Characterization of Non-Secretory Plasma Cell Myeloma (PCM)
Jeanette Ramos, Daisy Alapat, Robert Lorsbach. University of Arkansas for Medical Sciences, Little Rock, AR
Background: PCM is one of the most common lymphoid malignancies, and in the preponderance of cases is associated with the production of a monoclonal immunoglobulin molecule (MIg), which is detectable by various methodologies including serum protein electrophoresis, immunofixation electrophoresis (IFE) or serum free light chain analysis (FLC). However, a minor subset of PCM patients lacks a detectable MIg and is designated as non-secretory PCM (NS-PCM). The aim of this study was to characterize the pathologic and genetic features of bona fide NS-PCM, as stringently defined by negativity for a MIg by the most sensitive methods, i.e., IFE and FLC.
Design: The pathology laboratory information system at UAMS was queried to identify cases of NS-PCM. Such cases were defined as lacking a detectable MIg by IFE or FLC in either serum or urine. Immunohistochemistry (IHC), Ig light chain in situ hybridization (LC-ISH), and flow cytometry (FC) to characterize cytoplasmic LC expression were performed using routine methods. Fluorescent in situ hybridization (FISH) was performed to detect del(13q), del(17p), t(4;14)(p16.3;q32), t(11;14)(q13;q23), and t(14;16)(q32;q23).
Results: Eight cases were identified which fulfilled our criteria for NS-PCM. Of these, 6/7 cases were negative for LC expression by ISH, with 1 case weakly λ positive; the 8th case was κ positive by LC-IHC. Ig heavy chain (HC)-IHC was performed in 4 cases, with expression of α HC in 3 cases and γ HC in the third. By FC, all 8 cases were negative for LC expression. FISH and/or metaphase cytogenetics were available for all cases and revealed: t(11;14) in 5/8 cases, monosomy 13 in 4/8 cases, and del(17p13) in 2/5 cases by FISH.
Conclusions: In the past, many studies of NS-PCM included hyposecretory PCMs due to the unavailability of highly sensitive methods of MIg detection. In this study, we characterize 8 NS-PCM cases defined by the most stringent criteria of MIg negativity as assessed by both IFE and serum FLC analysis. The lack of Ig LC transcripts in 75% of analyzed cases suggests that the non-secretory status in most of these cases is attributable to defective LC gene expression or reduced LC transcript stability, rather than defective Ig assembly or secretion. HC expression was detected in 4/4 analyzed cases, 3 of which were LC-ISH negative, suggesting that defective Ig secretion is mainly due to abnormalities in LC gene and/or protein expression. Interestingly, in 4 cases where Ig HC expression was analyzed, 3/4 expressed α HC. Genetic analysis revealed that the t(11;14) is significantly over-represented in NS-PCM, being present in 62% of cases.
Wednesday, March 6, 2013 1:00 PM
Poster Session VI # 226, Wednesday Afternoon