Dogan A, Du M Q, Aiello A, Diss T C, Ye H T, Pan L X, Isaacson P G
Department of Histopathology, UCL Medical School, London, UK.
Blood. 1998 Jun 15;91(12):4708-14.
Follicular lymphomas are thought to arise from the follicle center B cells and are characterized by follicular structures that recapitulate many features of normal secondary lymphoid follicles. The neoplastic B cells of follicular lymphoma reside not only in follicles but also in the interfollicular zone in which they form a diffuse infiltrate. We have investigated the frequency, extent, and biological characteristics of this interfollicular component in 30 cases of follicular lymphoma. An interfollicular B-cell infiltrate of variable extent (minimal, moderate, or prominent) was present in all cases. Morphologically interfollicular neoplastic B cells were small centrocyte-like cells with lower grade cytology and lower proliferation fraction compared with the neoplastic follicles. The neoplastic phenotype of these cells (CD20+, light chain restricted) was confirmed in 18 cases. Clonal identity between the follicular and interfollicular components was shown in five cases using microdissection and PCR amplification of immunoglobulin heavy chain genes. Analysis of Ig heavy chain gene sequences showed identical variants of tumor subclones in both follicular and interfollicular compartments, indicating active tumor cell traffic between the two. In six cases in which frozen tissue was available, the immunophenotype of follicular and interfollicular tumor cells were compared using immunohistochemistry. Activation markers such as CD10, CD38, and CD95 and T-cell costimulatory molecules CD80 and CD86, which were expressed by neoplastic follicles, were either downregulated or absent in the interfollicular component in most of the cases. The low-grade cytological features, low proliferation fraction, and downregulation of activation markers in the interfollicular neoplastic B cells suggests that these are resting cells analogous to memory B cells of normal lymphoid tissues. The presence of such a resting tumor cell subpopulation in the majority of follicular lymphomas may partly account for the remarkable resistance to therapy of this disease.
滤泡性淋巴瘤被认为起源于滤泡中心B细胞，其特征是具有滤泡结构，这些结构概括了正常次级淋巴滤泡的许多特征。滤泡性淋巴瘤的肿瘤性B细胞不仅存在于滤泡中，也存在于滤泡间区，在该区域它们形成弥漫性浸润。我们研究了30例滤泡性淋巴瘤中这种滤泡间成分的频率、范围和生物学特性。所有病例均存在不同程度（轻微、中度或显著）的滤泡间B细胞浸润。形态学上，滤泡间肿瘤性B细胞是小的中心细胞样细胞，与肿瘤性滤泡相比，其细胞学分级较低，增殖分数也较低。在18例病例中证实了这些细胞的肿瘤表型（CD20 +，轻链受限）。使用显微切割和免疫球蛋白重链基因的PCR扩增，在5例病例中显示了滤泡和滤泡间成分之间的克隆一致性。Ig重链基因序列分析显示，滤泡和滤泡间区的肿瘤亚克隆具有相同的变异体，表明两者之间存在活跃的肿瘤细胞迁移。在6例有冰冻组织的病例中，使用免疫组织化学比较了滤泡和滤泡间肿瘤细胞的免疫表型。肿瘤性滤泡表达的激活标志物如CD10、CD38和CD95以及T细胞共刺激分子CD80和CD86，在大多数病例的滤泡间成分中要么下调要么缺失。滤泡间肿瘤性B细胞的低级别细胞学特征、低增殖分数和激活标志物的下调表明这些是类似于正常淋巴组织记忆B细胞的静止细胞。大多数滤泡性淋巴瘤中存在这样一个静止的肿瘤细胞亚群，可能部分解释了该疾病对治疗的显著抗性。
