Extramedullary plasmacytoma invading the bladder: case report and review of the literature

Urologic Oncology: Seminars and Original Investigations 21 (2003) 419 – 423

Review article

Extramedullary plasmacytoma invading the bladder: case report and review of the literature Alvin Lo´pez, M.D.a, Freddy Me´ndez, M.D.b,*, Antonio Puras-Ba´ez, M.D., F.A.C.S.a b

a Department of Urology, University of Puerto Rico, San Juan, Puerto Rico Department of Urology, Tulane University School of Medicine, New Orleans, LA, USA

Received 17 January 2003; received in revised form 1 April 2003; accepted 6 May 2003

Abstract Multiple myeloma is characterized by neoplastic proliferation of a single clone of plasma cells engaged in the production of a monoclonal protein. This condition affects mainly the bone marrow, but extramedullary manifestations can be seen in any organ. Urinary bladder involvement is extremely rare, with only 14 cases reported in the literature to our knowledge. Herein, we report a large extramedullary bladder plasmacytoma arising in a patient with history of multiple myeloma. A 78-year-old woman with history of multiple myeloma, currently in remission, presented with a large intravesical tumor. Because the tumor was considered to have characteristics of anaplastic neoplasm from transitional cell origin with evidence of deep muscular invasion, a radical cystectomy was performed. A subsequent microscopic evaluation of the cystectomy specimen revealed round cells with an eccentric cartwheel-like nucleus suggestive of plasmacytoma. The diagnosis was further confirmed with immunohistochemical studies. It is difficult, according to the literature, to distinguish bladder plasmacytoma from anaplastic transitional cell tumors. It is important to provide the pathologist with an appropriate history and to have a high index of suspicion for bladder plasmacytoma in patients with previous diagnosis of multiple myeloma and bladder mass. © 2003 Elsevier Inc. All rights reserved. Keywords: Multiple myeloma; Bladder tumor; Transitional cell carcinoma

1. Introduction

2. Case reports

Multiple myeloma is characterized by neoplastic proliferation of a single clone of plasma cells engaged in the production of a monoclonal protein. This condition is systemic in nature but originates and affects mainly the bone marrow in more than 90% of patients. Extramedullary manifestations of plasma cell dyscrasias may arise from any organ, either as a primary tumor or as part of systemic multiple myeloma. These solid lesions most commonly affect the upper respiratory tract, followed by lymphatic tissue, liver, kidneys, skin, and central nervous system (CNS) [1]. Urinary bladder involvement is exceptionally rare with only 14 cases reported in the literature, [2–15] two of these being diagnosed post mortem [6,9]. Herein, we report a patient with history of IgG-␭ monoclonal gammopathy who developed a large extramedullary bladder plasmacytoma treated with radical surgery.

In 1995, a 72-year-old woman with history of arterial hypertension and coronary artery disease was evaluated for symptoms of weakness and bone pain. Initial laboratory values revealed mild anemia with normal leukocyte and platelet counts. Blood urea nitrogen (BUN), creatinine, and serum electrolytes were normal. Serum globulin was 10.3 g/dl, and total protein was 12.5 g/dl with positive serum and urine electrophoresis for IgG-␭ paraprotein as well as positive Bence Jones proteinuria. Bone marrow aspirate was consistent with the diagnosis of multiple myeloma. Because a skeletal survey showed diffuse metastatic lesions throughout the ribs, hips, and extremities, the patient was diagnosed with stage III myeloma. The patient was treated with melphalan and prednisone chemotherapy, obtaining adequate response clinically and chemically with normalization of serum protein values and improved bone scan studies. Maintenance therapy was continued with interferon and pamidronate with sustained successful results. In April 2001, the patient began complaining of frequency, urgency, and occasional painless gross hematuria. She had no

* Corresponding author. Tel.: ⫹1-504-587-2066; fax: ⫹1-504-588-5059. E-mail address: [email protected] (F. Me´ndez). 1078-1439/$ – see front matter © 2003 Elsevier Inc. All rights reserved. doi:10.1016/S1078-1439(03)00076-0

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A. Lo´pez et al. / Urologic Oncology: Seminars and Original Investigations 21 (2003) 419 – 423

Fig. 1. Abdomen and pelvis CT scan showing bladder mass.

history of smoking and no history of past occupational hazards. Physical examination demonstrated right pelvic fullness at bimanual exam. Laboratory values presented normal hemogram, serum electrolytes, and protein levels. Urinalysis revealed microhematuria without evidence of plasma cells. Computerized tomography showed a large intravesical mass associated with thickening of the right lateral wall and dome of the bladder with possible extravesical local extension. There was no hydronephrosis or adenopathy (Figure 1). Cystoscopy revealed a broad base tumor extending from the right lateral wall to the dome of the bladder (Figure 2). Pathological examination from the transurethral resection of the bladder tumor (TURBT) was initially considered to show characteristics of anaplastic neoplasm from transitional cell origin infiltrating muscularis propria (Figure 3).

Neoadjuvant chemotherapy cycles with Paclitaxel (Taxol) and Carboplatin were given due to the advanced and aggressive nature of this tumor and to attempt to diminish the size of the mass to make it amenable to resection. Follow-up magnetic resonance imaging (MRI) showed no improvement with this treatment (Figure 4). In view of progressive worsening of her irritative symptoms and hematuria, radical cystectomy was performed in August 2001. Intraoperative findings revealed a large multinodular tumor extrinsically infiltrating the bladder wall, mostly at the right and posterior aspect. Postoperative recovery was uneventful. Pathological examination of the complete bladder specimen showed diffuse infiltration of characteristic oval or round cells with an eccentric cartwheel-like nucleus suggestive of plasmacytomas (Figure 5). This diagnosis was further confirmed with immunohistochemical studies positive for common leukocyte antigen, myeloid, plasma, T cells and B cells, and lambda light chains, along with negative staining for keratins (Figure 6). Review of the original pathology from the TURBT with immunohistochemical analysis also confirmed such diagnosis. The final staging of this tumor was T2b, Nx, Mx. The patient remained asymptomatic, still with normal serum electrolytes and protein values showing no other evidence of progression of her multiple myeloma, until several months after surgery when she suffered a massive heart attack, which led to her death. Patients with advanced multiple myeloma are at an increased risk for cardiac events because of the high incidence of anemia and hypercalcemia. Also, abnormal protein deposition in the myocardium can lead to cardiac amyloid resulting in thickening and malfunction of the interventricular septum.

3. Discussion

Fig. 2. Cystoscopy with bladder lesion.

Carcinoma of the urinary bladder is a common malignancy, accounting for 5.5% of all cancer cases in the United States [16]. Among bladder tumors, more than 90% are

A. Lo´ pez et al. / Urologic Oncology: Seminars and Original Investigations 21 (2003) 419 – 423

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Fig. 3. Pathology of bladder resection.

diagnosed as transitional cell carcinomas [17] being followed in decreasing incidence by squamous cell carcinomas, adenocarcinomas, nonurothelial bladder tumors such as small cell carcinoma, metastatic carcinomas and nonepi-

thelial bladder tumors such as pheochromocytoma, sarcomas, and plasmacytoma [18]. Due to the extreme rarity of this condition, the present case, as well as others previously reported, represented a

Fig. 4. Abdomen and pelvis MRI.

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A. Lo´ pez et al. / Urologic Oncology: Seminars and Original Investigations 21 (2003) 419 – 423

Fig. 5. Pathology of cystectomy.

diagnostic challenge to the pathologists. In 1982, Yang et al reported a case of bladder plasmacytoma originally considered to be advanced anaplastic carcinoma of the bladder only to be correctly diagnosed retrospectively after immunochemical pathological review [7]. Another case reported in 1984 by Chaitin et al revealed a partial cystectomy specimen initially interpreted as undifferentiated malig-

Fig. 6. Immunohistochemical studies of cystectomy specimen.

nancy later found to be plasmacytoma after immunoperoxidase studies upon consultation to MDAH [8]. An additional diagnostic dilemma is the extremely rare transitional cell carcinoma with plasmacytoid appearance as reported by Sahin et al [19] in 1991 and Zukerberg et al [20] in 1991. In both reports initial histological evaluation suggested the diagnosis of bladder plasmacytoma but immunohistochemical analysis with strongly positive staining for keratin and negative staining for ␬ and ␭ chains indicated the epithelial nature of the neoplasm. We may conclude from all these reports that the difficulty to distinguish between plasmacytoma and transitional cell carcinoma underlines the important role of immunohistochemical tests in the pathologic diagnosis of plasmacytoma. In our case, the specimen from the TURBT was interpreted as poorly differentiated tumor invading muscular layer. It was not until the radical cystectomy specimen was analyzed histologically that the correct diagnosis was suggested and then confirmed afterward by immunochemical studies. This also reflects the high index of suspicion necessary when a patient with prior history of multiple myeloma complains of lower urinary tract symptoms, even when the plasma cell dyscrasia has been in remission. It is evident, reviewing all previously published cases, that the response to treatment and the outcome in patients with solitary bladder plasmacytoma is better than in those who had lymph node metastasis and those who had systemic multiple myeloma (Table 1). All 10 cases in which there was no lymph node involvement showed favorable outcomes upon follow-up, as reported. Since it was first described in 1924 by Marion and Lereux [2], multiple treat-

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Table 1 Previously reported bladder plasmacytomas with presenting symptoms and follow-up Reference

Age/sex

Presenting symptom

Systemic MM

Lymphadenopathy

Urinary plasma cells

Treatment

Follow-up

Marion et al.2 Gorfain et al.3 Auvigne et al.4

44-M 39-M 62-F

n/a n/a n/a

n/a n/a n/a

no no no

n/a n/a n/a

Rtx Partial Sx ⫹ Rtx Sx

Zaffagnini et al.5 Hansen et al.6 Yang et al.7 Chaitin et al.8 Neal et al.9 Ozan et al.10 Thornhill et al.11 Weide et al.12 Matsumiya et al.13 Ho et al.14 Shpilberg et al.15 Present case

68-F 89-F 47-M 73-M 71-M 28-M 75-F 75-F 68-F 74-F 46-F 72-F

n/a none dysuria and hematuria hematuria hematuria and MM n/a irritative hematuria hematuria irritative irritative and hematuria irritative and hematuria

n/a n/a no no yes n/a yes yes no no yes yes

no yes yes no yes no no yes no no yes no

n/a n/a yes no yes n/a n/a no no n/a yes no

Partial none Ctx ⫹ Partial Ctx ⫹ Partial Ctx Ctx ⫹ Ctx Rtx ⫹ Rtx Sx

Good response, no f/u Disease free at 1.5 y Disease free at 4 y, died of other causes Disease free at 6 y Autopsy finding Disease free at 12 y Disease free at 7 y Died of metastatic disease Disease free at 4 y Good response, no f/u Died of metastatic disease Disease free at 2 y Disease free at 4 y Died of metastatic disease Disease free at 6 m, died of other causes

ment options have been offered for bladder plasmacytomas. Most of the experience treating extramedullary plasmacytomas has come from its most common presentation at the head and neck region. Controversy surrounds a standard treatment when the bladder is the involved organ mainly due to the lack of patients to support controlled trial studies. This condition has been treated with surgery, radiotherapy and chemotherapy, either as single modalities or in different combinations. In the present case the patient was initially treated unsuccessfully with chemotherapeutic agents for poorly differentiated neoplasm, after which radical surgery was performed, achieving excellent local response until the time of her death secondary to cardiac infarction. In patients with extramedullary plasmacytoma previously treated with chemotherapeutic agents, high dose chemotherapy treatment with malphalan can be instituted. The overall survival of patients in this group is no longer than four years. It is important to underline the high index of suspicion necessary to make the diagnosis of bladder plasmacytoma in patients with history of multiple myeloma. It is also important to provide the pathologist with adequate history during submission of tissue. References [1] Marsch WCH, Gross KM. Frequency and pathomorphology of extramedullary manifestations in plasma cell myeloma of the skeleton. Pathol Res Pract 1978;163:115–27. [2] Marion G, Lereux I. Plasmacytome vesical. J d’Urol 1924;18:121. [3] Gorfain AD. Extramedullary plasmacytoma of the bladder with local metastasis. California Med 1949;71:147– 8. [4] Auvigne R, Auvigne J, Kerneis JP. Un cas de plasmacytome de la vessie. J d’Urol 1956;62:85. [5] Zaffagnini V. A case of plasmacytoma of the bladder. J Urol Med Chir 1959;65:804.

Sx Rtx Sx Rtx Sx ⫹ Rtx Rtx Sx

[6] Hansen O. Zur Pathologie des extraossaren Plasmozytoms. Plasmozytome der Harnblase und des Uterus. Zentralbl Allg Path 1974; 118:333. [7] Yang C, Motteram R, Sandeman TF. Extramedullary plasmacytoma of the bladder: a case report and review of literature. Cancer 1982; 50:146 –9. [8] Chaitin BA, Manning JT, Ordon˜ ez NG. Hematologic neoplasms with initial manifestations in lower urinary tract. Urology 1984;23:35– 42. [9] Neal MH, Swearingen ML, Gawronski L, Cotelingam JD. Myeloma cells in the urine. Arch Pathol Lab Med 1985;109:870 –2. [10] Ozan O, Guler M. Extramedullary plasmacytoma of the bladder. Acta Urol Belg 1986;54:431–3. [11] Thornhill JA, Dervan P, Otridge BW, Fitzpatrick JM, Smith JS. Symptomatic plasmacytoma (myeloma) involving the bladder. Brit J Urol 1990;65:542–3. [12] Weide R, Pfluger KH, Gorg C, Rohrmoser L, Neumann K, Havemann K. Multiple myeloma of the bladder and vagina. Cancer 1990;66: 989 –91. [13] Matsumiya K, Kanayama Y, Yamaguchi S, Ueyama Y, Iwasaki M, Osafune M. Extramedullary plasmacytoma of urinary bladder. Urology 1992;40:67–70. [14] Ho DS, Patterson AL, Orozco RE, Murphy WM. Extramedullary plasmacytoma of the bladder: case report and review of the literature. J Urol 1993;150:473– 4. [15] Shpilberg O, Raviv G, Ramon J, Goldwasser B, Ben-Bassat I, Ramot B. Massive hematuria due to extramedullary plasmacytoma invading the bladder. Med Pediatr Oncol 1993;21:67–9. [16] Boring CC, Squires TS, Tong T, et al. Cancer statistics-1995. Cancer J Clin 1995;45:2– 6. [17] Koss LG. Tumors of the urinary bladder. In Firminger H, (ed): Atlas of Tumor 1975. Washington, D. C., Armed Forces Institute of Pathology, 1975. [18] Messing EM, Catalona W: Urothelial tumors of the urinary tract. In Walsh PC, Retik AB, Vaughan ED, Wein AJ (eds). Campbell’s Urology 1998. Philadelphia, 1998. [19] Sahin A, Myhre M, Ro JY, Sneige N, Dekmezian RH, Ayala AG. Plasmacytoid transitional cell carcinoma. Report of a case with initial presentation mimicking multiple myeloma. Acta Cytol 1991;35:277– 80. [20] Zukerberg LR, Harris NL, Young RH. Carcinomas of the urinary bladder simulating malignant lymphoma. A report of five cases. Amer J Surg Path 1991;15:569 –76.