Abstract：
Plasmablastic lymphoma (PBL) is an aggressive large B-cell lymphoma with a terminal B-cell differentiation phenotype and is frequently associated with immunodeficiency. We aimed to investigate the clinicopathological and immunophenotypic features, genetic alterations, and mutational landscape of PBL in Taiwan. We retrospectively recruited 26 cases. Five (5/18; 28%) patients were HIV-positive and 21 (81%) presented extranodally. There were two morphological groups: one with purely monomorphic large cells (85%) and the other comprising large cells admixed with plasmacytic cells (15%). Phenotypically, the tumors expressed MYC (8/10; 80%), CD138 (20/26; 77%), and MUM1 (20/20; 100%), but not CD20 (n = 26; 0%). Fourteen (54%) cases were positive for EBV by in situ hybridization; the EBV-positive cases were more frequently HIV infected (p = 0.036), with extranodal presentation (p = 0.012) and CD79a expression (p = 0.012), but less frequent light chain restriction (p = 0.029). Using fluorescence in situ hybridization, we identified 13q14 deletion, MYC rearrangement, and CCND1 rearrangement in 74%, 30%, and 5% cases, respectively, without any cases having rearranged BCL6 or IGH::FGFR3 fusion. In the 15 cases with adequate tissue for whole exome sequencing, the most frequent recurrent mutations were STAT3 (40%), NRAS (27%), and KRAS (20%). In conclusion, most PBL cases in Taiwan were HIV-unrelated. Around half of the cases were positive for EBV, with distinct clinicopathological features. Deletion of chromosome 13q14 was frequent. The PBL cases in Taiwan showed recurrent mutations involving JAK-STAT, RAS-MAPK, epigenetic regulation, and NOTCH signaling pathways, findings similar to that from the West.
摘要：
浆细胞淋巴瘤（PBL）是一种侵袭性大B细胞淋巴瘤，具有末端B细胞分化表型，通常与免疫缺陷有关。我们的目的是探讨临床病理和免疫表型特征，遗传改变,以及台湾PBL的突变景观。我们回顾性招募了26例。5例（5/18；28％）患者为HIV阳性，21例（81％）为结外。有两个形态学组：一个具有纯单形大细胞（85％），另一个包含与浆细胞混合的大细胞（15％）。表型，肿瘤表达MYC（8/10；80%），CD138（20/26；77%），和MUM1(20/20;100%)，但不是CD20（n=26；0%）。通过原位杂交，14例（54％）为EBV阳性；EBV阳性病例更频繁地感染HIV（p=0.036），结外表现（p=0.012）和CD79a表达（p=0.012），但较不常见的轻链限制（p=0.029）。使用荧光原位杂交，我们发现13q14缺失，MYC重排,和CCND1重排在74%，30%,5%的病例,分别,无任何病例重排BCL6或IGH::FGFR3融合。在15例具有足够组织进行全外显子组测序的病例中，最常见的复发突变是STAT3（40％），NRAS（27%），KRAS（20%）。总之,台湾的大多数PBL病例与HIV无关.大约一半的病例为EBV阳性，具有明显的临床病理特征。染色体13q14的缺失是频繁的。台湾的PBL病例显示涉及JAK-STAT的复发性突变，RAS-MAPK,表观遗传调控，和NOTCH信号通路，类似于西方的发现。
