MYD88 (L265P) Somatic Mutation in Marginal Zone B-cell Lymphoma. Am J Surg Pathol. 2015,[Epub ahead of print]

Abstract  MYD88 L265P is a somatic mutation that has been identified in about 90% of Waldenstr&ouml;m 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.

大约90%的Waldenstr&ouml;m巨球蛋白血症/淋巴浆细胞淋巴瘤（LPLs）中存在MYD88 L265P体细胞突变。MYD88 L265P体细胞突变也存在于一部分边缘区淋巴瘤（MZL）亚型中，但是这些突变的MZL的发生频率、临床与组织学特点仅部分有特征性。作者采用TaqMan等位基因-特异性聚合酶链反应研制出一种在石蜡包埋的组织中能够非常敏感的检测出这种突变的方法。本研究样本包括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例结外粘膜相关淋巴组织增生（MALT）和2例非特指B细胞淋巴瘤。通过综合分析突变的、组织学及临床资料，5例被重新分类为LPL。重新分类后，15%（13/86）的SMZL和79%（19/24）的LPL病例中发现MYD88 L265P，而NMZL和MALT病例缺乏这种突变。研究发现IgM单克隆蛋白血症与MYD88 L265P突变显著相关（P<0.0001）。同样MYD88 L265P突变阳性的SMZL病例与单克隆性IgM蛋白血症有关（4/13；P<0.0283），尽管少量病例存在血清蛋白血症；也可出现高频率的浆细胞分化（9/13），然而与突变和轻链限制性浆细胞的出现无关。尽管一些SMZL存在MYD88 L265突变，然而其不满足LPL的诊断标准，因此MYD88 L265突变的出现对于LPL的诊断是一非常有价值的指标。