Almeida J, Orfao A, Mateo G, Ocqueteau M, García-Sanz R, Moro M J, Hernandez J, Ortega F, Borrego D, Barez A, Mejido M, San Miguel J F
Departamento de Medicina, Universidad de Salamanca, Spain.
Pathol Biol (Paris). 1999 Feb;47(2):119-27.
In the present paper we review the immunophenotypic characteristics of plasma cells (PC) and the PC DNA contents from multiple myeloma (MM) and monoclonal gammopathy of undetermined significance (MGUS), and its value for the differential diagnosis between both entities. The strong reactivity for CD38 and the positivity for CD138 are the two best markers for identifying PC. Myelomatous PC display an heterogeneous phenotype consistent with the fact that the neoplastic clone is able to undergo a certain degree of differentiation. In addition, PC from MM patients usually lack surface expression of B-cell associated antigens and frequently display reactivity for markers which are not restricted to the B-cell lineage. In MGUS patients, two clearly defined and distinct PC subpopulations can be identified. One of these PC subpopulations shows phenotypic characteristics identical to those of normal PC, including a very strong reactivity for the CD38 antigen, intermediate/low light scatter characteristics and positivity for CD19, in the absence of CD56, and corresponds to the residual normal bone marrow PC. The second PC subpopulation shows an immunophenotype similar to that of myelomatous PC, characterized by a slightly lower reactivity for CD38 and strong CD56 expression, on the absence of positivity for CD19, these PC corresponding to the clonal counterpart. Using a simultaneous staining for PC and DNA, around 60% of MM and 73% of MGUS patients display DNA aneuploidy, the majority of them being hyperdiploid. However, in contrast to MM patients, in MGUS patients two clearly different PC subsets can be discriminated in most cases (73%): a diploid and an aneuploid (hyperdiploid) subset, corresponding to normal and clonal PC, respectively. Upon comparing hyperdiploid with diploid patients in MM, the former display a better prognosis, in line with the higher incidence of DNA hyperdiploidy in MGUS. A clear correlation between the percentage of S-phase PC and several prognosis features of MM has been found. In spite of these findings, no significant differences in the percentage of pathological S-phase PC are detected between MM and MGUS patients. Regarding the differential diagnosis between MGUS and MM, multivariate analysis shows that the ratio between the number of clonal and normal residual PC is the best single parameter.
在本文中，我们回顾了浆细胞（PC）的免疫表型特征以及多发性骨髓瘤（MM）和意义未明的单克隆丙种球蛋白病（MGUS）中PC的DNA含量，及其在这两种疾病鉴别诊断中的价值。CD38的强反应性和CD138的阳性是鉴定PC的两个最佳标志物。骨髓瘤性PC表现出异质性表型，这与肿瘤克隆能够进行一定程度的分化这一事实相符。此外，MM患者的PC通常缺乏B细胞相关抗原的表面表达，并且经常对不限于B细胞谱系的标志物产生反应。在MGUS患者中，可以鉴定出两个明确界定且不同的PC亚群。其中一个PC亚群表现出与正常PC相同的表型特征，包括对CD38抗原的非常强的反应性、中等/低光散射特征以及CD19阳性，且无CD56表达，对应于残留的正常骨髓PC。第二个PC亚群表现出与骨髓瘤性PC相似的免疫表型，其特征为对CD38的反应性略低且CD56表达强，无CD19阳性，这些PC对应于克隆性对应物。通过对PC和DNA进行同时染色，约60%的MM患者和73%的MGUS患者显示DNA非整倍体，其中大多数为超二倍体。然而，与MM患者不同，在MGUS患者中，大多数情况下（73%）可以区分出两个明显不同的PC亚群：一个二倍体亚群和一个非整倍体（超二倍体）亚群，分别对应于正常PC和克隆性PC。在MM中比较超二倍体患者和二倍体患者时，前者预后较好，这与MGUS中DNA超二倍体的较高发生率一致。已发现S期PC百分比与MM的几个预后特征之间存在明显相关性。尽管有这些发现，但在MM和MGUS患者之间未检测到病理性S期PC百分比的显著差异。关于MGUS和MM的鉴别诊断，多变量分析表明克隆性PC与正常残留PC数量之比是最佳单一参数。
