Risk Stratification of Plasma Cell Neoplasm: Insights From Plasma Cell-Specific Cytoplasmic Immunoglobulin Fluorescence in Situ Hybridization (cIg FISH) vs. Conventional FISH

We directly compared the results of routine fluorescence in situ hybridization (FISH) and plasma cell specific cytoplasmic immunoglobulin (clg) FISH from 75 paired samples for myeloma risk stratification. Clg FISH improves test specificity and sensitivity and tends to eliminate borderline results. It proves that most plasma cells (PCs) consistently carry the abnormality in myelomas with an IGH translocation, whereas routine FISH detects these cells only at variably low levels. Background: Routine cytogenetic analysis of plasma cell neoplasms (PCNs) has a low sensitivity. Conventional fluorescence in situ hybridization (FISH) is not plasma cell (PC) specific and results are diluted by other cells in the sample. Although PC-specific FISH testing has been recommended for multiple myeloma (MM) risk stratification, eg, by combining cytoplasmic immunoglobulin (clg) staining with FISH, the benefits of clg FISH have never been directly demonstrated in a controlled study. Patients and Methods: Seventy-five samples from patients with PCNs were analyzed by concomitant conventional FISH and clg FISH with probes for t(4;14), t(11;14), t(14;16), -13, 17p-, and +3. The results were compared for their reliability, specificity, and consistency. Results: Apart from marginally improving detection threshold in samples with low PC burden, clg FISH identified more abnormal cases (50 vs. 47 cases) and more chromosome abnormalities (113 vs. 103 events) than did conventional FISH. It differentiated del(13q) in myelodysplasia from MM. Remarkably, clg FISH consistently identified a high percentage of abnormal PCs in all cases. It detected IGH translocation in 78% to 100% of PCs in all but 2 positive cases, whereas conventional FISH detected 0% to 46% in these cases (median, 91% vs. 9%). The abnormal cells found in patients with 17p- were 19% to 96% by clg FISH vs. 0% to 13% by conventional FISH (median, 54% vs. 9%). Cases with insufficient PCs for clg FISH had only normal conventional FISH results. Conclusion: Clg FISH improves reliability of FISH testing for PCNs by eliminating borderline results. In myelomas with an IGH translocation, myeloma cells invariably carry the abnormality.