Hsu S M, Waldron J A, Fink L, King C, Xie S S, Mansouri A, Barlogie B
Department of Pathology, University of Arkansas for Medical Sciences, Arkansas Cancer Research Center, Little Rock.
Hum Pathol. 1993 Feb;24(2):126-31. doi: 10.1016/0046-8177(93)90290-w.
Patients with angioimmunoblastic lymphadenopathy (AILD)-type T-cell lymphoma may develop hypergammaglobulinemia. Among four cases of AILD-type T-cell lymphoma that we have studied, we detected a correlation between the number of plasma cells in tissue and the extent of interleukin-6 (IL-6) expression in lymphoma cells. We did not detect IL-6 in three patients who had no hypergammaglobulinemia and whose tissues showed only minimal plasma cell infiltration. In the fourth patient we observed an abundant IL-6 production by lymphoma cells, which accounted for a B-cell plasmacytic tissue response and for hypergammaglobulinemia. The pathogenic significance of IL-6 was substantiated by a concomitant decrease in the serum IL-6 level, measurable tumor mass, and immunoglobulin levels, as well as by a decline in the proportion of plasmacytoid cells in peripheral blood promptly on administration of chemotherapy. Plasmacytoid B cells could be maintained in culture in the presence of IL-6, but viability was lost on co-incubation with anti-IL-6. Interleukin-1 and tumor necrosis factor were not produced by T lymphoma cells and were incapable of sustaining plasmacytoid B-cell viability in vitro. Small amounts of IL-4 were noted in T lymphoma cells. Thus, in this case of AILD-type T-cell lymphoma, tumor cells with a T-cell phenotype produced IL-6 in large quantities, explaining the accompanying B-cell and plasmacytic histologic changes and humoral disease manifestations, including marked hypergammaglobulinemia. Although not all cases of AILD-type T-cell lymphoma have an accompanying plasma cell proliferation and hypergammaglobulinemia, and although the cytokine network in these patients may be more complex than has been recognized, this case with IL-6 expression serves to illustrate the utility of cytokine assays in the analysis of the histopathologic and clinical heterogeneities of peripheral T-cell lymphomas.
血管免疫母细胞性淋巴结病（AILD）型T细胞淋巴瘤患者可能会出现高球蛋白血症。在我们研究的4例AILD型T细胞淋巴瘤病例中，我们检测到组织中浆细胞数量与淋巴瘤细胞中白细胞介素-6（IL-6）表达程度之间存在相关性。在3例无高球蛋白血症且组织中仅有极少浆细胞浸润的患者中，我们未检测到IL-6。在第4例患者中，我们观察到淋巴瘤细胞大量产生IL-6，这导致了B细胞浆细胞性组织反应和高球蛋白血症。血清IL-6水平、可测量的肿瘤肿块和免疫球蛋白水平同时下降，以及化疗后外周血中浆细胞样细胞比例迅速下降，证实了IL-6的致病意义。浆细胞样B细胞在有IL-6存在的情况下可在培养中维持，但与抗IL-6共同孵育后活力丧失。T淋巴瘤细胞不产生白细胞介素-1和肿瘤坏死因子，且在体外无法维持浆细胞样B细胞的活力。在T淋巴瘤细胞中检测到少量IL-4。因此，在这例AILD型T细胞淋巴瘤中，具有T细胞表型的肿瘤细胞大量产生IL-6，解释了伴随的B细胞和浆细胞组织学变化以及体液疾病表现，包括明显的高球蛋白血症。尽管并非所有AILD型T细胞淋巴瘤病例都伴有浆细胞增殖和高球蛋白血症，尽管这些患者的细胞因子网络可能比已认识到的更为复杂，但这例有IL-6表达的病例有助于说明细胞因子检测在外周T细胞淋巴瘤组织病理学和临床异质性分析中的作用。
