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ANGIOSARCOMA ARISING IN A TESTICULAR TERATOMA
0022-5347/00/1636-1872/0 THE JOURNAL OF UROLOGY® Copyright © 2000 by AMERICAN UROLOGICAL ASSOCIATION, INC.®
Vol. 163, 1872–1873, June 2000 Printed in U.S.A.
ANGIOSARCOMA ARISING IN A TESTICULAR TERATOMA GRAEME S. STEELE, THOMAS E. CLANCY, MILTON W. DATTA, MICHAEL WEINSTEIN AND JEROME P. RICHIE From the Division of Urology, Departments of Surgery and Pathology, Brigham and Women’s Hospital, Harvard Medical School, Boston, Massachusetts KEY WORDS: testis, teratoma, hemangiosarcoma, germ cell tumor, neoplasm metastasis
Sarcomatous change in a primary germ cell tumor is rare but may develop as a result of malignant transformation within teratomatous foci and may lead to the erroneous diagnosis of embryonal carcinoma. We report a case of epithelioid angiosarcoma arising in a background of mature teratoma. To our knowledge only 2 other such cases have been described previously.1, 2 CASE REPORT
A 24-year-old man presented elsewhere with a 6-month history of an 8 ⫻ 7 cm. left testicular mass. Ultrasound findings were consistent with the clinical impression of a primary testicular tumor. Tumor markers were within normal limits. The patient underwent left radical inguinal orchiectomy. Pathological evaluation revealed a mixed nonseminomatous germ cell tumor with components of embryonal carcinoma (60%) and teratoma (40%). Metastatic evaluation with chest and abdominal computerized tomography (CT) showed approximately 15 small peripheral pulmonary nodules less than 5 mm. in diameter as well as left renal hilar lymphadenopathy 4 cm. in greatest diameter. Three cycles of cisplatin, etoposide and bleomycin were given. Repeat CT revealed resolution of all pulmonary nodules and regression of retroperitoneal lymphadenopathy to 1.5 cm. The patient refused further therapy but underwent serial chest and abdominal CT. However, 6 months later a 10 cm. left renal hilar mass was detected and the patient was referred to our institution. Reevaluation of the initial pathology specimens at our institution demonstrated high grade epithelioid angiosarcoma (90%) arising in a background of mature teratoma (10%) (fig. 1). Immunoperoxidase studies revealed sarcomatous elements positive for vascular marker CD31 in solid and vaso-
formative areas. Tumor invaded the rete testis, epididymis and soft tissue of the spermatic cord. Strong CD31 positivity and cytological similarity to the primary testicular tumor indicated that this tumor represented metastasis. Due to mature teratoma in the primary tumor the patient underwent bilateral retroperitoneal lymph node dissection as well as removal of the left renal hilar mass. Histological analysis revealed metastatic angiosarcoma in the tumor, and in 4 of 23 pre-aortic and interaortocaval lymph nodes. No teratomatous elements were present. Followup chest x-ray showed recurrent lung lesions 4 months later. Pleural fluid sampling and lung biopsy demonstrated metastatic angiosarcoma (fig. 2). The patient subsequently received 6 cycles of ifosfamide and doxorubicin with a near complete response but there was later recurrence. DISCUSSION
Our case illustrates the potential difficulties of diagnosing angiosarcoma in a germ cell tumor, which is an important distinction with respect to treatment as well as prognosis. The gross and microscopic appearance of embryonal carcinoma and epithelioid angiosarcoma may be similar. In our patient the epithelioid nature of the neoplasm probably led to the erroneous diagnosis of embryonal carcinoma. However, the diagnosis of epithelioid angiosarcoma was substantiated by associated hemorrhage instead of necrosis on histological analysis and diagnostic areas of angiosarcoma with branching irregular vascular spaces lined by plump neoplastic endothelial cells. Immunohistochemical studies for CD31 and factor VIII confirmed the diagnosis. Recognizing epithelioid angiosarcoma at presentation would clearly have altered management in our case because these
Accepted for publication January 14, 2000.
FIG. 2. A, mature glandular epithelial element of teratomatous FIG. 1. Epithelioid angiosarcoma of testis with vascular differen- component of primary testicular tumor. B, metastatic angiosarcoma tiation of tumor evidenced by formation of vascular spaces contain- in pleura was strongly positive for endothelial cell marker CD31. ing erythrocytes. H & E, reduced from ⫻50. CD31 immunohistochemical stain, reduced from ⫻25. 1872
ANGIOSARCOMA ARISING IN TESTICULAR TERATOMA
tumors reportedly do not respond well to cisplatin based chemotherapy.3 The presence of pure sarcoma after chemotherapy for germ cell tumors led to the postulation that chemotherapy may have eradicated residual germ cell elements, permitting the overgrowth of chemoresistant sarcoma cells.1 In our patient sarcomatous and teratomatous elements in the original specimen as well as the lack of teratomatous elements in the recurrence support such a selection process.
1873
REFERENCES
1. Ulbright, T. M., Clark, S. A. and Einhorn, L. H.: Angiosarcoma associated with germ cell tumors. Hum Pathol, 16: 268, 1985 2. Hughes, D. H., Allen, D. C. and O’Neill, J. J.: Angiosarcoma arising in a testicular teratoma. Histopathology, 18: 81, 1991 3. Motzer, R. J., Amsterdam, A., Prieto, V. et al: Teratoma with malignant transformation: diverse malignant histologies arising in men with germ cell tumors. J Urol, 159: 133, 1998
Vol. 163, 1872–1873, June 2000 Printed in U.S.A.
ANGIOSARCOMA ARISING IN A TESTICULAR TERATOMA GRAEME S. STEELE, THOMAS E. CLANCY, MILTON W. DATTA, MICHAEL WEINSTEIN AND JEROME P. RICHIE From the Division of Urology, Departments of Surgery and Pathology, Brigham and Women’s Hospital, Harvard Medical School, Boston, Massachusetts KEY WORDS: testis, teratoma, hemangiosarcoma, germ cell tumor, neoplasm metastasis
Sarcomatous change in a primary germ cell tumor is rare but may develop as a result of malignant transformation within teratomatous foci and may lead to the erroneous diagnosis of embryonal carcinoma. We report a case of epithelioid angiosarcoma arising in a background of mature teratoma. To our knowledge only 2 other such cases have been described previously.1, 2 CASE REPORT
A 24-year-old man presented elsewhere with a 6-month history of an 8 ⫻ 7 cm. left testicular mass. Ultrasound findings were consistent with the clinical impression of a primary testicular tumor. Tumor markers were within normal limits. The patient underwent left radical inguinal orchiectomy. Pathological evaluation revealed a mixed nonseminomatous germ cell tumor with components of embryonal carcinoma (60%) and teratoma (40%). Metastatic evaluation with chest and abdominal computerized tomography (CT) showed approximately 15 small peripheral pulmonary nodules less than 5 mm. in diameter as well as left renal hilar lymphadenopathy 4 cm. in greatest diameter. Three cycles of cisplatin, etoposide and bleomycin were given. Repeat CT revealed resolution of all pulmonary nodules and regression of retroperitoneal lymphadenopathy to 1.5 cm. The patient refused further therapy but underwent serial chest and abdominal CT. However, 6 months later a 10 cm. left renal hilar mass was detected and the patient was referred to our institution. Reevaluation of the initial pathology specimens at our institution demonstrated high grade epithelioid angiosarcoma (90%) arising in a background of mature teratoma (10%) (fig. 1). Immunoperoxidase studies revealed sarcomatous elements positive for vascular marker CD31 in solid and vaso-
formative areas. Tumor invaded the rete testis, epididymis and soft tissue of the spermatic cord. Strong CD31 positivity and cytological similarity to the primary testicular tumor indicated that this tumor represented metastasis. Due to mature teratoma in the primary tumor the patient underwent bilateral retroperitoneal lymph node dissection as well as removal of the left renal hilar mass. Histological analysis revealed metastatic angiosarcoma in the tumor, and in 4 of 23 pre-aortic and interaortocaval lymph nodes. No teratomatous elements were present. Followup chest x-ray showed recurrent lung lesions 4 months later. Pleural fluid sampling and lung biopsy demonstrated metastatic angiosarcoma (fig. 2). The patient subsequently received 6 cycles of ifosfamide and doxorubicin with a near complete response but there was later recurrence. DISCUSSION
Our case illustrates the potential difficulties of diagnosing angiosarcoma in a germ cell tumor, which is an important distinction with respect to treatment as well as prognosis. The gross and microscopic appearance of embryonal carcinoma and epithelioid angiosarcoma may be similar. In our patient the epithelioid nature of the neoplasm probably led to the erroneous diagnosis of embryonal carcinoma. However, the diagnosis of epithelioid angiosarcoma was substantiated by associated hemorrhage instead of necrosis on histological analysis and diagnostic areas of angiosarcoma with branching irregular vascular spaces lined by plump neoplastic endothelial cells. Immunohistochemical studies for CD31 and factor VIII confirmed the diagnosis. Recognizing epithelioid angiosarcoma at presentation would clearly have altered management in our case because these
Accepted for publication January 14, 2000.
FIG. 2. A, mature glandular epithelial element of teratomatous FIG. 1. Epithelioid angiosarcoma of testis with vascular differen- component of primary testicular tumor. B, metastatic angiosarcoma tiation of tumor evidenced by formation of vascular spaces contain- in pleura was strongly positive for endothelial cell marker CD31. ing erythrocytes. H & E, reduced from ⫻50. CD31 immunohistochemical stain, reduced from ⫻25. 1872
ANGIOSARCOMA ARISING IN TESTICULAR TERATOMA
tumors reportedly do not respond well to cisplatin based chemotherapy.3 The presence of pure sarcoma after chemotherapy for germ cell tumors led to the postulation that chemotherapy may have eradicated residual germ cell elements, permitting the overgrowth of chemoresistant sarcoma cells.1 In our patient sarcomatous and teratomatous elements in the original specimen as well as the lack of teratomatous elements in the recurrence support such a selection process.
1873
REFERENCES
1. Ulbright, T. M., Clark, S. A. and Einhorn, L. H.: Angiosarcoma associated with germ cell tumors. Hum Pathol, 16: 268, 1985 2. Hughes, D. H., Allen, D. C. and O’Neill, J. J.: Angiosarcoma arising in a testicular teratoma. Histopathology, 18: 81, 1991 3. Motzer, R. J., Amsterdam, A., Prieto, V. et al: Teratoma with malignant transformation: diverse malignant histologies arising in men with germ cell tumors. J Urol, 159: 133, 1998