Challenges in the Diagnosis of Epstein-Barr Virus-positive Inflammatory Follicular Dendritic Cell Sarcoma

Abstract

Epstein-Barr virus (EBV)-positive inflammatory follicular dendritic cell (FDC) sarcoma (EBV+ IFDCS) is a rare entity, and its histopathological characteristics have not been fully described. Here, we investigated the wide morphologic spectrum and immunophenotype of this tumor with the aim to help avoid misdiagnosis. Thirteen cases of EBV+ IFDCS were retrospectively analyzed, combined with a review of 70 cases reported in the literature. The median age of patients was 49 (range, 29 to 67 y). Six patients were male and 7 were female. Most cases (92.3%, 12/13) occurred in the liver or spleen, and only 1 case affected an extra-hepatosplenic site (lung, 7.7%, 1/13). Tumors were assessed for a variety of histologic features and assigned to the following morphologic groups: classic type (53.8%, 7/13), lymphoma-like subtype (38.5%, 5/13), and hemangioma-like subtype (7.7%, 1/13). The classic type had distinct EBV-positive neoplastic cells with a fascicular or storiform growth pattern, variable lymphoplasmacytic infiltrates, and blood vessels. The lymphoma-like subtype had extremely prominent lymphoplasmacytic infiltrates (resembling marginal zone lymphoma with plasmacytoid differentiation) with singly dispersed distinct EBV-positive neoplastic cells, highlighted by in situ hybridization for EBV-encoded small RNA. The hemangioma-like subtype had extremely prominent blood vessels with hyaline and/or fibrinoid degeneration, singly dispersed distinct EBV-positive neoplastic cells, and limited lymphoplasmacytic infiltrates. Immunohistochemically, the neoplastic cells showed variable staining for FDC markers (CD21, CD35, CD23, and SSTR2) and the fibroblastic marker SMA, with the staining ranging from very focal to extensive. The number of EBV-positive neoplastic cells ranged from 80 to 400/HPF. All cases showed variable expression of PD-ligand 1 (PD-L1) (CPS: 5-90). IgG4-positive cells ranged from rare up to 100/HPF. Interestingly, 2 cases satisfied the criteria proposed in a previous study, mimicking IgG4-related disease. EBV+ IFDCS is an entity with an extremely wide morphologic spectrum and immunophenotype. Awareness of the spectrum of morphologic presentations of this rare tumor, specifically the lymphoma-like subtype and hemangioma-like subtype, is important for accurate diagnosis.

EBV positive inflammatory follicular dendritic cell sarcoma of colon with clonal immunoglobulin receptor gene rearrangement: a case report and literature review

“…Goh et al [6]reports a case of colon EBV + in ammatory FDC sarcoma with obviously increased IgG4 + plasma cell in ltration, and without other pathological features of IgG4 related diseases, such as vasculitis obliterans and sclerotic stroma. Other studies have covered that several cases of EBV + in ammatory FDC sarcoma occurring in liver and spleen have a well IgG4 expression, satisfying the pathological criteria of IgG4 related disease, but lacking other evidence of IgG4 related diseases [12,13]. In our case, IgG and IgG4 staining were performed, with only a very small amount of IgG4-positive plasma cells were seen.…”

“…At present, there are few studies on molecular changes related to FDC sarcoma. It has been reported that clonal IGH (± IGK) gene rearrangements can occur in classical FDC sarcoma [12,13], suggesting that a subset of FDC sarcoma may inherited B-lymphocyte genotypes and derives from committed B-cell progenitors. As to EBV + in ammatory FDC sarcoma, molecular researches are even less.…”

“…As to EBV + in ammatory FDC sarcoma, molecular researches are even less. Li et al [12]describes a case of EBV + in ammatory FDC sarcoma in liver with clonal IG gene rearrangements, accompanied by clonal T cell receptor (TCR) gene rearrangements, while the underlying reason needs to be further explored. In the present study, we reported a case of EBV + in ammatory FDC sarcoma involving the descending colon and having a clonal IGH gene rearrangement.…”

Case report: EBV-positive epithelioid follicular dendritic cell sarcoma with CD30 expression: a highly challenging diagnosis

“…Compared with conventional type, it is more common in women and usually an isolated disease with a better prognosis. EBER positivity is an important clue for the diagnosis of the tumor ( 11 ). Our patient presented with multiple lymphadenopathy throughout the body; histology showed that the tumor cells were abundant, and there were obvious atypia, numerous mitoses, and necrosis.…”

Case Report: Identification of a novel STAT3 mutation in EBV-positive inflammatory follicular dendritic cell sarcoma

“…Tumor cells typically exhibit immunophenotypic characteristics of FDCs, such as the expression of CD21, CD23, CD35, D2-40, EGFR, and CXCL13. However, they may also exhibit myoid cell differentiation ( 5 ). A notable histological distinction from FDCS is the presence of a prominent reactive lymphoplasmacytic infiltrate, consisting of mixed B and T cells ( 1 , 6 , 7 ).…”