Peng Fangli, Igawa Takuro, Urata Tomohiro, Kobayashi Hiroki, Isoda Tetsuya, Ono Sawako, Tanaka Takehiro, Ennisshi Daisuke, Maeda Yoshinobu, Yamamoto Hidetaka
Departments of Pathology and Oncology.
Department of Hematology and Blood Transfusion, Kochi Health Sciences Center, Kochi, Japan.
Am J Surg Pathol. 2025 Feb 1;49(2):159-168. doi: 10.1097/PAS.0000000000002329. Epub 2024 Oct 31.
Primary sinonasal diffuse large B-cell lymphoma (PSDLBCL) is a rare aggressive lymphoma. Recently, genetic classification using Next Generation Sequencing (NGS) demonstrated that PSDLBCL largely consists of the MCD genotype, which has a poor prognosis mainly driven by MYD88 L265P and CD79B gene abnormalities. This study investigated the prevalence and clinicopathological significance of MYD88 L265P and CD79B Y196 mutations using droplet digital PCR in 55 patients with PSDLBCL, as well as the translocation of BCL2 / BCL6 / c-Myc with FISH. We found mutations in MYD88 L265P (29/55, 52.7%) and CD79B Y196 (20/55, 36.4%). The MCD-like subtype, defined by the mutation of MYD88 and/or CD79B , was found in 32 out of 55 cases (58.2%). This subtype largely consists of non-GCB type (31/32, 96.9%; P <0.01) and double-expressor cases (20/32, 62.5%; P =0.01) compared with the MYD88 / CD79B co-wild type, with BCL6 translocation in a small subset (2/32, 6.3%) and no translocations of BCL2 (0/32) or c-Myc (0/32). The MCD-like subtype tended to relapse in specific sites such as the central nervous system, testis, and/or skin compared with the co-wild type ( P =0.03), showing poorer outcomes in overall survival ( P =0.02) and progression-free survival ( P =0.01). In conclusion, our study highlights a high prevalence of MYD88 and CD79B mutations in PSDLBCL, identifying an aggressive MCD-like subtype with a distinct relapse pattern. This molecular subclassification can be helpful for both prognostic prediction and therapeutic strategy in patients with PSDLBCL.
原发性鼻窦弥漫性大B细胞淋巴瘤（PSDLBCL）是一种罕见的侵袭性淋巴瘤。最近，使用下一代测序（NGS）进行的基因分类表明，PSDLBCL主要由MCD基因型组成，其预后较差，主要由MYD88 L265P和CD79B基因异常驱动。本研究采用液滴数字PCR检测了55例PSDLBCL患者中MYD88 L265P和CD79B Y196突变的发生率及临床病理意义，以及采用荧光原位杂交（FISH）检测BCL2 / BCL6 / c-Myc的易位情况。我们发现MYD88 L265P突变（29/55，52.7%）和CD79B Y196突变（20/55，36.4%）。在55例病例中有32例（58.2%）发现了由MYD88和/或CD79B突变定义的MCD样亚型。与MYD88 / CD79B共野生型相比，该亚型主要由非生发中心B细胞（non-GCB）型（31/32，96.9%；P <0.01）和双表达型病例（20/32，62.5%；P =0.01）组成，一小部分存在BCL6易位（2/32，6.3%），而BCL2（0/32）或c-Myc（0/32）无易位。与共野生型相比，MCD样亚型倾向于在中枢神经系统、睾丸和/或皮肤等特定部位复发（P =0.03），总生存期（P =0.02）和无进展生存期（P =0.01）显示出较差的预后。总之，我们的研究突出了PSDLBCL中MYD88和CD79B突变的高发生率，确定了一种具有独特复发模式的侵袭性MCD样亚型。这种分子亚分类有助于PSDLBCL患者的预后预测和治疗策略制定。
