An updated histological classification system for multiple sclerosis lesions
An updated histological classification system for multiple sclerosis lesions
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DOI：
10.1007/s00401-016-1653-y
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发表时间：
2017-01-01
影响因子：
12.7
通讯作者：
Lassmann, Hans
中科院分区：
文献类型：
--
作者：
Kuhlmann, Tanja;Ludwin, Samuel;Lassmann, Hans
多发性硬化症是一种复杂的、异质性的、最可能是自身免疫性的中枢神经系统（CNS）脱髓鞘疾病。近年来，虽然不同的群体采用了许多CNS病变的组织学分类系统，但没有统一的分类。在本文中，我们提出了一种简单而统一的MS病变分类，结合了早期组织学系统的许多元素，旨在为神经病理学家和研究MS病变的研究人员提供指导，以便更好地比较用MS组织进行的不同研究，并有助于理解疾病的发病机制。根据巨噬细胞/小胶质细胞的存在/不存在和分布（炎症活动）以及正在进行的脱髓鞘的存在/不存在（脱髓鞘活动），我们建议区分活动性、混合性活动性/不活动性和非活动性病变，伴有或不伴有脱髓鞘。活动性病变以巨噬细胞/小胶质细胞遍布病灶区域为特征，而混合性活动性/非活动性病变以低细胞病变中心为特征，巨噬细胞/小胶质细胞局限于病灶边界。非活动性病变几乎完全缺乏巨噬细胞/小胶质细胞。活动性和混合性活动性/非活动性病变可进一步细分为髓磷脂破坏持续的病变（脱髓鞘病变）和髓磷脂破坏已经停止，但巨噬细胞仍然存在的病变（脱髓鞘后病变）。这种区别是基于巨噬细胞/小胶质细胞细胞质中髓磷脂降解产物的存在或不存在。对于MS病变的这种分类，用组织学染色（如luxol fast blue-PAS）或免疫组化使用针对髓鞘碱性蛋白（MBP）或蛋白脂质蛋白（PLP）的抗体来鉴定髓鞘，以及用抗cd68等检测巨噬细胞/小胶质细胞就足够了。活动性脱髓鞘病变可进一步细分为早期和晚期脱髓鞘病变。前者的定义是巨噬细胞中存在主要的和小分子的髓磷脂蛋白，如环核苷酸二磷酸酯酶（CNP）、髓磷脂少突胶质细胞糖蛋白（MOG）或髓磷脂相关蛋白（MAG），而后者的巨噬细胞仅存在主要的髓磷脂蛋白MBP或PLP。我们讨论了MS病变分类所需的组织学特征和染色技术，此外，还描述了皮层病理和弥漫性白质改变以及髓鞘再生的组织学特征。
Multiple sclerosis is a complex and heterogeneous, most likely autoimmune, demyelinating disease of the central nervous system (CNS). Although a number of histological classification systems for CNS lesions have been used by different groups in recent years, no uniform classification exists. In this paper, we propose a simple and unifying classification of MS lesions incorporating many elements of earlier histological systems that aims to provide guidelines for neuropathologists and researchers studying MS lesions to allow for better comparison of different studies performed with MS tissue, and to aid in understanding the pathogenesis of the disease. Based on the presence/absence and distribution of macrophages/microglia (inflammatory activity) and the presence/absence of ongoing demyelination (demyelinating activity), we suggest differentiating between active, mixed active/inactive, and inactive lesions with or without ongoing demyelination. Active lesions are characterized by macrophages/microglia throughout the lesion area, whereas mixed active/inactive lesions have a hypocellular lesion center with macrophages/microglia limited to the lesion border. Inactive lesions are almost completely lacking macrophages/microglia. Active and mixed active/inactive lesions can be further subdivided into lesions with ongoing myelin destruction (demyelinating lesions) and lesions in which the destruction of myelin has ceased, but macrophages are still present (post-demyelinating lesions). This distinction is based on the presence or absence of myelin degradation products within the cytoplasm of macrophages/microglia. For this classification of MS lesions, identification of myelin with histological stains [such as luxol fast blue-PAS] or by immunohistochemistry using antibodies against myelin basic-protein (MBP) or proteolipid-protein (PLP), as well as, detection of macrophages/microglia by, e.g., anti-CD68 is sufficient. Active and demyelinating lesions may be further subdivided into the early and late demyelinating lesions. The former is defined by the presence in macrophages of major and small molecular weight myelin proteins, such as cyclic nucleotide diphosphoesterase (CNP), myelin oligodendrocyte glycoprotein (MOG), or myelin-associated protein (MAG), whereas macrophages in the latter demonstrate merely the presence of the major myelin proteins MBP or PLP. We discuss the histological features and staining techniques required to classify MS lesions, and, in addition, describe the histological hallmarks of cortical pathology and diffuse white matter changes, as well as of remyelination.