—  SPECIALTY CONFERENCE  —

Hematopathology

Case 2 - Inflammatory Pseudotumor of Spleen

William R. Macon
Mayo Clinic
Rochester, MN


Click on each slide thumbnail image for an enlarged view
Clinical History
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.

Morphology
 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 spindle-shaped cells.

Immunophenotyping
Flow cytometry
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 and desmin.

Epstein-Barr Virus
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.

Diagnosis
Inflammatory pseudotumor of spleen.

Discussion
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.

References

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