A case report: spleen Epstein-Barr virus-positive inflammatory follicular dendritic cell sarcoma

Introduction

Follicular dendritic cell is a kind of antigen-presenting cell which is mainly scattered among the white pulp of the spleen, the folliculus lymphaticus of the lymph nodule, and the folliculi lymphatici aggregati of the intestinal tract. It plays an important role in triggering and maintaining B cell adaptive immune response. Follicular dendritic cell sarcoma (FDCS) is a rare low-grade malignant tumor of follicular dendritic cells with indolent behavior. Until now, tumor resection is the primary treatment for it. Histologically, FDCS is divided into two types: conventional FDCS and Epstein-Barr virus-positive (EBV⁺) inflammatory FDCS (IFDCS) (1). Conventional FDCS usually occurs inside lymph nodule, while EBV⁺ IFDCS is commonly found in internal abdominal organs, such as the liver and spleen. FDCS affects both genders with a similar frequency (2). EBV⁺ IFDCS shows a slight female predominance, most of the patients are asymptomatic, and significant inflammatory background is often observed under the microscope (3). Most of EBV⁺ IFDCS are incidentally found out during imaging examinations and are easily misdiagnosed. Here, we present a case of splenic IFDCS with EBV infection, with the aim of contributing to improved diagnosis rate for this disease. We present this case in accordance with the CARE reporting checklist (available at https://jgo.amegroups.com/article/view/10.21037/jgo-24-483/rc).

Case presentation

A 71-year-old woman was found to have a space-occupying lesion in the spleen incidentally 2 weeks ago by chest computed tomography (CT) scanning. She had dizziness and headache, without abdominal distention, fatigue, fever, weight loss, nor other discomfort. She had a lacunar infarction 1 month ago and was troubled by rheumatoid arthritis for 20 years. Physical examination and laboratory examination showed no abnormalities and tumor markers were normal.

CT showed a quasi-round isodense mass in the spleen. The mass showed uniform density. The boundary between the lesion and the spleen was not clear (Figure 1). Magnetic resonance imaging (MRI) showed a 45 mm × 38 mm × 40 mm unrepresentative round lump in the spleen. The lesion demonstrated slight hypointensity on in-phase T1-weighted imaging (T1WI) (Figure 2A); with no significant drop in intensity on out-of-phase T1WI. A central hyperintensity flake (Figure 2B, green arrow) and some peripheral hypointensity strips (Figure 2B, purple arrow) in the lump were observed on fat-saturated T2-weighted imaging (T2WI), but the lesion showed slight hypointensity on fat-saturated T2WI in general (Figure 2B). The lesion demonstrated slight hyperintensity on diffusion-weighted imaging (DWI) (Figure 2C); and hypointensity on apparent diffusion coefficient (ADC). Meanwhile, the flake and strips showed hypointensity on DWI and hyperintensity on ADC. In the arterial phase, the lesion was heterogeneous and obviously enhanced in general, but the degree of enhancement was lower than that of the spleen (Figure 2D). And the enhancement slightly decreased in the portal and delayed phase, but the degree of descent was less than that of the spleen (Figure 2E,2F). Simultaneously, the flaky and strips shadows showed no enhancement in the arterial and portal phase, and demonstrated obvious enhancement in the delayed phase. Overall, the enhancement pattern of the lump was reversal enhancement. The radiographic diagnosis was benign neoplastic disease, suspected to be sclerosing angiomatoid nodular transformation (SANT), with hamartoma to be ruled out. Initially, the clinical diagnosis was spleen SANT.

Figure 1 CT showed a quasi-round isodense mass (41 mm × 47 mm) in spleen. CT, computed tomography.

Figure 2 MRI showed an abnormal signal in spleen. (A) T1WI; (B) T2WI; (C) DWI; (D) arterial phase; (E) portal phase; (F) delayed phase. Green arrow: central flake; purple arrow: some peripheral strips. MRI, magnetic resonance imaging; T1WI, T1-weighted imaging; T2WI, T2-weighted imaging; DWI, diffusion-weighted imaging.

The patient underwent laparoscopic partial splenectomy for the lesion, followed by histopathological examination of the tumor specimens. Observation of postoperative histopathological examination showed that: the tissues of white pulp and red pulp of the spleen had disappeared. Against a background of lymphocytes, plasma cells, and multinuclear giant cells, scattered spindle-shaped to ovoid tumor cells exhibiting indistinct cell borders. These tumor cells were either scattered individually or form loose, whorled patterns within prominent lymphoplasmacytic infiltrates. Small focal necrosis and local fibrosis were also noted within the lesion (Figure 3A,3B). Observation of immunohistochemical staining showed that: CD21 (partial+), CD35 (scattered+). Observation of in situ hybridization for EBV-encoded RNA (EBER) showed that: EBER (+).

Figure 3 The microscopic images (H&E staining) of the spleen lesion. (A) Original magnification ×400; (B) original magnification ×200. H&E, hematoxylin-eosin.

Combined with the results of postoperative histopathological examination, immunohistochemical and in situ hybridization, led to a revised diagnosis of EBV⁺ IFDCS.

The patient was followed up for 6 months, and no recurrence or metastasis was found during a contrast-enhanced abdominal CT.

All procedures performed in this study were in accordance with the ethical standards of the institutional and/or national research committee(s) and with the Helsinki Declaration (as revised in 2013). Written informed consent was obtained from the patient for the publication of this case report and accompanying images. A copy of the written consent is available for review by the editorial office of this journal.

Discussion

EBV⁺ IFDCS is an extremely rare tumor. It was first reported by Shek et al. in 1996 (4) and later first described as a distinct variant of FDCS in 2001 (5). Since then, all subsequent case reports followed this definition. This peculiar form of FDCS was recognized as a separate variant and designated as inflammatory pseudotumor (IPT)-like FDCS by the World Health Organization (WHO) classification of tumors of hemopoietic and lymphoid tissues in the 2017 revised 4^th edition, and WHO classification of digestive system tumors 5^th edition renamed it as EBV⁺ IFDCS (6).

Patients with EBV⁺ IFDCS usually lack clinical symptoms; therefore, radiology examinations are often the first method for detection. In related articles (7,8), EBV⁺ IFDCS appears as a circular or quasi-round mass showing slightly hypodense or isodense on plain CT scan, with mild, continuous, and annular enhancement observed in the delayed phase. The plain CT signs described in these articles are largely consistent with those in our case. However, the patient did not undergo the enhanced CT, so we were unable to evaluate this case in further detail.

According to the article (7), generally speaking, the lesion shows hypointensity compared to skeletal muscle on T1WI, slight hypointensity with a hypointensity ring at the lesion’s margin on T2WI, slightly high or high signal intensity on DWI. Meanwhile, contrast enhancement can be divided into three types which are closely related to the tumor’s histopathological features: (I) centrifugal enhancement type; (II) marginal enhancement type; and (III) grid enhancement type. In our case, the lesion’s signals on T1WI and DWI are consistent with the statistical information of the article. The hypointensity ring on T2WI which can also be seen in this case hints at local fibrosis. And the enhancement behavior strongly supports the inference. There are two differences on MRI between those reported in other article and those of our case. The first difference is the central hyperintensity flake on T2WI. We speculate that this area is the small focal necrosis of which the histopathological examination has mentioned above. And due to slow leakage of contrast medium, this area eventually exhibited obvious enhancement in the delayed phase. The second difference is the enhancement type. Our case showed nodular enhancement type in the arterial and portal phase, and demonstrated reversal enhancement type in the delayed phase. This difference is closely related to the first observation.

Splenic hamartoma is a rare, benign tumor, and consists of splenic red pulp. It is usually asymptomatic. It appears isointensity on T1WI, slightly hyperintensity on T2WI, and shows heterogeneous enhancement in the arterial phase, then becomes relatively homogeneous enhancement (9). In our case, the enhancement pattern of the lesion differs from that typically observed in hamartomas. Therefore, it was not considered as the primary suspect in the final report.

It is crucial to carefully distinguish EBV⁺ IFDCS from SANT. SANT is a benign lesion and often incidentally discovered because patients usually are asymptomatic. According to previous articles (10,11), the lesion is homogeneously hypodense on CT. On MRI, SANT shows hypointensity or isointensity on T1WI and heterogeneously hypointensity on T2WI. On enhanced images, the lesion demonstrates progressive centripetal enhancement. Central or eccentral scar can sometimes be seen, reflecting delayed enhancement. It is apparent that the challenge in diagnosing our case lies in the fact that its imaging features closely resemble those of SANT. Thus, the radiologist considered SANT as the primary diagnosis.

The initial misdiagnosis of SANT and hamartoma in this case, along with the failure to consider EBV⁺ IFDCS as a suspect, maybe related to the rarity of EBV⁺ IFDCS and the absence of widely agreed characteristic imaging features of it.

Our study remains limited by the absence of contrast CT, which may provide more information for a more comprehensive understanding.

In recent years, with an increased number of reports on similar cases, our understanding of EBV⁺ IFDCS has improved. When intra-abdominal IPT-like lesion, especially in the spleen, are suspected, the diagnosis of EBV⁺ IFDCS can become relatively easy. MRI has the advantage of high-resolution and can offer valuable detailed information of the lesion for a more accurate diagnosis. Currently, the diagnosis of EBV⁺ IFDCS may still largely depend on immunohistochemical examination.

Conclusions

In conclusion, EBV⁺ IFDCS imaging characteristics of the case presented here are as follows: a quasi-round homogeneous isodense mass was detected in the spleen on CT. And the tumor demonstrated hypointensity on T1WI and slight hypointensity with hypointensity ring on T2WI, nodular enhancement in the arterial and portal phase and reversal enhancement in the delayed phase. DWI and ADC indicated that the lesion exhibited diffusion restriction.

Acknowledgments

Funding: This work was supported by the Guangdong Basic and Applied Basic Research Foundation (No. 2022A1515220015).

Footnote

Reporting Checklist: The authors have completed the CARE reporting checklist. Available at https://jgo.amegroups.com/article/view/10.21037/jgo-24-483/rc

Peer Review File: Available at https://jgo.amegroups.com/article/view/10.21037/jgo-24-483/prf

Conflicts of Interest: Both authors have completed the ICMJE uniform disclosure form (available at https://jgo.amegroups.com/article/view/10.21037/jgo-24-483/coif). The authors have no conflicts of interest to declare.

Ethical Statement: The authors are accountable for all aspects of the work in ensuring that questions related to the accuracy or integrity of any part of the work are appropriately investigated and resolved. All procedures performed in this study were in accordance with the ethical standards of the institutional and/or national research committee(s) and with the Helsinki Declaration (as revised in 2013). Written informed consent was obtained from the patient for the publication of this case report and accompanying images. A copy of the written consent is available for review by the editorial office of this journal.

Open Access Statement: This is an Open Access article distributed in accordance with the Creative Commons Attribution-NonCommercial-NoDerivs 4.0 International License (CC BY-NC-ND 4.0), which permits the non-commercial replication and distribution of the article with the strict proviso that no changes or edits are made and the original work is properly cited (including links to both the formal publication through the relevant DOI and the license). See: https://creativecommons.org/licenses/by-nc-nd/4.0/.

References

1. Xu X, Li X, Deng Q, et al. EBV-positive inflammatory follicular dendritic cell sarcoma of the colon with clonal immunoglobulin gene rearrangement: A case report and literature review. Heliyon 2024;10:e31947. [Crossref] [PubMed]
2. Yan S, Yue Z, Zhang P, et al. Case report: Hepatic inflammatory pseudotumor-like follicular dendritic cell sarcoma: a rare case and review of the literature. Front Med (Lausanne) 2023;10:1192998. [Crossref] [PubMed]
3. Jiang XN, Zhang Y, Xue T, et al. New Clinicopathologic Scenarios of EBV+ Inflammatory Follicular Dendritic Cell Sarcoma: Report of 9 Extrahepatosplenic Cases. Am J Surg Pathol 2021;45:765-72. [Crossref] [PubMed]
4. Shek TW, Ho FC, Ng IO, et al. Follicular dendritic cell tumor of the liver. Evidence for an Epstein-Barr virus-related clonal proliferation of follicular dendritic cells. Am J Surg Pathol 1996;20:313-24. [Crossref] [PubMed]
5. Cheuk W, Chan JK, Shek TW, et al. Inflammatory pseudotumor-like follicular dendritic cell tumor: a distinctive low-grade malignant intra-abdominal neoplasm with consistent Epstein-Barr virus association. Am J Surg Pathol 2001;25:721-31. [Crossref] [PubMed]
6. Nagtegaal ID, Odze RD, Klimstra D, et al. The 2019 WHO classification of tumours of the digestive system. Histopathology 2020;76:182-8. [Crossref] [PubMed]
7. Xu L, Ge R, Gao S. Imaging features and radiologic-pathologic correlations of inflammatory pseudotumor-like follicular dendritic cell sarcoma. BMC Med Imaging 2021;21:52. [Crossref] [PubMed]
8. Xue N, Xue X, Sheng C, et al. Imaging features of inflammatory pseudotumor-like follicular dendritic cell sarcoma of the spleen. Ann Palliat Med 2021;10:12140-8. [Crossref] [PubMed]
9. Lee H, Maeda K. Hamartoma of the spleen. Arch Pathol Lab Med 2009;133:147-51. [Crossref] [PubMed]
10. Lewis RB, Lattin GE Jr, Nandedkar M, et al. Sclerosing angiomatoid nodular transformation of the spleen: CT and MRI features with pathologic correlation. AJR Am J Roentgenol 2013;200:W353-60. [Crossref] [PubMed]
11. Ma J, Zhang W, Wang L, et al. Imaging Features of Sclerosing Angiomatoid Nodular Transformation in Spleen. J Comput Assist Tomogr 2019;43:863-9. [Crossref] [PubMed]