Novak P M, Mattson J C, Crisan D, Chen J, Poulik M D, Decker D
W.A. Foote Memorial Hospital, Jackson, MI, USA.
Eur J Haematol. 1995 Apr;54(4):254-61. doi: 10.1111/j.1600-0609.1995.tb00680.x.
The occurrence of multiple myeloma (MM) and a second B-cell neoplasm in the same patient is a rare event. We present 2 such patients, and provide evidence to support the presence of separate clones in these coexisting neoplasms. In the first case, MM became evident 14 months after the diagnosis of chronic lymphocytic leukemia (CLL). In past reports, most occurrences of this association, when investigated, have been regarded to be biclonal disease processes; however, with few exceptions, most were documented by immunologic studies alone. To establish the clonality in our case of CLL with MM, we examined both immunophenotypic data obtained by standard two-color flow cytometric analysis, and patterns of immunoglobulin gene rearrangement, using standard Southern analysis and hybridization with 32P-labelled JH and JK probes. This provided evidence for the presence in this patient of two separate monoclonal populations of B cells, manifested as light chain restrictions and gene rearrangements which differed in blood (CLL) and bone marrow (MM) samples. In the second case, MM presented simultaneously with bone marrow lymphocytosis and abnormal peripheral lymphocytes. Clonality studies on blood were not done. Bone marrow B-cell gene rearrangement studies, however, revealed the presence of three bands in the JK blot of significantly different intensities, suggestive of two monoclonal populations. A monoclonal population of small cells with surface B markers and surface IgM was demonstrated by flow cytometry, while a second population of larger cells with intracytoplasmic IgG matching the patient's serum monoclonal protein was detected by immunofluorescence microscopy. The results in these 2 cases expand previous findings of the rare association of MM with a second B-cell neoplasm, and demonstrate the usefulness of molecular diagnostic investigation.
同一患者同时发生多发性骨髓瘤(MM)和第二种B细胞肿瘤是一种罕见事件。我们报告了2例此类患者,并提供证据支持这些共存肿瘤中存在独立的克隆。在第一例中,慢性淋巴细胞白血病(CLL)诊断14个月后出现了MM。在过去的报告中,这种关联的大多数病例在进行研究时,都被认为是双克隆疾病过程;然而,除少数例外,大多数仅通过免疫学研究记录。为了确定我们这例CLL合并MM患者的克隆性,我们检查了通过标准双色流式细胞术分析获得的免疫表型数据,以及免疫球蛋白基因重排模式,采用标准的Southern分析并与32P标记的JH和JK探针杂交。这为该患者存在两个独立的B细胞单克隆群体提供了证据,表现为轻链限制以及血液(CLL)和骨髓(MM)样本中不同的基因重排。在第二例中,MM与骨髓淋巴细胞增多症和外周血淋巴细胞异常同时出现。未对血液进行克隆性研究。然而,骨髓B细胞基因重排研究显示,JK印迹中有三条强度明显不同的条带,提示存在两个单克隆群体。流式细胞术证实存在一群带有表面B标志物和表面IgM的小细胞单克隆群体,而免疫荧光显微镜检测到另一群带有与患者血清单克隆蛋白匹配胞内IgG的较大细胞。这2例病例的结果扩展了之前关于MM与第二种B细胞肿瘤罕见关联的发现,并证明了分子诊断研究的实用性。