Ashdin PublishingJournal of Case Reports in MedicineVol. 2 (2013), Article ID 235715, 4 pagesdoi:10.4303/jcrm/235715

ASHDINpublishing

Case Report

Epstein-Barr Virus-Associated Inflammatory Pseudotumor-LikeFollicular Dendritic Cell Tumor of the Spleen without Recurrencefor 3 Years after Splenectomy

Michiyo O. Asano,1 Yoshikazu Ito,1 Toshitaka Nagao,2 Jun Matsubayashi,2 Hiroshi Kusama,2 Yoshiaki Suzuki,3

Akihiko Tsuchida,3 Soichi Akata,4 Koichi Tokuuye,4 and Kazuma Ohyashiki1

1First Department of Internal Medicine, Tokyo Medical University, 6-7-1 Nishishinjuku, Shinjuku-ku, Tokyo 160-0023, Japan2Department of Pathology, Tokyo Medical University, 6-7-1 Nishishinjuku, Shinjuku-ku, Tokyo 160-0023, Japan3Third Department of Surgery, Tokyo Medical University, 6-7-1 Nishishinjuku, Shinjuku-ku, Tokyo 160-0023, Japan4Department of Radiology, Tokyo Medical University, 6-7-1 Nishishinjuku, Shinjuku-ku, Tokyo 160-0023, JapanAddress correspondence to Yoshikazu Ito, yito@tokyo-med.ac.jp

Received 2 July 2013; Revised 11 August 2013; Accepted 14 August 2013

Copyright © 2013 Michiyo O. Asano et al. This is an open access article distributed under the terms of the Creative Commons Attribution License,which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.

Abstract Inflammatory pseudotumor (IPT)-like follicular dendriticcell (FDC) tumor is a rare disease with distinct clinicopathologicalfeatures. We report a case of so-called Epstein-Barr virus (EBV)-associated IPT-like FDC tumor of the spleen. We found a splenicmass lesion during his annual checkup. After recognizing thegrowing mass, splenectomy was performed. Histopathological andimmunohistological studies revealed extensive proliferation of spindlecells positive for FDC markers. EBV was exclusively detected onthese spindle cells by in situ hybridization analysis. Based on thesefindings, a diagnosis of EBV-associated IPT-like FDC tumor wasmade. Of note, neither recurrence nor metastasis occurred within 3years postsplenectomy.

Keywords inflammatory pseudotumor; follicular dendritic cell tumor;Epstein-Barr virus; spleen

1. Introduction

Epstein-Barr virus (EBV)-associated inflammatorypseudotumor-like follicular dendritic cell (FDC) [EBV-associated IPT-like FDC] tumor is a distinct disease entityestablished in 2001. In 1989, Weiss et al. first reported thepossible association of EBV with the development of aninflammatory pseudotumor (IPT) in the spleen [20]. Theassociation of EBV with the formation of an IPT in the liverand spleen was confirmed in 1995 [2]. FDC markers (e.g.,CNA.42) were also positively detected in the same tumorin the liver and spleen [9,15,17]. Cheuk et al. establisheda disease entity and reported 11 cases that were differentfrom the common FDC tumors or other IPTs [7]. However,the clinical features of EBV-associated IPT-like FDC tumorhave not been completely clarified. We present a case ofa patient with EBV-associated IPT-like FDC tumor of thespleen which showed no recurrence or metastasis followingsplenectomy.

2. Case report

A patient visited our hospital and underwent a careful andprecise examination of a splenic mass lesion which wasfound during an annual medical checkup. Although thepatient was asymptomatic, abdominal ultrasound revealeda large splenic mass (Figure 1(a)). The medical history ofthe patient was uneventful except for a previous ureteroceleand a colon polyp. There was no lymphadenopathy oneither the surface or the depth. The manipulation of theabdomen demonstrated no abnormal findings. The liverand spleen were not palpable. No abnormal values werenoted on initial laboratory studies except an elevated serumIL-2 receptor level of 704 U/mL. Abdominal computedtomography confirmed a low-density, well-defined, roundmass of 3 cm diameter in the spleen (Figure 1(b)). Magneticresonance imaging (MRI) showed a hyperintense masson T1-weighted imaging and a hypointense mass on T2-weighted imaging (Figure 1(c)). On dynamic MRI, thelesion was enhanced with time (Figure 1(d)).

As tumor enlargement was observed after 6 months,laparoscopic-assisted splenectomy was performed. Thesize of the spleen was 13.5 × 10.5 × 5.5 cm. The cutsurface was well circumscribed and exhibited a solid,yellowish white to light tan tumor measuring 4 cm indiameter (Figure 2). Necrotic or hemorrhagic lesions werenot evident. Histopathologically, the lesion showed a solidtumor with epithelioid granuloma formation surroundedby spindle cells (Figure 3(a)), predominantly lymphocytesand plasma cells (Figure 3(b)). Immunohistochemicalanalysis revealed that the tumor cells were positive forCD21 (Figure 3(c)), CD23 (Figure 3(d)), and CNA.42

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Figure 1: Imaging findings. (a) Abdominal ultrasonography showing a homogeneous, hypoechoic solid mass in the lowerportion of the spleen. (b) Abdominal computed tomography scan showing a focal solid splenic mass (arrow). (c) Magneticresonance imaging (MRI) showing a hyperintense mass on a T1-weighted image. (d) Postcontrast subtracted image ondynamic MRI. The lesion was enhanced with time.

Figure 2: Cut surface of the spleen. It shows a well-circumscribed, yellowish white to light tan lesion.

(Figure 3(e)). In situ hybridization analysis for Epstein-Barrvirus (EBV)-encoded small RNA showed positivity almostexclusively in the spindle cells in the lesion (Figure 3(f)).On the basis of these findings, a definitive diagnosis ofIPT-like FDC tumor was made. The postoperative recoveryof the patient was uneventful, and follow-up for 3 yearsshowed no recurrence or metastasis.

3. Discussion

IPTs are usually localized benign lesions characterizedby spindle cell proliferation with abundant inflammatorycells, mainly lymphocytes and plasma cells [16,21], andthese tumors occur in any organ [1,3,8,18]. EBV-associatedIPT-like FDC tumor is a distinct disease entity differentfrom the common IPT. This disease entity was definitivelyestablished by Cheuk et al. in 2001 [7]. Although thecommon IPT is basically a benign disease, this diseaseentity may be included under non-benign tumors.

FDCs are known as antigen-presenting cells foundexclusively in the germinal center, which can be detectedin B-cell lymphomas as reactive bystander cells [11,19].FDC tumors are a rare disease derived from FDCs, andthese tumors most commonly occur in lymph nodes butthey may also develop in different extranodal sites. AmongFDC tumors in the liver or spleen, those that have anIPT-like morphology and are infected with EBV may beconsidered to be different from other FDC tumors withoutEBV infection.

In the late 1980s, Weiss et al. discovered a method todetect EBV using in situ hybridization [20]. During thedetection process, they confirmed the involvement of EBVin the development of a splenic IPT. Arber et al. examinedthe presence of EBV in various parts of an IPT and detectedEBV genomes in 4 cases of splenic lesion and 1 case of

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Figure 3: Histopathological and immunohistochemical findings. (a) Histopathological examination showing morphologicalfeatures indicative of an inflammatory pseudotumor (IPT) demarcated from the normal splenic tissue with fibrous septa(hematoxylin and eosin, ×12.5). (b) Histopathological examination showing the presence of spindle and inflammatory cells(plasmacytes and lymphocytes) (hematoxylin and eosin, ×400). (c) Immunohistochemistry showing CD21 positivity inspindle cells (×200). (d) Immunohistochemistry showing CD23 positivity in spindle cells (×200). (e) Immunohistochemistryshowing CNA.42 positivity in spindle cells (×200). (f) In situ hybridization for EBV-encoded RNAs: identification of EBVRNA in IPT (×200).

hepatic lesion [2]. In 1996, Delsol et al. [9] reported the firstcase of splenic IPT that was positive for both EBV and FDCmarkers [9,15,17]. In 2001, Cheuk et al. reported 11 casesof splenic IPT-like tumor positive for both EBV and FDCmarkers [7], which is considered to be a different diseaseentity from “follicular dendritic cell sarcoma” in the WorldHealth Organization Classification (version 4).

The clinical features of EBV-associated IPT-like FDCtumor, which is different from the common EBV-negativeFDC tumors, have been reported [4,5,10,12,13,14] asfollows. The tumor has a marked female predominanceand is generally observed to occur in the spleen or liver,although some cases occur in the peripancreatic region.There has been no report of extra-abdominal cases. Thelesion is usually solitary, fleshy and tan in color, and hascentral hemorrhage and necrosis. The clinical presentationof the tumor is nonspecific (i.e., weight loss and fever),and some patients are symptomatic. In many cases, theclinical course remains indolent. Although most patientsare completely cured by surgical resection, some casesmay have recurrence or metastasis. Unlike EBV-associatedIPT-like FDC tumor, common FDC tumors occur in variousanatomical sites without inducing any systemic symptoms.Recurrence may be observed in most cases within 1 year,and death occurs in many cases in 2 years. In the presentcase, some features were not typical. The patient did notcomplain of any symptoms pre- and postsplenectomy. All

the histopathological features were compatible with thisdisease entity, although the apparent granuloma formationwas not a typical feature. Interestingly, some cases of EBV-associated IPT-like FDC tumor of the liver easily recur [6].

In conclusion, when a solitary lesion in the spleen isencountered, it is important to consider the possibility ofan IPT-like FDC tumor. The differential diagnosis from thecommon IPT is occasionally difficult. Although the possiblerole of EBV in the pathogenesis of this IPT-like FDC tumorremains uncertain, either EBV clonality or positivity of FDCmarkers is necessary to discriminate indolent IPT-like FDCtumor from aggressive FDC tumor.

Acknowledgments The authors thank Dr. Masafumi Ito (M.D.) ofthe Department of Pathology of Japanese Red Cross Nagoya DaiichiHospital for his helpful comments. The authors are also indebted toDr. Clifford Kolba (Ed.D., D.O., M.P.H.) and Dr. Edward F. Barroga(Ph.D., Professor) of the Department of International Medical Com-munications of Tokyo Medical University for their editorial review ofthe English manuscript.

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