• myeloma;
  • immunohistochemistry;
  • flow cytometry;
  • gene expression

Nadav et al (2006) showed that in multiple myeloma (MM), flow cytometric analysis significantly underestimates the number of plasma cells (PCs) when compared with counting PCs in aspirate smears. They also presented evidence suggesting that the cause of this underestimation is that flow cytometry samples lack spicules, to which MM cells are adherent. These appear to be sound observations. As an extension of this concept, it is important to reference the consistent observation, published elsewhere as well as in this journal (Terpstra et al, 1992; Sukpanichnant et al, 1994) that, moreover, even aspirate smears significantly underestimate PCs, when compared with a trephine core biopsy. Using immunohistochemistry (IHC) in a study of >350 cases, we found that the core biopsy contained a greater percentage of PCs than the aspirate in 44% of cases and that the average difference exceeded 20% (Ely & Knowles, 2002). Because MM PCs express large quantities of adhesion molecules, such as CD138 and CD56, MM PCs bind strongly to other MM cells as well as to stroma. As such, a large proportion of the PCs often do not come out in the aspirate. Therefore, despite the persistent use of aspirates as diagnostic criteria, it is only through examination of an intact histologic section that the extent of a PC infiltrate can be made with confidence. This is probably why the percentage of core biopsy marrow space composed of PCs is a significant prognosticator while the percentage of PCs in an aspirate is not (Pich et al, 1997). Moreover, because MM contains niche-subpopulations, if investigators only examine MM proteins or RNA from an aspirate, it is likely that their data will not include the most adherent subpopulations. The impact of this exclusion is likely to be important. For these reasons, core biopsy IHC data are often superior to flow cytometry for immunophenotypic analysis in MM (Ely et al, 2005). It would be prudent, therefore, to include core biopsy IHC in any study of MM gene expression. Also, it would be prudent to include IHC percentages of PCs rather than aspirate findings as diagnostic criteria for MM.


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  2. References
  • Ely, S.A. & Knowles, D.M. (2002) Expression of CD56/NCAM correlates with the presence of lytic bone lesions in multiple myeloma and distinguishes myeloma from MGUS and lymphomas with plasmacytoid differentiation. American Journal of Pathology, 160, 12931299.
  • Ely, S., Diliberto, M., Niesvizky, R., Baughn, L.B., Cho, H., Hatada, E., Knowles, D.M., Lane, J. & Chen-Kiang, S. (2005) Mutually exclusive cyclin dependent kinase 4/cyclin D1 and cyclin dependent kinase 6/cyclin D2 pairing inactivates retinoblastoma and promotes cell cycle dysregulation in multiple myeloma. Cancer Research, 65, 1134511353.
  • Nadav, L., Katz, B.-Z., Baron, S., Yossipov, L., Polliack, A., Deutsch, V., Geiger, B. & Naparstek, B. (2006) Diverse niches within multiple myeloma bone marrow aspirates affect plasma cell enumeration. British Journal of Haematology, 133, 530532.
  • Pich, A., Chiusa, L., Marmont, F. & Navone, R. (1997) Risk groups of myeloma patients by histologic pattern and proliferative activity. American Journal of Surgical Pathology, 21, 339347.
  • Sukpanichnant, S., Cousar, J.B., Leelasiri, A., Graber, S.E., Greer, J.P. & Collins, R.D. (1994) Diagnostic criteria and histologic grading in multiple myeloma: histologic and immunohistologic analysis of 176 cases with clinical correlation. Human Pathology, 25, 308318.
  • Terpstra, W.E., Lokhorst, H.M., Blomjous, F., Meuwissen, O.J. & Dekker, A.W. (1992) Comparison of plasma cell infiltration in bone marrow biopsies and aspirates in patients with multiple myeloma. British Journal of Haematology, 82, 4649.