Open Journal of Pathology, 2012, 2, 155-158
Published Online October 2012 (http://www.SciRP.org/journal/ojpathology)
http://dx.doi.org/10.4236/ojpathology.2012.24029
1
Rapid Disappearance of Testicular Plasmacytoma after
Treatment with Lenalidomide plus Dexamethasone
Masao Hagihara1*, Morihiro Inoue1, Jian Hua1, Nobuyasu Iwaki1, Kosuke Yoshioka2,
Takeshi Kobayashi2
1Department of Hematology, Eiju General Ho sp ital, Tokyo, Japan; 2Hematology Division, Tokyo Metropolitan Cancer and Infectious
Diseases Center, Komagome Hospital, Tokyo, Japan.
Received June 2nd, 2012; revised July 6th, 2012; accepted July 18th, 2012
ABSTRACT
We describe a rare case of testicular plasmacytoma first manifesting as a relapse. The patient was initially diagnosed
with IgG-λ-type multiple myeloma and treated with melphalan and prednisolon e plus bortezomib, achieving a complete
remission. Four months later, his left scrotum began to swell and pathological investig ation of a need le biopsy sp ecimen
revealed proliferation of plasma cells expressing IgG-λ, confirming myeloma recurrence. However, bone marrow aspi-
ration samples showed no significant increase in myeloma cells and there was no skewed deviation of the

 ratio
on flow-cytometric analysis. The extramedullary tumors disappeared completely soon after treatment with lenalidomide
plus dexamethasone, and the patient was judged to be in very good partial remission based on negative M-protein re-
sults by serum immunoelectrophoresis. This is the first report, to our knowledge, describing complete disappearance of
a testicular plasmacytoma after treatment with lenalidomide as the key-drug.
Keywords: Plasmacytoma; Testis; Lenalidomide
1. Introduction
Extramedullary plasmacytoma (EMP) is a plasma cell
neoplasm that occurs as a solitary lesion or develops si-
multaneously or secondarily to multip le myeloma (MM).
EMP can involve a wide variety of anatomical sites, but
approximately 85% of all cases have disease in the head
and neck region [1]. Testicular plasmacytoma is ex-
tremely uncommon and estimated to account for 0.03% -
0.1% of all testicular malignancies or around 2% of all
plasma cell neoplasms [2-5]. In previous reports, the
majority of testicular plasmacytoma cases had been diag-
nosed based on local manifestation of sy st emi c pl asma cell
disorders rather than as having a solitary EMP [2,6-9].
Herein, we present a rare case in which testicular in-
volvement without bone marrow invasion was observed
4 months after the first complete remission of MM had
been achieved using a regimen that included bortezomib.
Furthermore, the extramedullary tumor disappeared com-
pletely after treatment with another novel anti-myeloma
reagent, lenalido mide.
2. Case Report
A 78-year-old man was admitted to our hospital in March
2011. Two years before (in 2009), the patient had com-
plained of pain in multiple b ones, which led to a diagno-
sis of IgG-λ-type MM, Durie-Salmon stage II, with mul-
tiple bone fractures (ribs, thoracic and lumbar vertebrae),
elevated serum IgG (6075 mg/dL) and proliferation of
plasma cells (18% of whole nucleated cells) in bone
marrow. After receiving 10 cycles of melphalan and
prednisolone plus bortezomib (MPV) treatment, he had
achieved a complete remission in October 2010. In Feb-
ruary 2011, swelling in his left scrotum manifested. Al-
though there were no significant changes in laboratory
data, his serum IgG level was slightly increased (1872
mg/dL) and a monoclonal band of IgG-λ was identified
by immunoelectrophoresis. At that time, a needle biopsy
of the left scrotum was performed, and the proliferation
of plasma cells was revealed by pathological investiga-
tion. As shown in Figure 1, the plasma cells expressed
the IgG-λ light chain and CD138 when examined immu-
nohistochemically, confirming the tumor to be a mye-
loma recurrence.
On admission, magnetic resonance imaging (MRI)
showed an enlarged mass in the left scrotum and chest
computed tomography (CT) demonstrated a tumor in the
right thoracic pleura (Figures 2(a) and (c)). However,
bone marrow aspiration samples showed no significant
*Corresponding a uthor.

Rapid Disappearance of Testicular Plasmacytoma after Treatment with Lenalidomide plus Dexamethasone
156
(a) (b)
(c) (d)
(e)
Figure 1. Proliferation of plasma cells in testicular tissue.
The sections were stained with (a) Hematoxylin and eosin;
(b) Anti-CD38; (c) Anti-IgG; (d) Anti-λ; (e) Anti-κ; Original
magnification 40.
(a) (b)
(c) (d)
Figure 2. MRI and CT findings at disease onset ((a) and (c ),
respectively) and after treatment ((b) and (d), respectively).
The masses in the left scrotum and right thoracic pleura
disappeared completely after Ld treatment.
increase of myeloma cells, and flow-cytometric analysis
did not reveal a skewed deviation of the
 ratio. The
patient was treated with len alidomide (L: 25 mg/day × 21
days) plus dexamethasone (d: 20 mg on days 1, 8, and
15). After 3 cycles of this treatment, total IgG decreased
to within normal range (less than half of the initial level)
and the left testicular and right thoracic tumors both dis-
appeared completely (Figures 2(b) and (d)). As of Oc-
tober 2011, the patient has continued to receive monthly
Ld treatments and is thought to have entered a period of
very good partial remission (VGPR) based on negative
M-protein results obtained using serum immunoelectro-
phoresis. During these treatments, a moderate skin erup-
tion transiently ap peared but resolved rapidly with shor t-
term application of an anti-allergic drug. The only other
adverse reaction was grade 3 neutropenia, From Decem-
ber 2011 through April 2012, the patient has received
maintenance therapy with low-do se lenalidomide therapy
(10 mg/dL × 3 weeks per every 28-day cycle) and has
remained in VGPR.
3. Discussion
EMP is a rare tumor that can appear at various anatomi-
cal sites but is most frequently found in the respiratory
system or gastrointestinal tract as well as the lymph
nodes or skin [5]. Although testicular plasmacytoma is a
relatively rare disorder, more than 50 cases have been
reported since its first description by Ulrich [10,11].
Anghel et al. reviewed 51 cases in 2002. According to
their report, the median age of patients was 51 years and
higher than th at of testicular cancer [12]. Moreover, they
mentioned that the occurrence of a solitary testicular
plasmacytoma without MM was unusual [6]. In fact, 34
of the 51 cases had previous or simultaneous MM and/or
EMP. Twenty of these 34 cases had a fatal clinical course
with progressive disease with only 4 patients surviving.
In one of Anghel’s cases, the plasmacytoma showed a
tendency to spread not only to the testis but also to other
sites including multiple bones, the lung, skin, and pan-
creas [6].
EMP is widely regarded as being radiosensitive and
can be successfully controlled with local radiotherapy
[13]. For testicular EMP, an orchiectomy followed by
chemotherapy or radiotherapy is considered to be a
therapeutic option [14]. Turk et al. recently reported a
case of MM that presented with a testicular plasmacy-
toma and multiple bone lesions [1]. The patient received
chemotherapy consisting of melphalan and prednisolone
and palliative radiotherapy after orchiecto my. In our case,
as the patient had an extramedullary tumor not only in
the testis but also in the thoracic wall, chemotherapy us-
ing lenalidomide plus low dose dexamethasone was se-
lected as a salvage regimen without orchiectomy.
Since the first d escription by Krauth et al., bortezomib
has been recognized as an effective agent for EMP
treatment [15,16]. However, thalidomide lacks efficacy
against soft-tissue plasmacytoma [17]. Lenalidomide, an
analogue of thalidomide, has much more potent anti-
tumor activity [18] and the response is unaffected by

Rapid Disappearance of Testicular Plasmacytoma after Treatment with Lenalidomide plus Dexamethasone 157
previous bortezomib treatment [19,20]. Rosenberg et al.
presented a case of testicular plasmacytoma with previ-
ous MM in which regression of the mass was achieved
using a combination of bortezomib and lenalidomide [21].
Furthermore, Carovo-Villas et al. recently reported that
lenalidomide in combination with dexamethasone was
effective against extramedullary plasmacytoma in pa-
tients with relapsed or refractory MM [22]. For their 18
reported cases, the overall response was 61%, including a
complete disappearance in 44% of these cases. It was
assumed that lenalidomide could have direct anti-prolif-
erative mechanisms on myeloma cells irrespective of its
existence in the bone marrow stroma or other tissue mi-
croenvironments [23]. Angiogenesis is promoted in plas-
macytoma tissue, such that lenalidomide might exhibit
anti-tumor activity especially through its anti-angiogenic
effects [24]. Adams et al. reported that bortezomib did
not penetrate into testicular tissue [25]. It might be the
reason why plasmacytoma appeared especially in testis.
Our experience might indicate that lenalidomide could
possibly be distributed in testis.
Carovo-Villas et al. noted that 3 of 11 patients re-
lapsed and new strategies were thus necessary to over-
come treatment resistance of the disease [22]. Recently,
abundant encouraging data have been accumulated re-
garding the clinical significance of maintenance therapy
using lenalidomid e [26]. Therefore, we are still now giv-
ing this patient low-dose lenalidomide alone, as mainte-
nance therapy, even though attained VGPR.
In conclusion, we demonstrated an excellent clinical
effect of lenalidomide on a rare type of testicular plas-
macytoma in a patient with relapse after administration
of bortezomib, the widely accepted first choice for the
EMP treatment.
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