MYD88 L265P is a somatic mutation that has been identified in about 90% of Waldenström macroglobulinemia/lymphoplasmacytic lymphomas (LPLs). It has also been detected in a subset of marginal zone lymphoma (MZL) cases, but the frequency and clinical and histologic features of these mutated MZL cases has only been partially characterized. We have developed a customized TaqMan allele-specific polymerase chain reaction for sensitive detection of this mutation in paraffin-embedded tissue. We analyzed samples from 19 patients with LPL, 88 patients with splenic marginal zone lymphoma (SMZL), 8 patients with nodal marginal zone lymphoma (NMZL), 21 patients with extranodal mucosa-associated lymphoid tissue (MALT), and 2 patients with B-cell lymphoma not otherwise specified. By integrating mutational, histologic, and clinical data, 5 cases were reclassified as LPL. After reclassification, MYD88 L265P was detected in 13/86 (15%) SMZL and in 19/24 LPL (79%) cases. The mutation was absent from NMZL and MALT cases. A strong correlation was found between the presence of an IgM monoclonal paraproteinemia and the MYD88 L265P mutation (P<0.0001). SMZL cases positive for MYD88 L265P were also associated with monoclonal IgM paraproteinemia (4/13 cases; P<0.0283), although with less serum paraproteinemia. They also had a higher frequency of plasmacytic differentiation (9/13) but with no correlation between the presence of mutation and of light chain-restricted plasma cells in tissue. Demonstration of the MYD88 L265 mutation is a valuable tool for the diagnosis of LPL, although some SMZL cases carrying the mutation do not fulfill the diagnostic criteria for LPL.
MYD88 L265P是一种存在于约90%的Waldenström巨球蛋白血症/淋巴浆细胞淋巴瘤（LPLs）中的体细胞突变。在某些亚型的边缘区淋巴瘤（体细胞突变MZL）中也可检测到该突变类型，但仅部分鉴定出MZL的突变频率、临床及组织学特征。作者拓展了TaqMan等位基因特异性聚合酶链反应技术，并探索一种在石蜡包埋组织中能敏感地检测该突变的方法。本组样本包括19例LPL、88例脾脏边缘区淋巴瘤（SMZL）、8例淋巴结内边缘区淋巴瘤（NMZL）、21例结外黏膜相关淋巴组织增生（MALT）和2例非特指B细胞淋巴瘤。通过整合突变、组织学及临床资料分析，其中5例被重新归类为LPL，重新归类后，MYD88L265P在13/86（15%）MALT及19/24（79%）LPL病例中阳性，而在NMZL及MALT病例中阴性。研究发现IgM单克隆蛋白血症与MYD88 L265P突变显著相关（P<0.0001）。尽管伴血清副蛋白血症的病例不多，MYD88 L265P阳性的SMZL病例同样与单克隆性IgM副蛋白血症有关（4/13，P<0.0283）。这些病例也具有高频率的浆细胞分化（9/13），而突变与组织中轻链限制性浆细胞的出现无关。尽管某些SMZL存在MYD88 L265突变这一现象不能满足LPL的诊断标准，但确定MYD88 L265突变对诊断LPL仍是一个有价值的指标。