CD30 and Epstein–Barr virus RNA expression in sclerosing angiomatoid nodular transformation of spleen

Abstract

Sclerosing angiomatoid nodular transformation (SANT) is a splenic lesion composed of angiomatoid/vascular nodules surrounded by hyalinized/sclerotic stroma, fibroblasts, myofibroblasts, and inflammatory cells. The endothelium within the nodules has a phenotype resembling splenic sinusoids, capillaries, and small veins. Martel et al. (Am J Surg Pathol 28:1268-1279, 2004) suggested that SANT may represent the final pathway of a variety of splenic lesions including inflammatory pseudotumors (IPTs). Epstein-Barr virus (EBV) has a role in the genesis of some splenic IPTs, but its presence in SANT has not been investigated. Six cases of SANT are reported. All were stained for CD31, CD34, CD8, CD68, smooth muscle actin, muscle-specific actin, and CD30 and were tested for EBV by in situ hybridization (EBER). All cases showed angiomatoid nodules with complex expression of CD31, CD34, and CD8, with focal CD68. Expression of CD30 by endothelial cells was also seen. One case had small diffuse areas lacking nodules resembling an IPT and was positive for EBV. The inflammatory cells and the normal spleen were negative for CD30 and EBER. In conclusion, SANT shows upregulation of CD30 with respect to normal spleen. The presence of EBV in the stromal cells of a case supports the notion that a subset of SANT may be related to IPT.

Detection of Epstein–Barr virus-encoded small RNA-expressed myofibroblasts and IgG4-producing plasma cells in sclerosing angiomatoid nodular transformation of the spleen

“…Immunohistochemistry revealed that the proliferating spindle cells were strongly positive for vimentin and α-SMA, but not for CD21, CD31, CD34, or CD68. These results revealed that the internodular lesions of SANT histologically resembled IPT, as described in the previous reports [14,19]. In addition, we determined that the myofibroblasts in the IPT-like area of SANT had a subpopulation of EBV-infected myofibroblasts in one of nine cases.…”

“…In addition, we determined that the myofibroblasts in the IPT-like area of SANT had a subpopulation of EBV-infected myofibroblasts in one of nine cases. Weinreb et al [19] first investigated EBV in SANT, and detected EBV RNA in one of six cases that had diffuse areas resembling IPT, and noted that SANT might be associated with EBV infection. However, there was no data regarding the immunophenotype of the EBER-positive spindle cells in SANT in their description.…”

“…All things considered, a common pathway of the inflammatory stromal proliferative process associated with EBV-infected BM-derived circulating stem cells in splenic inflammatory tumor-like lesions, including SANT, may exist. However, before reaching this conclusion, additional studies with a larger series of SANT are necessary because of EBV being detected in only two cases with SANT in two series, including ours [19]. The aspect of the combination of a proliferating stromal process and infiltration of inflammatory cells, such as plasma cells and lymphocytes in SANT, thus provided important insight into IgG4-related sclerosing disease.…”

“…Weinreb et al [19] reported both the expression of CD30 in endothelial cells and EBVencoded small RNA (EBER) in spindle cells in SANT, thus implying that SANT might be associated with a cytokinemediated inflammatory process induced by EBV. According to the proliferation of myofibroblasts in the IPT-like areas in SANT, the myofibroblasts, as one of the fibrogenic cell types, may play a pivotal role in the fibrotic process of SANT [14,19]. It has recently become known that myofibroblasts are derived from various progenitor cells such as locally residing fibroblasts, hepatic stellate cells, smooth muscle cells, epithelial cells, endothelial cells, and bone marrow (BM)-derived circulating stem cells [8,20].…”

“…However, it is unclear whether the pathogenesis of this splenic lesion is a de novo lesion or the end stage of a variety of benign splenic conditions including inflammatory pseudotumor (IPT), hamartoma, or hematoma [14]. Weinreb et al [19] reported both the expression of CD30 in endothelial cells and EBVencoded small RNA (EBER) in spindle cells in SANT, thus implying that SANT might be associated with a cytokinemediated inflammatory process induced by EBV. According to the proliferation of myofibroblasts in the IPT-like areas in SANT, the myofibroblasts, as one of the fibrogenic cell types, may play a pivotal role in the fibrotic process of SANT [14,19].…”