Kosmidis Perikles, Mankel Barbara, Fend Falko, Adam Patrick
Institute of Pathology and Neuropathology and Comprehensive Cancer Center (CCC), Eberhard-Karls-University Tübingen, Liebermeisterstr. 8, 72076, Tübingen, Germany.
Diagn Pathol. 2018 May 2;13(1):25. doi: 10.1186/s13000-018-0703-2.
The translocation t(14;18)(q32;q21) is the genetic hallmark of follicular lymphoma (FL) and can be observed in 85-90% of cases. Whether the translocation is restricted to cells with germinal center B-cell phenotype or can be observed in other cell types of the microenvironment remains debated. Of interest, cases of associated histiocytic and dendritic cell sarcomas arising in the background of FL have been shown to be clonally related and carry the t(14;18), suggesting a "transdifferentiation" of the malignant FL clone into a neoplasm of a different hematopoietic lineage.
We analyzed the presence of the t(14;18)(q32;q21) as a surrogate marker of the malignant clone in cells of the FL microenvironment using combined fluorescence immunophenotyping and interphase cytogenetics targeting the BCL2 gene locus. In addition to non-lymphoid cells in FL, we analysed FL with preserved IgD+ mantle zones and cases of in situ follicular neoplasia (ISFN) to investigate whether cells of non-germinal center B-cell phenotype are part of the malignant clone.
Six (40%) of 15 manifest FL cases with preserved IgD+ mantle zones did not harbour the t(14;18)(q32;q21) translocation. In all t(14;18) + FL cases, follicular dendritic cells and endothelial cells lacked the t(14;18) translocation. 2/9 FL revealed t(14;18)- IgD+ mantle zone B-cells. In the seven ISFN cases, the t(14;18) translocation was strictly confined to germinal center cells.
The t(14;18) translocation in follicular lymphoma is limited to B-cells. The origin of IgD+ mantle cells is heterogeneous, in the majority of cases belonging to the neoplastic clone, whereas a minority of cases of manifest FL show nonneoplastic mantle zones, similar to ISFN.
易位t(14;18)(q32;q21)是滤泡性淋巴瘤（FL）的遗传特征，在85% - 90%的病例中可观察到。这种易位是否仅限于生发中心B细胞表型的细胞，还是能在微环境的其他细胞类型中观察到，仍存在争议。有趣的是，已证明在FL背景下出现的相关组织细胞和树突状细胞肉瘤病例与克隆相关，并携带t(14;18)，提示恶性FL克隆“转分化”为不同造血谱系的肿瘤。
我们使用针对BCL2基因座的联合荧光免疫表型分析和间期细胞遗传学，分析t(14;18)(q32;q21)作为FL微环境细胞中恶性克隆替代标志物的存在情况。除了FL中的非淋巴细胞外，我们还分析了保留IgD + 套区的FL以及原位滤泡性肿瘤（ISFN）病例，以研究非生发中心B细胞表型的细胞是否是恶性克隆的一部分。
15例保留IgD + 套区的明显FL病例中有6例（40%）未携带t(14;18)(q32;q21)易位。在所有t(14;18)+ FL病例中，滤泡树突状细胞和内皮细胞缺乏t(14;18)易位。2/9的FL显示t(14;18)- IgD + 套区B细胞。在7例ISFN病例中，t(14;18)易位严格局限于生发中心细胞。
滤泡性淋巴瘤中的t(14;18)易位仅限于B细胞。IgD + 套细胞的起源是异质性的，在大多数情况下属于肿瘤克隆，而少数明显FL病例显示非肿瘤性套区，类似于ISFN。
