Frequent presence of the Epstein-Barr virus in inflammatory pseudotumor

Inflammatory pseudotumor is a presumably nonneoplastic, hematopoietic, and spindled fibrous proliferation that may occur at a variety of anatomic sites. The origin of these proliferations is generally unknown. To evaluate the role of the Epstein-Barr virus (EBV) in inflammatory pseudotumor, 18 specimens from 17 patients were studied by in situ hybridization for EBV ribonucleic acid (RNA), and the morphological and immunologic characteristics of the infected cells were evaluated. These specimens included 10 lymph nodes, six splenic masses, and two hepatic masses. Overall, EBV RNA was detected in 41.2% (seven of 18) of the cases. These included two of 10 (20%) lymph nodes, four of six (66.7%) splenic pseudotumors, and one of two (50%) hepatic lesions. The degree of EBV infection was significantly greater within the tumors in comparison with the surrounding, uninvolved tissue. Two morphologically different EBV-positive cell types, spindled and round cells, were evident, and the infected cell type differed significantly when the nodal and extranodal cases were compared. All of the positive extranodal cases shown, numerous EBV-positive spindled cells, whereas no positive spindle cells (only positive round cells, morphologically consistent with lymphocytes) were noted in the two EBV-positive lymph node pseudotumors. Double-labeling immunohistochemical and in situ hybridization studies in some cases identified rare EBV-positive B cells and rare EBV positive T cells in four and three cases, respectively. Most EBV-positive cells in all cases failed to immunoreact with any B- or T-cell markers. Three of five cases studied, however, did show a subpopulation of smooth muscle actin/EBV-positive spindled cells, five of seven cases showed vimentin/EBV-positive spindled cells, and one of four cases had EBV-positive spindled cells that immunoreacted as follicular dendritic cells. These results suggest that EBV plays a role in a significant number of cases of inflammatory pseudotumor with differences in the incidence of EBV infection and the cell type (spindled vs round cell) infected when extranodal and nodal cases are compared, suggesting a difference in pathogenesis. The cell type infected in extranodal cases seemed to be of mesenchymal origin but could not be clearly defined.