Skip to main content
Surgical Case Reports
Download PDF

Epstein–Barr virus-associated inflammatory pseudotumor variant of follicular dendritic cell sarcoma of the liver: a case report and review of the literature

Surgical Case Reports volume 8, Article number: 220 (2022) Cite this article

Abstract

Background

Follicular dendritic cell sarcoma is a rare stromal tumor with no standard treatment. However, some reports have revealed that follicular dendritic cell sarcoma has an inflammatory pseudotumor variant associated with Epstein–Barr virus infection that has a relatively good prognosis. In this report, we present a case of a resected inflammatory pseudotumor variant of follicular dendritic cell sarcoma of the liver, and have reviewed the literature on the clinicopathological, molecular, and genomic features of this tumor.

Case presentation

The inflammatory pseudotumor variant of follicular dendritic cell sarcoma originates only in the liver or spleen, causes no symptoms, and is more common in middle-aged Asian women. It has no characteristic imaging features, which partially explains why the inflammatory pseudotumor variant of follicular dendritic cell sarcoma is difficult to diagnose. Pathologically, the inflammatory pseudotumor variant of follicular dendritic cell sarcoma has spindle cells mixed with inflammatory cells and is variably positive for follicular dendritic cell markers (CD21, CD23, and CD35) and Epstein–Barr virus-encoded RNA. On genetic analysis, patients with this tumor high levels of latent membrane protein 1 gene expression and extremely low levels of host C–X–C Chemokine Receptor type 7 gene expression, indicating that the inflammatory pseudotumor variant of follicular dendritic cell sarcoma has a latent Epstein–Barr virus type 2 infection.

Conclusions

The inflammatory pseudotumor variant of follicular dendritic cell sarcoma is an Epstein–Barr virus-associated tumor and a favorable prognosis by surgical resection, similar to Epstein–Barr virus-associated gastric cancer.

Background

Follicular dendritic cells (FDCs), also known as dendritic reticulum cells, are located primarily in the germinal centers of primary or secondary lymphoid follicles in nodal and extra-nodal sites. FDCs are derived from mesenchymal precursors; thus, they can become sarcomas but not carcinomas or lymphomas [1]. Monda et al. first described this tumor in 1986 based on a series of four cases that originated in lymph nodes [2]. Previous reports have pointed out that follicular dendritic cell sarcoma (FDCS) is an aggressive tumor with a high recurrence and metastasis rate [3]. FDCS mainly occurs in lymph nodes; however, approximately half of FDCS cases were found to occur in other sites, such as the liver, spleen, and small intestine. We have no standard treatment for this sarcoma, not only because of its rare incidence and the lack of therapies targeted toward it.

A recent report revealed a new subtype of FDCS that is the inflammatory pseudotumor (IPT) variant of FDCS that occurs only in the liver and the spleen and has a more favorable prognosis by resection than the “conventional” FDCS [4]. Moreover, the IPT variant of FDCS is associated with Epstein–Barr virus (EBV) infection, while conventional FDCS is not associated with EBV infection.

EBV is a gamma herpes virus composed of a linear double-stranded DNA (170–180 kilo-base-pair in size). EBV also contributes to the development of human cancers of epithelial, mesenchymal, and lymphocytic origins, because EBV gene products which are expressed in its latent infection, such as latent membrane protein (LMP) or EBV nuclear antigen (EBNA), are considered to be viral oncogenes [5]. These tumors also have various malignant natures with different prognoses; however, there is no antiviral drug or molecular-targeted therapy for EBV-associated tumors because of the lack of information regarding the relationship between EBV infection and oncogenesis.

In this report, we have presented the case of a patient in whom an IPT variant of FDCS of the liver was resected using laparoscopic surgery, and review the literature on the clinicopathological features of this variant and the underlying molecular mechanisms for oncogenesis.

Case presentation

Clinical presentation

A 60-year-old asymptomatic woman presented to our hospital with a 4-cm tumor in segment IV of her liver detected incidentally during a routine medical checkup. Laboratory investigations showed normal liver function test results, no viral infection, and no elevated tumor markers. Abdominal ultrasound revealed a 4-cm solitary, well-defined hypoechoic mass with mosaic components and flow signals in liver segment IV (Fig. 1a). The tumor was a heterogeneously enhancing lesion, with peripheral enhancement observed in the arterial phase of dynamic computed tomography (Fig. 1b). The early enhancing area appeared iso-intense to the liver parenchyma, as seen in the equivalent phase of dynamic computed tomography (Fig. 1c). The lesion also included several patchy areas without enhancement through all phases. Fluorodeoxyglucose–positron emission tomography showed slight hyperaccumulation in the tumor (Fig. 1d). In the hepatobiliary phase of gadolinium–ethoxy benzyl-diethylenetriamine penta-acetic acid-enhanced magnetic resonance imaging, the signal in the tumor was markedly lower than that in the liver parenchyma (Fig. 1e). A high signal intensity on a diffusion-weighted image (b value of 1000 s/mm2) was obtained (Fig. 1f). Laparoscopic extended left hepatectomy with intraoperative cholangiography was performed as the tumor had extended to the middle hepatic vein and left Gleason sheath (Fig. 2a). There were no complications during the postoperative course, and the patient was discharged from the hospital on postoperative day 8. She experienced no relapse for 3 years and 6 months.

Fig. 1
figure 1

Preoperative imaging of a tumor. a Abdominal ultrasound showing a 4-cm mass in liver segment IV. b Tumor is heterogeneously enhanced with peripheral enhancement in the arterial phase of dynamic CT. c Early enhancing area is iso-intense to the liver parenchyma in the equivalent phase of dynamic CT. d FDG–PET shows slight hyperaccumulation in the tumor. e Signal of the tumor is markedly lower than that of the liver parenchyma in the hepatobiliary phase of gadolinium–ethoxybenzyl-diethylenetriamine penta acetic acid-enhanced MRI. f High signal intensity on diffusion-weighted image (b value of 1000 s/mm2) is noted. CT: computed tomography; FDG–PET: fluorodeoxyglucose–positron emission tomography; MRI: magnetic resonance imaging

Full size image
Fig. 2
figure 2

Intraoperative and macroscopic findings of EBV-associated FDCS. a Case underwent laparoscopic extended left hepatectomy (yellow arrow). b Mass measuring 3.5 cm in size, with a well-circumscribed margin, milky-white in color, and with necrotic components is noted. EBV: Epstein–Barr virus; FDCS: follicular dendritic cell sarcoma

Full size image

Pathological findings and final diagnosis

A 3.5-cm-sized mass was recognized with a well-circumscribed margin, milky-white color, and necrotic components, as shown in Fig. 2b. Microscopically, the lesion was composed of atypical spindle cells mixed with inflammatory cells, chiefly lymphocytes, plasma cells, histiocytes, and a few neutrophils (Fig. 3a). These spindle cells showed positive nuclear signals for EBV-encoded RNA (EBER)–in-situ hybridization (ISH) (Fig. 3b). The tumor cells were positive for CD23 (Fig. 3c) and negative for CD79α, CD3, CD5, CD35, D2–40, and anaplastic lymphoma kinase (ALK). Immunoglobulin G4 (IgG4) positive cells were identified to constitute less than 1%. Double staining for CD23 and EBER further revealed that EBV-infected FDCs had the capacity for tumorigenesis (Fig. 3d). The Ki-67 level was approximately 5% in this tumor (Additional file 1: Fig. S1).

Fig. 3
figure 3

EBER–ISH and immunohistochemistry for EBV-associated FDCS (scale bars = 25 µm). a Lesion is composed of atypical spindle cells admixed with infiltrating inflammatory cells on hematoxylin and eosin staining. b Nucleus of the spindle cells is diffusely positive for EBER–ISH. c Cytoplasmic positivity for CD23. d Double staining for CD23 immunohistochemistry (brown) and EBER–ISH (red) revealing that EBER–ISH positive cells show CD23 immunoreactive cytoplasm. EBER: Epstein–Barr virus enucleated RNA; ISH: in-situ hybridization; FDCS: follicular dendritic cell sarcoma

Full size image

The mass had the following characteristics: IPT variant of FDCS (EBV-positive follicular dendritic cell sarcoma), size of 35 × 32 × 31 mm, simple nodular type, expansive growth, formation of capsule positive, Infiltration to capsule negative, septal formation negative, n0, vp0, vv2 (left hepatic vein adventitia), va0, b0, im0, surgical margin negative, T3 N0 M0, and Stage III (Union for International Cancer Control 8th edition).

Genetic analysis

DNA sequence and single nucleotide polymorphisms of the IPT variant of FDCS

We obtained 900–1000-bp DNA fragments from the EBV-associated (IPT variant) FDCS using electrophoresis (Additional file 1: Fig. S2a). We extracted the DNA fragments and compared the sequence data with type 1 and 2 EBV genomes. The DNA fragments from the EBV-associated FDCS were 97% and 66% identical to the DNA of type 1 and type 2 EBV, respectively (Additional file 1: Fig. S2b).

Next, we performed multiple sequence alignments on the RPMS1 gene of EBV (Additional file 1: Fig. S3). Annotation of the DNA sequence revealed that single nucleotide polymorphisms (SNPs) C155389T and G155391A were not present on the RPMS1 gene in our case [6]. Moreover, in our case, the EBV DNA was identical to that isolated from B95-8 (lymphoblastoid cell line) and YCCEL1 (Korean gastric adenocarcinoma) but showed no similarity with the DNA isolated from GD2 and HKNPC1 (Chinese nasopharyngeal carcinomas [NPCs]) for SNP G155391A and from GD1 (Chinese NPC), Mutu (Kenyan Burkitt’s lymphoma), and AG876 (Ghanaian Burkitt’s lymphoma) for SNP C155389T.

LMP-1 and EBNA-2 (C–X–C Chemokine Receptor type 7 [CXCR7] in host cells) gene expression of the IPT variant of FDCS

EBV-associated tumors are subdivided into three latency types. Latency type I is expressed in gastric carcinoma, NPC, and Burkitt’s lymphoma. Latency type II corresponds to Hodgkin’s lymphoma and undifferentiated NPCs. Finally, cells from lymphoproliferative diseases arising in immunosuppressed hosts (e.g., patients with post-transplant lymphoproliferative disease and immunoblastic non-Hodgkin’s lymphoma) belong to latency type III [7, 8]. In previous reports, the LMP-1 gene was positive in 90% of cases with the IPT variant of FDCS [9]; thus, we considered that the IPT variant of FDCS occurs in the latency type II or III. The level of LMP-1 expression in this tumor was found to be 37.64 times that of the Namalwa cell line (Fig. 4a). In contrast, the level of EBNA-2 (CXCR7 in host cells) expression in this tumor was much lower than that of the Namalwa cell line and normal liver tissue (Fig. 4b). We also found that hepatocellular carcinoma (HCC) had a more than five times higher EBNA-2 expression than the Namalwa cell line did. Besides, immunohistochemistry of LMP-1 and EBNA-2 revealed that this tumor had a high expression of LMP-1, but negative expression of EBNA-2 (Additional file 1: Fig. S4).

Fig. 4
figure 4

Real-time PCR analysis for gene expression. a PCR products were analyzed using the ΔΔCt method, and the LMP-1 gene expression ratios in the tumor samples were calculated by setting the ratio for Namalwa cell line as 1. b PCR products were analyzed using the ΔΔCt method, and the EBNA-2 (human CXCR7) gene expression ratios in the tumor samples were calculated by setting the ratio for Namalwa cell line as 1. EBV: Epstein–Barr virus; FDCS: follicular dendritic cell sarcoma; HCC: hepatocellular carcinoma; CCC: cholangiocellular carcinoma; CRLM: colorectal liver metastasis; PCR: polymerase chain reaction; LMP: latent membrane protein; EBNA-2: EBV nuclear antigen-2; CXCR7: C–X–C Chemokine Receptor type 7

Full size image

Discussion

Epidemiology and clinical features

FDCs are stromal-derived cells that are important for the maintenance of the architecture of B cell follicles within lymph nodes and other secondary lymphoid organs [1]. Hence, they are derived from mesenchymal stem cells, not from myeloid stem cells. Therefore, the tumorigenesis of FDCs indicates the formation of a sarcoma [6]. Conventional FDCS of the liver is a rare neoplasm that usually presents clinically with abdominal pain and weight loss [10]. In general, conventional FDCS presents in various locations, including within lymph nodes (31%) and outside them (58%) [11]. Furthermore, conventional FDCS has a high rate of recurrence (44.6%) and metastasis with a poor prognosis [11].

The IPT variant of FDCS of the liver is even rarer, and the clinicopathological features of this type remain unknown [12]. The IPT variant of FDCS of the liver has been reported in only 30 cases worldwide, including this case (Table 1; our case is the 30th case) [4, 13,14,15,16,17,18,19,20,21,22,23,24,25,26,27,28,29,30,31,32]. According to these reports, the IPT variant of FDCS of the liver emerged predominantly in women (n = 24, 80%) and in middle-aged patients whose median age was 48.5 (19–82) years. Furthermore, the IPT variant of FDCS of the liver had a favorable prognosis and low recurrence rate (five out of 30 cases, 16.7%). Recurrence sites were reported to be the liver in two patients and intraabdominal dissemination in one patient (the location in the two remaining patients was not described). Finally, the most significant difference between the IPT variant and conventional FDCS is the existence of EBV infection.

Table 1 Literature review of EBV-associated FDCS of the liver
Full size table

Imaging findings

The IPT variant of FDCS cannot be diagnosed by imaging modalities, mainly because of its various presentations and the lack of specific findings, as in this case where it could have been misdiagnosed as a neuroendocrine tumor of the liver, liver metastasis, or HCC. The IPT variant of FDCS shows a high fluorodeoxyglucose uptake, but fluorodeoxyglucose–positron emission tomography may not be useful for the differentiation of the IPT variant of FDCS from other tumors, such as metastatic tumors or lymphomas, as they can also show a high fluorodeoxyglucose uptake [33]. Based on the present and previous cases, we can conclude that the IPT variant of FDCS of the liver is a heterogeneous tumor with necrotic components that can expand and compress major hepatic vessels.

Pathological findings

Since antigen loss is frequent, the diagnosis of FDCS requires support from immunohistochemistry, and the use of multiple FDC markers is often necessary. Tumor cells are variably positive for CD21, CD23, and CD35, which are specific markers of FDC [34, 35]. Liver IPT is a distinct disease that is often present on the differential with the IPT variant of FDCS. In the World Health Organization 2010 guidelines, liver IPT is subdivided into two types pathologically: IgG4-related and IgG4-negative, which are called the lymphoplasmacytic and fibrohistiocytic types, respectively [36]. The fibrohistiocytic type of IPT is frequently misdiagnosed as inflammatory myofibroblastic tumor, which is associated with ALK [37, 38]. Therefore, to diagnose the IPT variant of FDCS correctly, we must perform extensive immunohistochemical staining and recognize real tumor cells as positive for EBV markers (EBER–ISH, CD21, CD23, or CD35) and negative for IgG4 and ALK. From our results, we finally diagnosed that owing to the tumor cells, patients with the IPT variant of FDCS had an EBER-positive nucleus and a CD23-positive cytoplasm.

Treatment strategies

Conventional FDCS can be cured by surgery alone but may recur many times with a poor prognosis after a long period. One review of conventional FDCS revealed that local recurrences and distant metastases were observed in 28% and 27% of cases, respectively [11]. The main sites of metastasis are the lung, liver, lymph nodes, and bones. This review also referred to negative predictive factors, such as tumor size (≥ 6 cm) and lymphoplasmacytic infiltration in tumor tissue [11]. Previous reports have insisted that there were no adjuvant treatments of significant effect on disease-free survival after surgical resection. Although, the IPT variant of FDCS has a more favorable prognosis than conventional FDCS, but the recurrence rate is estimated to be 16.7%; therefore, surgery with complete resection is the mainstay of treatment. In the present case, we performed laparoscopic hepatectomy that resulted in no complications or recurrence. Laparoscopic hepatectomy has been recently adopted for liver tumors, suggesting that laparoscopic resection of the IPT variant of FDCS might be feasible and safe for the short- and long-term outcomes of patients.

EBV-associated tumors

Several types of EBV-associated tumors have been identified globally. First, EBV-associated gastric carcinoma (EBVaGC) constitutes approximately 10% of gastric carcinomas worldwide and is mainly observed in Asian countries [39], as EBV genomes discovered in EBVaGC are closely related to Asian-derived EBV strains, such as GD1 and 2, C666-1 (Chinese strain), or Akata (Japanese strain) [40, 41]. In addition, NPC is an EBV-associated epithelial carcinoma and is common in South China and Southeast Asia. More than 97% of NPC cases are caused by EBV infections, such as HKNPC 1 to 9. These Asian-derived EBV strains are categorized as type 1 EBV. In contrast, African Burkitt’s lymphoma is the most common in equatorial Africa and is designated as “endemic Burkitt’s lymphoma,” which is mainly caused by type 2 EBV [42]. Our research revealed that the IPT variant of FDCS in our case was derived from type 1 EBV, which was similar to the EBVaGC strain but different from NPC.

Genetic findings

Based on our experience with this case, we propose the mechanism of tumorigenesis for FDCS associated with EBV infection (Fig. 5). Type 1 EBV initially infects human B lymphocytes in the lymphoid follicles, which generate in the liver tissue and are similar to the germinal center in the spleen [43, 44]. Then, EBV becomes latent in B cells and starts infecting FDCs. EBER or LMP-1 protein is released from EBV to FDCs, which causes the inhibition of cell apoptosis and proliferation of FDCs by amplifying CD40 signaling pathways. Chen et al. supported the finding that LMP-1 was elevated in cases of IPT-variant FDCS [16]. This mechanism of oncogenesis is similar to Hodgkin lymphoma associated with EBV infection. The latter is attributed to the crosstalk between EBV-infected B cells and follicular helper T cells in the light zone of the germinal center and the proliferation of B cells induced by EBER and LMP-1 proteins [45]. We also found that EBNA-2 expression (CXCR7 expression in host cells) was much lower in IPT-variant FDCS than in the Namalwa cell line, while that in HCC was much higher than that in the Namalwa cell line. CXCR7 was reported to be overexpressed in various types of tumor endothelial cells, and the downregulation of CXCR7 significantly inhibited the migration and invasion of HCC [46, 47], suggesting that the use of drugs that target this receptor is a promising treatment options in the future [48]. It is also curious about how blood levels of LMP-1 or CXCR-7 in this patient, which will lead to future preoperative diagnosis tool of this rare tumor.

Fig. 5
figure 5

Oncogenesis of EBV-associated FDCS. Type 1 EBV initially infects human B lymphocytes and converts into the latency type. Then, it moves and infects the FDCs. EBER or LMP-1 protein released from the EBV to FDCs causes inhibition of cell apoptosis and proliferation of FDCs by amplification of the CD40 signaling pathways. IPT: inflammatory pseudotumor; FDCS: follicular dendritic cell sarcoma; EBV: Epstein–Barr virus; LMP-1: latent membrane protein-1; EBER: Epstein–Barr virus enucleated RNA

Full size image

Future challenging issues

Despite the development of treatment strategy for various kinds of tumors, we still have several unresolved issues regarding IPT-variant FDCS. First, we do not know why EBV-positive solid tumors, including IPT-variant FDCS, have a relatively better prognosis than those without EBV association. Next, there is no targeted chemotherapy for FDCS including IPT-variant FDCS. Complete surgical resection remains the only treatment option. IPT-variant FDCS is one of the EBV-associated tumors; however, there is no targeted chemotherapy for EBV-associated tumors and no anti-EBV drugs, because EBV only infects humans and clinical trials for drug discovery against EBV infection have been delayed compared to those for other herpes viruses, such as simple herpes virus or varicella-zoster virus.

In summary, because of the very limited data, there are no definite treatment strategies, such as radiotherapy, chemotherapy, and immunotherapy, for FDCS and IPT-variant FDCS.

Although IPT-variant FDCS is a rare sarcoma associated with EBV infection, we hope that research on this rare tumor will lead to the discovery of the exact mechanism of tumorigenesis and help with future treatment options.

Conclusions

IPT-variant FDCS is an EBV-associated tumor and may have a favorable prognosis following surgical resection, similar to EBV-associated gastric cancer.

Availability of data and materials

All data generated or analyzed during this study are included in this published article [and its supplementary information files].

Abbreviations

FDCS:

Follicular dendritic cell sarcoma

FDCs:

Follicular dendritic cells

IPT:

Inflammatory pseudotumor

EBV:

Epstein–Barr virus

LMP:

Latent membrane protein

CXCR7:

C–X–C Chemokine Receptor type 7

EBNA:

Epstein–Barr virus nuclear antigen

EBER:

Epstein–Barr virus-encoded ribonucleic acid

ISH:

In-situ hybridization

SNP:

Single nucleotide polymorphisms

ALK:

Anaplastic lymphoma kinase

NPC:

Nasopharyngeal carcinomas

PCR:

Polymerase chain reaction

HCC:

Hepatocellular carcinoma

IgG4:

Immunoglobulin G4

EBVaGC:

Epstein–Barr virus-associated gastric carcinoma

References

  1. Heesters BA, Van der Poel CE, Carroll MC. Follicular dendritic cell isolation and loading of immune complexes. Methods Mol Biol. 2017;1623:105–12.

    Article  CAS  Google Scholar 

  2. Monda L, Warnke R, Rosai J. A primary lymph node malignancy with features suggestive of dendritic reticulum cell differentiation: a report of 4 cases. Am J Pathol. 1986;122(3):562–72.

    CAS  Google Scholar 

  3. Wu A, Pullarkat S. Follicular dendritic cell sarcoma. Arch Pathol Lab Med. 2016;140:186–90.

    Article  CAS  Google Scholar 

  4. Cheuk W, Chan JK, Shek TW, Chang JH, Tsou MH, Yuen NW, 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(6):721–31.

    Article  CAS  Google Scholar 

  5. Song H, Lim Y, Im H, Bae JM, Kang GH, Ahn J, et al. Interpretation of eBV infection in pan-cancer genome considering viral life cycle: LieB (Life cycle of Epstein-Barr virus). Sci Rep. 2019;9(3465):1–10.

    Google Scholar 

  6. Facchetti F, Lorenzi L. Follicular dendritic cells and related sarcoma. Semin Diagn Pathol. 2016;33:262–76.

    Article  Google Scholar 

  7. Delison O, Barbara M, Joseph P. Viral carcinogenesis beyond malignant transformation: EBV in the progression of human cancers. Trends Microbiol. 2016;24(8):649–64.

    Article  Google Scholar 

  8. Iwakiri D. Molecular Mechanisms of Epstein-Barr virus-mediated carcinogenesis. Virus. 2014;64(1):49–56.

    CAS  Google Scholar 

  9. Lucchesi W, Brady G, Dittrich-Breiholz O, Kracht M, Russ R, Farrell P. Differential gene regulation by Epstein-Barr virus type 1 and type 2 EBNA2. J Virol. 2008;82(15):7456–66.

    Article  CAS  Google Scholar 

  10. Saygin C, Uzunaslan D, Ozguroglu M, Senocak M, Tuzuner N. Dendritic cell sarcoma: a pooled analysis including 462 cases with presentation of our case series. Crit Rev Oncol Hematol. 2013;88:253–71.

    Article  Google Scholar 

  11. Zhu H, Chen M, Du Y. Follicular dendritic cell sarcoma of the small intestine detected by double-balloon enteroscopy. Dig Endosc. 2017;29:723–32.

    Article  Google Scholar 

  12. Ma Y, Sun J, Yang C, Yuan D, Liu J. Follicular dendritic cell sarcoma: two rare cases and a brief review of the literature. Onco Targets Ther. 2015;8:1823–30.

    Article  CAS  Google Scholar 

  13. Selves J, Meggetto F, Bmusset P, Voigt JJ, Pradere B, Grasset D, et al. Inflammatory pseudotumor of the liver: evidence for follicular dendritic reticulum cell proliferation associated with clonal Epstein-Barr virus. Am J Surg Pathol. 1996;20:747–53.

    Article  CAS  Google Scholar 

  14. Shek TW, Ho FC, Ng IO, Chan AC, Ma L, Srivastava G. 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.

    Article  CAS  Google Scholar 

  15. Shek TW, Liu CL, Peh WC, Fan ST, Ng IO. Intra-abdominal follicular dendritic cell tumour: a rare tumour in need of recognition. Histopathology. 1998;33:465–70.

    Article  CAS  Google Scholar 

  16. Chen TC, Kuo TT, Ng KF. Follicular dendritic cell tumor of the liver: a clinicopathologic and Epstein-Barr virus study of two cases. Mod Pathol. 2001;14(4):354–60.

    Article  CAS  Google Scholar 

  17. Torres U, Hawkins WG, Antonescu CR, DeMatteo RP. Hepatic follicular dendritic cell sarcoma without epstein-barr virus expression. Arch Pathol Lab Med. 2005;129(11):1480–3.

    Article  Google Scholar 

  18. Bai LY, Kwang WK, Chiang IP, Chen PM. Follicular dendritic cell tumor of the liver associated with Epstein-Barr virus. Jpn J Clin Oncol. 2006;36(4):249–53.

    Article  Google Scholar 

  19. Yuan J, Li XH, Lü YL, Song X. Pathologic diagnosis of hepatic inflammatory pseudotumor and inflammatory pseudotumor-like follicular dendritic cell tumor. Linchuang Yu Shiyan Binglixue Zazhi. 2007;23:39–42.

    Google Scholar 

  20. Tu XY, Sheng WQ, Lu HF, Wang J. Clinicopathologic study of intraabdominal extranodal follicular dendritic cell sarcoma. Zhonghua Bing Li Xue Za Zhi. 2007;36:660–5.

    CAS  Google Scholar 

  21. Granados R, Aramburu JA, Rodriguez JM, Nieto MA. Cytopathology of a primary follicular dendritic cell sarcoma of the liver of the inflammatory pseudotumor-like type. Diagn Cytopathol. 2008;36(1):42–6.

    Article  Google Scholar 

  22. Zhang ZX, Cheng J, Shi QL. Follicular dendritic cell sarcoma: a clinicopathologic study of 8 cases. Zhonghua Bing Li Xue Za Zhi. 2008;37:395–9.

    Google Scholar 

  23. Liu Yh, Li L, Hu QL, Miranda RN. Inflammatory pseudotumor-like follicular dendritic cell tumor of the liver with expression of estrogen receptor suggests a pathogenic mechanism: a case report and review of the literature. J Hematopathol. 2010;3:109–15.

    Article  Google Scholar 

  24. Zhang SH, Zhou XG, Zheng YY, Zhang YN, Wang P, Xie JL, Jin Y, Zhang XD. Clinicopathological study on the follicular dendritic cell sarcoma. Zhonghua Zhong Liu Za Zhi. 2010;32:123–7.

    CAS  Google Scholar 

  25. Xu B, Yao LQ, Wu QS, Zheng X. Clinical pathological factors of hepatic inflammatory pseudo- tumor-like follicular dendritic cell tumor. Zho- ngliu Fangzhi Zazhi. 2011;38:183–7.

    Google Scholar 

  26. Martins PN, Reddy S, Martins AB, Facciuto M. Follicular dendritic cell sarcoma of the liver: unusual presentation of a rare tumor and literature review. Hepatobiliary Pancreat Dis Int. 2011;10(4):443–5.

    Article  Google Scholar 

  27. Tian BL, Gao AF, Xu C, Shu H, Jia CJ, Yang XH. Inflammatory pseudotumor-like follicular dendritic cell tumor of liver and spleen. Zhonghua Gandan Waike Zazhi. 2012;18:169–72.

    Google Scholar 

  28. Chen Y, Shi H, Li H, Zhen T, Han A. Clinicopathological features of inflammatory pseudotumour- like follicular dendritic cell tumour of the abdomen. Histopathology. 2016;68:858–65.

    Article  Google Scholar 

  29. Zhang X, Zhu C, Hu Y, Qin X. Hepatic inflammatory pseudotumour-like follicular dendritic cell tumor: a case report. Mol Clin Oncol. 2017;6:547–9.

    Article  Google Scholar 

  30. Endo Y, Hibi T, Shinoda M, Abe Y, Minagawa T, Kitagawa Y. A case who was performed left and caudate liver hepatectomy and dissection of para-aorta lymph nodes, for huge liver follicular dendritic cell sarcoma with para-aortic lymphadenopathy by imaging. SHUJYUTSU. 2018;72(12):1799–804.

    Google Scholar 

  31. Deng S, Gao J. Inflammatory pseudotumor-like follicular dendritic cell sarcoma: a rare presentation of a hepatic mass. Int J Clin Exp Pathol. 2019;12(8):3149–55.

    Google Scholar 

  32. Zhang BI, Chen ZH, Liu Y, Zeng YJ, Li YC. Inflammatory pseudotumor-like follicular dendritic cell sarcoma: a brief report of two cases. World J Gastrointest Oncol. 2019;11(12):1231–9.

    Article  Google Scholar 

  33. Kitamura Y, Takayama Y, Nishie A, Asayama Y, Ushijima Y, Fujita N, et al. Inflammatory pseudotumor-like follicular dendritic cell tumor of the spleen: case report and review of the literature. Magn Reson Med Sci. 2015;14(4):347–54.

    Article  Google Scholar 

  34. Deyrup AT. Epstein-Barr virus–associated epithelial and mesenchymal neoplasms. Hum Pathol. 2008;39:473–83.

    Article  CAS  Google Scholar 

  35. Horiguchi H, Matsui-Horiguchi M, Sakata H, Ichinose M, Yamamoto T, Fujiwara M, et al. Inflammatory pseudotumor-like follicular dendritic cell tumor of the spleen. Pathol Int. 2004;54:124–31.

    Article  Google Scholar 

  36. Bosman FT, Carneiro F, Hruban RH, Theise ND. WHO classification of tumours of the digestive system. 4th ed. Lyons: IARC Press; 2010.

    Google Scholar 

  37. Arber DA, Kamel OW, van de Rijn M, Eric D, Jeffery M, Elaine SJ, et al. Frequent presence of the Epstein-Barr virus in inflammatory pseudotumor. Hum Pathol. 1995;26:1093–8.

    Article  CAS  Google Scholar 

  38. Solomon GJ, Kinkhabwala MM, Akhtar M. Inflammatory myofibroblastic tumor of the liver. Arch Pathol Lab Med. 2006;130:1548–51.

    Article  Google Scholar 

  39. Nishikawa J, Iizasa H, Yoshiyama H, Nakamura M, Saito M, Sasaki S, et al. The role of epigenetic regulation in Epstein-Barr virus-associated gastric cancer. Int J Mol Sci. 2017;18(1606):1–14.

    Google Scholar 

  40. Kanda T, Furuse Y, Oshitani H, Kiyono T. Highly efficient CRISPR/Cas9-mediated cloning and functional characterization of gastric cancer-derived Epstein-Barr virus strains. J Virol. 2016;90:4383–93.

    Article  CAS  Google Scholar 

  41. Tsai MH, Lin X, Shumilov A, Katharina B, Regina F, Remy P, et al. The biological properties of different Epstein-Barr virus strains explain their association with various types of cancers. Oncotarget. 2017;8:10238–54.

    Article  Google Scholar 

  42. Correia S, Bridge R, Wegner F, Venturini C, Palser A, Middeldorp J, et al. Sequence Variation of Epstein-Barr Virus: Viral Types, Geography, Codon Usage, and Diseases. J Virol. 2018;92(22):1–15.

    Article  Google Scholar 

  43. Mahjoub F, Izadyar M. Lymphoid follicle formation in portal areas of liver with no evidence of liver disease. J Pediatr Hematol Oncol. 2007;29(5):350–1.

    Article  Google Scholar 

  44. Nishikawa H. Clinical and histological studies on formation of lymphoid follicles in various liver diseases. KANZO. 1987;28(11):1428–38.

    Article  Google Scholar 

  45. Ise W, Fujii K, Shiroguchi K, Ito A, Kometani K, Takeda K, et al. T follicular helper cell-germinal center B cell interaction strength regulates entry into plasma cell or recycling germinal center cell fate. Immunity. 2018;48:702–15.

    Article  CAS  Google Scholar 

  46. Wu Y, Tian L, Xu Y, Zhang M, Xiang S, Zhao J, et al. CXCR7 silencing inhibits the migration and invasion of human tumor endothelial cells derived from hepatocellular carcinoma by suppressing STAT3. Mol Med Rep. 2018;18:1644–50.

    CAS  Google Scholar 

  47. Chen Y, Teng F, Wang G, Nie Z. Overexpression of CXCR7 induces angiogenic capacity of human hepatocellular carcinoma cells via the AKT signaling pathway. Oncol Rep. 2016;36:2275–81.

    Article  CAS  Google Scholar 

  48. Ding BS, Cao Z, Lis R, Nolan DJ, Guo P, Simons M, et al. Divergent angiocrine signals from vascular niche balance liver regeneration and fibrosis. Nature. 2014;505:97–103.

    Article  Google Scholar 

Download references

Acknowledgements

We are grateful to the Fourth Laboratory of the Department of Pathology in Keio University School of Medicine for assistance with tissue processing and staining. We would like to thank Kazumasa Fukuda, a staff member of the Department of Surgery at Keio University School of Medicine, for his help in preparing this manuscript. We also appreciate the efforts of Kenichi Imadome, who belongs to the National Center for Child Health and Development.

Funding

There were no funding resources.

Author information

Authors and Affiliations

  1. Department of Surgery, Keio University School of Medicine, Shinanomachi 35, Shinjuku-Ku, Tokyo, 160-8582, Japan

    K. Abe, M. Kitago, S. Matsuda, M. Shinoda, H. Yagi, Y. Abe, G. Oshima, S. Hori, Y. Endo, T. Yokose & Y. Kitagawa

  2. Department of Pathology, Keio University School of Medicine, Tokyo, Japan

    E. Miura, N. Kubota, A. Ueno, Y. Masugi, H. Ojima & M. Sakamoto

Authors
  1. K. Abe
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. M. Kitago
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. S. Matsuda
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. M. Shinoda
    View author publications

    You can also search for this author in PubMed Google Scholar

  5. H. Yagi
    View author publications

    You can also search for this author in PubMed Google Scholar

  6. Y. Abe
    View author publications

    You can also search for this author in PubMed Google Scholar

  7. G. Oshima
    View author publications

    You can also search for this author in PubMed Google Scholar

  8. S. Hori
    View author publications

    You can also search for this author in PubMed Google Scholar

  9. Y. Endo
    View author publications

    You can also search for this author in PubMed Google Scholar

  10. T. Yokose
    View author publications

    You can also search for this author in PubMed Google Scholar

  11. E. Miura
    View author publications

    You can also search for this author in PubMed Google Scholar

  12. N. Kubota
    View author publications

    You can also search for this author in PubMed Google Scholar

  13. A. Ueno
    View author publications

    You can also search for this author in PubMed Google Scholar

  14. Y. Masugi
    View author publications

    You can also search for this author in PubMed Google Scholar

  15. H. Ojima
    View author publications

    You can also search for this author in PubMed Google Scholar

  16. M. Sakamoto
    View author publications

    You can also search for this author in PubMed Google Scholar

  17. Y. Kitagawa
    View author publications

    You can also search for this author in PubMed Google Scholar

Contributions

Conceptualization, KA and MK; methodology, SM and AU; software, YE and TY; validation, HY, YA, GO, and SH; formal analysis, KA and SM; investigation, YE and EM; resources, KA and YE; data curation, YE and NK; writing—original draft preparation, KA; writing—review and editing, MK; visualization, YE; supervision, YM and HO; project administration, MS and YK; funding acquisition, KA. All authors have read and agreed to the published version of the manuscript. All authors read and approved the final manuscript.

Corresponding author

Correspondence to M. Kitago.

Ethics declarations

Ethics and approval and consent to participate

The study was approved by the Human Experimentation Committee of Keio University Hospital (No. 20120443, No. 20170086) and was conducted in accordance with the 1975 Declaration of Helsinki.

Consent for publication

We agree with publication of this manuscript.

Competing interests

The other authors declare that they have no conflicts of interest.

Additional information

Publisher's Note

Springer Nature remains neutral with regard to jurisdictional claims in published maps and institutional affiliations.

Supplementary Information

Additional file 1.

Supplementary Figures and Tables.

Rights and permissions

Open Access This article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons licence, and indicate if changes were made. The images or other third party material in this article are included in the article's Creative Commons licence, unless indicated otherwise in a credit line to the material. If material is not included in the article's Creative Commons licence and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this licence, visit http://creativecommons.org/licenses/by/4.0/.

Reprints and permissions

About this article

Check for updates. Verify currency and authenticity via CrossMark

Cite this article

Abe, K., Kitago, M., Matsuda, S. et al. Epstein–Barr virus-associated inflammatory pseudotumor variant of follicular dendritic cell sarcoma of the liver: a case report and review of the literature. surg case rep 8, 220 (2022). https://doi.org/10.1186/s40792-022-01572-w

Download citation

  • Received:

  • Accepted:

  • Published:

  • DOI: https://doi.org/10.1186/s40792-022-01572-w

Keywords