New Clinicopathologic Scenarios of EBV+ Inflammatory Follicular Dendritic Cell Sarcoma

Abstract

EBV+ inflammatory follicular dendritic cell (FDC) sarcoma is an indolent malignant neoplasm of spindled FDCs with a rich lymphoplasmacytic infiltrate and a consistent association with Epstein-Barr virus (EBV). It occurs exclusively in the liver and spleen, with the exception of a few colonic examples. In this study, we report 9 extrahepatosplenic cases, including 4 occurring in previously undescribed sites, but all apparently anatomically related to the aerodigestive tract. The cases included 5 gastrointestinal tumors all presenting as colonic pedunculated polyps, 2 presenting as mesocolon mass, and 2 involving the palatine or nasopharyngeal tonsils. One patient with a colonic tumor was complicated by paraneoplastic pemphigus. The patients had a median age of 58 years, with female predominance (female:male=7:2). A favorable outcome was observed in 7 patients. Histologically, EBV+ inflammatory FDC sarcomas arising from these anatomic sites were similar to their hepatosplenic counterparts. Spindled to oval neoplastic cells with ill-defined cell borders were dispersed or formed loose whorled fascicles in a dense lymphoplasmacytic background. They had vesicular nuclei with distinct nucleoli and typically exhibited a range of nuclear atypia in the same case. The neoplastic cells showed variable expression of FDC markers and were labeled for Epstein-Barr virus–encoded RNA on in situ hybridization. These 9 cases thus broaden the clinicopathologic scenarios of EBV+ inflammatory FDC sarcoma. Recognition of the potential existence of this tumor type in extrahepatosplenic sites permits a correct diagnosis to be made.

Epstein–Barr Virus—Associated Malignancies and Immune Escape: The Role of the Tumor Microenvironment and Tumor Cell Evasion Strategies

“…Only a small number of infected individuals develop chronic EBV-associated pathologies, which are often related to immune deficiencies, genetic pre-disposition and environmental factors [16]. Chronic EBV infection of different tissues of mainly epithelial and lymphocytic origin has been associated with malignant diseases such as carcinomas, lymphomas/lymphoproliferative disorders and soft-tissue tumors [17][18][19][20][21]. Geographically, EBV-associated neoplasia is present worldwide but is more frequent in Asia and Africa compared to the Western world [17,[22][23][24][25] with a higher incidence in males than in females [2,26].…”

Hepatic Follicular Dendritic Cell Sarcoma with Epithelioid Morphology: Histopathologist's Perspective

“…There are two types of FDC sarcoma, namelya) conventional type and b) inflammatory pseudotumor (IPT)-like follicular/fibroblastic dendritic cell sarcoma. 3,4 These two entities have a few clinical, pathogenetic, histomorphological, and immunohistochemical differences rendering their distinction from each other. The IPT-like FDC sarcoma predominantly occurs in females, involves intra-abdominal viscera, especially liver and spleen, gives rise to constitutional symptoms, shows an abundance of inflammatory cells in histomorphology, and is almost always associated with EBV while the conventional type does not have any gender…”

“…Besides, the conventional type is rarely associated with EBV. [3][4][5][6] EBV is implicated in approximately 12% of the FDC sarcoma with a stronger association with IPT-like FDC sarcoma. 2,7 Moreover, about 10-20% of the FDC sarcoma is associated with hyaline vascular Castleman disease.…”

“…This includes the immunopositivity for the markers of FDC (CD21, CD23, HLA-DR, and D2-40) and immunonegativity for other histiocyte-lineage cells (CD163, CD1a, and S100). 3,4,29 Ultrastructural features can also be useful in difficult cases. The FDC sarcoma shows microtubuloreticular structures while LCH shows Birbeck granules.…”

“…Immunopositivity for R4/23, Ki-M4, Ki-FDC1p, and CNA.42 are also documented. 3,4,16,29 This has to be coupled with immunonegativity for other histiocytic and mesenchymal tumor markers as described. EBV-LMP and EBV-encoded RNA-in situ hybridization often aid in the classification of the tumor.…”