Angiosarcoma of the Prostate: Report of 2 Cases and Review of the Literature

0022-534 7/86/1352-0382$02.00/0 Vol. 135, February

THE JOURNAL OF UROLOGY

Copyright© 1986 by The Williams & Wilkins Co.

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ANGIOSARCOMA OF THE PROSTATE: REPORT OF 2 CASES AND REVIEW OF THE LITERATURE DOUGLAS M. SMITH,* CARLOS MANIVEL, DONALD KAPPS AND JOHN UECKER From the Department of Pathology and Microbiology, University of Nebraska Medical Center, Omaha, Nebraska, and Department of Laboratory Medicine and Pathology, University of Minnesota Medical Center, Minneapolis, Department of Pathology, Mercy Medical Center, Coon Rapids and Department of Pathology, Midway Hospital, St. Paul, Minnesota

ABSTRACT

We report 2 cases of angiosarcoma of the prostate gland. The patients were 42 and 60 years old, which is in sharp contrast to the presentation of rhabdomyosarcoma, which occurs primarily in children. Immunoperoxidase staining for factor VIII associated antigen was positive in both cases, and was particularly useful in confirming the diagnosis in 1 case that was otherwise poorly differentiated. One patient is alive without evidence of recurrence 2 years after surgical excision, while- the other presented with unresectable tumor and died 6 months after presentation. Angiosarcoma represents less than 2 per cent of sarcomas of the prostate but it should be considered in the differential diagnosis of poorly differentiated sarcomas, particularly those occurring in adults. Angiosarcomas are malignant tumors of mesenchymal origin demonstrating morphological and/or biochemical evidence of differentiation toward vascular endothelial cells. They are extremely rare in the prostate gland. The first such case was described by Matthias in 1889.1 In 1934 Lowsley and Kimball reported 127 cases of sarcoma of the prostate collected from the literature and found 4 additional angiosarcomas. 2 More recent series have not included any additional examples. 3 - 9 Therefore, angiosarcoma represents less than 2 per cent of the reported sarcomas of the prostate, and sarcomas represent 0.1 per cent of all malignant tumors of the prostate. We report 2 such cases and review the literature. CASE REPORTS

Case 1. A 60-year-old white man presented in March 1983 with a decreased urinary stream and frequency. Examination revealed an enlarged firm prostate and an excretory urogram (IVP) showed partial ureteral obstruction. The patient underwent cystoscopy and transurethral resection of the prostate. At operation the right ureteral obstruction appeared to be owing to mucosal edema. A total of 32 gm. of prostatic tissue was resected. Microscopic examination showed an infiltrating malignant tumor that varied in appearance (fig. 1, A). Some fields displayed solid sheets of round or pleomorphic cells with abundant cytoplasm and enlarged, hyperchromatic, pleomorphic nuclei. In other areas tumor cells lined slit-like spaces containing blood and formed prominent tufts. lmmunochemical staining for factor VIII associated antigen 10 showed intense cytoplasmic positivity in numerous tumor cells as well as in nonmalignant capillaries (fig. 1, B). Diagnosis was angiosarcoma of the prostate, based on the light microscopic appearance and immunochemical staining. Electron microscopy failed to reveal any Weibel-Palade bodies or other ultrastructural evidence of differentiation (fig. 1, C). The postoperative course was complicated by bleeding per urethram and a second transurethral resection was performed. The tissue obtained showed microscopic features similar to those found previously. No evidence of metastatic spread was found and in May the patient underwent radical cystoprostatectomy with partial reAccepted for publication September 27, 1985. * Requests for reprints: Department of Pathology and Microbiology, University of Nebraska Medical Center, 42nd and Dewey Aves., Omaha, Nebraska 68105. 382

moval of the pubic bone, ureteroileal diversion and bilateral pelvic lymph node dissection. On gross examination the prostate was diffusely replaced by a soft reddish tumor, 5 cm. in diameter, extending into the base of the bladder and into the periprostatic fat. Microscopic examination revealed an appearance identical to that described previously. The tumor extended to the pelvic wall margin and was unresectable. In addition, 12 of 22 lymph nodes showed metastatic tumor. Adjuvant chemotherapy was contraindicated owing to liver damage related to alcoholism. The patient appeared cachectic and was believed to be terminally ill. At the request of the patient and his family, he was discharged from the hospital and died at home in September, 6 months after presentation. No autopsy was performed. Case 2. A 42-year-old white man presented in July 1981, complaining of a 3-month history of pain in the suprapubic area, left groin, low back, and left side of the buttock and thigh. Physical examination showed only a tender, slightly enlarged, boggy prostate. X-ray and laboratory evaluations were normal, except for a slightly elevated white blood count. The patient was treated with antibiotics and the pain improved initially but it returned and gradually worsened during the next 5 months. Followup examination in October revealed a decrease in hemoglobin from 13.5 to 11.5 gm./dl. The patient was scheduled for further evaluation but typical symptoms of left renal colic and left costovertebral angle tenderness suddenly developed. On rectal examination the left lobe of the prostate was tender but not fluctuant. At hospitalization the patient had a white blood count of 16,900 and microscopic hematuria. An IVP showed partial obstruction of the left ureter, whereas one taken several months previously had been normal. Cystoscopy revealed an extrinsic mass on the left side of the trigone of the bladder with severe edema of the overlying mucosa. A biopsy from this area showed infiltration by a poorly differentiated malignant tumor. A computerized tomography (CT) scan of the pelvis showed a mass in the left lobe of the prostate. Metastatic studies were negative and, therefore, complete resection of the tumor was attempted. In January 1982 the patient underwent radical cystoprostatectomy with lymphadenectomy and ureteroileal diversion. The tumor involved the entire left lobe of the prostate and an adjacent area of the bladder wall in the area of the trigone. It penetrated the capsule of the prostate and extended into the retroprostatic fat but it did not involve the right lobe, prostatic urethra or distal ureter. The tumor did not extend to the

383

Al\JGIOSARCOIVIA OF PROSTATE

FIG. l. Case l. A, anastomosing vascular spaces lined by neoplastic endothelium. Note part of normal gland in upper right corner. B, immunoperoxidase cytoplasmic staining for factor VIII associated antigen (arrows). C, neoplastic cells lack ultrastructural evidence of differentiation.

diagnosis was differentiated angiosarcoma of the prostate. The patient started adjuvant chemotherapy 2 months postoperatively, consisting of 70 mg./m. 2 doxorubicin hydrochloride followed at 3-week intervals with 75 mg./m.2, for a total of 6 courses. The groin and leg pain improved initially and there was no clinical evidence of recurrence but the pain returned and became severe during the next year. Therefore, surgical exploration of the pelvis was performed in March 1983. No recurrent tumor was found and it was believed that the pain was due to entrapment of nerves in scar tissue. In an attempt to control these symptoms, left sympathectomy was performed in April. In October a CT scan of the pelvis showed no evidence of recurrent tumor. The patient continues to complain of pain but he is clinically free of tumor 2 years postoperatively. DISCUSSION

F!G. 2. Case 2. A, solid neoplasm composed of pleomorphic cells. B, rare vascular lined by neoplastic cells (arrows). C, higher power view shows cv,,w,Hrn,~ vacuolization (arrows). D, immunoperoxidase for factor VIII associated antigen (arrows). cytoplasmic

resection margins, and all local and regional lymph nodes were free of tumor. Microscopically, the tumor consisted of pleomorphic cells that varied from elongated spindle to large and plump. The nuclei varied from small and pyknotic to large and vacuolated with clumped chromatin, containing one or more nucleoli. The stroma was abundant and composed of dense collagenous tissue. Significantly, the tumor cells were predominantly arranged in solid sheets and only rarely formed vascular structures lined with malignant cells (fig. 2). Immunochemical stainings for keratin, prostatic specific antigen and factor VIII associated antigen were performed. 10 The tumor did not stain for keratin or prostatic specific antigen but it showed intense cytoplasmic staining for factor VIII associated antigen (fig. 2). Electron microscopy failed to reveal any ultrastructural evidence of differentiation. The light microscopic features of this tumor were consistent with a poorly differentiated sarcoma with some features suggestive of angiosarcomatous differentiation. In view of the immunochemical evidence of endothelial differentiation,

The cases previously reported are summarized in the table.1·11-13 Lowsley and Kimball refer to a 50-year-old man with angiosarcoma described by Burckhardt in 190~, who survived 2 years but gave no literature citation. We found a case reported by Burckhardt in 1894, which describes a fibrosarcoma of the prostate in a 50-year-old man who survived 2 years 14 but, despite extensive searching, we have not found another report by the same author. The case reported by Matthias was not examined microscopically and the clinical course was characterized by metastases to the lumbar vertebrae with slow progression to paraplegia in an elderly man. 1 This would seem to be more characteristic of an adenocarcinoma. The case reported by Mogi was characterized by prominent metaplastic bone formation. 12 This tumor most likely represents osteogenic sarcoma similar to that described by Meeter and Richards 15 or it may be analogous to the spontaneous adenocarcinoma of the prostate in rats, described by Dunning, 16 which shows osteometaplasia. The cases of Botesco, 11 and Salleras and Vilar 13 give adequate histological descriptions that are consistent with angiosarcoma. The addition of our 2 cases brings the total number of reliable reports of angiosarcoma of the prostate to 4. Although we cannot entirely rule out a retroprostatic origin for these tumors, in both cases the bulk of the tumor and the most extensive replacement of the normal tissue were within the prostate. Our case 1 showed morphological characteristics of angiosarcoma and would have been diagnosed as such even withont immunochemical staining. Our case 2 was sufficiently undifferentiated that a definite diagnosis would not have been made on the basis of morphology alone. In both cases electron microscopy showed only the lack of ultrastructural differentiation of the individual tumor cells and, therefore, we found immunochemical staining for factor VIII associated antigen invaluable for the diagnosis or its confirmation. The small number of cases reported limits the conclusions we can draw about the natural history of this lesion. However, we can note that the average patient age was 34 years and only l child was described. This contrasts sharply with the presentation of prostatic rhabdomyosarcoma, which generally occurs in young children. Bladder outlet obstruction was the presenting complaint in all of these patients and some had hematuria or constipation. Both of our patients had ureteral outlet obstruction caused by mucosa! edema and tumor involving the muscularis of the trigone. The child reported on by Botesco died of complications of urinary retention shortly after hospitalization and at autopsy he had no evidence of metastases. 11 Little followup is available for the case reported by Salleras and Vilar but the tumor grew rapidly and there was no clinical evidence of metastases. 13 Our patient 1 had an unresectable tumor and died 6 months after presentation. No autopsy was performed but he had extensive local lymph node metastases at operation. In our case 2 the tumor was resected successfully and there was no evidence of disease 2 years postoperatively. This contrasts with the behav-

384

SMITH AND ASSOCIATES

Literature review Matthias' Age (yrs.) Presenting symptoms

Histological appearance

70 Dysuria, constipation, pain, weight loss, paraplegia Soft, hemorrhagic Vertebrae, regional lymph nodes Not performed

Treatment Outcome

None Died, 6 mos.

Gross appearance Metastases

Botesco"

Mogi12

Salleras and Vilar13

Dysuria, constipation

38 Dysuria, constipation, hematuria

32 Dysuria, pain, weight loss

Hard, smooth, white None

Hard to soft and cystic None

Soft, hemorrhagic None (no autopsy)

Numerous neoplastic blood vessels, degenerative connective tissue, lymphocytic infiltrate External drainage Died, 1 day

Numerous blood vessels and metaplastic bone

Numerous vascular spaces with round or spindled, sometimes multinucleated cells

None Died, 4 mos.

Incisional biopsy Lost to followup, 1 mo. (terminally ill)

2

ior of angiosarcomas of the spleen,1 7 breast18• 19 and liver, 20 which grow rapidly and metastasize early via hematogenous routes. This behavior is more like angiosarcomas of the skin, which grow slowly, although aggressively, with a tendency toward local recurrence and late metastases to regional lymph nodes. 21 In summary, 4 cases diagnosed as angiosarcomas of the prostate were collected from the literature and reviewed. Only 2 of these reports give adequate histological descriptions consistent with angiosarcoma. We report 2 cases with histological, immunochemical and electron microscopic examination. Immunochemical staining for factor VIII associated antigen was positive in both cases and proved useful in their classification. Angiosarcomas of the prostate, in contrast to angiosarcomas in some other locations, may not metastasize as early and, therefore, local excision may be curative. If angiosarcoma is considered in the differential diagnosis of poorly differentiated tumors of the prostate and immunochemical techniques are used to explore this possibility, this entity may be encountered more frequently. Additional reports are needed before definite conclusions can be made about the natural history and response to therapy of this disease. Drs. John Soucheray, Dexter Jeffords and Elwin Fraley provided clinical information and followup. REFERENCES

1. Matthias, H.: Zur Casuistik der Tumoren der Prostata. Munchen: Inaug. Diss., 1889. 2. Lowsley, 0. S. and Kimball, F. N.: Sarcoma of the prostate: with a review of the literature. Brit. J. Urol., 6: 328, 1934. 3. Longley, J.: Sarcoma of prostate and bladder. J. Urol., 73: 417, 1955. 4. Mackenzie, A. R., Whitmore, W. F., Jr. and Melamed, M. R.: Myosarcomas of the bladder and prostate. Cancer, 22: 833, 1968. 5. Melicow, M. M., Pelton, T. H. and Fish, G. W.: Sarcoma of the prostate gland: review of literature; table of classification; report

of four cases. J. Urol., 49: 675, 1943. 6. Narayana, A. S., Loening, S., Weimar, G. W. and Culp, D. A.: Sarcoma of the bladder and prostate. J. Urol., 119: 72, 1978. 7. Smith, B. H. and Dehner, L. P.: Sarcoma of the prostate gland. Amer. J. Clin. Path., 58: 43, 1972. 8. Stirling, W. C. and Ash, J. E.: Sarcoma of the prostate. J. Urol., 41: 515, 1939. 9. Tannenbaum, M.: Sarcomas of the prostate gland. Urology, 5: 810, 1975. 10. Mukai, K. and Rosai, J.: Applications of immunoperoxidase techniques in surgical pathology. In: Progress in Surgical Pathology. Edited by C. M. Fenoglio and M. Wolff. New York: Masson Publishing, vol. 1, chapt. 3, pp. 15-49, 1980. 11. Botesco, M.: Sarcome primitif de la prostate chez un enfant de deux ans et neuf mois. Bull. Mem. Soc. Chir. Bucarest, 5: 77, 1902. 12. Mogi, I.: A case of primary osteoplastic sarcoma of the prostate gland. Verhandl. Jap. Path. Gesellsch., 1: 109, 1911. 13. Salleras, J. and Vilar, G.: Consideraciones a proposito de un sarcoma primitivo de la prostata en un sujeto de 32 aiios prostatectomia perineal. Semana Med., Buenos Aires, 31: 1275, 1924. 14. Burckhardt, E.: Zur Kasuistik und Therapie des Prostatasarkoms. Centralbl. f. d. Krankh. D. Harn-u. Sex.-Org. Leipz., 5: 152, 1894. 15. Meeter, U. L. and Richards, J. N.: Osteogenic sarcoma of the prostate. J. Urol., 84: 654, 1960. 16. Dunning, W. F.: Prostate cancer in the rat. Natl. Cancer Inst. Monogr., 12: 351, 1963. 17. Wilkinson, H. A., III, Lucas, J. C. and Foote, F. W., Jr.: Primary splenic angiosarcoma. A case report. Arch. Path., 85: 213, 1968. 18. Gulesserian, H. P. and Lawton, R. L.: Angiosarcoma of the breast. Cancer, 24: 1021, 1969. 19. Merino, M. J., Carter, D. and Berman, M.: Angiosarcoma of the breast. Amer. J. Surg. Path., 7: 53, 1983. 20. Ludwig, J. and Hoffman, H. N.: Hemangiosarcoma of the liver. Spectrum of morphologic changes and clinical findings. Mayo Clin. Proc., 50: 255, 1975. 21. Hodgkinson, D. J., Soule, E. H. and Woods, J. E.: Cutaneous angiosarcoma of the head and neck. Cancer, 44: 1106, 1979.