间质病样肺血管内大B细胞淋巴瘤的临床病理及基因分析

Clinicopathological and genetic analysis of interstitial disease-like pulmonary intravascular large B cell lymphoma

目的探讨肺血管内大B细胞淋巴瘤的临床病理及基因突变特征。方法回顾性分析中日友好医院2018年4月至2023年5月病理确诊的8例肺血管内大B细胞淋巴瘤患者的临床及病理资料,二代测序(NGS)方法检测其中6例基因突变情况,并对患者进行随访。结果患者男1例,女7例,中位年龄64(45~66)岁,临床症状以呼吸系统症状最常见(7例),B症状2例,继发噬血细胞综合征2例;胸部高分辨率CT均显示双肺多发弥漫磨玻璃影,肺功能检查轻至中度通气或弥散功能障碍6例,血气分析示低氧血症2例,伴Ⅰ型呼吸衰竭2例;血清LDH升高(7/8),β2微球蛋白升高(2/8),神经元特异性烯醇化酶升高(7/8),外周血淋巴细胞总数减少(7/8),临床分期均为Ⅳ期。组织学特征:肿瘤细胞充满肺泡间隔的小静脉和毛细血管,肿瘤细胞体积大,核仁明显,核分裂象常见,8例均可见肿瘤细胞浸润血管外周围肺组织。免疫表型:8例肿瘤细胞均弥漫表达B细胞抗原CD20、CD79a,血管内皮标志CD31和CD34染色显示肿瘤细胞位于血管内、血管壁及血管周围;1例为生发中心型,7例为非生发中心型,2例为双表达淋巴瘤,所有病例EB病毒编码的小RNA(EBER)均阴性。NGS检测突变频率前5位的基因分别为MYD88(5/6)、PIM1(5/6)、CD79B(4/6)、TCF3(4/6)、TP53(3/6)。8例中的7例接受R-CHOP方案为基础的化疗,6例化疗后完全缓解,1例死亡,1例失访。结论肺血管内大B细胞淋巴瘤罕见,影像学表现与间质性肺病鉴别困难,经支气管镜肺活检是确诊的有效方法,基于分子分型联合布鲁顿酪氨酸酶抑制剂的免疫化疗未来可以让患者生存获益。

ObjectiveTo investigate the clinicopathological features and genetic mutation status of pulmonary intravascular large B cell lymphoma.MethodsThe clinicopathological data of eight patients diagnosed with pulmonary intravascular large B cell lymphoma,from April 2018 to May 2023,were retrospectively analyzed.The genetic profile of six patients was detected via next-generation sequencing(NGS)and followed up.ResultsAll patients included one male and seven females,with a median age of 64 years(ranging from 45 to 66 years).Respiratory symptoms were the most common(7 cases),B symptoms in two cases,hemophagocytic syndrome in two cases.Multiple diffuse ground-glass opacities in both lungs were observed based on the high-resolution chest CT scan.Six cases of mild to moderate ventilation or diffusion dysfunction were observed based on the pulmonary function tests.Moreover,two cases of hypoxemia and two cases with typeⅠrespiratory failure were recorded.The serum lactate dehydrogenase level increased(7/8),β2-MG level increased(2/8),neuron-specific enolase level increased(7/8),total number of peripheral blood lymphocytes decreased(7/8),and clinical stages were all stageⅣ.The neoplastic lymphoid cells were lodged in the lumina of venules and capillaries of the alveolar septum;the tumor cells were large,with prominent nucleoli and frequent mitotic figures.The malignant cells were detected in the extravascular surrounding lung tissue in all cases.The tumor cells expressed mature B cell-associated antigens CD20 and CD79a,and the vascular endothelial markers CD31 and CD34 showed that the tumor cells were filled in the blood vessels,infiltrated blood vessel walls,and perivascular areas.One case was germinal center-type,seven cases were non-germinal center-type,two cases were double-expressing lymphoma,and all cases were EBER-negative.Furthermore,the top five genes with mutation frequencies detected by NGS were MYD88(5/6),PIM1(5/6),CD79B(4/6),TCF3(4/6),and TP53(3/6).Of the eight cases,seven patients received R-CHOP-based chemotherapy,six cases had complete remission after chemotherapy,one case died,and one case was lost to follow-up.ConclusionsPulmonary vascular large B cell lymphoma is rare,which shares similar patterns with interstitial lung disease on imaging.Transbronchial lung biopsy is an effective method to confirm the diagnosis.Immunochemotherapy with BTK inhibitors can provide a survival advantage for patients in the future based on molecular typing.