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Osteosarcoma of the Urinary Bladder Occurring Simultaneously With Prostate and Bowel Carcinomas: Report of a Case and Review of the Literature.

Primary osteogenic sarcoma of the urinary bladder is an extremely rare disease. The occurrence of such a tumor in association with prostate and bowel carcinomas is even more unusual. The rarity of this condition prompted us to report the following case, which to our knowledge is the 29th example to be described in this organ. In this article, we review the clinical and pathologic features of osteosarcoma of the bladder and discuss the differential diagnosis with other bone tumors of the bladder.

REPORT OF A CASE

A 75-year-old man referred to the hematuria clinic was found to have a large polypoid tumor of the urinary bladder, which on microscopic examination proved to be a primary osteosarcoma with superficial invasion. His prostate felt benign. A chest radiograph and computed tomographic scan of his abdomen and pelvis revealed no secondary lesions. Radical cystoprostatectomy and ileal conduit urinary diversion were performed. A synchronous tumor of the ascending colon was found during surgery, and consequently a right hemicolectomy was performed. Definitive histology showed primary osteosarcoma of the bladder with superficial invasion of detrusor muscle (pT2a) and vascular invasion.

Prostatic adenocarcinoma (Gleason grade 5 [2+3]) was also found. The bowel segment showed moderately differentiated mucinous adenocarcinoma of the colon (Dukes stage B).

Six months postoperatively the patient was readmitted with a right pleural effusion, and a computed tomographic scan of the chest confirmed metastasis. The patient's condition gradually deteriorated, and he died 7 months after initial presentation.

PATHOLOGIC FINDINGS

Macroscopy

The cystoprostatectomy specimen measured 15 x 12 x 4 cm. The mucosa of the bladder in the midposterior wall showed a polypoid appearance in an area measuring 3 x 2 cm. Toward the left lateral wall there was another polypoid area at the margin of an ulcerated creamy white nodule measuring 2 x 2 x 1.5 cm. The prostate gland showed a multinodular appearance. No gross photographs were taken at the time of the procedure.

Microscopy

Multiple sections from the polypoid tumor showed a highly pleomorphic neoplasm composed of myxoid spindle cell sarcomatous elements, more closely packed spindle cells with malignant osteoid production, and large numbers of multinucleated giant cells (Figure). In some areas, the tumor cells showed a more epithelioid appearance, but immunocytochemistry on several sections for cytokeratin (clone AE1/AE3, BioGenex, San Ramon, Calif) was negative. Immunostains were performed with and without antigen retrieval. Antigen retrieval was done using trypsin digestion. The sarcoma infiltrated vascular spaces in the lamina propria. It invaded into the superficial detrusor muscle (pT2a) and was also present in the muscular wall of a vein, but did not infiltrate into the lumen of the blood vessel. The urothelium adjacent to the tumor showed hyperplasia and active chronic inflammation consistent with an acute or chronic "papillary" cystitis. Random sections from the lateral and posterior walls showed active chronic inflammation, in places with numerous eosinophils in the infiltrate and urothelial hyperplasia. Dysplasia was absent in all adjacent overlying urothelium. In the posterior wall, there were also bizarre multinucleated stromal giant cells, showing basophilic granular cytoplasm and very prominent nucleoli. The resected urethral margin was free from the sarcomatous tumor, but the prostate gland at the apex contained foci of high-grade prostatic intraepithelial neoplasia and several foci of well-differentiated prostatic adenocarcinoma (Gleason grade 5 [2+3]). The ureters, their resection margins, and internal orifices were free from tumor.

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COMMENT

Sarcomas of the bladder are uncommon. Osteosarcomas of the urinary bladder are exceedingly rare, the current case being only the 29th example reported in the literature to date.[1-19] The published cases show a male-female ratio of 4 to 1. The patients have ranged from 41 to 86 (mean 64) years of age and have presented with hematuria. In one case the tumor developed 27 years after radiation therapy for urothelial carcinoma,[20,21] whereas 3 patients had concurrent urinary schistosomiasis.[22] Grossly, osteosarcoma of the bladder is a large, polypoid, and deeply infiltrative tumor. The most common single location is the trigone.[23] Histologically, it is a high-grade sarcoma with osteoid production.[24,25]

Sarcomatoid urothelial carcinoma and urothelial carcinomas with osseous metaplasia must be considered in the differential diagnosis of osteosarcoma.[24-26] Distinction from carcinosarcoma does not have major therapeutic implications, as both tumors require aggressive therapy, but distinction from a transitional cell carcinoma with osseous metaplasia is important if the carcinoma is low grade.[25]

Osteoid formation can be seen in sarcomatoid carcinoma (carcinosarcoma),[26] in which the tumor cells are of epithelial origin despite their resemblance to sarcoma. Therefore, immunostains for keratin or ultrastructural presence of desmosomes are seen and can confirm their true carcinomatous nature. Similarly in urothelial carcinoma with osseous metaplasia, the tumor cells are of epithelial origin, whereas the osteoid elements are benign with mature lamellar architecture and no cytologic atypia. Carcinosarcoma, on the other hand, can be more difficult to distinguish from primary osteogenic sarcoma, especially if the sarcomatous elements in the former condition produce osteoid. However, one should be able to confirm the presence of at least focal epithelial differentiation in carcinosarcoma.

It must be remembered that bone is occasionally found in the bladder in nonneoplastic conditions.[27] In one instance, the lesion appears to have been an example of encrusted cystitis, and in another, a case of polypoid cystitis glandularis. With the exception of the differential diagnosis already discussed, the diagnosis of osteosarcoma of the bladder should not be difficult. Because of its rarity the diagnosis may not be considered, particularly if osteoid is sparse.

It is well recognized that poorly differentiated epithelial neoplasms may mimic osteosarcoma or other sarcomas.[28] Immunohistochemical stains have been of help in the differential diagnosis in such cases. The biopsy specimen was stained in several sections by immunoperoxidase technique for the epithelial cytokeratin; the results were negative. If the cells in the biopsy specimen represented transitional cell carcinoma, one would have expected cytokeratin stains to yield a positive reaction.[29-31] We did not perform electron microscopic examination on this tumor, therefore the possibility of the presence of rare desmosomes was not completely excluded.

The prognosis for vesical osteosarcoma has been dismal; 22 of 25 patients with follow-up were dead within 6 months, most as a result of local spread with urinary tract obstruction and secondary infection. Distant metastases are uncommon. In our case, simultaneous prostate and bowel carcinomas were found. The microscopic appearances of the prostatic and the colonic carcinomas were distinct from the bladder tumor and therefore posed no problems in the differential diagnosis. Although colonic carcinoma has been associated with other extraintestinal carcinomas in Lynch syndrome, such as the endometrium, transitional cell carcinoma of the ureter and renal pelvis, and carcinomas of other sites,[32] we are unaware of association with bladder mesenchymal tumors. Furthermore, our patient lacked the known criteria for the diagnosis of hereditary nonpolyposis colorectal cancer, such as early age of onset and family history of colonic carcinomas in successive generations. However, we should emphasize that we did not perform genetic studies for microsatellite instability to confirm or rule out this possibility.

In conclusion, osteosarcoma of the bladder is an uncommon tumor with a very poor prognosis. It is one of 3 major categories of malignant bladder tumors associated with bone formation. The precise histologic identification is important, since other tumors in this group, carcinosarcoma and carcinomas with osseous metaplasia of their stroma, have a better prognosis.

References

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[10.] Crane AR, Tremblay RG. Primary osteogenic sarcoma of the bladder. Ann Surg. 1943;118:887-908.

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[12.] Beneke R. Ein Fall von Osteoid-chondrosarcom der Harnblase (mit Bemerkungen uber Metaplasie). Virchows Arch. 1900;161:70-114.

[13.] Nourse MH. Primary osteogenic sarcoma of the bladder. J Urol. 1957;77:634-638.

[14.] Pang LSC. Bony and cartilaginous tumors of the urinary bladder. J Pathol Bacteriol. 1958;76:357-377.

[15.] Nicolai CH, Spjut HJ. Primary osteogenic sarcoma of the bladder. J Urol. 1959;82:497.

[16.] Beltrami CA, Fabris G, Siciliano C, Bighi G. Osteocondrosarcoma vescicale primitivo. Riv Patol Clin Sper. 1970;11:213-221.

[17.] Chityo ME. Primary osteogenic sarcoma of the urinary bladder. J Pathol. 1973;111:53-56.

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[19.] Narayama AS, Lowning S, Weimar GW, Culp DA. Sarcoma of the bladder and prostate. J Urol. 1978;119:72-76.

[20.] Ferrie BG, Imrie JEA, Paterson PJ. Osteosarcoma of bladder 27 years after local radiotherapy. J R Soc Med. 1984;77:962-963.

[21.] Kim JH, Chu FC, Woodard HQ, Melamed MR, Huvos A, Cautin J. Radiation-induced soft-tissue and bone sarcoma. Radiology. 1978;129:501-508.

[22.] El Boulkainy MN, Ghoneim MA, Mansour MA. Carcinoma of bilharzial bladder in Egypt. Br J Urol. 1972;44:561-570.

[23.] Kikuchi K, Nakamura K, Nakajima F, Ohmuro H. An autopsy case of primary osteogenic sarcoma of the urinary bladder. Acta Pathol Jpn. 1965;15:287-293.

[24.] Delides GS. Bone and cartilage in malignant tumors of the urinary bladder. Br J Urol. 1972;44:571-581.

[25.] Toma H, Yamashita N, Nakazawa H, Yamaguchi Y. Transitional cell carcinoma with osteoid metaplasia. Urology. 1986;27:174-176.

[26.] Young RH. Carcinosarcoma of the urinary bladder. Cancer. 1987;59:1333-1339.

[27.] Collings CW, Welebir F. Osteoma of the bladder. J Urol. 1941;46:494-498.

[28.] Yunis EJ, Barnes L. The histologic diversity of osteosarcoma. Pathol Annu. 1986;21(pt 1):121-141.

[29.] Espinoza CG, Azar HA. Immunohistochemical localization of keratin-type proteins in epithelial neoplasms: correlation with electron microscopic findings. Am J Clin Pathol. 1982;78:500-507.

[30.] Ramaekers F, Huysmans A, Moesker O, Schaart G, Herman C, Vooijs P. Cytokeratin expression during neoplastic progression of human transitional cell carcinomas as detected by a monoclonal and a polyclonal antibody. Lab Invest. 1985;52:31-38.

[31.] Schlegel R, Banks-Schlegel S, Macleod JA, Pinkus GS. Immunoperoxidase localization of keratin in human neoplasms. Am J Pathol. 1980;101:41-49.

[32.] Lynch HT, Smyrk TC, Watson P, Lanspa SJ, Lynch PM, Cavalieri RJ. Genetics, natural history, tumor spectrum, and pathology of hereditary non-polyposis colorectal cancer: an updated review. Gastroenterology. 1993;104:1535-1549.

Accepted for publication December 15, 2000.

From the Departments of Urology (Drs Ghalayini and Bani-Hani) and Pathology (Dr Almasri), Faculty of Medicine, Jordan University of Science & Technology, Irbid, Jordan.

Reprints: Ibrahim F. Ghalayini, MD, FRCS; Department of Urology, Jordan University of Science & Technology, PO Box 940165, Amman 11194, Jordan.
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Author:Ghalayini, Ibrahim F.; Bani-Hani, Ibrahim H.; Almasri, Nidal M.
Publication:Archives of Pathology & Laboratory Medicine
Date:Jun 1, 2001
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