Department of Pathology, Helmholtz Sina-German Research Laboratory for Cancer, Tangdu Hospital, Air Force Medical University, Xi'an, People's Republic of China.
Department of Thoracic Surgery, Tangdu Hospital, Air Force Medical University, Xi'an, People's Republic of China.
Ann Surg Oncol. 2023 Mar;30(3):1646-1655. doi: 10.1245/s10434-022-12936-9. Epub 2022 Dec 12.
Our previous studies have demonstrated that human parvovirus B19 (B19V) is involved in the pathogenesis of thymic hyperplasia-associated myasthenia gravis (MG). However, more cases need to be assessed to further elucidate the relationship between this virus and thymoma-associated MG.
The clinicopathological characteristics, presence of B19V DNA, and B19V VP2 capsid protein expression of 708 cases of thymomas were investigated using nested polymerase chain reaction (PCR), TaqMan quantitative (q) PCR, immunohistochemistry, fluorescent multiplex immunohistochemistry, and electron microscopy.
Patients with MG or ectopic germinal centers (GCs) were significantly younger than those without MG (P < 0.0001) or GCs (P = 0.0001). Moreover, significantly more GCs were detected in thymomas associated with MG than in those without MG (P < 0.0001). The results of nested PCR and TaqMan qPCR were consistent, and B19V DNA positivity was only associated with presence of GCs (P = 0.011). Immunohistochemically, positive staining was primarily detected in neoplastic thymic epithelial cells (TECs) and ectopic GCs. The positive rate of B19V VP2 was significantly higher in thymoma with MG or GCs than in thymoma without MG (P = 0.004) or GCs (P = 0.006). Electron microscopy showed B19V particles in the nuclei of neoplastic TECs and B cells from GCs.
We conclude that the pathogenesis of MG is closely associated with the presence of GCs, and B19V infection is plausibly an essential contributor to formation of ectopic GCs in thymoma. To the best of the authors' knowledge, this is the first study to elucidate the role of B19V in thymoma-associated MG and provide new ideas for exploring the etiopathogenic mechanism of MG.
我们之前的研究表明，人细小病毒 B19（B19V）参与了胸腺增生相关重症肌无力（MG）的发病机制。然而，需要更多的病例来进一步阐明这种病毒与胸腺瘤相关 MG 之间的关系。
采用巢式聚合酶链反应（PCR）、TaqMan 定量（q）PCR、免疫组织化学、荧光多重免疫组织化学和电子显微镜检测 708 例胸腺瘤的临床病理特征、B19V DNA 存在情况和 B19V VP2 衣壳蛋白表达情况。
MG 或异位生发中心（GC）患者明显比无 MG（P<0.0001）或 GC（P=0.0001）患者年轻。此外，MG 相关胸腺瘤中 GC 的数量明显多于无 MG 患者（P<0.0001）。巢式 PCR 和 TaqMan qPCR 的结果一致，B19V DNA 阳性仅与 GC 存在相关（P=0.011）。免疫组化染色主要在肿瘤性胸腺样上皮细胞（TEC）和异位 GC 中检测到阳性。MG 或 GC 患者的胸腺瘤中 B19V VP2 阳性率明显高于无 MG（P=0.004）或 GC（P=0.006）患者。电子显微镜显示 B19V 病毒颗粒存在于肿瘤性 TEC 和 GC 中的 B 细胞的细胞核内。
我们得出结论，MG 的发病机制与 GC 的存在密切相关，B19V 感染可能是胸腺瘤中形成异位 GC 的重要因素。据作者所知，这是首次阐明 B19V 在胸腺瘤相关 MG 中的作用，并为探索 MG 的病因发病机制提供新的思路。
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