—  SPECIALTY CONFERENCE  —

Surgical Pathology

Case 1 - Inflammatory Pseudotumor of Spleen

Elaine S. Jaffe
National Institutes of Health
Bethesda, MD





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History
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.

Diagnosis:
Inflammatory pseudotumor of spleen


Case 1 - Slide 1
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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 4 - At the periphery numerous foamy histiocytes are admixed with plasma cells.
Case 1 - Figure 5 - In areas a marked plasmacytosis is seen.
Case 1 - Figure 6 - Fibrin thrombi are seen in some vascular spaces.

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.


Differential Diagnosis
  • Hamartoma

  • Littoral cell angioma

  • Multinodular hemangioma

  • Sclerosing angiomatoid nodular transformation (SANT)

  • Follicular dendritic cell tumor

Discussion
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.

References:
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