These disorders are diagnosed by a multiparametric approach which includes clinical, radiological, and
laboratory data. Bone marrow aspirate and biopsy is used to assess the number, the distribution pattern,
and the degree of cytologic differentiation of the plasma cells. In multiple myeloma, the plasma cells
usually account for 20% or more of the marrow nucleated cells and frequently appear arranged in cell
clusters or large sheets in the bone marrow biopsy.
Plasma cell enumeration
CD138, which is an optimal marker for plasma cell detection in bone marrow aspirates analyzed by flow
cytometry, can be used to identify and enumerate these cells in paraffin embedded bone marrow biopsies. All
cases of MM, including plasmablastic and leukemic cases, show strong CD138 immunoreactivity. Conversely,
B-cell lymphomas, are usually negative. In lymphoplasmacytic lymphoma (LPC), the plasma cell component
expresses CD138 while the lymphocytes are negative. The combination of CD20 positive lymphocytes
intermingled with CD138 positive plasma cells is a characteristic findings observed in LPC involved marrows.
Light chain restriction
Immunohistochemistry for immunoglobulin light chains is generally used to document the presence of a clonal
plasma cell population in cases of plasma cell dyscrasia and multiple myeloma. We have found that the
assessment of clonality by this technique becomes difficult when the marrow contains less than 5% plasma
cells (Wolf et al., 1990).
Immunoglobulin heavy chain stainin, which is usually accompanied by a high nonspecific background uptake
that makes the interpretation difficult or impossible, is only rarely used. However, heavy chain stains can
be useful in cases of heavy chain disease. Other antigens (e.g. CD56, cyclin D1) can be found expressed in
myeloma cells (San Miguel et al., 1995). Cyclin D1 has been associated with an aggressive clinical behavior
(Hoechtlen-Vollmar et al., 2000).
Amyloid can be seen in the bone marrow in various types of immunosecretory disorders. Amyloid is usually
demonstrated by its characteristic apple-green birefringence with Congo red staining. The distinction
between primary (AL) and secondary (AA) amyloidosis can occasionally be required. The presence of a clonal
plasma cell population in the same biopsy in which amyloid is found usually suggests type AL amyloidosis.
AL and AA amyloid can be more specifically distinguished by the preincubation of biopsy sections with
potassium permanganate followed by Congo red staining. AL amyloid retains its reactivity but Congo red
staining of AA is lost. Immunohistochemical techniques can also be used for amyloid typing. Commercially
available antibodies reactive with various amyloid fibril proteins in routinely processed sections include
anti AL-kappa and lambda, anti AA peptide, transthyretin, beta2-microglobulin, and prealbumin. We have had
little experience with these reagents.
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- Costes V, Magen V, Legouffe E et al.: The Mi15 monoclonal antibody (anti-syndecan-1) is a reliable
marker for quantifying plasma cells in paraffin-embedded bone marrow biopsy specimens. Hum Pathol.
- Chilosi M, Adami F, Lestani M et al.: CD138/syndecan-1: a useful immunohistochemical marker of normal
and neoplastic plasma cells on routine trephine bone marrow biopsies. Mod Pathol. 1999;12:1101-6.
- Hoechtlen-Vollmar W, Menzel G, Bartl R, Lamerz R, Wick M, Seidel D: Amplification of cyclin D1 gene in
multiple myeloma: clinical and prognostic relevance. Br J Haematol. 2000;109:30-8.
- Maia DM, Kell DL, Goates JJ, Warnke RA. The significance of light chain-restricted bone marrow plasma
cells after peripheral blood stem cell transplantation for multiple myeloma. Am J Clin Pathol
- Menke DM, Horny HP, Grisser H, Atkinson EJ, Kaiserling E, Kyle RA. Immunophenotypic and genotypic
characterisation of multiple myelomas with adverse prognosis characterised by immunohistological expression
of the T cell related antigen CD45RO (UCHL-1). J Clin Pathol 1998;51:432-7.
- Pruneri G, Fabris S, Baldini L et al: Immunohistochemical analysis of cyclin D1 shows deregulated
expression in multiple myeloma with the t(11;14). Am J Pathol. 2000: 156:1505-13.
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myeloma. Baillieres Clin Haematol 1995;8:735-59.
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immunohistological staining for immunoglobulin light chains in the diagnosis of benign and malignant plasma
cell proliferations. Histopathology 1993;22:423-8.
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cells in multiple myeloma express a natural killer cell-associated antigen: CD56 (NKH-1; Leu-19). Blood
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