Waldenström Macroglobulinaemia: The Impact of Cytogenetic Analysis.
Authors: Jimenez-Zepeda Victor H. , Chng Wee-Joo , Fonseca Rafael 
Published: April 2020

Background Waldenström macroglobulinaemia (WM) is an uncommon indolent B-cell lymphoproliferative characterized by bone marrow infiltration by lymphoplasmacytic cells and an IgM paraproteinemia. This study analyzed the impact of cytogenetics in WM and the pattern of evolution in 73 cases from the Mitelman database and 14 cases evaluated at the Mayo Clinic Arizona (MCA).

Patients and Methods The Mitelman database of Chromosome aberrations in cancer (Mitelman et al., 2007) was searched, and 73 WM karyotypes were selected. We also evaluated 14 cases seen at MCA with karyotype analysis at diagnosis. An Excel spreadsheet in which the rows of the first column were labeled to represent each band of a 360-band human chromosome ideogram was created as previously described (Hoglund et al., 2001; Horsman et al., 2003) All karyotypes were scored individually in successive columns for net gain and loss of each chromosome band (loss=0 and gain=1). Recurrent abnormalities were defined as those that were involved in &gt;5% of cases. Histograms of the number of abnormalities per tumor (NAPT) were then plotted, and the modal value extracted as variable called time to occurrence. Statistics correlation between the presence and absence of different abnormalities was analyzed using Spearman correlation matrices. P value of &lt;0.05 was considered as statistical significan

Results In total 73 cases of newly diagnosed WM from the Mitelman database were included in the analysis. The median chromosome number was 46 (Range 40 to 49).The most common abnormalities were loss of 6q21 (10%) (Fig 1), +3 (7.1%), loss of X (6%) and −10, −20, −21, +12, +18 and +5 (5.71% respectively). The most common translocation was t(8;14) (4%).The most recurrent breakpoints in our series include: 14q32 (6%), 6q21 (5%), 8q24 (5%), 18q21 (4%) and 19q13 (4%). In the MCA cohort, 14 karyotypes were reviewed and only 3 cases exhibited an abnormal result. Deletion of 6q21, 20q11 and a Robertsonian translocation t(13;14) were reported (3/11, 21%). In the 6q21 case, FISH analysis confirmed the deletion of BLIMP1 on 6q. One case exhibited a 20q deletion in a WM with kidney amyloidosis patient.

Discussion In this comprehensive analysis we show a very small complexity of recurrent abnormalities expressed by conventional karyotype analysis in WM. The incidence of 6q21 deletion was 10% by conventional cytogenetics and it is been reported as high as 34% when analysed by FISH (54% when cytoplasmic immunoglobulin M-FISH was used). Interestingly we report the case of a patient with 20q deletion at diagnosis in the MCA cohort. To date, only a limited number of cases with del(20q) as a sole cytogenetic anomaly have been reported in plasma cell dyscrasias, either at diagnosis or later in the disease course. The recurrent immunoglobulin gene translocation is known to be involved in the initial oncogenetic events in plasma cell dyscrasias and, so it is important to identify whether there are any masked translocations involving immunoglobulin genes and 20q in these cases.

Figure 1. 6q21 deletion and Waldenstrom Macroglobulinaemia Figure 1. 6q21 deletion and Waldenstrom Macroglobulinaemia