IgM monoclonal gammopathy of undetermined significance is a pre-malignant condition for Waldenstrom Macroglobulinaemia (WM) and other B-cell malignancies, defined by asymptomatic circulating IgM monoclonal protein below 30 g/l with a lymphoplasmacytic bone marrow infiltration of less than 10%. A significant proportion, however develop unique immunological and biochemical manifestations related to the monoclonal protein itself in the absence of overt malignancy and are termed IgM-related disorders or more recently Monoclonal Gammopathy of Clinical Significance (MGCS). Treatment indication in these patients is dictated by the pathological characteristics of the circulating IgM rather than the tumour itself. The clinical workup and treatment options vary widely and differ from the regular treatment for WM. The aim of this review is to alert clinicians to IgM MGCS and to provide practical guidance of when to screen for these phenotypes. We discuss clinical characteristics, the underlying clonal profile, diagnostic workup and treatment considerations for five important subtypes: Cold agglutinin disease, type I and II cryoglobulinemia, IgMassociated peripheral neuropathy (PN), Schnitzler syndrome and IgM-associated AL Amyloidosis. The inhibition of the pathogenetic effects of the IgM has led to great success in cold agglutinin disease and Schnitzler syndrome, whereas the other treatments are centred on eradicating the underlying clone. Treatment approaches in cryoglobulinemia and PN are the least well developed. A multidisciplinary approach is required particularly for IgM-related neuropathies and Schnitzler syndrome. Future work exploring novel clone directed agents and pathogenetic IgM-directed therapies is welcomed.

中文翻译：

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具有临床意义的 IgM 单克隆丙种球蛋白病：诊断和管理。

意义不明的 IgM 单克隆丙种球蛋白病是 Waldenstrom 巨球蛋白血症 (WM) 和其他 B 细胞恶性肿瘤的恶变前状态，其定义为无症状的循环 IgM 单克隆蛋白低于 30 g/l，骨髓淋巴浆细胞浸润低于 10%。然而，很大一部分在没有明显恶性肿瘤的情况下发展出与单克隆蛋白本身相关的独特免疫学和生化表现，并被称为 IgM 相关疾病或更近的具有临床意义的单克隆丙种球蛋白病 (MGCS)。这些患者的治疗指征取决于循环 IgM 的病理特征，而不是肿瘤本身。临床检查和治疗选择差异很大，与 WM 的常规治疗不同。本综述的目的是提醒临床医生注意 IgM MGCS，并为何时筛查这些表型提供实用指导。我们讨论了五种重要亚型的临床特征、潜在克隆特征、诊断检查和治疗注意事项：冷凝集素病、I 型和 II 型冷球蛋白血症、IgM 相关周围神经病 (PN)、Schnitzler 综合征和 IgM 相关 AL 淀粉样变性。IgM 致病作用的抑制在冷凝集素病和 Schnitzler 综合征方面取得了巨大成功，而其他治疗则集中在根除潜在的克隆。冷球蛋白血症和 PN 的治疗方法最不发达。对于 IgM 相关的神经病变和 Schnitzler 综合征，尤其需要多学科方法。