我们对 41 名伴有淋巴浆细胞分化的 B 细胞疾病患者的福尔马林固定石蜡包埋和脱钙骨髓环钻活检进行了分子分析，以实现更精确的诊断并描述潜在的预后和治疗相关突变。使用市售的下一代测序 (NGS) 淋巴瘤组（Lymphoma Solution，SophiaGenetics）进行分析。结果与临床和病理参数相关。我们的小组涵盖了一系列具有浆细胞分化的 B 细胞疾病，从华氏巨球蛋白血症 (WM) 到具有浆细胞分化的小 B 细胞淋巴瘤 (SBCL-PC) 到 IgM 骨髓瘤 (MM)。最有用的诊断标准包括形态学和免疫表型，作为解释分子分析的先决条件。 MYD88 突变存在于几乎所有 WM 中，但也存在于 50% 的 SBCL-PC 中，而 MM 始终呈阴性。 TP53等驱动突变在相应疾病的早期就已被检测到，表明进展、转化和无进展生存期降低的风险较高。此外，我们在一例进行性 WM 病例中报告了一种新的 BIRC3 移码突变。我们的数据表明，LPL/WM 患者可能会受益于彻底的病理检查和详细的分子分析，以实现精确诊断和有针对性的治疗分配。© 2023。作者。

We performed a molecular analysis of formalin-fixed paraffin embedded and decalcified bone marrow trephine biopsies of 41 patients with a B-cell disorder with lymphoplasmacytic differentiation to enable a more precise diagnosis and to describe potentially prognostic and therapeutic relevant mutations. Analysis was performed with a commercially available next-generation sequencing (NGS) lymphoma panel (Lymphoma Solution, SophiaGenetics). Results were correlated with clinical and pathological parameters. Our group covered a spectrum of B-cell disorders with plasmacytic differentiation ranging from Waldenstroem's macroglobulinemia (WM), to small-B-cell lymphomas with plasmacytic differentiation (SBCL-PC) to IgM myeloma (MM). The most helpful diagnostic criteria included morphology and immuno-phenotype as a prerequisite for the interpretation of molecular analysis. MYD88 mutation was present in nearly all WM, but also in 50% of SBCL-PCs, while MM were consistently negative. Driver mutations, such as TP53, were already detectable early in the course of the respective diseases indicating a higher risk of progression, transformation, and reduced progression-free survival. In addition, we report on a novel BIRC3 frameshift mutation in one case of a progressive WM. Our data indicate that patients with LPL/WM might benefit from thorough pathological work-up and detailed molecular analysis in terms of precise diagnosis and targeted treatment allocation.© 2023. The Author(s).