PDF(Pubmed)
Abstract：
Primary cranial neurolymphomatosis (PCNL) is a rare subtype of primary CNS lymphoma (PCNSL) in which infiltrative lymphomatous involvement is confined to cranial nerves. Here, we report a case of PCNL with successful genomic profiling. A 57-year-old male had a lengthy prediagnostic phase spanning approximately 30 months, characterized by multiple episodes of cranial neuropathies managed by steroids. At the time of diagnosis, the patient had right-sided cranial neuropathies involving cranial nerves (CN) V, VI, and VII. Pathological findings of the right cavernous lesion biopsy were consistent with large B-cell lymphoma-infiltrating nerve fibers. The clinical course was aggressive and refractory, characterized by relentless progression with the development of cervical spinal neurolymphomatosis, cerebrospinal fluid involvement, and ependymal and intraparenchymal cerebral involvement, despite multiple lines of therapy, including chemoimmunotherapy, Bruton\'s tyrosine kinase inhibitor, radiation, autologous stem cell transplant, chimeric antigen receptor T-cell therapy (CAR-T), and whole-brain radiation. The patient survived for 22 months from the time of the initial diagnosis and 52 months after the first episode of cranial neuropathy. Next-generation sequencing identified mutations (MYD88, CD79b, and PIM1) that are frequently observed in PCNSL. The unusual findings included a total of 22 mutations involving PIM1, indicating a highly active aberrant somatic hypermutation and two missense CXCR4 mutations. CXCR4 mutations have never been described in PCNSL and may have implications for disease biology and therapeutic interventions. We provide a literature review to further elucidate PCNL.
摘要：
原发性颅神经淋巴瘤病（PCNL）是原发性CNS淋巴瘤（PCNSL）的一种罕见亚型，其中浸润性淋巴瘤受累仅限于颅神经。这里,我们报告了一例成功进行基因组分析的PCNL病例.一名57岁的男性经历了大约30个月的漫长的诊断前阶段，以由类固醇管理的多次颅神经病发作为特征。在诊断的时候,患者患有右侧颅神经病变，涉及颅神经（CN）V，VI,和七。右侧海绵状病变活检病理结果与大B细胞淋巴瘤浸润神经纤维一致。临床过程是积极的和难治性的，其特征是随着颈脊髓神经淋巴瘤病的发展而不断发展，脑脊液受累，室管膜和脑实质内受累，尽管有多种治疗方法，包括化学免疫疗法，布鲁顿酪氨酸激酶抑制剂，辐射,自体干细胞移植，嵌合抗原受体T细胞疗法（CAR-T），和全脑辐射。患者从最初诊断时和第一次颅神经病变发作后52个月存活了22个月。下一代测序确定的突变(MYD88，CD79b，和PIM1）在PCNSL中经常观察到。不寻常的发现包括涉及PIM1的总共22个突变，表明高度活跃的异常体细胞超突变和两个错义CXCR4突变。CXCR4突变从未在PCNSL中描述过，可能对疾病生物学和治疗干预有影响。我们提供了文献综述以进一步阐明PCNL。
