Epstein-Barr virus (EBV)-positive plasmacytoma is a rare plasma cell neoplasm. It remains unclear whether EBV-positive plasmacytoma represents a distinct entity or a variant of plasmacytoma. It shares morphologic features with plasmablastic lymphoma (PBL) and may cause diagnostic uncertainty. To better understand EBV-positive plasmacytoma and explore diagnostic criteria, this study describes 19 cases of EBV-positive plasmacytoma, compared with 27 cases of EBV-negative plasmacytoma and 48 cases of EBV-positive PBL. We reviewed the clinicopathologic findings and performed immunohistochemistry, in situ hybridization for EBV, fluorescence in situ hybridization for MYC, and next-generation sequencing. We found that 63.2% of patients with EBV-positive plasmacytoma were immunocompromised. Anaplastic features were observed in 7/19 cases. MYC rearrangement was found in 25.0% of them, and extra copies of MYC in 81.3%. EBV-positive and EBV-negative plasmacytomas possessed similar clinicopathologic features, except more frequent cytologic atypia, bone involvement and MYC aberrations in the former group. The survival rate of patients with EBV-positive plasmacytoma was comparable to that of patients with EBV-negative plasmacytoma. In comparison to PBL, EBV-positive plasmacytoma is less commonly associated with a “starry-sky” appearance, necrosis, absence of light chain expression, and a high Ki67 index (>75%). The most recurrently mutated genes/signaling pathways in EBV-positive plasmacytoma are epigenetic regulators, MAPK pathway, and DNA damage response, while the most frequently reported mutations in PBL are not observed. Collectively, EBV-positive plasmacytoma should be regarded as a biological variant of plasmacytoma. Thorough morphologic examination remains the cornerstone for distinguishing EBV-positive plasmacytoma and PBL, and molecular studies can be a valuable complementary tool.

EB 病毒 (EBV) 阳性浆细胞瘤是一种罕见的浆细胞肿瘤。目前尚不清楚 EBV 阳性浆细胞瘤是否代表浆细胞瘤的独特实体或变体。它与浆母细胞淋巴瘤(PBL) 具有相同的形态学特征，可能会导致诊断的不确定性。为了更好地了解EBV阳性浆细胞瘤并探索诊断标准，本研究描述了19例EBV阳性浆细胞瘤，与27例EBV阴性浆细胞瘤和48例EBV阳性PBL进行比较。我们回顾了临床病理学结果，并进行了免疫组织化学、EBV 原位杂交、 MYC荧光原位杂交和新一代测序。我们发现 63.2% 的 EBV 阳性浆细胞瘤患者免疫功能低下。7/19 例观察到间变性特征。其中 25.0% 发现MYC重排， 81.3% 发现MYC额外拷贝。EBV 阳性和 EBV 阴性浆细胞瘤具有相似的临床病理特征，除了前者更常见的细胞学异型性、骨受累和MYC畸变之外。EBV阳性浆细胞瘤患者的生存率与EBV阴性浆细胞瘤患者相当。与 PBL 相比，EBV 阳性浆细胞瘤与“星空”外观、坏死、轻链表达缺失和高 Ki67 指数 (>75%) 的相关性较少。EBV 阳性浆细胞瘤中最常发生突变的基因/信号通路是表观遗传调节因子、MAPK 通路和 DNA 损伤反应，而 PBL 中最常报告的突变未观察到。总的来说，EBV 阳性浆细胞瘤应被视为浆细胞瘤的生物学变异型。彻底的形态学检查仍然是区分 EBV 阳性浆细胞瘤和 PBL 的基石，分子研究可以成为有价值的补充工具。