Mayo Clinic Arizona, Phoenix, AZ, USA.
University of Pittsburgh School of Medicine, Pittsburgh, PA, USA.
Mod Pathol. 2022 Jan;35(1):60-68. doi: 10.1038/s41379-021-00938-z. Epub 2021 Oct 2.
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.
滤泡性淋巴瘤伴浆细胞分化（FL-PCD）包括两个主要亚型：一个主要为滤泡间浆细胞分化，通常具有 BCL2 重排（BCL2-R），另一个主要为滤泡内浆细胞分化，且常缺乏 BCL2-R。有人提出，这些病例与边缘区淋巴瘤（MZL）有一些共同特征。为了在更大的 FL-PCD 队列中进一步探索这一假说，对 25 例此类病例进行了临床病理研究，包括对其突变情况的分析。10 例滤泡间 FL-PCD 表现为典型的滤泡内中心细胞/中心母细胞（90%）、CD10 表达（90%）、完全浆细胞分化，包括浆细胞表达 CD138（100%），且具有类别转换的免疫球蛋白重链（70%）。这些病例均为 BCL2-R 阳性（100%），BCL6-R 阳性占 30%，无额外的 BCL2 拷贝，仅 22%有额外的 BCL6 拷贝。与经典的 FL 相似，80%的滤泡间 FL-PCD 存在表观遗传调节因子 KMT2D（70%）、CREBBP（40%）和/或 EZH2（30%）的突变。相比之下，11 例滤泡内 FL-PCD 中仅有 45%表现为典型的滤泡内中心细胞/中心母细胞，55%为 CD10（-），80%含有 IgM+浆细胞，仅 27%存在 BCL2-R。27%的滤泡内 FL-PCD 存在 BCL6-R，而 60%显示 BCL2 的额外拷贝，50%显示 BCL6 的额外拷贝，分别与染色体 18 和 3 的完全或部分三体相一致。只有 54%的滤泡内 FL-PCD 存在表观遗传调节因子的突变。这两种亚型与经典 FL 相比都有突变差异，但只有滤泡间亚型与结内 MZL 报道的不同。另外 4 例表现为混合的滤泡内和滤泡间浆细胞分化。这些结果提示 FL-PCD 具有一些独特的特征，并支持存在两个主要亚型。滤泡间 PCD 亚型与经典 FL 有许多共同特征。滤泡内的 FL-PCD 则更加异质性，与经典 FL 有差异，与 MZL 在形态学、免疫表型和遗传学上有更大的重叠。
