Hsu S M, Waldron J A, Xie S S, Barlogie B
Department of Pathology, University of Arkansas for Medical Sciences, Arkansas Cancer Research Center, Little Rock.
Hum Pathol. 1993 Aug;24(8):833-9. doi: 10.1016/0046-8177(93)90132-z.
Although mixed forms of Castleman's disease (CD) may occur, two classically recognized forms are the angiofollicular (hyaline vascular [V]) variant and the plasma cell (P) variant. The two forms of CD differ greatly in their clinical and histopathologic manifestations. Plasma cell CD is characterized by the presence of hyperplastic germinal centers (GCs) and sheets of plasma cells in the interfollicular areas. In this study we demonstrated an abundant expression of interleukin-6 (IL-6) in most GC B cells and in the numerous immunoblastoid B cells in the mantle zone and interfollicular areas in CD-P. Patients with CD-P also have an elevated serum IL-6 level. The increased IL-6 production is responsible for the marked plasma cell infiltration in lymph nodes and bone marrow as well as for the elevated gammaglobulin level in serum. In contrast, CD-V is distinguished by the presence of atrophic GCs, which often are populated by cytologically atypical follicular dendritic reticulum (FDR) cells, as well as by sheets of T-zone plasmacytoid histiocytes and increased numbers of capillaries in the interfollicular areas. In contrast to the findings in CD-P, we did not observe significant expression of IL-6 in GC cells or in immunoblastoid cells in CD-V; this may account for the paucity of plasma cells in this form of CD. The reason for the atypical changes in FDR cells as well as the increases in T-zone plasmacytoid histiocytes and capillaries seen in CD-V are not known inasmuch as no cytokines, such as IL-1, IL-4, IL-6, IL-7, IL-8, IL-9, tumor necrosis factor-alpha, granulocyte-macrophage colony-stimulating factor, or granulocyte colony-stimulating factor, were detectable in tissues. It is possible that in CD-V the atypical change in FDR cells could lead to a disturbance of B-lymphocyte/FDR cell interaction and subsequently to poor development of GCs. The study clearly indicates that the histopathologic and clinical features of CD vary greatly depending on the capacity of activated B cells to produce IL-6. However, lack of IL-6 secretion by GC cells alone cannot explain the histopathologic alterations in CD-V.
尽管可能会出现混合形式的卡斯特曼病（CD），但经典认可的两种形式是血管滤泡性（透明血管型[V]）变体和浆细胞型（P）变体。CD的这两种形式在临床和组织病理学表现上有很大差异。浆细胞型CD的特征是存在增生的生发中心（GCs）以及滤泡间区域成片的浆细胞。在本研究中，我们证实在浆细胞型CD（CD-P）的大多数GC B细胞以及外套层区域和滤泡间区域众多免疫母细胞样B细胞中白细胞介素-6（IL-6）表达丰富。CD-P患者血清IL-6水平也升高。IL-6产生增加是导致淋巴结和骨髓中显著浆细胞浸润以及血清中γ球蛋白水平升高的原因。相比之下，透明血管型CD（CD-V）的特征是存在萎缩的GCs，这些GCs通常由细胞学上非典型的滤泡树突状网状（FDR）细胞占据，以及滤泡间区域成片的T区浆细胞样组织细胞和毛细血管数量增加。与CD-P的发现相反，我们在CD-V的GC细胞或免疫母细胞样细胞中未观察到IL-6的显著表达；这可能解释了这种形式CD中浆细胞的稀少。CD-V中FDR细胞的非典型变化以及T区浆细胞样组织细胞和毛细血管增加的原因尚不清楚，因为在组织中未检测到诸如IL-1、IL-4、IL-6、IL-7、IL-8、IL-9、肿瘤坏死因子-α、粒细胞-巨噬细胞集落刺激因子或粒细胞集落刺激因子等细胞因子。在CD-V中，FDR细胞的非典型变化可能导致B淋巴细胞/FDR细胞相互作用紊乱，进而导致GCs发育不良。该研究清楚地表明，CD的组织病理学和临床特征因活化B细胞产生IL-6的能力不同而有很大差异。然而，仅GC细胞缺乏IL-6分泌并不能解释CD-V中的组织病理学改变。
