Baylor University Medical Center Proceedings April 2017 - 192

Plasma cell myeloma with lymphoplasmacytic morphology
and cyclin D1 expression, an uncommon variant
Daniel A. Hale, MD, and John R. Krause, MD

The genetic complexity of multiple myeloma is due in part to the
accumulation of mutations, with primary and secondary events. One
such secondary event is the development of a gene mutation that may
result in overexpression of cyclin D1. The pathway involving cyclin D1 is
intricately involved in cell cycle regulation from the G1 to S phase, and
alterations may contribute to tumorigenesis. We present a case of cyclin
D1-positive multiple myeloma with lymphoplasmacytic morphology and
discuss potential diagnostic pitfalls and effects on prognosis.

he molecular pathway of tumorigenesis in multiple
myeloma (MM) has been extensively studied but
remains to be fully elucidated. A common model for
clonal evolution of MM begins with a primary event,
such as a chromosomal translocation, deletion, or a hyperdiploid state. The accumulation of secondary events occurs next
and is believed to result in progression to MM. Secondary events
include additional chromosomal translocations, deletions, and
mutations involving speciﬁc genes such as KRAS, NRAS, MAF,
and MAFB. One secondary event that can occur is the development of a mutation in cyclin D1. Up to 75% of plasma cell
disorders have at least one mutation of retinoblastoma protein,
p16INK4a, cyclin D1, or a related kinase in the G regulatory
pathway commonly targeted in tumorigenesis (1). It has also
been shown that overexpression of cyclin D1 in MM can present with diﬀerent plasma cell morphologies (2). Cyclin D1 is
involved in the regulation of the cell cycle, and inhibition of
cyclin D1 function can reduce the proliferation of many different cell types (3). Several mechanisms exist that may result
in overexpression of cyclin D1, including the translocation
t(11;14)(q13;q32) involving the immunoglobulin heavy chain
promoter and cyclin D1 (4). One recent study showed that
overexpression of cyclin D1 in MM is an independent negative prognostic variable for overall survival (5). The potential
for shorter overall survival with varied plasma cell morphology
leading to diagnostic pitfalls makes this unique entity one to
be aware of in the ﬁeld of hematology.
CASE REPORT
A 51-year-old woman presented with anemia and chronic
back pain. A workup revealed a compression fracture of L1
192

with an abnormal signal. Serum protein electrophoresis was
negative at presentation, and the peripheral blood showed no
abnormalities. A bone marrow biopsy was performed, and the
aspirate smear showed few scattered plasma cells with numerous
lymphoplasmacytic cells. The classic plasma cell morphology
exhibiting an eccentric nucleus, perinuclear hof, and basophilic
cytoplasm was seen in only 3% of cells on the diﬀerential count.
Lymphoplasmacytic cells accounted for 25% of cells and were
smaller with a markedly increased nuclear-to-cytoplasmic ratio
as compared to the deﬁnitively identiﬁed plasma cell population (Figure 1). A diﬀerential diagnosis of lymphoplasmacytic
lymphoma (LPL) versus lymphoid-appearing MM was entertained. The biopsy and clot preparation showed a 50% to 55%
normocellular marrow with numerous lymphoplasmacytoid
cells and only a few plasma cells.
Immunohistochemistry (IHC) was performed on the clot
preparation, and CD138 showed 65% to 70% positive plasma
cells. Cyclin D1 was diﬀusely positive in the plasma cells
(Figure 1e). The plasma cells were CD56 positive, and a 25%
to 30% subset of plasma cells was positive for CD20. In situ
hybridization showed a >20-to-1 ratio of kappa to lambda. IHC
conﬁrmed that the number of plasma cells was underestimated
and convincingly showed that the lymphoplasmacytic cells were
indeed plasma cells.
Flow cytometry found 21% variably sized plasma cells
expressing CD20, CD56, CD138, and cytoplasmic kappa, but
not CD45. No clonal B-cell population was identiﬁed in the
specimen. Because of the lymphoplasmacytic morphology, the
specimen had been sent for MYD88 L265P mutation testing
and was negative in our case. Chromosome analysis showed
no abnormalities. The ﬁndings were consistent with a cyclin
D1-positive lymphoplasmacytic MM involving 65% to 70%
of marrow cellularity.
The patient received four cycles of Revlimid-Velcadedexamethasone induction with partial response measured by
From the Department of Pathology (Hale) and the Division of Hematopathology
(Krause), the Charles A. Sammons Cancer Center, Dallas, Texas, and Baylor
University Medical Center at Dallas.
Corresponding author: Daniel A. Hale, MD, Department of Pathology, Baylor
University Medical Center at Dallas, 3500 Gaston Avenue, Dallas, TX 75246
(e-mail: Daniel.Hale@BSWHealth.org).
Proc (Bayl Univ Med Cent) 2017;30(2):192-194

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