中国滤泡性淋巴瘤的免疫表型特征和 t(14;18)(q32;q21)易位有助于鉴别亚组。

Immunophenotypic features and t(14;18) (q32;q21) translocation of Chinese follicular lymphomas helps to distinguish subgroups.

机构信息

Department of Pathology, Guangdong General Hospital, Guangdong Academy of Medical Science, Guangzhou 510080, China.

出版信息

Diagn Pathol. 2013 Sep 18;8:154. doi: 10.1186/1746-1596-8-154.

DOI:10.1186/1746-1596-8-154

PMID:24047469

原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC3853627/

Abstract

BACKGROUND

The revised 2008 World Health Organization classification maintains a histological grading system (grades 1-3) for follicular lymphoma (FL). The value of grading FL has been debated. This study will yield deeper insights into the morphologic, immunophenotypic characterization and t(14;18) translocation in FL and explore their significance of diagnosis of Chinese FL subgroups.

METHODS

We retrospectively reviewed the FL diagnoses according to the 2008 WHO classification in all diagnostic specimens from a multicentric cohort of 122 Chinese patients. Upon review, 115 cases proved to be truly FL. CD10, BCL6, MUM1, BCL2 and t(14;18) (q32;q21) translocation were detected by Envision immunostaining technique and fluorescence in situ hybridization.

RESULTS

FL1 has larger proportion of follicular pattern (93.0%) than that of FL2 (73.7%, P = 0.036), FL3B (63.6%, P = 0.003) and FL3A (77.4%, P = 0.053), although the last P value was more than 0.05 (Pearson's chi-squared test). Areas of DLBCL were present in 25.8% (8/31) of FL3A and more frequent in FL3B (59.1%, 13/22; P = 0.015). The positivity of CD10 and BCL2 in FL1-2 were significantly higher than those in FL3 (P < 0.001, P = 0.043, respectively). The positivity of MUM1 in FL1-2 was significantly lower than that in FL3 (10.2% vs. 51.0%; P < 0.001). Furthermore the positivity of MUM1 in FL3A was significantly lower than that in FL3B (37.9% vs. 68.2%; P = 0.032). The positivity of t(14;18) was higher in FL1-2 than in FL3 (73.5% vs. 35.6%, P < 0.001), and was higher in FL3A than in FL3B (51.9% vs. 11.1%, P = 0.005). t(14;18) was significantly correlated with CD10+ (R = 0.453, P < 0.001) and MUM1+ (R = -0.482, P < 0.001).

CONCLUSIONS

FL1 and FL2 were immunophenotypically and genomically similar, while FL3A and FL3B were partly immunophenotypically similar but morphologically, genomically distinct. FL3A was genomically closer to FL1-2, whereas FL3A was genomically closer DLBCL. Thus we hypothesize that FL may in fact be a heterogeneous indolent lymphoma encompassing entities with distinct molecular pathogenesis and genetic characteristics. Immunohistochemical and genetic characterization helps to distinguish subgroups of FLs.

VIRTUAL SLIDES

The virtual slide(s) for this article can be found here: http://www.diagnosticpathology.diagnomx.eu/vs/1334018129864616.

摘要

背景

修订后的 2008 年世界卫生组织分类法为滤泡性淋巴瘤（FL）保留了组织学分级系统（1-3 级）。FL 分级的价值一直存在争议。本研究将深入了解 FL 的形态学、免疫表型特征和 t（14；18）易位，并探讨其在中国 FL 亚组诊断中的意义。

方法

我们回顾性分析了来自 122 例中国患者的多中心队列中所有诊断标本的 2008 年 WHO 分类 FL 诊断。经复查，115 例证实为真正的 FL。采用 Envision 免疫组化技术和荧光原位杂交检测 CD10、BCL6、MUM1、BCL2 和 t（14；18）（q32；q21）易位。

结果

FL1 的滤泡模式比例（93.0%）大于 FL2（73.7%，P=0.036）、FL3B（63.6%，P=0.003）和 FL3A（77.4%，P=0.053），尽管最后一个 P 值大于 0.05（皮尔逊卡方检验）。在 31 例 FL3A 中有 25.8%（8/31）存在 DLBCL 区，FL3B 中更常见（59.1%，13/22；P=0.015）。FL1-2 中 CD10 和 BCL2 的阳性率明显高于 FL3（P<0.001，P=0.043）。FL1-2 中 MUM1 的阳性率明显低于 FL3（10.2% vs. 51.0%；P<0.001）。此外，FL3A 中 MUM1 的阳性率明显低于 FL3B（37.9% vs. 68.2%；P=0.032）。FL1-2 中的 t（14；18）阳性率高于 FL3（73.5% vs. 35.6%，P<0.001），FL3A 中的 t（14；18）阳性率高于 FL3B（51.9% vs. 11.1%，P=0.005）。t（14；18）与 CD10+（R=0.453，P<0.001）和 MUM1+（R=-0.482，P<0.001）呈显著正相关。

结论

FL1 和 FL2 在免疫表型和基因组上相似，而 FL3A 和 FL3B 在部分免疫表型上相似，但在形态学和基因组上存在差异。FL3A 在基因组上更接近 FL1-2，而在基因组上更接近 DLBCL。因此，我们假设 FL 实际上可能是一种具有不同分子发病机制和遗传特征的异质性惰性淋巴瘤。免疫组织化学和遗传特征有助于区分 FL 亚组。