Rapid Disappearance of Testicular Plasmacytoma after Treatment with Lenalidomide plus Dexamethasone

doi:10.4236/ojpathology.2012.24029

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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

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.

Email: *[email protected]

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)

(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)

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.

REFERENCES

[1] H. M. Turk, S. Komurcu, A. Ozet, O. Kuzhan and O.

Gunhan, “An Unusual Presentation of Extramedullary

Plasmacytoma in Testis and Review of the Literature,”

Medical Oncology, Vol. 27, No. 4, 2010, pp. 1378-1380.

doi:10.1007/s12032-009-9390-x

[2] H. S. Levin and F. K. Mostofi, “Symptomatic Plasmacy-

toma of the Testis,” Cancer, Vol. 25, No. 5, 1970, pp.

1193-1203.

doi:10.1002/1097-0142(197005)25:5<1193::AID-CNCR2

820250527>3.0.CO;2-6

[3] G. Chica, D. E. Johnson and A. G. Ayala, “Plasmacytoma

of Testis Presenting as Primary Testicular Tumor,” Urol-

ogy, Vol. 11, No. 1, 1978, pp. 90-92.

doi:10.1016/0090-4295(78)90213-3

[4] N. F. Gowing, “Malignant Lymphoma of the Testis,”

British Journal of Urology, Vol. 36, 1964, pp. 85-94.

[5] D. W. Hayes, W. A. Bennett and F. J. Heck, “Extrame-

dullary Lesions in Multiple Myeloma: Review of Litera-

ture and Pathologic Studies,” AMA Archives of Pathology,

Vol. 53, No. 3, 1952, pp. 262-272.

[6] G. Anghel, N. Petti, D. Remotti, C. Ruscio, F. Blandino

and I. Majolino, “Testicular Plasmacytoma: Report of a

Case and Review of the Literature,” American Journal of

Hematology, Vol. 71, No. 2, 2002, pp. 98-104.

doi:10.1002/ajh.10174

[7] A. M. Avitable, T. S. Gansler, J. E. Tomaszewski, P.

Hanno and M. I. Goldwein, “Testicular Plasmacytoma,”

Urology, Vol. 34, No. 1, 1989, pp. 51-54.

doi:10.1016/0090-4295(89)90159-3

[8] P. I. Oppenheim, S. Cohen and K. H. Anders, “Testicular

Plasmacytoma. A Case Report with Immunohistochemi-

cal Studies and Literature Review,” Archives of Pathol-

ogy & Laboratory Medicine, Vol. 115, No. 6, 1991, pp.

629-632.

[9] M. Castagna, P. Gaeta, M. Cecchi, G. L. Pagni and R.

Pingitore, “Bilateral Synchronous Testicular Involvement

in Multiple Myeloma. Case Report and Review of the Lit-

erature,” Tumori, Vol. 83, No. 4, 1997, pp. 768-771.

[10] J. A. Ferry, R. H. Young and R. E. Scully, “Testicular and

Epididymal Plasmacytoma: A Report of 7 Cases, Include-

ing Three That Were the Initial Manifestation of Plasma

Cell Myeloma,” The American Journal of Surgical Pa-

thology, Vol. 21, No. 5, 1997, pp. 590-598.

doi:10.1097/00000478-199705000-00013

[11] H. Ulrich, “Multiple Myeloma,” Archives of Internal

Medicine, Vol. 64, No. 5, 1939, pp. 994-1016.

doi:10.1001/archinte.1939.00190050100008

[12] S. D. Fossa, M. Cvancarova, L. Chen, A. L. Allan, J.

Oldenburg, D. R. Peterson and L. B. Travis, “Adverse

Prognostic Factors for Testicular Cancer-Specific Sur-

vival: A Population-Based Study of 27,948 Patients,”

Journal of Clinical Oncology, Vol. 26, No. 6, 2011, pp.

963-970. doi:10.1200/JCO.2010.32.3204

[13] N. A. Mayr, B. C. Wen, D. H. Hussey, C. P. Burns, J. J.

Staples, J. F. Doornbos and A. P. Vigliotti, “The Role of

Radiation Therapy in the Treatment of Solitary Plas-

macytoma s,” Radiotherapy and Oncology: Journal of the

European Society for Therapeutic Radiology and Oncol-

ogy, Vol. 17, No. 4, 1990, pp. 293-303.

doi:10.1016/0167-8140(90)90003-F

[14] M. Alvarez-Mugica, A. J. Monzon, V. B. Vazquez, C. A.

Andrea, J. M. F. Gomez, R. C. G. Alvarez and F. J. R.

Sejas, “Secondary Testicular Plasmocytoma,” Archivos

Espanoles de Urologia, Vol. 60, No. 1, 2007, pp. 99-102.

[15] M. T. Krauth, A. Bankier, P. Valent, P. Kalhs and J.

Drach, “Sustained Remission Including Marked Regres-

sion of a Paravertebral Plasmacytoma in a Patient with

Heavily Pretreated, Relapsed Multiple Myeloma after

Treatment with Bortezomib,” Leukemia Research, Vol.

29, No. 12, 2005, pp. 1473-1477.

doi:10.1016/j.leukres.2005.05.003

[16] R. Laura, M. T. Cibeira, C. Uriburu, S. Yantorno, O.

Salamero, J. Blade and E. Montserrat, “Bortezomib: An

Effective Agent in Extramedullary Disease in Multiple

Myeloma,” European Journal of Haematology, Vol. 76,

No. 5, 2006, pp. 405-408.

doi:10.1111/j.0902-4441.2005.t01-1-EJH2462.x

[17] G. Damaj, M. Mohty, N. Vey , E. Dincan, R. Bouabdallah,

Rapid Disappearance of Testicular Plasmacytoma after Treatment with Lenalidomide plus Dexamethasone

158

C. Faucher, A. M. Stoppa and J. A. Gastaut, “Features of

Extramedullary and Extraosseous Multiple Myeloma: A

Report of 19 Patients from a Single Center,” European

Journal of Haematology, Vol. 73, No. 6, 2004, pp. 402-

406. doi:10.1111/j.1600-0609.2004.00331.x

[18] M. Dimopoulos, A. Spencer, M. Attal, H. M. Prince, J. L.

Harousseau, A. Dmoszynska, J. San Miguel, A. Hellmann,

T. Facon, R. Foa, A. Corso, Z. Masliak, M. Olesnyckyj, Z.

Yu, J. Patin, J. B. Zeldis and R. D. Knight, “Lenalido-

mide plus Dexamethasone for Relapsed or Refractory

Multiple Myeloma,” The New England Journal of Medi-

cine, Vol. 357, No. 21, 2007, pp. 2123-2132.

doi:10.1056/NEJMoa070594

[19] M. A. Dimopoulos, E. Kastritis, D. Christoulas, M. Mig-

kou, M. Gavriatopoulou, M. Gkotzamanidou, M. Ia kovaki,

C. Matsouka, D. Mparmparoussi, M. Roussou, E. Ef-

stathiou and E. Terpos, “Treatment of Patients with Re-

lapsed/Refractory Multiple Myeloma with Lenalidomide

And Dexamethasone with or without Bortezomib: Pro-

spective Evaluation of the Impact of Cytogenetic Abnor-

malities and of Previous Therapies,” Leukemia: Official

Journal of the Leukemia Society of America, Vol. 24, No.

10, 2010, pp. 1769-1778. doi:10.1038/leu.2010.175

[20] E. Kneppers, H. M. Lokhorst, C. M. Eeltink, G. Huls, M.

J. Kersten, J. Koedam, M. C. Minnema, M. H. van Oers,

R. A. Raymakers, M. R. Schaafsma, E. Vellenga, P. W.

Wijermans, S. Wittebol, P. Sonneveld and S. Zweegman,

“Analysis of Efficacy and Prognostic Factors of Le-

nalidomide Treatment as Part of a Dutch Compassionate

Use Program,” Clinical lymphoma, Myeloma & Leukemia,

Vol. 10, No. 2, 2010, pp. 138-143.

doi:10.3816/CLML.2010.n.020

[21] S. Rosenberg, N. Shapur, O. Gofrit and R. Or, “Plas-

macytoma of the Testis in a Patient with Previous Multi-

ple Myeloma: Is the Testis a Sanctuary Site?” Journal of

Clinical Oncology: Official Journal of the American So-

ciety of Clinical Oncology, Vol. 28, No. 27, 2010, pp.

e456-e458.

[22] J. M. Calvo-Villas, A. Alegre, C. Calle, M. T. Hernandez,

R. Garcia-Sanchez and G. Ramirez, “Lenalidomide Is Ef-

fective for Extramedullary Disease in Relapsed or Re-

fractory Multiple Myeloma,” European Journal of Hae-

matology, Vol. 87, No. 3, 2011, pp. 281-284.

doi:10.1111/j.1600-0609.2011.01644.x

[23] T. Fukushima, T. Nakamura, H. Iwao and H. Umehara,

“Rapid Response of Plasmacytomas to Lenalidomide plus

Low-Dose Dexamethasone Therapy in a Patient with Re-

lapsed Multiple Myeloma,” American Journal of Hema-

tology, Vol. 86, No. 10, 2011, p. 893.

doi:10.1002/ajh.22110

[24] S. Kumar, R. Fonseca, A. Dispenzieri, M. Q. Lacy, J. A.

Lust, L. Wellik, T. E. Witzig, M. A. Gertz, R. A. Kyle, P.

R. Greipp and S. V. Rajkumar, “Prognostic Value of An-

giogenesis in Solitary Bone Plasmacytoma,” Blood, Vol.

101, No. 5, 2003, pp. 1715-1717.

doi:10.1182/blood-2002-08-2441

[25] J. Adams, V. J. Palombella, E. A. Sausville, J. Johnson, A.

Destree, D. D. Lazarus, J. Maas, C. S. Pien, S. Prakash

and P. J. Ellott, “Proteasome Inhibitors: A Novel Class of

Potent and Effective Antitumor Agents,” Cancer Re-

search, Vol. 59, No. 11, 1999, pp. 2615-2622.

[26] A. Palumbo, F. Gay, P. Fa lco, C. Crippa, V. Montefusco,

F. Patriarca, F. Rossini, S. Caltagirone, G. Benevolo, N.

Pescosta, T. Guglielmelli, S. Bringhen, M. Offidani, N.

Giuliani, M. T. Petrucci, P. Musto, A. M. Liberati, G.

Rossi, P. Corradini and M. Boccadoro, “Bortezomib as

Induction before Autologous Transplantation, Followed

by Lenalidomide as Consolidation-Maintenance in Un-

treated Multiple Myeloma Patients,” Journal of Clinical

Oncology, Vol. 28, No. 5, 2010, pp. 800-807.

doi:10.1200/JCO.2009.22.7561