13例淋巴瘤合并周围神经病变临床分析

Clinical analysis of 13 cases with lymphoma-associated peripheral neuropathy

目的对淋巴瘤合并周围神经病变的临床特点、辅助检查结果进行分析,并探讨其发病机制。方法回顾分析13例淋巴瘤合并周围神经病变患者诊断、治疗经过,排除继发性带状疱疹病毒感染、相关治疗的不良反应及其他导致周围神经病变的病因。其中T细胞性非霍奇金淋巴瘤(NHL-T)3例,B细胞性非霍奇金淋巴瘤(NHL-B)9例,1例具体病理类型不详。对其周围神经受累的类型和部位、脑脊液细胞学和免疫组织化学、影像学、电生理学以及腓肠神经活体组织病理学检查结果等进行分析。结果13例中10例周围神经系统症状出现于淋巴瘤明确诊断之前,其中8例以周围神经系统症状首发;11例脑神经受累,8例腰骶神经根受累,6例同时合并听力减退及腰骶神经根受累。脑脊液检查主要呈现蛋白定量(13例)、白细胞计数(8例)以及脑脊液压力(5例)升高,葡萄糖水平降低(7例);细胞学检查可见异型淋巴细胞(9例);免疫组织化学染色及基因重排检测主要表现为B细胞标记抗原(CD19、CD20、CD79α)阳性(3例),CD20阳性细胞数目增加(1例),以及CD4阳性细胞数目增加、T细胞(抗原识别)受体阳性和抗体IgH阴性(1例)。肌电图检查显示,周围神经轴索病变或合并髓鞘损害(9例)。腓肠神经活体组织病理学检查呈轴索变性和(或)脱髓鞘病变且无淋巴瘤细胞浸润(3例)。头部及腰骶部MRI检查显示,双侧听神经及马尾神经根增粗、强化或脑膜强化。13例中9例系由淋巴瘤细胞直接浸润脑脊膜神经根所致,1例为淋巴瘤转移和局部肿大淋巴结压迫引起,其余3例无明确肿瘤细胞浸润证据,结合临床特点和实验室检查结果,考虑副肿瘤综合征可能。结论淋巴瘤可通过肿瘤细胞直接浸润或副肿瘤综合征导致周围神经病变;周围神经系统症状在淋巴瘤明确诊断前即可出现,临床应对此提高认识。

Objective To analyse clinical features, atlxiliary examination and mechanisms of lymphoma-associated peripheral neuropathy. Methods We retrospectively reviewed the medical records of 13 cases with lymphoma-associated peripheral neuropathy, including 3 cases of T cell non-Hodgkin lymphoma （NHL-T）, 9 cases of B cell non-Hodgkin lymphoma （NHL-B）, and one case of unknown. Secondary herpes zoster virus infection, drug-induced or other possible causes of peripheral neuropathy were excluded. The type and location of peripheral neuropathy, cytological study and immunohistochemistry of cerebrospinal fluid （CSF）, imaging, electrophysiology and sural nerve biopsy were evaluated. Results Peripheral neuropathy preceded the diagnosis of lymphoma in 10 cases. Peripheral neuropathy emerged as the first symptoms in 8 cases. Among all the cases, cranial nerves were involved in 11 cases. Lumbosacral nerve roots were involved in 8 cases. Auditory nerve and lumbosacral nerve roots were involved simultaneously in 6 cases. All of the cases performed lumbar puncture. CSF pressure was increased in 5 cases. Protein elevation was increased in all of the cases. The glucose level was decreased in 7 cases. White blood cell count was increased in 8 cases. CSF cytology studies showed atypical lymphocyte in 9 cases. Of the 5 cases performed immunohistochemical studies of the CSF lymphocytes, 3 showed monoclonal B-lymphocytes （CD19, CD20, CD79α）, one showed the increased of CD20 positive lymphocyte. One showed CD4 positive lymphocytes were absolutely dominant with positive TCR, negative IgH, which was consistent with the pathologic results （NHL-T）. Nine cases performed electromyography showed axonal damage and/or demyelination. Three cases performed sural nerve biopsy revealed axonal degeneration and/or demyelination without infiltration of lymphocyte. Of the 5 cases performed MRI of the brain, one showed thickening of bilateral auditory nerves with enhancement, one showed leptomeningeal enhancement. Of the 5 cases performed MRI of the lumbosacral region, 4 showed the enhancement of the nerve roots of cauda equina. Peripheral neuropathy of 9 cases were associated with lymphoma infiltrated nerve root of meninges. Lymphoma metastasis and compression of lymphadenectasis were diagnosed in one case. In 3 cases, there were no evidence of lymphomatous infiltration. We considered them paraneoplastic syndrome according to the clinical features and laboratory examination, Conclusion Peripheral nervous system abnormaiities can occur in lymphoma even before the diagnosis of lymphoma. The mechanisms include infiltration and paraneoplastic syndrome.