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Serologic data regarding monoclonal paraprotein for this cohort was available in 40 LPL cases (89%).
The MYD88 L265P mutation was detected in 42 of 45 cases (XX%) originally diagnosed as LPL, 2 of 53 MZL cases (XX%), and 6 of 220 cases (XX%) originally diagnosed as CLL.
In all 3 cases originally called LPL, atypical features were noted on review.
The consensus diagnosis, on review of the case, was low-grade, chronic B-cell leukemia/ lymphoma, favoring LPL" (Figure 2, A through F).
With the final, revised diagnoses for cases 2 and 11, pyrosequencing identified the MYD88 L265P mutation in 43 of 45 confirmed LPL cases (96%), 2 of 53 MZL cases (4%), and 5 of 219 confirmed CLL cases (2%).
(23, 24) It is also present in small B-cell lymphomas and is widely prevalent in LPL (Table 1).
First, as demonstrated in Table 1, the percentage of LPL cases that were positive for the MYD88 mutation appears to be dependent upon the type of assay used.
Second, not all studies of MYD88 in small B-cell lymphoma have included formal clinicopathologic review of "outlier" cases (ie, LPL without the mutation, and MZL or CLL with the mutation).
In this case, the presence of an exclusive plasma cell infiltrate in a patient with an IgM paraprotein on thalidomide treatment raised the possibility of IgM plasma cell myeloma, which is a rare entity that is difficult to separate from plasma cell-predominant LPL. In the absence of additional clinical information, the reviewers felt that IgM myeloma could not be excluded, and this MYD88- case was excluded from the statistical calculation of the assays performance.
In case 1, the polymorphous appearance was within the range of morphology described as acceptable in cases of polymorphous LPL. (26) However, the remote history of poorly characterized "hairy cell leukemia" raised the possibility of transformation of another subtype of B-cell lymphoma/leukemia, and in this case, bone marrow examination would have been especially useful in the differential diagnosis with MZL.
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