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Radiation-Induced Prostatic Sarcoma: A Case Report
0022-534 7 /90/1443-0746$02.00/0 THE JOURNAL OF UROLOGY Copyright© 1990 by AMERICAN UROLOGICAL ASSOCIATION, INC.
Vol. 144, September
Printed in U.S.A.
RADIATION-INDUCED PROSTATIC SARCOMA: A CASE REPORT J. MICHAEL SCULLY, JOHN M. UNO, MICHAEL McINTYRE AND STEPHEN MOSELY From the Departments of Surgery and Pathology, Bay Area Hospital, Coos Bay, and Good Samaritan Hospital and Medical Center, Portland, Oregon
ABSTRACT
A 64-year-old man had a prostatic sarcoma 8 years after transurethral prostatectomy and radical bilateral pelvic lymph node dissection with insertion of 125iodine implants for stage BlN carcinoma of the prostate. Therapy for the sarcoma consisted of isolated pelvic perfusion and then pelvic exenteration with creation of an ileal conduit and colostomy. The pathology report showed well encapsulated grade 2 spindle cell sarcoma of the prostate. Multiple small metallic particles were embedded in the tumor specimen. (J. Urol., 144: 746-748, 1990) (fig. 3). 6 Diagnosis was reconfirmed with a second pathological opinion and cytochemical staining (see table). Also noted were atrophic glands with reactive atypia consistent with prostatic tissue with radiation artifact. The patient underwent a 2-stage therapeutic approach. He had isolated pelvic perfusion with 200 mg./m. 2 cisplatin with 500 mg./m. 2 dimethyl-triazeno imidazole carboxamine given systemically before perfusion of the pelvis. Ten days later the patient underwent pelvic exenteration with an ileal conduit and colostomy. He tolerated both procedures well and left the hospital 1 week after the definitive operation. Aggressive radical resection with perfusion was believed to be the best chance for palliation and potential cure. Preoperative computerized tomography, PAP and acid phosphatase levels appeared to show that the lesion was confined to the pelvic region with no signs of metastatic spread. Pathological report showed the lesion to be at the anal verge, distending into the anal canal and measuring 4 X 1.8 X 1.5 cm. On sectioning, the lesion had a light tan to yellow color and extended into the surrounding soft tissue. The plane of resection was free of tumor. Multiple small metallic seeds were noted in an area of pronounced scarring and induration. This appeared to be the area of residual prostatic tissue. Rectal biopsies and the surgical specimen contained poorly differentiated grade 2 spindle cell sarcoma.
Radiation-induced malignancy has been a well described phenomenon1 since the first reports of Frieben in 1902 2 and Perthes in 1904. 3 Radiation-induced sarcomas were described by Beck in 1922. 4 Radiation-induced sarcoma has been described in the bone, chest wall, skin, uterus, breast, retroperitoneum, liver, mediastinum, pelvis, blood, muscle, thyroid and parathyroid tissue, lung and stomach but to date there has been no report of radiation-induced sarcoma of the prostate. We report on a 64-year-old man with sarcoma of the prostate that developed 8 years after radiation therapy for adenocarcinoma of the prostate. CASE REPORT
The patient first presented in July 1981 when he was 59 years old with bladder outflow obstruction. A prostatic nodule 1 cm. in diameter was noted in the apex of the left lobe. Based on the Jewett system 5 this nodule was classified as a stage Bl lesion. Biopsy confirmed carcinoma of the prostate (fig. 1). The patient underwent transurethral prostatectomy for bladder outflow obstruction, radical bilateral pelvic lymph node dissection and insertion of 125iodine (1 251) implants. Approximately 6 to 8 gm. of prostatic tissue were removed at transurethral prostatectomy. Pathological study showed that all lymph nodes were negative. A total of 3·3 seeds was implanted in the right lobe and 35 in the left lobe, for a total matched peripheral dose of 27,000 rad. Followup consisted of quarterly examinations for 1 year and then biannual examinations every year thereafter. Radioimmunoassay, prostatic acid phosphatase (PAP) and acid phosphatase levels were all normal on multiple occasions, as were bone scans done in 1981 and 1983. In 1983 rectal examination revealed a prostatic nodule for which the patient underwent cystoscopic examination and biopsy. This examination was negative and the prostatic tissue did not show any signs of recurrent malignancy (fig. 2, A). In 1986 the patient had an area of induration, and repeat cystoscopy and biopsy of the area showed no signs of malignancy (fig. 2, B). In both cases cystoscopic examination showed scarring and a few metallic particles without evidence of recurrence. In 1989 the patient presented with a chief complaint of rectal pain. Evaluation at that time showed a mass that was extrinsic to the rectum, located anteriorly and seemingly contiguous with the prostate. The mucosa of the rectum was free of erosion. However, the tissue surrounding the rectum anteriorly appeared to be somewhat dense and perhaps invaded. Needle and open biopsies confirmed a spindle cell sarcoma which was classified grade 2 according to the National Cancer Institute Accepted for publication April 6, 1990.
DISCUSSION
We report a case of sarcoma occurring after prostatic irradiation with 1251 implants. The criteria for diagnosis of radiationinduced malignancy are specific and have been well described by Cahan and associates. 7 Initially, the lesion must be localized in a previously irradiated area. Also, there must be a clear cytological difference between the primary and the new lesion. Finally, there must be a latent interval between the radiation therapy and the presence of a new lesion. Whereas the first 2 criteria were well met by our patient, our latent interval is perhaps less than the average cited. However, this seems to be dependent on the age of the patient and the type of tissue irradiated. The average range in the literature extends to 30 years. In cases of radiation-induced leukemias 5 to 8 years seems to be the average latent period. The average interval is 21 years for skin cancers, 27 years for thyroid cancer, 15 years for breast cancer and approximately 10 years for pelvic malignancies. With this wide range in mind, we believe that 8 years, while perhaps not as long as the average, certainly falls within range for some of the radiation-induced malignancies reported in the literature. Because of the dismal course of these patients any clinically suspicious nodule in an area of previous irradiation should be
746
747
RADIATION-INDUCED PROSTATIC SARCOMA
Fm. 1. Prostate needle biopsy in 1981 shows well differentiated prostate adenocarcinoma on right side and benign prostate glands in center. Reduced from XlOO.
Fm. 3. Sarcoma arising in region of prostate-1989 specimen. A, reduced from XlOO. B, reduced from X400.
Special stains Immunoperoxidase Specific Diagnostic Application
Antigen Prostate specific antigen* PAP* Cytokeratin (AE1/AE3)t Vimentint,:j: Desmint,:j: HHF 35t,§ a<-1, anti-trypsin*,11
s-100*,II
Prostate Ca Prostate Ca Ca Sarcoma Myogenic tumors Myogenic tumors Histiocytic differen tiation~ Nerve sheath tumors, smooth muscle~
Result Neg. Neg. Neg. Pos. Neg. Focally neg. Focally pos. Pos.
Results of trichrome stain were negative.
* Polyclonal antibody. t Monoclonal antibody. :j: Biogenics. § Muscle specific antigen.
II Biomedia. ~
Fm. 2. Prostate needle biopsies show benign tissue with scarring. A, 1983. B, 1986. Reduced from XlOO.
In addition to other specificities.
when a suspicious lesion arises in a field of prior irradiation therapy. Mr. Robert Vega provided technical assistance.
biopsied, particularly if it occurs remotely from the initial therapy. Valuable time is lost if these lesions are considered to be local recurrences and if further radiation therapy is begun. 8• 9 Our experience with this patient and review of other cases of radiation-induced sarcoma have given us an increased awareness of radiation-induced neoplasia. Careful, long-term followup is needed in all patients who have received radiation therapy. This should be continued even after the initial lesion has been cured. Appropriate diagnostic steps should be taken
REFERENCES
1. Scanlon, E. F., Berk, R. S. and Khandekar, J. D.: Post irradiation neoplasia: a symposium. Curr. Prob. Cancer, 3: 4, Dec. 1978. 2. Adam, Y. G. and Reif, R.: Radiation-induced fibrosarcoma following treatment for breast cancer. Surgery, 81: 421, 1977. 3. Gane, N. F. C., Lindup, R., Strickland, P. and Bennett, M. H.: Radiation-induced fibrosarcoma. Brit. J. Cancer, 24: 705, 1970. 4. Beck, A.: Zur Frage des Rontgenasarkoms, zugleich ein Beitrag zur Pathogenes des Sarkoms. Mnch. Med. Wchnschr., 69: 623, 1922.
748
SCULLY AND ASSOCIATES
5. Catalona, W. J. and Scott, W. W.: Carcinoma of the prostate. In: Campbell's Urology, 4th ed. Edited by J. H. Harrison, R. F. Gittes, A. D. Perlmutter, T. A. Stamey and P. C. Walsh. Philadelphia: W. B. Saunders Co., vol. 2, chapt. 31, pp. 1093-1095, 1979. 6. Costa, J., Wesley, R. A., Glatstein, E. and Rosenberg, S. A.: The grading of soft tissue sarcomas. Results of a clinicohistopathologic correlation in a series of 163 cases. Cancer, 53: 530, 1984.
7. Cahan, W. G., Woodward, H. G. and Higenbothom, N. L.: Sarcoma arising in irradiated bone: report of 11 cases. Cancer, 1: 3, 1948. 8. O'Neil, M. B., Jr., Cocke, W., Mason, D. and Hurley, E. J.: Radiation-induced soft-tissue fibrosarcomas: surgical therapy and salvage. Ann. Thorac. Surg., 33: 624, 1982. 9. Oberman, H. A. and Oneal, R. M.: Fibrosarcoma of the chest wall following resection and irradiation of carcinoma of the breast. Amer. J. Clin. Path., 53: 407, 1970.
Vol. 144, September
Printed in U.S.A.
RADIATION-INDUCED PROSTATIC SARCOMA: A CASE REPORT J. MICHAEL SCULLY, JOHN M. UNO, MICHAEL McINTYRE AND STEPHEN MOSELY From the Departments of Surgery and Pathology, Bay Area Hospital, Coos Bay, and Good Samaritan Hospital and Medical Center, Portland, Oregon
ABSTRACT
A 64-year-old man had a prostatic sarcoma 8 years after transurethral prostatectomy and radical bilateral pelvic lymph node dissection with insertion of 125iodine implants for stage BlN carcinoma of the prostate. Therapy for the sarcoma consisted of isolated pelvic perfusion and then pelvic exenteration with creation of an ileal conduit and colostomy. The pathology report showed well encapsulated grade 2 spindle cell sarcoma of the prostate. Multiple small metallic particles were embedded in the tumor specimen. (J. Urol., 144: 746-748, 1990) (fig. 3). 6 Diagnosis was reconfirmed with a second pathological opinion and cytochemical staining (see table). Also noted were atrophic glands with reactive atypia consistent with prostatic tissue with radiation artifact. The patient underwent a 2-stage therapeutic approach. He had isolated pelvic perfusion with 200 mg./m. 2 cisplatin with 500 mg./m. 2 dimethyl-triazeno imidazole carboxamine given systemically before perfusion of the pelvis. Ten days later the patient underwent pelvic exenteration with an ileal conduit and colostomy. He tolerated both procedures well and left the hospital 1 week after the definitive operation. Aggressive radical resection with perfusion was believed to be the best chance for palliation and potential cure. Preoperative computerized tomography, PAP and acid phosphatase levels appeared to show that the lesion was confined to the pelvic region with no signs of metastatic spread. Pathological report showed the lesion to be at the anal verge, distending into the anal canal and measuring 4 X 1.8 X 1.5 cm. On sectioning, the lesion had a light tan to yellow color and extended into the surrounding soft tissue. The plane of resection was free of tumor. Multiple small metallic seeds were noted in an area of pronounced scarring and induration. This appeared to be the area of residual prostatic tissue. Rectal biopsies and the surgical specimen contained poorly differentiated grade 2 spindle cell sarcoma.
Radiation-induced malignancy has been a well described phenomenon1 since the first reports of Frieben in 1902 2 and Perthes in 1904. 3 Radiation-induced sarcomas were described by Beck in 1922. 4 Radiation-induced sarcoma has been described in the bone, chest wall, skin, uterus, breast, retroperitoneum, liver, mediastinum, pelvis, blood, muscle, thyroid and parathyroid tissue, lung and stomach but to date there has been no report of radiation-induced sarcoma of the prostate. We report on a 64-year-old man with sarcoma of the prostate that developed 8 years after radiation therapy for adenocarcinoma of the prostate. CASE REPORT
The patient first presented in July 1981 when he was 59 years old with bladder outflow obstruction. A prostatic nodule 1 cm. in diameter was noted in the apex of the left lobe. Based on the Jewett system 5 this nodule was classified as a stage Bl lesion. Biopsy confirmed carcinoma of the prostate (fig. 1). The patient underwent transurethral prostatectomy for bladder outflow obstruction, radical bilateral pelvic lymph node dissection and insertion of 125iodine (1 251) implants. Approximately 6 to 8 gm. of prostatic tissue were removed at transurethral prostatectomy. Pathological study showed that all lymph nodes were negative. A total of 3·3 seeds was implanted in the right lobe and 35 in the left lobe, for a total matched peripheral dose of 27,000 rad. Followup consisted of quarterly examinations for 1 year and then biannual examinations every year thereafter. Radioimmunoassay, prostatic acid phosphatase (PAP) and acid phosphatase levels were all normal on multiple occasions, as were bone scans done in 1981 and 1983. In 1983 rectal examination revealed a prostatic nodule for which the patient underwent cystoscopic examination and biopsy. This examination was negative and the prostatic tissue did not show any signs of recurrent malignancy (fig. 2, A). In 1986 the patient had an area of induration, and repeat cystoscopy and biopsy of the area showed no signs of malignancy (fig. 2, B). In both cases cystoscopic examination showed scarring and a few metallic particles without evidence of recurrence. In 1989 the patient presented with a chief complaint of rectal pain. Evaluation at that time showed a mass that was extrinsic to the rectum, located anteriorly and seemingly contiguous with the prostate. The mucosa of the rectum was free of erosion. However, the tissue surrounding the rectum anteriorly appeared to be somewhat dense and perhaps invaded. Needle and open biopsies confirmed a spindle cell sarcoma which was classified grade 2 according to the National Cancer Institute Accepted for publication April 6, 1990.
DISCUSSION
We report a case of sarcoma occurring after prostatic irradiation with 1251 implants. The criteria for diagnosis of radiationinduced malignancy are specific and have been well described by Cahan and associates. 7 Initially, the lesion must be localized in a previously irradiated area. Also, there must be a clear cytological difference between the primary and the new lesion. Finally, there must be a latent interval between the radiation therapy and the presence of a new lesion. Whereas the first 2 criteria were well met by our patient, our latent interval is perhaps less than the average cited. However, this seems to be dependent on the age of the patient and the type of tissue irradiated. The average range in the literature extends to 30 years. In cases of radiation-induced leukemias 5 to 8 years seems to be the average latent period. The average interval is 21 years for skin cancers, 27 years for thyroid cancer, 15 years for breast cancer and approximately 10 years for pelvic malignancies. With this wide range in mind, we believe that 8 years, while perhaps not as long as the average, certainly falls within range for some of the radiation-induced malignancies reported in the literature. Because of the dismal course of these patients any clinically suspicious nodule in an area of previous irradiation should be
746
747
RADIATION-INDUCED PROSTATIC SARCOMA
Fm. 1. Prostate needle biopsy in 1981 shows well differentiated prostate adenocarcinoma on right side and benign prostate glands in center. Reduced from XlOO.
Fm. 3. Sarcoma arising in region of prostate-1989 specimen. A, reduced from XlOO. B, reduced from X400.
Special stains Immunoperoxidase Specific Diagnostic Application
Antigen Prostate specific antigen* PAP* Cytokeratin (AE1/AE3)t Vimentint,:j: Desmint,:j: HHF 35t,§ a<-1, anti-trypsin*,11
s-100*,II
Prostate Ca Prostate Ca Ca Sarcoma Myogenic tumors Myogenic tumors Histiocytic differen tiation~ Nerve sheath tumors, smooth muscle~
Result Neg. Neg. Neg. Pos. Neg. Focally neg. Focally pos. Pos.
Results of trichrome stain were negative.
* Polyclonal antibody. t Monoclonal antibody. :j: Biogenics. § Muscle specific antigen.
II Biomedia. ~
Fm. 2. Prostate needle biopsies show benign tissue with scarring. A, 1983. B, 1986. Reduced from XlOO.
In addition to other specificities.
when a suspicious lesion arises in a field of prior irradiation therapy. Mr. Robert Vega provided technical assistance.
biopsied, particularly if it occurs remotely from the initial therapy. Valuable time is lost if these lesions are considered to be local recurrences and if further radiation therapy is begun. 8• 9 Our experience with this patient and review of other cases of radiation-induced sarcoma have given us an increased awareness of radiation-induced neoplasia. Careful, long-term followup is needed in all patients who have received radiation therapy. This should be continued even after the initial lesion has been cured. Appropriate diagnostic steps should be taken
REFERENCES
1. Scanlon, E. F., Berk, R. S. and Khandekar, J. D.: Post irradiation neoplasia: a symposium. Curr. Prob. Cancer, 3: 4, Dec. 1978. 2. Adam, Y. G. and Reif, R.: Radiation-induced fibrosarcoma following treatment for breast cancer. Surgery, 81: 421, 1977. 3. Gane, N. F. C., Lindup, R., Strickland, P. and Bennett, M. H.: Radiation-induced fibrosarcoma. Brit. J. Cancer, 24: 705, 1970. 4. Beck, A.: Zur Frage des Rontgenasarkoms, zugleich ein Beitrag zur Pathogenes des Sarkoms. Mnch. Med. Wchnschr., 69: 623, 1922.
748
SCULLY AND ASSOCIATES
5. Catalona, W. J. and Scott, W. W.: Carcinoma of the prostate. In: Campbell's Urology, 4th ed. Edited by J. H. Harrison, R. F. Gittes, A. D. Perlmutter, T. A. Stamey and P. C. Walsh. Philadelphia: W. B. Saunders Co., vol. 2, chapt. 31, pp. 1093-1095, 1979. 6. Costa, J., Wesley, R. A., Glatstein, E. and Rosenberg, S. A.: The grading of soft tissue sarcomas. Results of a clinicohistopathologic correlation in a series of 163 cases. Cancer, 53: 530, 1984.
7. Cahan, W. G., Woodward, H. G. and Higenbothom, N. L.: Sarcoma arising in irradiated bone: report of 11 cases. Cancer, 1: 3, 1948. 8. O'Neil, M. B., Jr., Cocke, W., Mason, D. and Hurley, E. J.: Radiation-induced soft-tissue fibrosarcomas: surgical therapy and salvage. Ann. Thorac. Surg., 33: 624, 1982. 9. Oberman, H. A. and Oneal, R. M.: Fibrosarcoma of the chest wall following resection and irradiation of carcinoma of the breast. Amer. J. Clin. Path., 53: 407, 1970.