Case 2 -
Inflammatory Pseudotumor of Spleen
William R. Macon
Click on each slide thumbnail image for an enlarged view
An 81-year old female presented with epigastric pain and was
subsequently found to have a solitary splenic mass on abdominal CT scan. The patient was followed for 7
months, during which time the splenic mass gradually enlarged and developed central necrosis.
Splenectomy was then performed, and the 200g spleen had a well-circumscribed 6.5 cm mass.
Case 2 - Figure 1 - Cross-section of spleen demonstrating a fleshy mass that replaces much of the splenic parenchyma. There is central hemorrhage and necrosis.
Case 2 - Figure 2 - Spleen, low magnification. The normal splenic tissue is well-demarcated from the mass by dense fibrous tissue.
Case 2 - Figure 3 - Spleen, high magnification. Occasional spindle cells (arrow) are present within a background of numerous plasma cells, small lymphocytes, and histiocytes.
Case 2 - Figure 4 - In situ hybridization for Epstein-Barr virus-encoded nuclear RNA1 and RNA2 shows strong and diffuse staining in the spindle cells.
Case 2 - Figure 5 - Epstein-Barr virus Southern blot. Left to right. Lane 1 contains DNA from a negative control lacking EBV DNA. Lanes 2 and 4 contain positive control DNA from a clonal EBV-infected neoplasm diluted 1:10 and 1:1 with negative control DNA. Lane 3 contains the patient's DNA; the single high-intensity band indicates EBV monoclonality.
The cut surface of the tumor was tan and fleshy with areas of
hemorrhage and central necrosis. The remainder of the spleen was compressed but otherwise grossly
unremarkable. Microscopically, incomplete fibrous bands separated portions of the lesion from the
residual normal spleen. Most of the tumor was hypercellular and contained a polymorphic population of
inflammatory cells, including lymphocytes, plasma cells neutrophils, and histiocytes, some forming
nonnecrotizing granulomas. Interspersed throughout the inflammatory cells were large epithelioid to
Predominance of T-cells with normal
phenotype, polyclonal surface immunoglobulin-expressing B-cells, and polyclonal cytoplasmic
immunoglobulin expressing plasma cells. Paraffin immunoperoxidase stains: Epithelioid and spindle cells
positive for vimentin and CD68 (weak), and negative for CD20, CD45RO, CD21, CD23, CD35, clusterin, S-100
In situ hybridization
studies on paraffin-embedded sections of the splenic mass using probes for EBV encoded RNA (EBER) showed
numerous EBV-positive spindle cells. Southern blot analysis performed on fresh frozen splenic mass
tissue showed clonal EBV genome.
Inflammatory pseudotumor of spleen.
Inflammatory pseudotumor of spleen is a very unusual lesion
with approximately 30 cases reported in the literature. They are solitary masses that are typically
found incidentally (approximately 50% of patients) in middle-aged to older adults (median age: 53 years,
range: 19-87 years). There is no gender preference. Patients who are symptomatic generally experience
left upper quadrant or epigastric pain. Resection is curative; no cases have recurred or metastasized.
These lesions are well-circumscribed. They are non-encapsulated, but incomplete fibrous bands often
separate them from uninvolved spleen. Central necrosis is often present. There is always a mixed
inflammatory cell infiltrate and spindle cell proliferation. The reaction contains small lymphocytes
(T-cells > B-cells), scattered immunoblasts, polyclonal plasma cells, histiocytes that may be
multi-nucleate and form granulomas, neutrophils (most concentrated near areas of necrosis), and
eosinophils. The spindle cells are benign-appearing and have rare mitoses. They are typically
vimentin-positive. Some of the splenic inflammatory pseudotumors contain actin-positive spindle cells
suggesting a myofibroblastic cell origin. Other cases contain CD21-positive spindle cells suggesting a
follicular dendritic cell origin like those that arise in the liver. The spindle cells are EBV-positive
in approximately 40-60% of inflammatory pseudotumors of spleen and liver. The EBV genome has been clonal
in two hepatic cases that were studied. The lack of EBV in inflammatory pseudotumors of other organs
suggest those arising in the spleen and liver are distinct.
The cause of splenic inflammatory pseudotumors is unknown. Hypotheses include infectious, vascular,
autoimmune and neoplastic processes. No infectious agents (excluding EBV) have been identified by
special stains and microbiologic cultures despite the frequency of necrosis in the lesions. There have
been no consistent findings of vascular obstruction, vasculitis or intraparenchymal hemorrhage to support
vascular disturbances as the cause. Some authors have likened the histologic and immunophenotypic
features to those associated with Riedel's thyroiditis and idiopathic retroperitoneal fibrosis (T-cell
and histiocytic reaction within a spindle cell proliferation) in support of an autoimmune etiology. The
presence of monoclonal EBV genome in some hepatic inflammatory pseudotumors and in this splenic
inflammatory pseudotumor suggest (see reference 1) a neoplastic process. Furthermore, the increased
number of follicular dendritic cells in some of the EBV-positive cases have led some to regard them as
"inflammatory follicular dendritic cell tumors" of the spleen and liver.
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