Department of Pathology, Christian-Albrechts-University Kiel, Arnold-Heller-Str. 3/14, D-24105, Kiel, Germany.
Medical Department V, Amyloidosis Center, University of Heidelberg, Heidelberg, Germany.
Virchows Arch. 2019 Mar;474(3):353-363. doi: 10.1007/s00428-019-02527-7. Epub 2019 Jan 24.
Immunoglobulin light chain-derived (AL) amyloidosis may occur as a systemic disease usually with dismal prognosis and a localized variant with favorable outcome. We report 29 patients with AL amyloidosis and associated lymphoplasmacytic infiltrate spatially related to amyloid deposits. In 17 cases, the amyloid deposits were classified as ALλ and 12 as ALκ Histopathology in all cases showed relatively sparse plasma cells and B cells without tumor or sheet formation by the lymphoplasmacytic infiltrate. The B cells predominantly showed an immunophenotype of the marginal zone. In situ, hybridization revealed 17 cases with λ- and 10 with κ light chain restricted plasma cells, which was concordant with the AL subtype in each case. Clonal immunoglobulin heavy variable gene (IGHV) or κ light chain rearrangement was found in 23/29 interpretable cases. A single case harbored a MYD88-mutation. Taken together, we detected 27 (93%) cases of AL amyloidosis with an associated light chain restricted and predominantly molecularly clonal plasma cell population. Clinical data were available in 18 patients. Five patients suffered from systemic lymphoma and two from systemic AL amyloidosis. The remaining cases were classified as localized with regard to both, the AL amyloidosis and the light chain restricted plasma cell population. To the best of our knowledge, we herein present the largest cohort of AL amyloidosis associated with a light chain restricted and predominantly molecularly clonal plasma cell population, which we designate as a distinct disease entity: "AL amyloidosis with a localized B cell neoplasia of undetermined significance".
免疫球蛋白轻链衍生的（AL）淀粉样变性症可能作为一种全身系统性疾病发生，通常预后较差，也可能以局部变异型出现，预后较好。我们报告了 29 例伴有淋巴浆细胞浸润的 AL 淀粉样变性症和相关淀粉样沉积物的患者。在 17 例病例中，淀粉样沉积物被归类为 ALλ，12 例为 ALκ。所有病例的组织病理学均显示相对稀疏的浆细胞和 B 细胞，淋巴浆细胞浸润无肿瘤或片状形成。B 细胞主要表现为边缘区的免疫表型。原位杂交显示 17 例存在 λ 轻链限制性浆细胞，10 例存在 κ 轻链限制性浆细胞，与每个病例中的 AL 亚型相符。在可解释的 29 例病例中的 23 例中发现了克隆性免疫球蛋白重可变基因（IGHV）或 κ 轻链重排。仅 1 例存在 MYD88 突变。综合来看，我们检测到 27 例（93%）AL 淀粉样变性症，伴有相关的轻链限制性和主要为分子克隆性浆细胞群体。在 18 例患者中获得了临床数据。5 例患者患有系统性淋巴瘤，2 例患有系统性 AL 淀粉样变性症。其余病例在淀粉样变性症和轻链限制性浆细胞群体两方面均被归类为局限性。据我们所知，我们在此提出了与轻链限制性和主要为分子克隆性浆细胞群体相关的最大 AL 淀粉样变性症队列，我们将其指定为一种独特的疾病实体：“具有局部意义未明的 B 细胞肿瘤的 AL 淀粉样变性症”。
