Splenic Inflammatory Pseudotumor-Like Follicular Dendritic Cell Tumor

Inflammatory pseudotumors constitute a heterogenous group of reactive lesions characterized by a mixture of inflammatory cells and a minor component of spindle cells [1]. This benign lesion needs to be distinguished from an inflammatory pseudotumor-like follicular dendritic cell (IPT-like FDC) tumor, a distinctive low-grade malignant neoplasm with consistent Epstein-Barr virus (EBV) association that has a similar morphology [2]. The IPT-like variant of FDC tumor is usually found in the spleen or liver and appears to be much more indolent compared to conventional FDC sarcoma [2]. Splenic IPT-like FDC tumors are extremely rare lesions, and only a few cases have been previously reported. Some of the cases referred to as IPT in the literature should be reclassified as IPT-like FDC tumors, especially when spindle cells are positive for EBV and there are no data for the expression of FDC markers within the lesion [3]. We present a case of a splenic IPT-like FDC tumor that was incidentally found in a 61-year-old man and increased gradually in size during a period of 3 months. Despite abdominal computed tomography (CT) and magnetic resonance imaging (MRI) findings, the definitive diagnosis was established only after immunohistochemical study of the resected spleen.

A 61-year-old male was admitted to the Emergency Surgical Department of our hospital due to a car accident. He presented with mild abdominal pain without having any external signs of injury. Basic laboratory tests of peripheral blood on admission were within normal range, and physical examination was unremarkable.

Abdominal ultrasonography examination incidentally revealed a well-circumscribed splenic mass 4 cm in diameter. Abdominal CT confirmed the presence of a well-circumscribed isodense lesion 4.2 × 4 cm in size in the splenic hilum with subtle inhomogenous enhancement in the early-phase images (fig. 1). MRI of the abdomen with contrast showed inhomogenous enhancement on Gd-enhanced images (fig. 2) with areas of mildly increased signal intensity οn T2-weighted images (fig. 3), measuring 5 × 5 cm. The differential diagnosis according to our radiology department included hamartoma and lymphoma. Carcinoembrionic antigen, cancer antigen 19-9 and α-fetoprotein were within normal range. A follow-up MRI scan of the abdomen 3 months later confirmed the above-mentioned findings regarding the same signal characteristics on T1- and T2-weighted images, but the tumor had increased in size and measured 7.5 × 6 × 6 cm. Two months later, the patient was referred to our surgical department for operative intervention and definite diagnosis. Preoperatively, he received vaccination against hemophilus, pneumococcus and meningococcus, and an uncomplicated open splenectomy was performed.

On gross examination, the spleen measured 13 × 11 × 7 cm and weighed 422 g. The cut surfaces of the tumor revealed a well-circumscribed solid tumor 10 × 8 × 7 cm, milky white with a central necrotic area measuring 5 cm. There were no lymph nodes in the splenic hilum. Under microscopic examination, the lesion was an admixture of lymphocytes, plasma cells and a smaller percentage of spindle cells (fig. 4). Mitotic figures were not observed in the spindle cells. All of the spindle cells were stained with CD35 and a smaller percentage with CD21 and CD23. In situ hybridization analysis for EBV-encoded small RNA revealed that most of the spindle cells in the lesion were positive for EBV. T-lymphocytes predominated within the lesion compared to B-lymphocytes. The plasma cell population was found to be polyclonal. IPT-like FDC sarcoma was diagnosed based on immunohistochemical study.

The patient had an uneventful postoperative course and was discharged 3 days later. The patient remains disease-free with no evidence of recurrence on the last follow-up 1 year postoperatively.

FDCs are part of the accessory immune system and are found in the primary and secondary lymphoid follicles serving as antigen-presenting cells for B cells that stimulate B cell proliferation and differentiation [4]. FDC sarcoma is a neoplasmatic proliferation of spindled to ovoid cells showing morphologic and immumophenotypic features of FDCs [5]. It is usually observed as lymphadenopathy, but it can also be present in a variety of extranodal sites and intra-abdominal organs, including the spleen [2]. FDC sarcomas are rare neoplasms with less than 200 cases previously reported in the literature [3] and constitute a heterogenous group of tumors with subtypes showing different histologic appearances and behavior.

The IPT-like variant of FDC sarcoma was first classified as a distinct variant of FDC sarcoma by Cheuk et al. [2]. It differs from conventional FDC sarcoma in the following basic aspects: it is characterized by consistent association with EBV, selective localization in intra-abdominal organs and female predominance. Most importantly, it exhibits less aggressive behavior compared to conventional FDC sarcoma [2]. The IPT-like variant of FDC tumors is composed of a polymorphic population of inflammatory cells including B-lymphocytes, T-lymphocytes, plasma cells and spindle cells in addition to the expression of FDC markers and EBV expression.

Clinicopathologic characteristics and radiologic findings of the previously published cases of IPT-like FDC tumors are summarized in table 1. There is a slight female predominance (female/male: 8/7), the median age of patients with IPT-like FDC tumors is 62 years, and the mean tumor diameter 7.2 cm. The maximum tumor diameter ranged from 3.2 to 22 cm [2,3]. The most significant fact is that most of the patients are asymptomatic and without evidence of recurrence during a follow-up period that reaches 4 years or 6.5 years in some studies [3,12].

The pathogenesis of IPT-like FDC tumors is not clear. Lewis et al. [6] proposed that these tumors may arise from a common mesenchymal cell that is capable of differentiating along different pathways. Under the stimuli of EBV, some of them would differentiate to a myofibroblastic phenotype with expression of vimentin and SMA, while others would acquire FDC characteristics with expression of FDC markers, such as CD21, CD23 or CD35. Similarly, Shia et al. [4] proposed that the mesenchymal cells in IPT-like conditions would undergo transformation in FDC tumors under certain oncologic stimuli, such as EBV infection, and eventually become neoplastic.

CT and MRI findings of IPT-like FDC tumors seem to be similar to the conventional IPT lesions due to their similar morphology and due to the presence of inflammatory cells and fibrotic stroma in both cases [7]. On CT scans, they are usually found as hypodense masses with occasional calcifications and heterogenous slow enhancement [8]. MRI depicts a low to isointense mass on T1-weighted images and highly intense areas with surrounding low intensity on T2-weighted images [8]. Imaging findings of IPT-like FDC tumors of the spleen are described in only a few studies due to the rarity of the disease [7]. Of the 13 previously reported studies of IPT-like FDC tumors of the spleen, 5 describe imaging findings on CT. All of them are characterized by low-density lesions on plain or enhanced CT. MRI findings are available in only one case other than ours, and according to this, the lesion had areas of low signal intensity on T2-weighted images and was isointense on T1-weighted images [7]. Nevertheless, the degree and distribution of inflammatory cells and proliferating capillaries in IPT and IPT-like FDC lesions influence the staining patterns observed in CT/MRI examination, and there is not a single imaging modality that can distinguish IPT from other splenic tumors [7,9]. Similar CT/MRI findings are observed in primary splenic lymphoma and hamartoma, metastasis and angiosarcoma [8]. Therefore, it is difficult to discriminate safely benign lesions as IPT and malignant tumors as lymphoma.

The IPT-like variants of FDC tumors found in the spleen are low-grade malignant neoplasms, and their prognosis seems to be excellent. From the previously published data for localized disease, total splenectomy is the mainstay of treatment without need of adjuvant therapy [14]. Nevertheless, due to the rarity of the disease, the short follow-up and the incompleteness of the published data, it is difficult to assess the need and benefit of adjuvant treatment. This is the first study that demonstrates a significant increase in size during a short period preoperatively and provides both CT and MRI imaging findings.