UROPATJSOLOGY
EXTRAMEDULLARY PLASMACYTOMA (EMP) OF URINARY BLADDER KIYOMI MATSUMIYA, M.D. YOSHIO KANAYAMA, M.D. SEIJI YAMAGUCHI, M.D.
YUYA UEYAMA, M.D. MASAYUKI IWASAKI, M.D. MASAO OSAFUNE, M.D.
From the Departments of Urology and Internal Medicine, Minoo City Hospital, and the Second Department of Internal Medicine, Osaka University Hospital, Osaka, Japan
ABSTRACT-An extramedullary plasmacytoma (EMP) is presented with an isolated lesion in the urinay bladder accompanying an IgG-K paraproteinemia. After a short-term oral melphalan administration, the tumor soon regressed together with the paraprotein, and has never recurred during the twoyear follow-up. This is the fourth case of prima y EMP of the urinary bladder reported in the literature.
Extramedullary plasmacytoma (EMP) is an unusual extraskeletal presentation of plasma cell myelomas. It may arise in any site of human tissue and organ, but the majority have been reported in the upper respiratory tract; thus an extremely rare occurrence has been documented in the genitourinary tract. In fact only 3 cases of EMP of the urinary bladder were available so far in the literature. We report on a case of EMP, with a profound involvement in the bladder wall in which a remission was achieved after administration of melphalan. This report will also review the EMP involving the genitourinary tract. Case Report A sixty-eight-year-old Japanese woman, previously in good health, visited our clinic in January 1984, complaining of macroscopic hematuria persisting for the previous two months. Gross hematuria and proteinuria were shown, but microscopic examination revealed no abnormality except for a massive sedimentation of erythrocytes. On cystoscopic examination, a broad basic tumor was found to extend from the posterior wall to the dome of the bladder. The right lateral wall, though covered with
UROLOGY
/ JULY 1992
/ VOLUME
40, NUMBER
1
normal mucosa, was also protruded into the lumen, and the posterior bladder mucosa was studded with reddish nodules. The patient had no other abnormal sign on physical examination. She was admitted to our hospital on January 23, 1984. Urine cytologic test demonstrated no abnormal findings. Intravenous pyelogram showed an intact upper urinary tract. Computerized tomography (CT) scan and transurethral ultrasonography revealed a thickening of the right lateral wall and the dome of the bladder (Fig. 1A). Enlargement of lymph nodes was noted in neither CT scan nor lymphogram. The histologic examination of a biopsy specimen obtained from the posterior bladder wall showed a diffuse infiltration of uniform cells mixed with fine reticular bundles of numerous blood vessels. Since each infiltrating cell had a characteristic round or oval shape with an eccentric cartwheel-like nucleus (Fig. 2), a diagnosis of plasmacytoma was suggested. Serum total protein was 5.9 g/dL with 19.4 percent gamma-globulin. Monoclonal peak was not apparent, but a trace of monoclonal IgG-K was identified by immunoelectrophoresis. Urinary Bence-Jones protein was undetectable.
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FIGURE 2. Photomicrograph of tumor shows plasmacytic proliferation: uniform cells of characteristic round or oval shape with eccentric cartwheel-like nucleus and perinuclear halo.
FIGURE 1. (A) Before treatment, transurethral ultrasonography of bladder shows mass of right lateral wall and dome. (B) Note disappearance of mass after treatment.
Chest x-ray film was clear. Bone scan and skeletal survey were normal. Minute examination of airway and upper, gastrointestinal series, including endoscopic observation and gastric mucosal biopsy, showed no abnormal findings. Bone marrow aspirates from the sternum and the iliac crest revealed abnormality neither in the number nor in morphology of the plasma cells. All the other routine laboratory examinations showed no abnormality. PAP-immunoperoxidase staining performed on the paraffin-embedded biopsy material demonstrated that the tumor cells had both gamma and kappa chains but none of alpha, mu, and lambda chains. Our immunoelectron microscopic study further revealed that the proliferating cells contained the IgG-K in the cisterns of perinuclear space and rough endoplasmic reticulum (Fig. 3). Based on these findings,
Immunoelectron FIGURE 3. microscopy shows presence of gamma chain (left) and kappa chain (right) in cisterns of perinuclear space and rough endoplasmic reticulum.
68
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/ JULY 1992 / VOLUME 40, NUMBER 1
the diagnosis of primary extramedullary plasmacytoma (EMP) of the urinary bladder was established. Systemic chemotherapy with melphalan was chosen as an initial treatment. When the patient received melphalan, 8 mg/day orally, for a week, anorexia and severe myelosuppression with marked thrombocytopenia and granulocytopenia developed. After the therapy was discontinued for thirty days, a reduced dose of melphalan, 2 mg/day, was administered for an additional seven weeks. On July 3, 1984, however, she refused to continue the drug, being unable to stand these unpleasant adverse effects, and she was discharged. At that time, transurethral ultrasonography already identified a reduced thickening of the bladder wall. On June 26, 1985, she returned to our clinic for reevaluation of the tumor extension. Then, to our surprise, cystoscopic examination no longer showed abnormality. Transurethral ultrasonography also revealed only a slight submucosal edema at the dome (Fig. 1B). Histologically, the biopsy material from the dome demonstrated no tumor cells. Immunoelectrophoresis at this time detected no monoclonal protein, and other laboratory tests remained within normal limits. She has been doing well without any recurrence to the present time. Comment Besides the immunologic detection of extracellular monoclonal products, the diagnosis of plasmacytoma depends on histologic examination. Our immunohistochemical study’ disclosed monoclonal cytoplasmic IgG-K in the tumor cells involving the urinary bladder, and confirmed the plasmacytic nature suggested by the histologic examination. The accompanying monoclonal IgG-K paraprotein and its disappearance after the regression of the tumor were thus well correlated to the extent of the myelomatous proliferation in the bladder. Since our clinical survey could not detect any other lesion except for an isolated lesion in the urinary bladder, the present case would deserve a primary extramedullary plasmacytoma (EMP) of the urinary bladder. Plasma cell neoplasia may develop extraskeleta1 lesions in every tissue or organ, either as a part of disseminated myelomatosis or as a primary EMP2 The majority of primary EMP have been reported in the upper respiratory tract or the gastrointestinal tract, and have been rarely encountered in the genitourinary
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JULY 1992
/
VOLUME 40, NUMBER 1
tract. Siemers and CoeP reported a case of an EMP of the kidney. Steinbe& reported a case of EMP of the testis that had been previously treated for EMP of nasopharynx. Steinberg also reviewed 4 cases of a primary EMP of testis. Recently Terzian et al. 5 reported a case of an EMP of testis. In the urinary bladder only 3 cases of primary EMP have been previously documented in the literature.e-8 Urinary sediments may provide diagnostic information in some cases of myeloma of the genitourinary tract. g Conceivably, such tumor cells may migrate into the urine from involved parenchymal tissues, or may fall into the urine from the ulcerated lesion. In this case, urine cytologic test failed to detect abnormality, probably because the plasmacytoma was covered with normal mucosa. Localized EMP has a smaller amount of Mprotein and more favorable prognosis than bone marrow multiple myelomas, possibly because of the smaller tumor burden. Therefore, surgical procedure is indicated as a curative procedure. Furthermore, as Gorfain’ and Yang and Sandernan reported, bladder plasmacytoma is very sensitive to radiation therapy. Wiltshowl also stated the same for localized plasmacytoma of testis. On the other hand, Yang and Sandernan suggested that cyclophosphamide might effectively help the tumor reduction of the bladder plasmacytoma. Because our patient refused any surgical treatment, we chose a chemotherapeutic regimen with melphalan as an initial therapy rather than irradiation, considering the possibility of subclinical dissemination. But the tumor unexpectedly began to regress soon after an administration of melphalan, and disappeared within a year together with accompanying Mprotein. Our clinical observations so far allow us to conclude either the tumor spontaneously regressed or the chemotherapy achieved an immediate complete remission. But we favor the latter possibility, because the tumor had begun to reduce soon after starting the therapy and continued to reduce for several months after the therapy was completed. We think that a chemotherapeutic regimen with melphalan also may be an effective treatment against EMP of the genitourinary tract. Minoo City Hospital Kayano 5-7-l Minoo, Osaka 562, Japan (DR. MATSUMIYA)
69
References 1. Katagiri S, er al: lXvo distinct human myeloma cell lines originating from one patient with myeloma, Int J Cancer 36: 241 (1985). 2. Corwin J, and Lindberg RD: Solitary plasmacytoma of bone vs. extramedullary plasmacytoma and their relationship to multiple myeloma, Cancer 43: 1007 (1979). 3. Siemers PT, and Coel MN: Solitary renal plasmacytoma with palisading tumor vascularity, Radiology 123: 597 (1977). 4. Steinberg D: Plasmacytoma of the testis, Cancer 36: 1470 (1975). 5. Terzian N, et al: Plasmacytoma of the testis, J Urol137: 745
70
(1987). 6. Marion G, and Leroux M: Plasmacytome vesical, J d-urol 18: 121 (1924). 7. Gorfain AD: Extramedullary plasmacytoma of the bladder with local metastasis. California Med 71: 147 (1949). 8. Yang C, and Sandeman TF: Extramedullary plasmacytoma of the bladder, Cancer 50: 146 (1982). 9. Neal MH, and Swearingen ML: Myeloma cells in the urine, Arch Path01 Lab Med 109: 870 (1985). 10. Wiltshow E: The natural history of extramedullary plasmacytoma and its relation to solitary myeloma of bone and myelomatosis, Medicine 55: 217 (1976).
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/ JULY 1992
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40, NUMBER
1
EXTRAMEDULLARY PLASMACYTOMA (EMP) OF URINARY BLADDER KIYOMI MATSUMIYA, M.D. YOSHIO KANAYAMA, M.D. SEIJI YAMAGUCHI, M.D.
YUYA UEYAMA, M.D. MASAYUKI IWASAKI, M.D. MASAO OSAFUNE, M.D.
From the Departments of Urology and Internal Medicine, Minoo City Hospital, and the Second Department of Internal Medicine, Osaka University Hospital, Osaka, Japan
ABSTRACT-An extramedullary plasmacytoma (EMP) is presented with an isolated lesion in the urinay bladder accompanying an IgG-K paraproteinemia. After a short-term oral melphalan administration, the tumor soon regressed together with the paraprotein, and has never recurred during the twoyear follow-up. This is the fourth case of prima y EMP of the urinary bladder reported in the literature.
Extramedullary plasmacytoma (EMP) is an unusual extraskeletal presentation of plasma cell myelomas. It may arise in any site of human tissue and organ, but the majority have been reported in the upper respiratory tract; thus an extremely rare occurrence has been documented in the genitourinary tract. In fact only 3 cases of EMP of the urinary bladder were available so far in the literature. We report on a case of EMP, with a profound involvement in the bladder wall in which a remission was achieved after administration of melphalan. This report will also review the EMP involving the genitourinary tract. Case Report A sixty-eight-year-old Japanese woman, previously in good health, visited our clinic in January 1984, complaining of macroscopic hematuria persisting for the previous two months. Gross hematuria and proteinuria were shown, but microscopic examination revealed no abnormality except for a massive sedimentation of erythrocytes. On cystoscopic examination, a broad basic tumor was found to extend from the posterior wall to the dome of the bladder. The right lateral wall, though covered with
UROLOGY
/ JULY 1992
/ VOLUME
40, NUMBER
1
normal mucosa, was also protruded into the lumen, and the posterior bladder mucosa was studded with reddish nodules. The patient had no other abnormal sign on physical examination. She was admitted to our hospital on January 23, 1984. Urine cytologic test demonstrated no abnormal findings. Intravenous pyelogram showed an intact upper urinary tract. Computerized tomography (CT) scan and transurethral ultrasonography revealed a thickening of the right lateral wall and the dome of the bladder (Fig. 1A). Enlargement of lymph nodes was noted in neither CT scan nor lymphogram. The histologic examination of a biopsy specimen obtained from the posterior bladder wall showed a diffuse infiltration of uniform cells mixed with fine reticular bundles of numerous blood vessels. Since each infiltrating cell had a characteristic round or oval shape with an eccentric cartwheel-like nucleus (Fig. 2), a diagnosis of plasmacytoma was suggested. Serum total protein was 5.9 g/dL with 19.4 percent gamma-globulin. Monoclonal peak was not apparent, but a trace of monoclonal IgG-K was identified by immunoelectrophoresis. Urinary Bence-Jones protein was undetectable.
67
FIGURE 2. Photomicrograph of tumor shows plasmacytic proliferation: uniform cells of characteristic round or oval shape with eccentric cartwheel-like nucleus and perinuclear halo.
FIGURE 1. (A) Before treatment, transurethral ultrasonography of bladder shows mass of right lateral wall and dome. (B) Note disappearance of mass after treatment.
Chest x-ray film was clear. Bone scan and skeletal survey were normal. Minute examination of airway and upper, gastrointestinal series, including endoscopic observation and gastric mucosal biopsy, showed no abnormal findings. Bone marrow aspirates from the sternum and the iliac crest revealed abnormality neither in the number nor in morphology of the plasma cells. All the other routine laboratory examinations showed no abnormality. PAP-immunoperoxidase staining performed on the paraffin-embedded biopsy material demonstrated that the tumor cells had both gamma and kappa chains but none of alpha, mu, and lambda chains. Our immunoelectron microscopic study further revealed that the proliferating cells contained the IgG-K in the cisterns of perinuclear space and rough endoplasmic reticulum (Fig. 3). Based on these findings,
Immunoelectron FIGURE 3. microscopy shows presence of gamma chain (left) and kappa chain (right) in cisterns of perinuclear space and rough endoplasmic reticulum.
68
UROLOGY
/ JULY 1992 / VOLUME 40, NUMBER 1
the diagnosis of primary extramedullary plasmacytoma (EMP) of the urinary bladder was established. Systemic chemotherapy with melphalan was chosen as an initial treatment. When the patient received melphalan, 8 mg/day orally, for a week, anorexia and severe myelosuppression with marked thrombocytopenia and granulocytopenia developed. After the therapy was discontinued for thirty days, a reduced dose of melphalan, 2 mg/day, was administered for an additional seven weeks. On July 3, 1984, however, she refused to continue the drug, being unable to stand these unpleasant adverse effects, and she was discharged. At that time, transurethral ultrasonography already identified a reduced thickening of the bladder wall. On June 26, 1985, she returned to our clinic for reevaluation of the tumor extension. Then, to our surprise, cystoscopic examination no longer showed abnormality. Transurethral ultrasonography also revealed only a slight submucosal edema at the dome (Fig. 1B). Histologically, the biopsy material from the dome demonstrated no tumor cells. Immunoelectrophoresis at this time detected no monoclonal protein, and other laboratory tests remained within normal limits. She has been doing well without any recurrence to the present time. Comment Besides the immunologic detection of extracellular monoclonal products, the diagnosis of plasmacytoma depends on histologic examination. Our immunohistochemical study’ disclosed monoclonal cytoplasmic IgG-K in the tumor cells involving the urinary bladder, and confirmed the plasmacytic nature suggested by the histologic examination. The accompanying monoclonal IgG-K paraprotein and its disappearance after the regression of the tumor were thus well correlated to the extent of the myelomatous proliferation in the bladder. Since our clinical survey could not detect any other lesion except for an isolated lesion in the urinary bladder, the present case would deserve a primary extramedullary plasmacytoma (EMP) of the urinary bladder. Plasma cell neoplasia may develop extraskeleta1 lesions in every tissue or organ, either as a part of disseminated myelomatosis or as a primary EMP2 The majority of primary EMP have been reported in the upper respiratory tract or the gastrointestinal tract, and have been rarely encountered in the genitourinary
UROLOGY
I
JULY 1992
/
VOLUME 40, NUMBER 1
tract. Siemers and CoeP reported a case of an EMP of the kidney. Steinbe& reported a case of EMP of the testis that had been previously treated for EMP of nasopharynx. Steinberg also reviewed 4 cases of a primary EMP of testis. Recently Terzian et al. 5 reported a case of an EMP of testis. In the urinary bladder only 3 cases of primary EMP have been previously documented in the literature.e-8 Urinary sediments may provide diagnostic information in some cases of myeloma of the genitourinary tract. g Conceivably, such tumor cells may migrate into the urine from involved parenchymal tissues, or may fall into the urine from the ulcerated lesion. In this case, urine cytologic test failed to detect abnormality, probably because the plasmacytoma was covered with normal mucosa. Localized EMP has a smaller amount of Mprotein and more favorable prognosis than bone marrow multiple myelomas, possibly because of the smaller tumor burden. Therefore, surgical procedure is indicated as a curative procedure. Furthermore, as Gorfain’ and Yang and Sandernan reported, bladder plasmacytoma is very sensitive to radiation therapy. Wiltshowl also stated the same for localized plasmacytoma of testis. On the other hand, Yang and Sandernan suggested that cyclophosphamide might effectively help the tumor reduction of the bladder plasmacytoma. Because our patient refused any surgical treatment, we chose a chemotherapeutic regimen with melphalan as an initial therapy rather than irradiation, considering the possibility of subclinical dissemination. But the tumor unexpectedly began to regress soon after an administration of melphalan, and disappeared within a year together with accompanying Mprotein. Our clinical observations so far allow us to conclude either the tumor spontaneously regressed or the chemotherapy achieved an immediate complete remission. But we favor the latter possibility, because the tumor had begun to reduce soon after starting the therapy and continued to reduce for several months after the therapy was completed. We think that a chemotherapeutic regimen with melphalan also may be an effective treatment against EMP of the genitourinary tract. Minoo City Hospital Kayano 5-7-l Minoo, Osaka 562, Japan (DR. MATSUMIYA)
69
References 1. Katagiri S, er al: lXvo distinct human myeloma cell lines originating from one patient with myeloma, Int J Cancer 36: 241 (1985). 2. Corwin J, and Lindberg RD: Solitary plasmacytoma of bone vs. extramedullary plasmacytoma and their relationship to multiple myeloma, Cancer 43: 1007 (1979). 3. Siemers PT, and Coel MN: Solitary renal plasmacytoma with palisading tumor vascularity, Radiology 123: 597 (1977). 4. Steinberg D: Plasmacytoma of the testis, Cancer 36: 1470 (1975). 5. Terzian N, et al: Plasmacytoma of the testis, J Urol137: 745
70
(1987). 6. Marion G, and Leroux M: Plasmacytome vesical, J d-urol 18: 121 (1924). 7. Gorfain AD: Extramedullary plasmacytoma of the bladder with local metastasis. California Med 71: 147 (1949). 8. Yang C, and Sandeman TF: Extramedullary plasmacytoma of the bladder, Cancer 50: 146 (1982). 9. Neal MH, and Swearingen ML: Myeloma cells in the urine, Arch Path01 Lab Med 109: 870 (1985). 10. Wiltshow E: The natural history of extramedullary plasmacytoma and its relation to solitary myeloma of bone and myelomatosis, Medicine 55: 217 (1976).
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