与 Merkel 细胞癌相关的副肿瘤神经系统综合征。
Paraneoplastic Neurologic Syndromes Associated With Merkel Cell Carcinoma.
机构信息
From the French Reference Center on Paraneoplastic Neurological Syndromes and Autoimmune Encephalitis (N.L.C.-P., S.M.-C., M.V.-G., A.F., V.W., L.D.D., V.R., G.P., B.J., J.H.), Hospices Civils de Lyon, Hôpital Neurologique, Bron; MeLiS - UCBL-CNRS UMR 5284 - INSERM U1314 (N.L.C.-P., S.M.-C., M.V.-G., A.F., V.W., L.D.D., V.R., G.P., B.J., J.H.), Université Claude Bernard Lyon 1, France; Instituto de Investigación Biomédica de Málaga y Plataforma en Nanomedicina-IBIMA Plataforma BIONAND (N.L.C.-P.); Red Andaluza de Investigación Clínica y Traslacional en Neurología (NeuroRECA) (N.L.C.-P.), Málaga, Spain; Center for Sleep Sciences and Medicine (S.M.-C.), Stanford University, Palo Alto, CA; Department of Neuroscience (A.F.), Psychology, Pharmacology and Child Health. University of Florence, Italy; Clinical Neurology (A.V.), Santa Maria della Misericordia University Hospital, Azienda Sanitaria Universitaria Friuli Centrale (ASU FC); Department of Medicine (DMED) (A.V.), University of Udine, Udine, Italy; Sorbonne Université (C.B.), Inserm, CNRS, UMR S 1127, Institut du Cerveau, ICM, AP-HP, Hôpitaux Universitaires La Pitié Salpêtrière - Charles Foix, Service de Neurologie 2-Mazarin; OncoNeuroTox Group (C.B.), Center for Patients with Neurological Complications of Oncologic Treatments, GH Pitié-Salpetrière et Hôpital Percy, Paris; Immunology Department (D.G., F.N.), Hôpital Lyon Sud, Hospices Civils de Lyon, Pierre-Bénite; Service de Neurologie (O.F.), Centre Hospitalier de la Côte Basque, Bayonne; Department of Neurology (C.D.), University Hospital of Tours; and Service de Neurologie (A.B.), Centre Hospitalo-Universitaire Rennes, France.
出版信息
Neurol Neuroimmunol Neuroinflamm. 2024 Nov;11(6):e200260. doi: 10.1212/NXI.0000000000200260. Epub 2024 Oct 7.
BACKGROUND AND OBJECTIVES
To define the clinical and immunologic profile of patients with paraneoplastic neurologic syndromes (PNSs) associated with Merkel cell carcinoma (MCC).
METHODS
Retrospective analysis was conducted on patients with suspected MCC-related PNS assessed at the French Reference Center, and cases were identified by a systematic review of the literature (MEDLINE, Embase) following the Preferred Reporting Items for Systematic Reviews and Meta-Analyses guidelines.
RESULTS
A total of 17 patients were identified in our center and 30 in the systematic review, resulting in an overall cohort of 47 patients. The median age was 65 years (range 41-90), and 30 of 46 (65%) were men. Lambert-Eaton myasthenic syndrome (LEMS) (14/47, 29%), rapidly progressive cerebellar syndrome (11/47, 23%), and encephalomyelitis (EM) (8/47, 17%) were the most common associated clinical phenotypes. The most frequently associated neural antibodies (Abs) were voltage-gated calcium channel (VGCC)-Abs (14/45, 31%), followed by Hu-Abs (8/45, 17%) and neurofilament (NF)-Abs (8/45, 17%). Patients with NF-Abs only exhibited CNS disorders (8/8, 100%) and often had antibodies against >1 NF subunit (6/8, 75%). At onset, 26 of 43 patients (60%) had no identifiable primary skin tumor but had lymph node metastasis; these patients were more frequently men (21/26, 80%, vs 7/17, 41%; = 0.007), had more frequently VGCC-Abs (12/26, 46%, vs 2/17, 11%, = 0.02) predominantly among those with LEMS, and presented reduced mortality than patients with a known primary tumor (5/25, 20%, vs 8/15, 53%; = 0.02).
DISCUSSION
MCC-related PNSs present as a heterogeneous clinical spectrum including central and/or peripheral nervous system disorders such as LEMS, RCPS, and EM, mainly associated with VGCC-Abs, NF-Abs, and Hu-Abs. NF-Abs were only seen among patients with CNS disorders. At onset, the absence of a primary skin tumor but presence of lymph node metastasis is frequently observed, and this particular clinical presentation is linked to reduced mortality, highlighting distinctive clinical and immunologic features of MCC-related PNS.
背景与目的
定义与 Merkel 细胞癌（MCC）相关的副肿瘤性神经综合征（PNS）患者的临床和免疫特征。
方法
对在法国参考中心评估的疑似与 MCC 相关的 PNS 患者进行回顾性分析，并通过系统回顾文献（MEDLINE、Embase）按照系统评价和荟萃分析的首选报告项目进行病例识别。
结果
在我们的中心发现了 17 例患者，在系统综述中发现了 30 例患者，因此总体队列中有 47 例患者。中位年龄为 65 岁（范围 41-90），46 例中有 30 例（65%）为男性。Lambert-Eaton 肌无力综合征（LEMS）（14/47，29%）、快速进展性小脑综合征（11/47，23%）和脑脊髓炎（EM）（8/47，17%）是最常见的相关临床表型。最常见的相关神经抗体（Abs）是电压门控钙通道（VGCC）-Abs（14/45，31%），其次是 Hu-Abs（8/45，17%）和神经丝（NF）-Abs（8/45，17%）。仅具有 NF-Abs 的患者表现出中枢神经系统疾病（8/8，100%），并且经常具有针对 >1 个 NF 亚单位的抗体（6/8，75%）。在发病时，43 例患者中有 26 例（60%）无明显的原发性皮肤肿瘤，但有淋巴结转移；这些患者更多为男性（21/26，80%，vs 7/17，41%； = 0.007），更多地存在 VGCC-Abs（12/26，46%，vs 2/17，11%； = 0.02），主要存在于 LEMS 患者中，并且死亡率低于有已知原发性肿瘤的患者（5/25，20%，vs 8/15，53%； = 0.02）。
讨论
与 MCC 相关的 PNS 表现为包括中枢和/或周围神经系统疾病在内的异质性临床谱，如 LEMS、RCPS 和 EM，主要与 VGCC-Abs、NF-Abs 和 Hu-Abs 相关。NF-Abs 仅见于中枢神经系统疾病患者。在发病时，无原发性皮肤肿瘤但存在淋巴结转移是常见的，这种特殊的临床表现与降低的死亡率相关，突出了 MCC 相关 PNS 的独特临床和免疫特征。
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