Case 1 -
Inflammatory Pseudotumor of Spleen
Elaine S. Jaffe
National Institutes of Health
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The patient is a 45-year-old female who presented with left upper quadrant pain. CT and ultrasound
showed a 5.6 cm mass within the inferior pole of the spleen. Laparoscopic splenectomy was performed.
Inflammatory pseudotumor of spleen
Case 1 - Slide 1
Case 1 - Figure 1 - At low power the spleen contains a nodule with central necrosis. While not encapsulated, the nodule is relatively sharply defined from the surrounding spleen.
Case 1 - Figure 2 - A pseudocapsule of dense fibrosis is at the margin of the lesion.
Case 1 - Figure 3 - A polymorphous lymphoid infiltrate surrounds an area of fibrinoid necrosis.
Case 1 - Figure 7 - An SMA stain demonstrates increased positive spindle cells within the lesion.
Case 1 - Figure 8 - The nuclei of the admixed spindle cells are positive with EBER in situ hybridization for EBV.
- Littoral cell angioma
- Multinodular hemangioma
- Sclerosing angiomatoid nodular transformation (SANT)
- Follicular dendritic cell tumor
Inflammatory pseudotumor (IPT) of the spleen is a distinctive lesion, often presenting incidentally,
or with localizing symptoms, as in the present case. First described in 1984 by Cotelingam and Jaffe, it
was postulated to be an unusual reactive process, possibly secondary to a prior infectious insult. The
lesions have a zonal pattern of organization, usually with central necrosis, surrounded by a polymorphous
cellular reaction including abundant plasma cells, foamy histiocytes and epithelioid granulomas. The
lesions are usually sharply demarcated from the surrounding spleen, which is usually unremarkable and
generally not significantly enlarged. There may be a fibrous rim or pseudocapsule between the lesion and
surrounding spleen. The lesions range in size, but in most cases are under 10 cm in diameter.
Arber et al. showed a relationship to the Epstein Barr virus (EBV) in 1995. In contrast to many
EBV-associated disorders affecting lymphoid tissues, the EBV was shown to be in spindle cells, and not
lymphoid cells of either T-cell or B-cell origin. The nature of the EBV-infected cells remains somewhat
controversial. The spindle cells are uniformly positive for vimentin, and in many cases there appears to
be an increase of spindle cells positive for smooth muscle actin (SMA). Thus, it was suggested that the
proliferating cells were myofibroblasts. Cheuk et al. suggested that the EBV-positive cells in
inflammatory pseudotumors of the spleen, and also the liver, were follicular dendritic cells. They
reported variable positivity for the FDC markers CD21, CD35, CD23, and CAN.42. As CD21 represents a
receptor for EBV, the presence of this antigen would provide a portal of entry for the Epstein-Barr
virus. However, in some cases FDC markers are not demonstrable (as in the present case), in which CD21,
CD23 and clusterin were all negative. Moreover, it is notable that FDC neoplasms in nodal sites are only
very rarely positive for EBV. Thus, the possibly of diverse cellular origins for these tumors remains.
It is interesting to postulate that EBV causes the characteristic histological reaction pattern seen
in these lesions. EBV-infected cells may elaborate chemokines, which can lead to vascular damage and
thrombosis. In the present case there are fibrin thrombi and vessels showing fibrinoid necrosis,
possibly a consequence of this pathogenetic process. EBV may also elicit the prominent inflammatory
reaction pattern that is a feature of many EBV-positive tumors, including non-hematopoietic tumors such
as lymphoepithelial carcinoma.
The differential diagnosis of inflammatory pseudotumor includes localized tumor and tumor-like lesions
of the spleen. Hamartoma may present as an isolated lesion. It is composed entirely of red pulp
elements, lacks necrosis, and is readily distinguished from IPT. A variety of vascular tumors can
present as an isolated mass in the spleen, but inflammatory pseudotumors usually lack significant
vascularity. One should consider a localized infectious process, such as an isolated splenic abscess.
Generally, the centrally necrotic areas in IPT do not contain neutrophilic microabscesses, although
neutrophils may be abundant in the lesion.
Finally, sclerosing angiomatoid nodular transformation (SANT) resembles IPT, at least grossly. It
presents as a well-circumscribed firm fibrotic mass. Necrosis is usually absent, but the connective
tissue may have a fibrinoid appearance. SANT has a distinctive multi-nodular appearance with concentric
fibrosis surrounding angiomatoid nodules. The fibrotic stroma may resemble IPT, with
myofibroblastic-like cells accompanied by plasma cells and lymphocytes. The angiomatoid nodules contain
cells with a distinctive phenotype, recapitulating to some extent the sinusoids of the spleen, with
variable expression of CD8, CD31 and CD34. SANT is not felt to be a neoplasm, although it resembles in
many respects a angioma/ hemangioma.
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