To comprehensively describe the pathological features of neurons in patients with ovarian teratomas and paraneoplastic anti-NMDAR encephalitis (anti-NMDARE), emphasizing on NMDA-receptor expression and infiltrating lymphocytes. A retrospective study was performed in a large series of 159 patients from the West China Hospital. We retrospectively identified 12 patients with paraneoplastic anti-NMDARE (11 case with ovarian teratomas and 1 case with mixed germ cell tumor), which were compared to 35 patients with teratomas and no encephalitis and to 147 patients with anti-NMDARE and no evidence for tumors. Patient history and outcome were reviewed from the clinical charts and compared between all three groups. Histopathological examination, including double-immunofluorescence of NMDAR subunits and IgG was performed in all teratoma tissues. Magnetic Luminex Assay Human Premixed Multi-Analyte Kit was performed to investigate cytokines profile of CSF. Patients with paraneoplastic anti-NMDARE had a more severe clinical presentation, i.e. they required more mechanical ventilation and intensive care (p < 0.001). Though immunotherapy was initiated earlier in this group, repeated intravenous immunoglobulin administration (IVIG) was more common (p = 0.002) and with higher cerebrospinal fluid (CSF) antibody titres (p = 0.004). Following tumor resection, the outcome did not differ between groups. A peculiar population of floating-frog like dysplastic neurons were observed only in teratomas of patients with paraneoplastic anti-NMDARE, co-expressing NR1, NR2A, NR2B subunits and IgG. Also, CD20 positive B-cells were more common in anti-NMDARE teratomas. In CSF of paraneoplastic anti-NMDARE patients, TNF-α, IL-10 and GM-CSF concentrations were higher than in negative symptom control and VEGF-A and IL-1a were lower than in anti-NMDARE patients (0.25 < p < 0.05). Patients with teratomas and paraneoplastic anti-NMDARE revealed a cellular population of dysplastic neurons co-expressing NMDAR subunits, which were the potential source of autoantigens triggering anti-NMDARE. Some inflammatory cytokines may be involved in pathogenesis of paraneoplastic anti-NMDARE.

中文翻译：

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副肿瘤性NMDA-受体-脑炎患者畸胎瘤的增生性神经元中NMDA-受体亚基NR1，NR2A和NR2B的共表达：回顾性159例临床病理研究。

要全面描述卵巢畸胎瘤和副肿瘤性抗NMDAR脑炎（anti-NMDARE）患者神经元的病理特征，重点在于NMDA受体表达和浸润淋巴细胞。对华西医院的159例患者进行了回顾性研究。我们回顾性鉴定了12例副肿瘤性抗NMDARE患者（11例卵巢畸胎瘤和1例混合生殖细胞肿瘤患者），将其与35例畸胎瘤，无脑炎患者和147例抗NMDARE且无肿瘤证据的患者进行了比较。 。从临床图表中回顾患者的病史和结局，并在所有三组之间进行比较。在所有畸胎瘤组织中进行了组织病理学检查，包括NMDAR亚基和IgG的双重免疫荧光检查。进行了磁性Luminex分析人类预混合多分析试剂盒以研究CSF的细胞因子谱。副肿瘤性抗NMDARE患者的临床表现更为严重，即他们需要更多的机械通气和重症监护（p <0.001）。尽管该组中的免疫治疗开始较早，但重复静脉内免疫球蛋白（IVIG）给药更为常见（p = 0.002），并且脑脊液（CSF）抗体滴度较高（p = 0.004）。肿瘤切除后，各组的结果无差异。仅在副肿瘤性抗NMDARE，共表达NR1，NR2A，NR2B亚基和IgG的患者的畸胎瘤中观察到特殊的浮蛙样异常增生神经元。同样，CD20阳性B细胞在抗NMDARE畸胎瘤中更为常见。在副肿瘤性抗NMDARE患者的CSF中，TNF-α，IL-10和GM-CSF浓度高于阴性症状对照，而VEGF-A和IL-1a低于抗NMDARE患者（0.25 <p <0.05 ）。畸胎瘤和副肿瘤性抗NMDARE的患者揭示了细胞共表达NMDAR亚基的增生异常神经元，这是触发抗NMDARE的自身抗原的潜在来源。某些炎性细胞因子可能与副肿瘤性抗NMDARE的发病机制有关。它们是触发抗NMDARE的自身抗原的潜在来源。某些炎性细胞因子可能与副肿瘤性抗NMDARE的发病机制有关。它们是触发抗NMDARE的自身抗原的潜在来源。某些炎性细胞因子可能与副肿瘤性抗NMDARE的发病机制有关。