Clinicopathological Spectrum of EBV-Related Primary Splenic Tumors Identified by Splenectomy: A Case Series.

Background: Epstein-Barr virus (EBV)-related primary splenic tumors are exceptionally rare and encompass a heterogeneous group of entities, including inflammatory pseudotumor (IPT), IPT-like follicular dendritic cell (FDC) tumors or sarcomas, and EBV-positive diffuse large B-cell lymphoma (DLBCL). Because clinical presentation and imaging findings are often nonspecific, establishing a definitive diagnosis remains challenging and frequently necessitates splenectomy for histopathologic confirmation. Methods: We retrospectively reviewed patients who underwent laparoscopic splenectomy for suspected primary splenic lesions at a single tertiary institution between June 2014 and August 2025. Among 67 patients, five consecutive patients were pathologically confirmed as EBV-related primary splenic tumors. Clinical characteristics, imaging features, histopathologic and immunophenotypic findings, EBV in situ hybridization results, treatment, and follow-up outcomes were analyzed. Results: This case series comprised four spindle cell-predominant EBV-related tumors (IPT or IPT-like FDC tumors/sarcomas) and one EBV-positive DLBCL. All patients presented with splenic masses that could not be definitively characterized by preoperative imaging alone and therefore required splenectomy. EBV in situ hybridization was positive in tumor cells in all cases. Patients with non-lymphomatous tumors achieved durable disease control following splenectomy alone, with disease-free survival of up to five years. In contrast, the patient with EBV-positive DLBCL required postoperative systemic immunochemotherapy. Conclusions: EBV-related primary splenic tumors represent a diagnostically challenging and clinically diverse disease spectrum. This case series highlights the pivotal role of splenectomy in establishing definitive diagnosis and guiding subsequent management, particularly for isolated splenic lesions with indeterminate imaging findings.