Butzmann Alexandra, Kumar Jyoti, Sridhar Kaushik, Gollapudi Sumanth, Ohgami Robert S
Agilent Technologies, Santa Clara, CA 95051, USA.
Department of Pathology, Stanford University, Stanford, CA 94305, USA.
Biology (Basel). 2021 Mar 24;10(4):251. doi: 10.3390/biology10040251.
Castleman disease (CD) is a rare lymphoproliferative disorder known to represent at least four distinct clinicopathologic subtypes. Large advancements in our clinical and histopathologic description of these diverse diseases have been made, resulting in subtyping based on number of enlarged lymph nodes (unicentric versus multicentric), according to viral infection by human herpes virus 8 (HHV-8) and human immunodeficiency virus (HIV), and with relation to clonal plasma cells (POEMS). In recent years, significant molecular and genetic abnormalities associated with CD have been described. However, we continue to lack a foundational understanding of the biological mechanisms driving this disease process. Here, we review all cases of CD with molecular abnormalities described in the literature to date, and correlate cytogenetic, molecular, and genetic abnormalities with disease subtypes and phenotypes. Our review notes complex karyotypes in subsets of cases, specific mutations in N666S in 10% of unicentric CD (UCD) and L261F in 23% of idiopathic multicentric CD (iMCD) cases. Genes affecting chromatin organization and abnormalities in methylation are seen more commonly in iMCD while abnormalities within the mitogen-activated protein kinase (MAPK) and interleukin signaling pathways are more frequent in UCD. Interestingly, there is a paucity of genetic studies evaluating HHV-8 positive multicentric CD (HHV-8+ MCD) and POEMS-associated CD. Our comprehensive review of genetic and molecular abnormalities in CD identifies subtype-specific and novel pathways which may allow for more targeted treatment options and unique biologic therapies.
卡斯特曼病（CD）是一种罕见的淋巴增生性疾病，已知至少有四种不同的临床病理亚型。我们在对这些不同疾病的临床和组织病理学描述方面取得了重大进展，从而根据肿大淋巴结的数量（单中心与多中心）、是否感染人类疱疹病毒8型（HHV - 8）和人类免疫缺陷病毒（HIV）以及与克隆性浆细胞的关系（POEMS）进行了亚型分类。近年来，已经描述了与CD相关的显著分子和基因异常。然而，我们仍然缺乏对驱动这一疾病进程的生物学机制的基本理解。在此，我们回顾了迄今为止文献中描述的所有伴有分子异常的CD病例，并将细胞遗传学、分子和基因异常与疾病亚型及表型相关联。我们的综述指出，部分病例存在复杂核型，10%的单中心型CD（UCD）有N666S特异性突变，23%的特发性多中心型CD（iMCD）病例有L261F突变。影响染色质组织的基因和甲基化异常在iMCD中更常见，而丝裂原活化蛋白激酶（MAPK）和白细胞介素信号通路的异常在UCD中更频繁。有趣的是，评估HHV - 8阳性多中心型CD（HHV - 8 + MCD）和POEMS相关CD的基因研究很少。我们对CD的基因和分子异常进行的全面综述确定了亚型特异性和新的途径，这可能会带来更有针对性的治疗选择和独特的生物疗法。
