Baylor University Medical Center Proceedings April 2017 - 193


be related to MM, but it has been determined to be a separate entity and
is now classified as LPL. Greater than
90% of bone marrow-based LPLs are
positive for the MYD88 L265P mutation (6). Our case was negative for
the MYD88 L265P mutation, and
flow cytometry further helped rule
out WMG by finding a clonal plasma
cell population with no clonal B-cell
population. In our case, it was difficult morphologically to distinguish
a subset of lymphoplasmacytic cells
from lymphocytes or plasma cells; in
a setting of limited IHC, molecular,
e
c
d
and cytogenetic testing, it is an important diagnostic consideration to
include both LPL and MM in the
differential diagnosis.
There is conflicting data regarding the clinical significance of cyclin
D1 expression in MM. Cyclin D1
overexpression was found to identify a subset of MM patients who
are more likely to have prolonged
duration of remission and eventfree survival following autologous
transplantation (7). However, data
from the same study found that
there was not a statistically signifiFigure 1. (a) Scattered lymphoplasmacytic cells with occasional small perinuclear hof and eccentric nuclei with
cant difference in overall survival
rare definitive plasma cell. (b) Higher magnification of plasma cell morphology to include small plasma cells with a
high nuclear-to-cytoplasm ratio. (c) Hematoxylin and eosin section of clot preparation showing numerous lympho- between cyclin D1-positive and cyplasmacytic cells. (d) CD138 immunostain showing a cluster of positive plasma cells. (e) Cyclin D1 immunostain clin D1-negative groups (7). While
the aforementioned study related to
showing a cluster of positive plasma cells.
transplantation, Moreau et al conducted a study to further investigate the prognostic value of
decreasing free light chains. Due to side effects, the regimen
specific chromosome rearrangements in MM patients treated
was altered, resulting in disease progression measured by rising
with intensive chemotherapy. They found that patients with
free light chains. If a very good partial response is achieved,
chromosomal translocation t(11;14) displayed favorable outthen the patient will be evaluated for autologous stem cell
transplantation.
comes in the form of longer overall survival as compared to
patients with neither t(4;14) or t(11;14) (8). Cook et al also
DISCUSSION
showed that IHC staining for cyclin D1 overexpression is associThe diagnosis of cyclin D1-positive MM in our case was
ated with a longer overall survival time (9). Yet another study
established by IHC, flow cytometry, and molecular testing.
revealed that cyclin D1 expression in MM treated with novel
These tests allowed us to rule out entities with lymphoplasmaagents predicts a shorter overall survival as compared to cyclin
cytoid morphology such as Waldenström's macroglobulinemia
D1-negative MM cases (5). This study's participants consisted
(WMG), mantle cell lymphoma, and chronic lymphocytic
of a predominantly non-transplant-eligible population.
leukemia. It is important to keep a high suspicion for cyclin
The wide variability in results for cyclin D1 overexpression
suggests there are numerous unaccounted-for variables affectD1-positive plasma cells in cases that show few classic plasma
ing disease progression relative to cyclin D1 levels. This large
cells and numerous lymphoplasmacytic cells, which might
number of variables may contribute to the lack of consensus
lead to a misdiagnosis of lymphoma if additional testing is not
regarding cyclin D1 expression in MM.
performed.
Initially WMG was the primary consideration. WMG is a
1. Chandler A, Schultheis B, Bergmann J, Willer A, Hegenbart U, Ho AD,
neoplasm of small B-cell lymphocytes, plasmacytoid lymphoGoldschmidt H, Hehlmann R. Alterations of the cyclin D1/pRb/
cytes, and plasma cells with bone marrow involvement and an
p16(INK4A) pathway in multiple myeloma. Leukemia 2002;16(9):1844-
IgM monoclonal gammopathy. WMG was once considered to
1851.
a

April 2017

b

Plasma cell myeloma with lymphoplasmacytic morphology and cyclin D1 expression, an uncommon variant

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