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 (cIg) FISH from 75 paired samples for myeloma risk stratification. CIg 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 (cIg) staining with FISH, the benefits of cIg FISH have never been directly demonstrated in a controlled study.


METHODS
Seventy-five samples from patients with PCNs were analyzed by concomitant conventional FISH and cIg 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, cIg 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, cIg 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 cIg FISH vs. 0% to 13% by conventional FISH (median, 54% vs. 9%). Cases with insufficient PCs for cIg FISH had only normal conventional FISH results.


CONCLUSIONS
CIg FISH improves reliability of FISH testing for PCNs by eliminating borderline results. In myelomas with an IGH translocation, myeloma cells invariably carry the abnormality.
Esoterix Genetic Laboratories, LLC, New York, NY 10019, USA. dongy@labcorp.com
Henry
H
Dong
Hai-Su
HS
Yang
Sundar
S
Jagannath
Christine F
CF
Stephenson
Pauline
P
Brenholz
Amitabha
A
Mazumder
Ajai
A
Chari
D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D002869:Chromosome Aberrations; D020732:Cytogenetic Analysis / Q000379:methods*; D003593:Cytoplasm / Q000235:genetics / Q000378:metabolism; D005260:Female; D006801:Humans; D007136:Immunoglobulins / Q000737:chemistry*; D017404:In Situ Hybridization, Fluorescence / Q000379:methods*; D008297:Male; D008875:Middle Aged; D009101:Multiple Myeloma / Q000175:diagnosis / Q000235:genetics / Q000378:metabolism; D054219:Neoplasms, Plasma Cell / Q000175:diagnosis* / Q000235:genetics / Q000378:metabolism; D010950:Plasma Cells / Q000378:metabolism; D015203:Reproducibility of Results; D012680:Sensitivity and Specificity; D055815:Young Adult
D007136:Immunoglobulins