Epstein-Barr Virus-Associated Splenic Mesenchymal Tumor – A Proposal of Comprehensive Tumor Entity
Tomoko Mitsuhashi, Yutaka Hatanaka, Kanako Kubota, Tadashi Hasegawa, Tatsuro Takahashi, Yoshihiro Matsuno. Hokkaido University Hospital, Sapporo, Hokkaido, Japan; Sapporo Medical University School of Medicine, Sapporo, Hokkaido, Japan; Kushiro Rosai Hospital, Kushiro, Hokkaido, Japan
Background: Inflammatory pseudotumors (IPTs) are uncommon neoplasms of unknown etiology that have been reported in a variety of anatomic sites. In contrast to those occurring in other anatomic sites, the IPTs that occur in the spleen and liver are typically associated with Epstein-Barr virus (EBV) suggesting a distinctly different pathogenetic pathway in these locations. Morphologically IPT is one of the numerous spindle cell lesions with a number of variants and heterogeneity concerning its histogenesis. Although majority of spindle cells in IPT are α-smooth muscle actin (SMA)+ myofibroblasts (MFs), follicular dendritic cell (FDC) marker+ cells are intermingled in the same tumor. The aim of this study is to clarify the mechanism of tumorigenesis of splenic IPT.
Design: Three cases of splenic IPT (age:56-79, tumor size:4.0-8.0cm) were studied. Immunohistochemistry for SMA and 3 FDC markers (CD21, CD35, and FDC) was performed on formalin-fixed, paraffin-embedded sections from those surgically excised tumors. EBER1-in situ hybridization and subsequent immunohistochemical stain for SMA were performed (EBER1-SMA double stain). In addition, EBV clonality analysis was done by southern blot using frozen tissues obtained from 2 of 3 cases.
Results: The majority of spindle cells in all three cases showed double-positive signals for SMA and EBER1 (SMA+EBER1+), but SMA negative, EBER1 positive (SMA-EBER1+) subset was intermixed in a variety of portion in these tumors. The latter subset was confirmed as FDC by immunohistochemical studies using 3 FDC markers. Two of two cases studied by southern blot revealed the presence of clonal EBV DNA.
Conclusions: Splenic IPT is a true neoplasm associated with EBV infection on both MF and FDC, showing the presence of clonal EBV DNA. Since FDCs are considered as a specialized form of MFs and derive from bone marrow stromal cell progenitors, these cells are closely related to each other in the process of tumorigenesis of splenic IPT. Our findings suggest that splenic IPTs may represent a spectrum of tumors ranging from typical EBV-associated FDC proliferations to those resembling conventional IPTs with only focal EBV expression and minimal to absent FDC proliferations. The current study suggests a comprehensive tumor entity of EBV-associated MF-FDC tumors in the spleen, the EBV-associated splenic mesenchymal tumor.
Wednesday, March 21, 2012 9:30 AM
Poster Session V # 209, Wednesday Morning