接受帕博利珠单抗治疗的三阴性乳腺癌患者中暴发性副肿瘤性Ma2（PNMA2）和小脑锌指蛋白4（ZIC4）抗体阳性脑炎
Fulminant paraneoplastic Ma2 (PNMA2) and zinc finger protein of the cerebellum 4 (ZIC4) antibody-positive encephalitis in triple-negative breast cancer treated with pembrolizumab.
摘要(中文译文)
与三阴性乳腺癌（TNBC）相关的副肿瘤性神经系统综合征（PNS）极为罕见。我们报告一例中年TNBC女性患者暴发性脑炎的病例，该患者同时存在PNMA2（Ma2/Ta）、ZIC4和恢复蛋白（recoverin）抗体阳性。患者最初出现亚急性小脑综合征，表现为下跳性眼震、步态共济失调和复视。全面评估发现左侧腋窝淋巴结FDG高摄取，活检证实为高级别TNBC，PD-L1 CPS为77。她按照标准机构方案（紫杉醇、卡铂、表柔比星、环磷酰胺和帕博利珠单抗）接受了新辅助化疗-免疫治疗。第六周期后，她出现难治性局灶性癫痫发作，进展为癫痫持续状态，MRI表现符合皮质脑炎。尽管接受了包括糖皮质激素、静脉注射免疫球蛋白和利妥昔单抗在内的积极免疫抑制治疗，病情仍难治。最终尽管给予最大程度支持治疗，仍不幸死亡。本病例展示了一种罕见的副肿瘤性重叠综合征，即TNBC中PNMA2相关脑炎合并ZIC4相关小脑变性，突出了当免疫检查点抑制剂可能放大既存的肿瘤神经免疫时的诊断挑战，并强调了尽管积极免疫治疗，细胞内抗体介导的神经系统综合征预后极差。
Abstract
Paraneoplastic neurological syndromes (PNS) associated with triple-negative breast carcinoma (TNBC) are exceptionally rare. We report a case of fulminant encephalitis in a middle-aged woman with TNBC presenting with concurrent PNMA2 (Ma2/Ta), ZIC4 and recoverin antibody positivity. The patient initially developed a subacute cerebellar syndrome characterised by downbeat nystagmus, gait ataxia and diplopia. Comprehensive evaluation revealed FDG-avid left axillary lymphadenopathy and biopsy confirmed high-grade TNBC with PD-L1 CPS of 77. She received neoadjuvant chemo-immunotherapy as per standard institutional protocol (paclitaxel, carboplatin, epirubicin, cyclophosphamide and pembrolizumab). Following the sixth cycle, she developed refractory focal seizures progressing to status epilepticus with MRI findings consistent with cortical encephalitis. Despite aggressive immunosuppression including corticosteroids, intravenous immunoglobulin and rituximab, her condition proved refractory. She ultimately succumbed despite maximal supportive care. This case illustrates a rare paraneoplastic overlap syndrome combining PNMA2-associated encephalitis and ZIC4-associated cerebellar degeneration in TNBC, highlights diagnostic challenges when immune checkpoint inhibitors may amplify pre-existing onconeural immunity and underscores the dismal prognosis of intracellular antibody-mediated neurological syndromes despite aggressive immunotherapy.
如何引用
AMA
Prabhat Gautam Roy, Aniket B Jagtap, Ajay Gogia. Fulminant paraneoplastic Ma2 (PNMA2) and zinc finger protein of the cerebellum 4 (ZIC4) antibody-positive encephalitis in triple-negative breast cancer treated with pembrolizumab.. BMJ case reports. 2026; doi:10.1136/bcr-2025-269510.
APA
Prabhat Gautam Roy, Aniket B Jagtap, Ajay Gogia (2026). Fulminant paraneoplastic Ma2 (PNMA2) and zinc finger protein of the cerebellum 4 (ZIC4) antibody-positive encephalitis in triple-negative breast cancer treated with pembrolizumab.. BMJ case reports. https://doi.org/10.1136/bcr-2025-269510
GB/T 7714
Prabhat Gautam Roy, Aniket B Jagtap, Ajay Gogia. Fulminant paraneoplastic Ma2 (PNMA2) and zinc finger protein of the cerebellum 4 (ZIC4) antibody-positive encephalitis in triple-negative breast cancer treated with pembrolizumab.[J]. BMJ case reports, 2026 doi:10.1136/bcr-2025-269510.
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