边缘区淋巴瘤 (MZL) 包括多种惰性淋巴组织增生性疾病；然而，一些患者出现组织学转化 (HT)，并迅速进展为侵袭性淋巴瘤。 43 例患有 HT 的 MZL (HT-MZL)、535 例 MZL 和 174 例无 MYC 重排的新生弥漫性大 B 细胞淋巴瘤 (DLBCL)，收集BCL2和BCL6。其中，22个HT-MZL、39个MZL和174个DLBCL进行了148个基因靶向外显子组测序。将HT-MZL患者的临床病理特征及其基因改变与MZL和DLBCL患者进行比较。所有43例HT-MZL均对应于DLBCL。没有 HT-MZL 含有 BCL2 和 MYC 和/或 BCL6 重排。 HT-MZL 中的骨髓受累和较高水平的乳酸脱氢酶明显比 MZL 中更常见。此外，在 HT-MZL 中比在 MZL 中更频繁地观察到 BCL6、MUM1、C-MYC 和 Ki-67 表达上调。 TBL1XR1 是 HT-MZL 中最常改变的基因 (63.6%)，其次是 CCND3 (31.8%)、CARD11、ID3 和 TP53 (22.7%)。观察到 TBL1XR1 突变患者无进展生存期较差的趋势。与 MZL 和非生发中心 B 细胞 (GCB) 型 DLBCL 相比，HT-MZL 中 TBL1XR1 和 ID3 突变的频率明显更高。 PIM1突变频繁发生在DLBCL中，并且与TBL1XR1突变显着相关，但在具有TBL1XR1突变的HT-MZL中突变较少。目前的研究结果揭示了HT-MZL的临床病理和遗传特征，表明这些肿瘤可能构成一个不同于TBL1XR1突变的群体。 MZL 和从头非 GCB 型 DLBCL。 TBL1XR1 突变可能被认为是 MZL 中 HT 的预测因子。© 2023 美国癌症协会。

Marginal zone lymphomas (MZLs) comprise a diverse group of indolent lymphoproliferative disorders; however, some patients develop histologic transformation (HT) with rapid progression to aggressive lymphoma.Forty-three MZLs with HT (HT-MZLs), 535 MZLs, and 174 de novo diffuse large B-cell lymphomas (DLBCLs) without rearrangements of MYC, BCL2, and BCL6 were collected. Among these, 22 HT-MZLs, 39 MZLs, and 174 DLBCLs were subjected to 148-gene targeted exome sequencing. The clinicopathologic features of patients who had HT-MZL and their genetic alterations were compared with those of patients who had MZLs and DLBCLs.All 43 HT-MZLs corresponded to DLBCLs. No HT-MZLs harbored BCL2 and MYC and/or BCL6 rearrangements. Bone marrow involvement and higher levels of lactate dehydrogenase were significantly more common in HT-MZLs than in MZLs. Furthermore, upregulated BCL6, MUM1, C-MYC, and Ki-67 expression was observed more frequently in HT-MZLs than in MZLs. TBL1XR1 was the most frequently altered gene (63.6%) in HT-MZLs, followed by CCND3 (31.8%), CARD11, ID3, and TP53 (22.7%). A trend toward worse progression-free survival in patients with TBL1XR1 mutations was observed. Compared with MZLs and non-germinal center B-cell (GCB) type DLBCLs, significantly higher frequencies of TBL1XR1 and ID3 mutations were identified in HT-MZLs. PIM1 mutations frequently occurred in DLBCLs and were significantly associated with TBL1XR1 mutations but were mutated less in HT-MZLs that had TBL1XR1 mutations.The current findings reveal the clinicopathologic and genetic features of HT-MZLs, suggesting that these tumors might constitute a group distinct from MZL and de novo non-GCB type DLBCL. TBL1XR1 mutations may be considered a predictor of HT in MZL.© 2023 American Cancer Society.