淋巴浆细胞淋巴瘤/华氏巨球蛋白血症27例临床病理特征及预后分析

Lymphoplasmacytic lymphoma: a clinicopathological and prognostic analysis of 27 cases

目的探讨淋巴浆细胞淋巴瘤/华氏巨球蛋白血症(LPL/WM)的临床病理特点、诊断与鉴别诊断、治疗以及预后。方法收集广东省人民医院2016年1月至2020年12月诊断的LPL/WM 27例,回顾性分析其临床表现、组织学形态、免疫表型、MYD88 L265P突变结果及治疗和预后情况。结果患者男性19例,女性8例,中位年龄63岁;临床表现多以贫血相关的乏力、疲倦为首发症状。所有病例均侵犯骨髓,11例伴有淋巴结肿大,10例伴脾大。25例分泌单克隆IgM型蛋白,符合华氏巨球蛋白血症(WM)诊断标准。组织学形态表现为骨髓或淋巴结中小淋巴细胞、浆样淋巴细胞或浆细胞弥漫或灶状浸润,表达B细胞标志物,免疫球蛋白轻链限制性表达,不表达CD5,极少数表达CD23、CD10,Ki-67阳性指数通常较低。MYD88 L265P突变阳性率为73.9%(17/23)。初次治疗多采用利妥昔单抗与烷化剂、核苷类似物或免疫调节剂联用方案,少数复发或进展患者改用伊布替尼治疗。本组病例随访时间3~168个月,9例出现疾病复发或进展。血小板减少、β2微球蛋白升高、高危组与疾病复发或进展相关(P<0.05)。高危组患者的总生存率、无进展生存率均明显低于低-中危组(P<0.05)。结论LPL/WM的诊断为排除性诊断,MYD88 L265P突变具有很高的诊断价值,但并非特异性诊断指标,需结合临床表现、血清IgM蛋白水平、免疫表型等情况综合判断。LPL/WM总体预后好,但仍有少数高危患者进展迅速,因此对于有症状的患者需准确诊断、及时治疗。

Objective To study the clinical manifestations,pathologic features,diagnosis and differential diagnosis,treatment and prognosis of lymphoplasmacytic lymphoma/Waldenström′s macroglobulinemia(LPL/WM).Methods Twenty-seven cases of LPL from January 2016 to December 2020 at Guangdong Provincial People′s Hospital were collected.The clinical data,histomorphology,immunophenotype,MYD88 L265P mutation,treatment and prognosis were analyzed retrospectively.Results There were 19 males and 8 female patients,with median age of 63 years.The most common initial symptoms were fatigue related to anemia.Bone marrow was involved in all cases,lymphadenopathy was seen in 11 cases and splenomegaly in 10 cases.Monoclonal IgM type protein was detected in 25 cases,meeting the diagnostic criteria of WM.Microscopically,bone marrow and lymph nodes were infiltrated by small lymphocytes,plasmacytoid lymphocytes or plasma cells.The cells expressed pan B-cell markers and showed immunoglobulin light chain restriction.There was no expression of CD5,and low expression of CD23 and CD10;Ki-67 index was usually low.The positive rate of MYD88 L265P mutation was 73.9%(17/23).Most of the patients were treated with rituximab combined with alkylating agents,nucleoside analogues or immunomodulators,and the few patients with relapse or progression were treated with Ibutinib.During the 3-168 months′follow-up period,recurrence or progression were seen in nine cases.Thrombocytopenia,elevatedβ2-microglobulin and high-risk group were associated with recurrence or progression of the disease(P<0.05).The overall survival(OS)and progression-free survival(PFS)of the high-risk patients were significantly lower than those of the low-medium risk patients(P<0.05).Conclusions LPL/WM is an exclusive diagnosis;the detection of MYD88 L265P mutation has high diagnostic value,but it is not specific.These cases should be assessed comprehensively for their clinical manifestation,serum IgM protein level and immunophenotype.The overall prognosis of LPL/WM is good,but there are still a small number of high-risk patients with rapid progress,and so the symptomatic patients should be diagnosed accurately and treated in a timely manner.