Characterization of Inflammation in Syphilitic Villitis and in Villitis of Unknown Etiology PAYAL KAPUR, 1 DINESH RAKHEJA, 1 ANA M. GOMEZ, 1 JEANNE SHEFFIELD, 2 PABLO SANCHEZ, 3 AND BEVERLY BARTON ROGERS 1 * 1 Department of Pathology, The University of Texas Southwestern Medical School, Dallas, TX, USA 2 Department of Obstetrics and Gynecology, The University of Texas Southwestern Medical School, Dallas, TX, USA 3 Department of Pediatrics, The University of Texas Southwestern Medical School, Dallas, TX, USA Received December 19, 2003; accepted April 21, 2004; published online July 30, 2004. ABSTRACT Chronic villitis is a histologic diagnosis that may be either associated with infection, or termed villitis of un- determined etiology (VUE). The lymphocytic infiltrate in VUE has been reported to consist of maternal lympho- cytes, but the origin of the lymphocytic infiltrate in in- fectious villitis has not been identified. The purpose of our study was to compare the maternal vs. fetal origin of the infiltrating lymphocytes in VUE and syphilitic villitis, and to expand the immunophenotypic data provided by previous studies. Paraffin-embedded placentas from four males with VUE and two males with syphilitic vil- litis were subjected to fluorescence in situ hybridization (FISH) for the X and Y chromosomes. Serial sections were stained with antibodies to CD3, CD4, CD8, CD68, HLA-DR, and CD20. Quantitation of the relative number of cells marking with each antibody was done for four villi in each slide. CD3 lymphocytes predominated in both VUE and syphilitic villitis, with slightly more CD8 cells compared to CD4 cells. CD68 and HLA-DR positive cells were as frequent as CD3 cells, and B-lymphocytes were rare. Maternal cells were the predominant intravil- lous population in both VUE and syphilitic villitis, and neutrophils in syphilitic villitis were also maternal. These data indicate that the immune response in both syphilitic villitis and VUE is similar, raising the possibil- ity of a similar immunopathogenetic pathway. Key words: chronic villitis, syphilis, villitis of undeter- mined etiology INTRODUCTION Chronic villitis occurs in 5–10% of consecutive pla- centas, and is characterized by lymphocytic and histiocytic infiltration of placental villi [1,2]. Some cases of chronic villitis are of known infectious etiology, associated with hematogenous infections including cytomegalovirus, rubella, syphilis, and toxoplasmosis. However, at least 95% of the cases of chronic villitis are of unknown or undetermined etiology (VUE) [3]. The etiopathogenesis of VUE has been con- troversial, with some researchers favoring an in- fectious etiology, and others suggesting a maternal isoimmune response to the placenta. Altshuler and Hyde believe that VUE is a fetal response to an unidentified infectious agent [4]. Redline and Patterson studied affected villi in placentas diag- nosed with VUE from male infants [5]. Using im- munohistochemistry for CD3 and CD45, and in situ hybridization for X and Y chromosomes, they demonstrated the presence of maternal T-lympho- cytes in these foci of VUE. With the help of immu- nohistochemistry, Labarrere et al. have also shown *Corresponding author, e-mail: beverly.rogers@childrens.com Pediatric and Developmental Pathology 7, 453– 458, 2004 DOI: 10.1007/s10024-004-2124-3 © 2004 Society for Pediatric Pathology