- 报道 7 例免疫豁免部位原发性大 B 细胞淋巴瘤伴 IRF4 重排（IP-LBCL-IRF4-R）：中枢神经系统 4 例、睾丸 3 例；均免疫功能正常，随访期间均存活。
- 形态为中心母/免疫母样中–大 B 细胞弥漫增生；6/7 非生发中心表型，5/7 BCL2/C-MYC 双表达，EBER 全阴。
- FISH 均检出 IRF4 重排（仅 1 例明确 IGH::IRF4）；NGS 高频 IRF4/PIM1/MYD88 等，LymphGen 多归 MCD——提示 IP-LBCL 分子异质性中的少见遗传学事件。
摘要
免疫豁免部位原发性大 B 细胞淋巴瘤（IP-LBCL）是一种侵袭性 B 细胞淋巴瘤，发生于中枢神经系统、玻璃体视网膜及睾丸；伴 IRF4 重排的 IP-LBCL（IP-LBCL-IRF4-R）分子特征仍不清楚。本文报告 7 例 IP-LBCL-IRF4-R，均经荧光原位杂交（FISH）证实存在 IRF4 重排。队列含男性 6 例、女性 1 例，中位年龄 58 岁（范围 34–73 岁）；患者均免疫功能正常。肿瘤累及中枢神经系统（n = 4）与睾丸（n = 3）。中位随访 10 个月（范围 3–45 个月），患者均存活。组织学上，全部 IP-LBCL-IRF4-R 呈中心母细胞样和/或免疫母细胞样形态的中–大 B 细胞弥漫增生。免疫表型方面，1 例归为生发中心 B 细胞亚型，6 例为非生发中心 B 细胞亚型。5 例呈 BCL2/C-MYC 双表达，7 例 Epstein-Barr 病毒编码小 RNA（EBER）均为阴性。断裂探针 FISH 在全部 7 例检出 IRF4 重排，仅 1 例检出 IGH::IRF4 融合；3 例伴 BCL6 重排，未检出 BCL2 或 MYC 重排。二代测序识别出反复突变：IRF4 与 PIM1（各 6/7，85.7%），其次为 MYD88（5/7，71.4%）以及 BTG1、CD79B 与 LRP1B（各 3/7，42.9%）。LymphGen 2.0 将 5 例归为 MCD 亚型、2 例归为 Other。本研究提示 IRF4 重排是 IP-LBCL 中的少见遗传学事件，并进一步揭示该病种的分子异质性。
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Abstract
Primary large B-cell lymphoma of immune-privileged sites (IP-LBCL) is an aggressive B-cell lymphoma arising in the central nervous system, vitreoretina, and testis, whereas the molecular features of IP-LBCL with IRF4 rearrangement (IP-LBCL-IRF4-R) remain poorly characterized. Here, we report seven cases of IP-LBCL-IRF4-R, all showing IRF4 rearrangement confirmed by fluorescence in situ hybridization. The cohort included six males and one female, with a median age of 58 years (range, 34-73 years); all patients were immunocompetent. Tumors involved the central nervous system (n = 4) and testis (n = 3). With a median follow-up of 10 months (range, 3-45 months), all patients were alive. Histologically, all IP-LBCL-IRF4-R cases showed diffuse proliferation of medium-to-large B cells with centroblast-like and/or immunoblast-like morphology. Immunophenotypically, one case was classified as the germinal center B-cell subtype and six as the non-germinal center B-cell subtype. Five cases showed BCL2/C-MYC double expression, and all seven cases were negative for Epstein-Barr virus-encoded small RNA. IRF4 rearrangement was detected in all seven cases by break-apart probes, and an IGH::IRF4 fusion was detected in only one case; three cases harbored BCL6 rearrangements, and no BCL2 or MYC rearrangements were detected. Next-generation sequencing identified recurrent mutations in IRF4 and PIM1 (6/7, 85.7% each), followed by MYD88 (5/7, 71.4%) and BTG1, CD79B, and LRP1B (3/7, 42.9% each). LymphGen 2.0 classified five cases as the MCD subtype and two as Other. Our study highlights IRF4 rearrangement as a rare genetic event in IP-LBCL and provides further insights into the molecular diversity of this entity.
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