J. Roberts (6), C. Maureen Sander (7) Keywords: avascular villi; fetal thrombotic vasculopathy; hemorrhagic endovasculitis; nomenclature; placenta; reproducibility; villitis of unknown etiology Abstract: The purpose of this study was to assemble and test the reliability of a complete set of the placental reaction patterns seen with chronic fetal vascular obstruction in the hope that this might provide a standardized diagnostic framework useful for practicing pathologists. Study cases (14 with fetal vascular obstructive lesions, 6 controls) were reviewed blindly by seven pathologists after agreement on a standard set of diagnostic criteria. Majority vote served as the gold standard and 80% of the 180 diagnoses rendered (9 diagnoses each for 20 cases) were agreed upon by at least six of the seven scores. The sensitivity of individual diagnosis relative to the group consensus averaged 83% (range, 69--100%) and specificity averaged 91% (range, 86--100%). Reproducibility was measured by unweighted kappa-values and interpreted as follows: &lt 0.2, poor 0.2--0.6, fair/moderate &gt 0.6, substantial. Kappa values for lesions of distal villi were generally superior to those for lesions involving large fetal vessels: avascular villi (0.49), villous stromal-vascular karyorrhexis (0.58), and villitis of unknown etiology (VUE) with stem villitis and avascular villi (0.65) versus large vessel thrombi (any vessel, 0.34 chorionic plate vessel, 0.40) and intimal fibrin cushions (recent, 0.47 remote, 0.78). Reproducibility for a global impression of any villous change consistent with chronic fetal vascular obstruction was substantial (0.63), while that for a more severe subgroup was moderate (0.44). Three points are worthy of emphasis. Our system separately recognizes, but later combines, uniformly avascular villi and villous stromal-vascular karyorrhexis as manifestations of the same underlying process. We propose that this combined group of villous lesions be dichotomized with the terms fetal thrombotic vasculopathy or extensive avascular villi (and/or villous stromal-vascular karyorrhexis) being reserved for the group with 15 or more affected terminal villi per section. Scattered foci of avascular villi (and/or villous stromal-vascular karyorrhexis) could be used to describe less severe cases. Finally, we distinguish VUE with stem villitis and avascular villi (obliterative fetal vasculopathy) as a distinct process with substantial perinatal morbidity. Author Affiliation: (1) Department of Pathology, University Hospitals of Cleveland and Case Western Reserve University, 11100 Euclid Avenue, Cleveland, OH 44106 , USA (2) Department of Pathology, Hadassah University Hospital, Jerusalem, Israel (3) Department of Pathology, New York--Presbyterian Hospital--Weill Cornell Medical Center, New York, NY, USA (4) Department of Pathology, British Columbia Children's Hospital, Vancouver, BC, Canada (5) Department of Obstetrics and Gynecology, Washington University School of Medicine, St. Louis, MO, USA (6) Department of Pathology, Massachusetts General Hospital, Boston, MA, USA (7) Placental Tissue Registry, Michigan State University, East Lansing, MI, USA Article History: Registration Date: 01/01/2004 Received Date: 08/02/2004 Accepted Date: 16/04/2004 Online Date: 30/07/2004