Mansueto Gelsomina, Di Vito Anna, Belluomo Clara, Murino Patrizia, Natella Valentina, Camastra Caterina, Presta Ivan, Malara Natalia, de Rosa Gaetano, Donato Giuseppe, Mignogna Chiara
Advanced Biomedical Sciences, Pathology Section, University of Naples "Federico II", Italy.
Department of Clinical and Experimental Medicine, University "Magna Graecia" of Catanzaro, Italy.
Neuropathology. 2016 Oct;36(5):496-503. doi: 10.1111/neup.12300. Epub 2016 Apr 18.
Intravascular large B cell lymphoma (IVLBCL) is a rare extranodal non-Hodgkin lymphoma characterized by proliferation of malignant cells within the lumen of small vessels, with a predilection for the CNS and the skin. IVLBCL clinical course is highly aggressive, clinical signs and symptoms are not specific and may consist of neurological and cognitive impairment, fever of unknown origin and cutaneous lesions, lacking of a typical neuroimaging pattern. For all these reasons the diagnosis is commonly missed and the exitus is frequent, therefore post mortem evaluation is necessary to clarify the clinical history. We present a case of IVLBCL in a 62-year-old woman with unusual symptomatology, mimicking a vascular, multi-infarctual cerebropathy. Hachinski Ischemic Score was 7 suggesting a vascular dementia. Autopsy was unable to define the nature of the disease. Immunohistochemical analysis for cluster of differentiation 20 (CD20) revealed the ubiquitous presence of malignant lymphoid B-cells into the vessel of all organs analyzed, allowing the definitive diagnosis of IVLBCL. The atypical cells expressed high levels of anti-apoptotic proteins B-cell lymphoma 2 (Bcl-2) and Galectin-3, and showed cellular myelocytomatosis (c-Myc) staining in <50% of tumor nuclei. Conversely, cells were immunonegative for multiple myeloma-1 (MUM1), CD3, CD44, CD30, CD34 and CD133. Fluorescent in situ hybridization analysis for MYC rearrangements was negative. The high expression of Galectin-3 provides new insights in the understanding of molecular pathogenesis of IVLBCL; indeed, such a finding represents a prognostic factor for other types of lymphoma and should, in the same way, be taken into account in IVLBCL.
血管内大B细胞淋巴瘤（IVLBCL）是一种罕见的结外非霍奇金淋巴瘤，其特征为小血管腔内恶性细胞增殖，好发于中枢神经系统和皮肤。IVLBCL的临床病程极具侵袭性，临床体征和症状不具特异性，可能包括神经和认知功能障碍、不明原因发热及皮肤病变，缺乏典型的神经影像学表现。由于所有这些原因，诊断常常被漏诊，死亡很常见，因此需要进行尸检以明确临床病史。我们报告一例62岁女性的IVLBCL病例，其症状不寻常，类似血管性多梗死性脑病。哈金斯基缺血评分是7分，提示血管性痴呆。尸检无法明确疾病性质。对分化簇20（CD20）进行免疫组化分析显示，在所有分析器官的血管中均普遍存在恶性B淋巴细胞，从而确诊为IVLBCL。非典型细胞高表达抗凋亡蛋白B细胞淋巴瘤2（Bcl-2）和半乳凝素-3，且在<50%的肿瘤细胞核中显示细胞性髓细胞瘤（c-Myc）染色。相反，细胞对多发性骨髓瘤-1（MUM1）、CD3、CD44、CD30、CD34和CD133免疫阴性。MYC重排的荧光原位杂交分析为阴性。半乳凝素-3的高表达为理解IVLBCL的分子发病机制提供了新的见解；事实上，这一发现是其他类型淋巴瘤的一个预后因素，在IVLBCL中也应同样予以考虑。
