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Mixed mesodermal tumor of urinary bladder
MIXED MESODERMAL
TUMOR OF URINARY BLADDER*
A Light and Electron Microscopic Study HUNG AARON
DINH
DUONG,
G. JACKSON,
JOSEPH
KOVI,
JOSEPH
R. RANSOME,
GEORGE
W. JONES,
M.D. M.D.
M.D. M.D. M.D.
From the Departments of Pathology and Surgery, Division of Urology, Howard University College of Medicine, Washington, D.C.
ABSTRACT - Light and ultrastructuraljndings in a mixed mesodermal tumor of the urinary bladder are reported. The mesenchymal component of the tumor contained undifferentiated mesenchymal cells and cells with chondroblastic differentiation. The neoplastic chondrocytes displayed an abundance of cytoplasmic microfilaments and had a scalloped cell surface.
Primary tumors of the urinary bladder containing either bone or cartilage are rare. The first case was described by Ordonez in 1856.’ Since then 46 cases have been reported.‘*16 Although the ultrastructural pathology of the urinary bladder in man has been studied extensively, *’ no report could be found in the literature on the fine structure of mixed mesodermal tumor of bladder. We herein describe the light and electron microscopic appearance of a mixed mesodermal tumor of the bladder. Case Report
dermal tumor. Repeat cystoscopy in January, 1980, was negative. Past history revealed a right radical mastectomy in 1965 for breast cancer with apparent cure and hysterectomy for benign disease one year later. In March, 1980, the patient had a second transurethral resection. At this time two independent neoplastic growths were removed. One was located in the left anterolateral wall of the bladder and was considered as a residual or recurrent mixed mesodermal tumor of the bladder. The other growth occupied the left ureteral orifice and proved to be a pure transitional cell carcinoma. The patient underwent a five-day 2,0OO-rad course of radiation therapy after which in April, 1980, ileal conduit and radical cystectomy were done with open intraoperative irradiation to the cystectomy bed and immediate environs. Approximately 3,000 rad were delivered in twenty minutes.
A sixty-five-year-old black woman with a oneyear history of suprapubic discomfort, dysuria, and recent onset of gross hematuria underwent transurethral resection of the bladder in November, 1979. Cystoscopy had revealed the presence of a ball-like tumor attached by a narrow stalk to the left anterolateral wall of the urinary bladder. The resected tumor was diag_ nosed histologically as a malignant mixed meso-
Pathologic findings
*Supported Institute.
in part by Grant CA-26679 from the National Cancer
The cystectomy specimen showed two separate tumors. The first one was located in the left anterolateral wall. It was a pedunculated
UROLOGY
/ APRIL 1981
/ VOLUME
XVII, NUMBER
4
377
FIGURE 1. Radical cystectomy specimen with mixed mesodermal tumor in upper part and transitional cell carcinoma in lower part.
1.7 cm. in the polypoid mass, measuring The surface of the tumor greatest diameter. had a tannish gray color and appeared to be ulcerated. On cut section, the tumor had a short stalk of white color and of hard consistency. The second tumor, located at the left ureteral orifice had a round shape and measured I.2 cm. in diameter. Its surface was tan and somewhat ulcerated. On cut section, it was firm and seemed to invade the entire thickness of the bladder wall (Fig. 1). Histologic examination of the recurrent tumors confirmed that the growth on the left anterolateral wall was a malignant mixed mesodermal tumor, while the second neoplasm at the left ureteral orifice was a pure transitional cell carcinoma. About 85 per cent of the malignant mixed mesodermal tumor was sarcomatous and
by osteoblasts and osteoclasts on left and malignant cartilage on FIGURE 2. (A) Bony trabeculae surrounded right. (B) Closely associated transitional cell carcinoma and malignant cartilage showing great variability in size and shape of neoplastic cells. (C) Nests of transitional cell carcinoma with hyperchromatic and pleomorphic nuclei. (D) Electron micrograph of undiff erentiated mesenchymal cells. Cell at right characterized by numerous short branching segments of rough endoplasmic reticulum; cell at left contains number of lipid droplets {original magnijcation X 4,000).
378
UROLOGY
/ APRIL1931 i VOLUMEXVII,NUMBER4
composed of islands of cartilage and bone. The remaining portion of the tumor was carcinoma and was intimately associated with the sarcoma. Islands of cartilage and bone were separated one from another by a stroma of primitive mesenchymal cells and matrix. These stromal cells possessed hyperchromatic nuclei and displayed frequent mitotic activity. The neoplastic cartilage exhibited abnormal mitoses, hyperchromatic and pleomorphic nuclei also. The bony islands revealed both osteoid and mature bone formation. Osteoblasts and osteoclasts were observed frequently. A transitional zone between the mesenchymal tissue and the malignant cartilage and bone was clearly discerned in many areas (Fig. 2A). The malignant transitional cell element had a papillary configuration at the margin of the tumor. In many areas the epithelium penetrated into the cartilaginous and bony areas. The neoplastic transitional cells were large; the nuclei were pleomorphic and showed numerous mitotic figures (Fig. 2B).
The tumor removed from the left ureteral orifice proved to be a pure transitional cell carcinoma (Fig. 2C). Ultrastructurally, in the mesenchymal component of the mixed mesodermal tumor, two types of cells were visualized. One ceil type was characterized by large, irregular nuclei with prominent nucleoli. The cytoplasm was fairly rich in short, slender profiles of the rough endoplasmic reticulum. Occasionally large, fat vacuoles and cytoplasmic microfilaments were noted (Fig. 2D). The other cell type had a plasma membrane which was rather irregular with both coarse and slender surface projections. The most prominent feature of that cell type was markedly dilated rough endoplasmic reticulum. The distended profiles of the endoplasmic reticulum contained a moderately electron-dense, flocculent, finely granular material. The cytoplasm was exceedingly rich in cytoplasmic filaments (Fig. 3A). The cytoplasmic microfilaments were of undetermined length, measured about
FIGURE 3. {A) Poorly differentiated chondrocyte, note scalloped cell surface and markedly distended cisternae of rough endoplasmic reticulum. Cystoplasm exceedingly rich in microfilaments (L == lysosomej (original magnification X 7,000). (B) Distended profiles of rough endoplasmic reticulum contain moderately electron-dense,Jocculent granular material. Cytoplasmic microfilaments measure 60-80 A in width x 12,000). and form bundles (original mugnijication (C) Peculiar invagination of mitochondria into markedly distended cisternae of rough endoplasmic reticulum; individual mitochondria appears to be surrounded by inverted profiles of RER (original magni$cation X 16,000).
UROLOGY
/
APRIL
1981 /
\‘OLUME
XVII. NlrMBER
4
379
60 to 80 A in diameter and frequently formed bundles (Fig. 3B). Into the markedly dilated cisternae of the rough endoplasmic reticulum, invagination of mitochondria was observed (Fig. 3C). The extracellular matrix of the tumor cells consisted of a variable number of fine filaments separated by electron-lucent amorphous material. The surface of the epithelial cells in the tumor contained many microvilli, however, the cell cytoplasm was generally poorly preserved. Comment Since Ordonez’ reported a malignant bladder neoplasm containing cartilage, 46 tumors including our case containing either bone or cartilage have been added to this group of neoplasms. Of these rare bladder tumors, 20 are malignant mixed mesodermal tumors, 17 are osteosarcomas and chondrosarcomas, and 10 are carcinomas with osseous metaplasia. ‘-” The histogenesis of mixed mesodermal tumors of urinary bladder is still controversial. Several hypothesis have been considered: (1) metaplasia of transitional cell epithelium; (2) stromal metaplasia; (3) transfer of osteoblasts through the blood; and (4) development of osteoblasts from the immature mesenchyme of the wolffian body from which the trigone develops. l3 Electron microscopic study of the mixed mesodermal tumor showed that in contrast to the neoplastic chondronormal chondrocytes, cytes were devoid of glycogen. Rich glycogen content is characteristic of the tumor cells in socalled clear-cell chondrosarcoma. 21 It has been reported, however, that in poorly differentiated chondrosarcoma glycogen particles are decreased or absent.18,20 The neoplastic chondrocytes in the mixed mesodermal tumor were very rich in cytoplasmic microfilaments. In a study comparing the ultrastructure of low-to-high-grade chondrosarcomas, it was found that cytoplasmic filaments were considerably increased in number in higher grade (highly malignant) chondrosarcoma. lg In the present study, peculiar invagination of mitochondria into the markedly distended cisternae of the rough endoplasmic reticulum was noted. Similar findings in the neoplastic cells from the patients with chondrosarcoma were reported. “J In this patient two separate malignant neoplasms were found in the urinary bladder. The
380
mixed mesodermal tulnor was located in the left anterolateral wall, the transitional cell carcinoma was situated at the left ureteral orifice. The chronologic findings of the transurethral resections suggested that the initially detected neoplasm (mixed mesodermal tumor) may have given rise to a metastatic focus in the bladder in which only the epithelial components of the tulnor were expressed. Washington, D.C. 20059 (DR. DUONG) ACKNOWLEDGMENT.
Elliot,
and Tamara
To Kathryn 51. Blanc for their
Berry, Benjamin assistance.
F.
References 1. Ordonez MEC: 2” transformation cartilagineuse de la vessie chez un vieillard, series 3, Gazz. Med. Paris, 11: 824 (1856). 2. Crane rlR, and Tremblay RG: Primary osteogenic sarcoma of the bladder. Complete review of sarcoma of the bladder, Ann. Surg. 118: 887 (1943). 3. Willis RA: Malignant mixed tumor of bladder, Tex. Med. 46: 627 (1950). 4. Powers JH, Hawn C, Van 2, and Carter RD: Osteogenic sarcoma and transitional cell carcinoma occurring simultaneously in the urinary bladder, J. Urol. 76: 263 (1956). 5. Nourse MH: Primary osteogenic sarcoma of the bladder, ibid. 77: 634 (1957). 6. Pang LSC: Bony and cartilagineous tumors of the urinary bladder, J. Pathol. Bacterial. 76: 357 (1958). 7. Nicolai CH, and Spjut HJ: Primary osteogenic sarcoma of the bladder, J. Ural. 82: 497 (1959). 8. Kikuchi K, Nakamura K, and Nakazima 1: An autopsy case of primary osteogenic sarcoma of the urinary bladder, Acta Pathol. Jpn. 15: 287 (1965). 9. Bialik BL: Carcino-osteochondrosarcoma of urinary bladder, Arkh. Patol. 30: 61 (19%). 10. Brinton JA, lto Y, and Olson BS: Carcinosarcoma of the urinary bladder, Cancer 25: 1183 (1970). 11. Beltrami CA, et al: Primary osteochondrosarcoma of the bladder, Riv. Patol. Cli. Sper. 11: 213 (1970). 12. Delides GS: Bone and cartilage in lnalignant tmnors of the urinary bladder, Br. J. Ural. 44: 571 (1972). 13. Chitiyo ME: Primary osteogenic sarcoma of the urinary bladder, J. Pathol. 111: 53 (1973). 14. Koss LG: Tumors of the urinary bladder, in Atlas of Tumor Pathology, series 2, part XII, Washington, D.C., Armed Forces Institute of Pathology, 1974, pp. 93-95. 15. Patterson TH, and Dale GA: Carcinosarcoma of the bladder, J. Ural. 115: 753 (1976). 16. Babaian RJ, et al: Mixed mesodermal tumor of urinary bladder: prognosis and management, Urology 15: 261 (1980). 17. Tannenbaum M: Ultrastructural pathology of the human urinary bladder, in Diagnosis Electron .Microscopy, vol. 2, New York, John Wiley & Sons, Inc., 1979, pp. 221-267. 18. Schajowicz F, et al: Ultrastructure of chondrosarcoma, Clin. Orthop. 100: 378 (1974). 19. Erlandson RA, and Huvos AG: Chondrosarcoma: a light and electron microscopic study, Cancer 34: 1624 (1974). 20. Kahn LB: Chondrosarcoma with dedifferentiated foci. A comparative and ultrastructural study, ibid. 37: 1365 (1976). 21. Le charpentier Y, et al: Clear-cell chondrosarcoma. A report of five cases including ultrastructural study, ihid. 44: 622 (1979).
UROLOGY
/
APRIL
1981
/
VOLUME
XVII, NUMBER
4
TUMOR OF URINARY BLADDER*
A Light and Electron Microscopic Study HUNG AARON
DINH
DUONG,
G. JACKSON,
JOSEPH
KOVI,
JOSEPH
R. RANSOME,
GEORGE
W. JONES,
M.D. M.D.
M.D. M.D. M.D.
From the Departments of Pathology and Surgery, Division of Urology, Howard University College of Medicine, Washington, D.C.
ABSTRACT - Light and ultrastructuraljndings in a mixed mesodermal tumor of the urinary bladder are reported. The mesenchymal component of the tumor contained undifferentiated mesenchymal cells and cells with chondroblastic differentiation. The neoplastic chondrocytes displayed an abundance of cytoplasmic microfilaments and had a scalloped cell surface.
Primary tumors of the urinary bladder containing either bone or cartilage are rare. The first case was described by Ordonez in 1856.’ Since then 46 cases have been reported.‘*16 Although the ultrastructural pathology of the urinary bladder in man has been studied extensively, *’ no report could be found in the literature on the fine structure of mixed mesodermal tumor of bladder. We herein describe the light and electron microscopic appearance of a mixed mesodermal tumor of the bladder. Case Report
dermal tumor. Repeat cystoscopy in January, 1980, was negative. Past history revealed a right radical mastectomy in 1965 for breast cancer with apparent cure and hysterectomy for benign disease one year later. In March, 1980, the patient had a second transurethral resection. At this time two independent neoplastic growths were removed. One was located in the left anterolateral wall of the bladder and was considered as a residual or recurrent mixed mesodermal tumor of the bladder. The other growth occupied the left ureteral orifice and proved to be a pure transitional cell carcinoma. The patient underwent a five-day 2,0OO-rad course of radiation therapy after which in April, 1980, ileal conduit and radical cystectomy were done with open intraoperative irradiation to the cystectomy bed and immediate environs. Approximately 3,000 rad were delivered in twenty minutes.
A sixty-five-year-old black woman with a oneyear history of suprapubic discomfort, dysuria, and recent onset of gross hematuria underwent transurethral resection of the bladder in November, 1979. Cystoscopy had revealed the presence of a ball-like tumor attached by a narrow stalk to the left anterolateral wall of the urinary bladder. The resected tumor was diag_ nosed histologically as a malignant mixed meso-
Pathologic findings
*Supported Institute.
in part by Grant CA-26679 from the National Cancer
The cystectomy specimen showed two separate tumors. The first one was located in the left anterolateral wall. It was a pedunculated
UROLOGY
/ APRIL 1981
/ VOLUME
XVII, NUMBER
4
377
FIGURE 1. Radical cystectomy specimen with mixed mesodermal tumor in upper part and transitional cell carcinoma in lower part.
1.7 cm. in the polypoid mass, measuring The surface of the tumor greatest diameter. had a tannish gray color and appeared to be ulcerated. On cut section, the tumor had a short stalk of white color and of hard consistency. The second tumor, located at the left ureteral orifice had a round shape and measured I.2 cm. in diameter. Its surface was tan and somewhat ulcerated. On cut section, it was firm and seemed to invade the entire thickness of the bladder wall (Fig. 1). Histologic examination of the recurrent tumors confirmed that the growth on the left anterolateral wall was a malignant mixed mesodermal tumor, while the second neoplasm at the left ureteral orifice was a pure transitional cell carcinoma. About 85 per cent of the malignant mixed mesodermal tumor was sarcomatous and
by osteoblasts and osteoclasts on left and malignant cartilage on FIGURE 2. (A) Bony trabeculae surrounded right. (B) Closely associated transitional cell carcinoma and malignant cartilage showing great variability in size and shape of neoplastic cells. (C) Nests of transitional cell carcinoma with hyperchromatic and pleomorphic nuclei. (D) Electron micrograph of undiff erentiated mesenchymal cells. Cell at right characterized by numerous short branching segments of rough endoplasmic reticulum; cell at left contains number of lipid droplets {original magnijcation X 4,000).
378
UROLOGY
/ APRIL1931 i VOLUMEXVII,NUMBER4
composed of islands of cartilage and bone. The remaining portion of the tumor was carcinoma and was intimately associated with the sarcoma. Islands of cartilage and bone were separated one from another by a stroma of primitive mesenchymal cells and matrix. These stromal cells possessed hyperchromatic nuclei and displayed frequent mitotic activity. The neoplastic cartilage exhibited abnormal mitoses, hyperchromatic and pleomorphic nuclei also. The bony islands revealed both osteoid and mature bone formation. Osteoblasts and osteoclasts were observed frequently. A transitional zone between the mesenchymal tissue and the malignant cartilage and bone was clearly discerned in many areas (Fig. 2A). The malignant transitional cell element had a papillary configuration at the margin of the tumor. In many areas the epithelium penetrated into the cartilaginous and bony areas. The neoplastic transitional cells were large; the nuclei were pleomorphic and showed numerous mitotic figures (Fig. 2B).
The tumor removed from the left ureteral orifice proved to be a pure transitional cell carcinoma (Fig. 2C). Ultrastructurally, in the mesenchymal component of the mixed mesodermal tumor, two types of cells were visualized. One ceil type was characterized by large, irregular nuclei with prominent nucleoli. The cytoplasm was fairly rich in short, slender profiles of the rough endoplasmic reticulum. Occasionally large, fat vacuoles and cytoplasmic microfilaments were noted (Fig. 2D). The other cell type had a plasma membrane which was rather irregular with both coarse and slender surface projections. The most prominent feature of that cell type was markedly dilated rough endoplasmic reticulum. The distended profiles of the endoplasmic reticulum contained a moderately electron-dense, flocculent, finely granular material. The cytoplasm was exceedingly rich in cytoplasmic filaments (Fig. 3A). The cytoplasmic microfilaments were of undetermined length, measured about
FIGURE 3. {A) Poorly differentiated chondrocyte, note scalloped cell surface and markedly distended cisternae of rough endoplasmic reticulum. Cystoplasm exceedingly rich in microfilaments (L == lysosomej (original magnification X 7,000). (B) Distended profiles of rough endoplasmic reticulum contain moderately electron-dense,Jocculent granular material. Cytoplasmic microfilaments measure 60-80 A in width x 12,000). and form bundles (original mugnijication (C) Peculiar invagination of mitochondria into markedly distended cisternae of rough endoplasmic reticulum; individual mitochondria appears to be surrounded by inverted profiles of RER (original magni$cation X 16,000).
UROLOGY
/
APRIL
1981 /
\‘OLUME
XVII. NlrMBER
4
379
60 to 80 A in diameter and frequently formed bundles (Fig. 3B). Into the markedly dilated cisternae of the rough endoplasmic reticulum, invagination of mitochondria was observed (Fig. 3C). The extracellular matrix of the tumor cells consisted of a variable number of fine filaments separated by electron-lucent amorphous material. The surface of the epithelial cells in the tumor contained many microvilli, however, the cell cytoplasm was generally poorly preserved. Comment Since Ordonez’ reported a malignant bladder neoplasm containing cartilage, 46 tumors including our case containing either bone or cartilage have been added to this group of neoplasms. Of these rare bladder tumors, 20 are malignant mixed mesodermal tumors, 17 are osteosarcomas and chondrosarcomas, and 10 are carcinomas with osseous metaplasia. ‘-” The histogenesis of mixed mesodermal tumors of urinary bladder is still controversial. Several hypothesis have been considered: (1) metaplasia of transitional cell epithelium; (2) stromal metaplasia; (3) transfer of osteoblasts through the blood; and (4) development of osteoblasts from the immature mesenchyme of the wolffian body from which the trigone develops. l3 Electron microscopic study of the mixed mesodermal tumor showed that in contrast to the neoplastic chondronormal chondrocytes, cytes were devoid of glycogen. Rich glycogen content is characteristic of the tumor cells in socalled clear-cell chondrosarcoma. 21 It has been reported, however, that in poorly differentiated chondrosarcoma glycogen particles are decreased or absent.18,20 The neoplastic chondrocytes in the mixed mesodermal tumor were very rich in cytoplasmic microfilaments. In a study comparing the ultrastructure of low-to-high-grade chondrosarcomas, it was found that cytoplasmic filaments were considerably increased in number in higher grade (highly malignant) chondrosarcoma. lg In the present study, peculiar invagination of mitochondria into the markedly distended cisternae of the rough endoplasmic reticulum was noted. Similar findings in the neoplastic cells from the patients with chondrosarcoma were reported. “J In this patient two separate malignant neoplasms were found in the urinary bladder. The
380
mixed mesodermal tulnor was located in the left anterolateral wall, the transitional cell carcinoma was situated at the left ureteral orifice. The chronologic findings of the transurethral resections suggested that the initially detected neoplasm (mixed mesodermal tumor) may have given rise to a metastatic focus in the bladder in which only the epithelial components of the tulnor were expressed. Washington, D.C. 20059 (DR. DUONG) ACKNOWLEDGMENT.
Elliot,
and Tamara
To Kathryn 51. Blanc for their
Berry, Benjamin assistance.
F.
References 1. Ordonez MEC: 2” transformation cartilagineuse de la vessie chez un vieillard, series 3, Gazz. Med. Paris, 11: 824 (1856). 2. Crane rlR, and Tremblay RG: Primary osteogenic sarcoma of the bladder. Complete review of sarcoma of the bladder, Ann. Surg. 118: 887 (1943). 3. Willis RA: Malignant mixed tumor of bladder, Tex. Med. 46: 627 (1950). 4. Powers JH, Hawn C, Van 2, and Carter RD: Osteogenic sarcoma and transitional cell carcinoma occurring simultaneously in the urinary bladder, J. Urol. 76: 263 (1956). 5. Nourse MH: Primary osteogenic sarcoma of the bladder, ibid. 77: 634 (1957). 6. Pang LSC: Bony and cartilagineous tumors of the urinary bladder, J. Pathol. Bacterial. 76: 357 (1958). 7. Nicolai CH, and Spjut HJ: Primary osteogenic sarcoma of the bladder, J. Ural. 82: 497 (1959). 8. Kikuchi K, Nakamura K, and Nakazima 1: An autopsy case of primary osteogenic sarcoma of the urinary bladder, Acta Pathol. Jpn. 15: 287 (1965). 9. Bialik BL: Carcino-osteochondrosarcoma of urinary bladder, Arkh. Patol. 30: 61 (19%). 10. Brinton JA, lto Y, and Olson BS: Carcinosarcoma of the urinary bladder, Cancer 25: 1183 (1970). 11. Beltrami CA, et al: Primary osteochondrosarcoma of the bladder, Riv. Patol. Cli. Sper. 11: 213 (1970). 12. Delides GS: Bone and cartilage in lnalignant tmnors of the urinary bladder, Br. J. Ural. 44: 571 (1972). 13. Chitiyo ME: Primary osteogenic sarcoma of the urinary bladder, J. Pathol. 111: 53 (1973). 14. Koss LG: Tumors of the urinary bladder, in Atlas of Tumor Pathology, series 2, part XII, Washington, D.C., Armed Forces Institute of Pathology, 1974, pp. 93-95. 15. Patterson TH, and Dale GA: Carcinosarcoma of the bladder, J. Ural. 115: 753 (1976). 16. Babaian RJ, et al: Mixed mesodermal tumor of urinary bladder: prognosis and management, Urology 15: 261 (1980). 17. Tannenbaum M: Ultrastructural pathology of the human urinary bladder, in Diagnosis Electron .Microscopy, vol. 2, New York, John Wiley & Sons, Inc., 1979, pp. 221-267. 18. Schajowicz F, et al: Ultrastructure of chondrosarcoma, Clin. Orthop. 100: 378 (1974). 19. Erlandson RA, and Huvos AG: Chondrosarcoma: a light and electron microscopic study, Cancer 34: 1624 (1974). 20. Kahn LB: Chondrosarcoma with dedifferentiated foci. A comparative and ultrastructural study, ibid. 37: 1365 (1976). 21. Le charpentier Y, et al: Clear-cell chondrosarcoma. A report of five cases including ultrastructural study, ihid. 44: 622 (1979).
UROLOGY
/
APRIL
1981
/
VOLUME
XVII, NUMBER
4