Histopathologic, immunophenotypic, and mutational landscape of follicular lymphomas with plasmacytic differentiation
Histopathologic, immunophenotypic, and mutational landscape of follicular lymphomas with plasmacytic differentiation
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DOI：
10.1038/s41379-021-00938-z
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发表时间：
2021-10-02
期刊：
影响因子：
7.5
通讯作者：
Swerdlow, Steven H.
中科院分区：
文献类型：
--
作者：
Gibson, Sarah E.;Liu, Yen-Chun;Swerdlow, Steven H.
具有浆细胞分化的滤泡性淋巴瘤（FL-PCD）包括两种主要亚型：一种主要具有滤泡间PCD，通常具有BCL 2重排（BCL 2-R），另一种主要具有滤泡内PCD并且经常缺乏BCL 2-R。有人建议，这些后者的情况下，共享一些功能与边缘区淋巴瘤（MZL）。为了进一步探讨这一假说在一个扩大的队列FL-PCD，临床病理学调查25例进行了包括分析其突变景观。10个滤泡间FL-PCD表现出典型的滤泡内中心细胞/中心母细胞（90%），CD 10表达（90%），完整的PCD包括浆细胞（PC）表达CD 138（100%），以及具有类别转换免疫球蛋白重链的PC（70%）。这些病例是BCL 2-R阳性（100%），BCL 6-R阳性30%，缺乏额外的BCL 2拷贝，只有22%有额外的BCL 6拷贝。与经典FL相似，80%的滤泡间FL-PCD在表观遗传调节因子KMT 2D（70%）、CREBBP（40%）和/或EZH 2（30%）中携带突变。相比之下，11个滤泡内FL-PCD中只有45%表现出典型的滤泡内中心细胞/中心母细胞，55%为CD 10（-），80%含有IgM+ PC，只有27%含有BCL 2-R。在27%的滤泡内FL-PCD中鉴定出BCL 6-Rs，而60%显示出BCL 2的额外拷贝和BCL 6的50%的额外拷贝，分别与染色体18和3的完全或部分三体一致。只有54%的滤泡内FL-PCD表现出表观遗传调节基因突变。两种亚型均显示与经典FL相比的突变差异，但仅滤泡间亚型显示与所报道的结MZL的差异。另外4例病例显示混合的滤泡内和滤泡间PCD。这些结果表明，FL-PCD有一些独特的功能，并支持存在两个主要亚型。滤泡间PCD亚型与经典FL共享许多特征。滤泡内FL-PCD更异质，与经典FL有差异，与MZL有更大的形态学、免疫表型和遗传重叠。
Follicular lymphomas with plasmacytic differentiation (FL-PCD) include two major subtypes: one with predominantly interfollicular PCD that usually harbors a BCL2 rearrangement (BCL2-R), and a second that has predominantly intrafollicular PCD and the frequent absence of a BCL2-R. It is proposed that these latter cases share some features with marginal zone lymphomas (MZL). To further explore this hypothesis in an expanded cohort of FL-PCD, a clinicopathologic investigation of 25 such cases was undertaken including an analysis of their mutational landscape. The 10 interfollicular FL-PCDs exhibited typical intrafollicular centrocytes/centroblasts (90%), CD10 expression (90%), full PCD including expression of CD138 by the plasma cells (PC) (100%), and PCs with class-switched immunoglobulin heavy chains (70%). These cases were BCL2-R positive (100%), BCL6-R positive in 30%, lacked extra BCL2 copies, and only 22% had extra copies of BCL6. Similar to classic FLs, 80% of interfollicular FL-PCDs harbored mutations in epigenetic regulators KMT2D (70%), CREBBP (40%), and/or EZH2 (30%). In contrast, only 45% of 11 intrafollicular FL-PCDs demonstrated typical intrafollicular centrocytes/centroblasts, 55% were CD10(-), 80% contained IgM+ PCs, and only 27% harbored BCL2-Rs. BCL6-Rs were identified in 27% of intrafollicular FL-PCD, while 60% showed extra copies of BCL2 and 50% extra copies of BCL6, consistent with complete or partial trisomies of chromosomes 18 and 3, respectively. Only 54% of intrafollicular FL-PCDs showed mutations in epigenetic regulators. Both subtypes showed mutational differences compared to classic FL, but only the interfollicular subtype showed differences from what is reported for nodal MZL. Four additional cases showed mixed intra- and interfollicular PCD. These results suggest that FL-PCD has some distinctive features and supports the existence of two major subtypes. The interfollicular PCD subtype shares many features with classic FL. The intrafollicular FL-PCDs are more heterogeneous, have differences from classic FL, and have a greater morphologic, immunophenotypic, and genetic overlap with MZL.