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Management of Spermatic Cord Liposarcoma in Renal Transplant Recipients: Case Report
Management of Spermatic Cord Liposarcoma in Renal Transplant Recipients: Case Report T.M. Manzia, G. Gravante, L. Toti, G. Iaria, A. Anselmo, S. Fratoni, R. Angelico, D. Sforza, M. Manuelli, and G. Tisone ABSTRACT Herein, we report the case of a 52-year-old man with a spermatic cord liposarcoma that developed 4 years after renal transplantation. The patient was admitted with a diagnosis of inguinal hernia. During surgical exploration, a solid mass was found arising from the spermatic cord. Histologic analysis demonstrated a well-differentiated sclerosing liposarcoma. EVELOPMENT OF NEOPLASMS in kidney transplant recipients is 3- to 5-fold higher than the overall cancer incidence in the general population.1 Prolonged use of immunosuppression therapy leads to changes in immune surveillance and is associated with increased risk of cancer; 20% of transplant recipients are affected after 10 years of immunosuppression therapy.2 After the diagnosis is made, changes in standard treatment strategies are necessary to balance the necessity for immunosuppression therapy against immune surveillance for cancer control.1,2 The most frequently observed neoplasms after solidorgan transplantation include nonmelanoma skin cancer and Kaposi sarcoma, as well as posttransplantation lymphoproliferative disorders.3 Liposarcomas have been rarely reported in end-stage kidney disease4 or after renal transplantation,5– 8 and include 1 report of paratesticular liposarcoma.9 Herein, we report the case of a renal transplant recipient in whom a liposarcoma of the spermatic cord developed on the same side as the graft at 4 years posttransplantation.
D
CASE REPORT A 52-year-old man underwent renal transplantation in December 2003 because of autosomal dominant polycystic kidney disease. The donor age was 56 years. Kidney cold and warm ischemia time was 420 and 45 minutes, respectively, and operative time was 180 minutes. The kidney was implanted into the left iliac fossa according to standard surgical technique, without intraoperative complications. Immunosuppression therapy included tacrolimus, mycophenolate mofetil, and steroids. No postoperative complications occurred, and the patient was discharged after 7 days, with standard outpatient follow-up. After 4 years, the patient had painless left inguinal swelling that had been growing over 3 months. The mass was in the left groin, and was solid, firm, and painless. It did not touch the testis, and could not be placed into the abdominal cavity. The testis seemed to
be normal and not involved with the mass. The ipsilateral hemiscrotum and contralateral groin and hemiscrotum were normal, as were locoregional lymph nodes. The provisional diagnosis was irreducible inguinal hernia, and surgical exploration was planned. During the operation, a solid 4-mm gray-white mass, harder than a classic lipoma, was found in the spermatic cord. Cordal structures were easily detached, and the mass was sent for histologic analysis. The final histologic report described a well-differentiated sclerosing liposarcoma (Fig 1). At immunohistochemistry, the tumor was vimentin-positive, ␣-actin negative, desmin-negative, CD34-positive, and S100-negative. A computed tomography scan obtained after surgery was negative for any regional lymph node or distant metastasis. Immunosuppression therapy was changed from tacrolimus to sirolimus. After 3-year follow-up, the patient was disease-free with a functioning graft, and has not experienced any adverse effects of sirolimus therapy.
DISCUSSION
Liposarcoma of the spermatic cord is a rare malignant neoplasm that accounts for 3% to 7% of all sarcomas.10 Histologically, it is composed of adipose, fibromatous, and myxomatous cells,10 –12 which suggests the emergence of a single primordial cell clone capable of differentiating into various fibroblastic, lipoblastic, and osteoblastic matrices.13 Clinically, it develops primarily in adults. It may range in size from a few centimeters to 4.5 kg.14 It is generally painless. Liposarcoma of the spermatic cord frequently is confused with other pathologic conditions such as inguinal From the UOC Trapianti d’Organo (T.M.M., L.T., G.I., A.A., R.A., D.S., M.M., G.T.) and Department of Histopathology (S.F.), Sant’ Eugenio Hospital, University “Tor Vergata,” Rome, Italy, and the Department of Hepatobiliary and Pancreatic Surgery, University Hospitals of Leicester, Leicester, England (G.G.). Address reprint requests to Tommaso Maria Manzia, MD, UOC Trapianti d’Organo, Sant’ Eugenio Hospital, Piazzale dell’Umanesimo 10, Rome, Italy. E-mail: [email protected]
© 2010 by Elsevier Inc. All rights reserved. 360 Park Avenue South, New York, NY 10010-1710
0041-1345/–see front matter doi:10.1016/j.transproceed.2010.03.043
Transplantation Proceedings, 42, 1355–1357 (2010)
1355
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MANZIA, GRAVANTE, TOTI ET AL
Fig 1. Upper panels, Fibrous lesion with loose and densely mature collagen fibers and spindle fibroblasts with sporadic hyperchromatic atypical nuclei. Lower panels, Occasionally, atypical cells with large vacuolated cytoplasm and hyperchromatic indented nuclei (lipoblasts) are present.
hernia or lipoma, epididymal or funicular cyst, and testicular tumor. Ultrasonography yields little information about paratesticular sarcomas, some of which are visualized as homogeneous and isoechogenic, and others as dyshomogeneous. Their echodensity is quite variable. On computed tomography scans, liposarcomas demonstrate low density. They may be well demarcated but exhibit no pathognomonic features to differentiate benign from malignant masses.15 Local radical excision is the treatment of choice; however, the tumor may recur in as many as 50% of patients.16 –18 Approximately 200 sarcomas of the spermatic cord have been reported in the literature. About 60 were paratesticular19; only 1 was observed in a renal transplant recipient.9 The peculiar therapeutic implications are as follows. First, the preoperative diagnosis was inguinal hernia, and in renal transplant recipients, the presence of a herniated ureter is not uncommon.20,21 Both conditions require immediate repair to avert obstructive uropathy.22–24 Second, at exploratory surgery, the mass appeared to be a preperitoneal lipoma; however, a reactive inflammatory node due to an inflammatory-immunologic reaction to the adjacent graft could not be ruled out. Complete excision was necessary for the definitive diagnosis. Third, entire removal of the spermatic cord and orchiectomy were necessarily avoided because they may be potentially dangerous for graft survival.25,26 This was not the case in the patient of Zavos et al,9 in whom the mass was scrotal, not inguinal, and close to the testis. Fourth, most important in our patient, immu-
nosuppression therapy was changed from a tacrolimusbased regimen to a sirolimus-based regimen. The peculiarity of our case compared with that of Zavos et al9 is that it is the first since the introduction of sirolimus into clinical practice. The choice to change the immunosuppression regimen was supported by the antiproliferative and antitumoral effects of sirolimus, as demonstrated in preclinical and clinical studies, and favorable outcome in transplant recipients with de novo malignant lesions.1,2,27 Similar to the patient of Zavos et al,9 our patient is alive and disease-free at 3-year follow-up. Whether changing the immunosuppression regimen is beneficial for outcome needs to be further investigated in appropriate prospective studies. Local adjuvant radiation therapy, as some authors have recommended,11,17,18 is useful in incidences of local recurrence; however, it has not been administered routinely because of the close proximity of the transplanted kidney to the radiation field.9 Systemic chemotherapy was not considered because of the possibility that its adverse effects could compromise the function of the adjacent graft.9 REFERENCES 1. Wong G, Chapman JR: Cancers after renal transplantation. Transplant Rev (Orlando) 22:141, 2008 2. Kapoor A: Malignancy in kidney transplant recipients. Drugs 68:11, 2008 3. Zafar SY, Howell DN, Gockerman JP: Malignancy after solid organ transplantation: an overview. Oncologist 13:769, 2008
SPERMATIC CORD LIPOSARCOMA 4. Hora M, Hes O, Reischig T, et al: Tumours in end-stage kidney. Transplant Proc 40:3354, 2008 5. Campistol JM, Eris J, Oberbauer R, et al: Sirolimus therapy after early cyclosporine withdrawal reduces the risk for cancer in adult renal transplantation. J Am Soc Nephrol 17:581, 2006 6. Padilla Nieva J, Lecumberri Castaños D, et al: Retroperitoneal liposarcoma in a patient with renal transplantation [in Spanish]. Actas Urol Esp 25:527, 2001 7. Tahara H, Imanishi M, Ishii T, et al: Myxoid liposarcoma surrounding non-functioning transplanted kidney after living renal transplantation: a case report [in Japanese]. Nippon Hinyokika Gakkai Zasshi 89:854, 1998 8. Kunikata S, Akiyama T, Kurita T, et al: Clinical study of pediatric kidney transplantation at Kansai [in Japanese]. Nippon Hinyokika Gakkai Zasshi 87:50, 1996 9. Zavos G, Papadoukakis S, Kiriakou V, et al: Paratesticular liposarcoma in a transplanted patient. Urol Int 67:254, 2001 10. Schwartz SL, Swierzewski SJ III, Sondak VK, et al: Liposarcoma of the spermatic cord: report of 6 cases and review of the literature. J Urol 153:154, 1995 11. Ballo MT, Zagars GK, Pisters PW, et al: Spermatic cord sarcoma: outcome, patterns of failure and management. J Urol 166:1306, 2001 12. Grey LF, Sorial RF, Shaw WH: Spermatic cord sarcoma: leiomyosarcoma and retroperitoneal lymph node dissection. Urology 27:28, 1986 13. Hajdu SI: Soft tissue sarcomas: classification and natural history. CA Cancer J Clin 31:271, 1981 14. Kent J: Giant liposarcoma of the spermatic cord. Med J Australia 148:600, 1988 15. Cardenosa G, Papanicolaou N, Fung CY, et al: Spermatic cord sarcomas: sonographic and CT features. Urol Radiol 12:163, 1990
1357 16. Blitzer PH, Dosoretz DE, Proppe KH, et al: Treatment of malignant tumors of the spermatic cord: a study of 10 cases and a review of the literature. J Urol 126:611, 1981 17. Fagundes MA, Zietman AL, Althausen AF, et al: The management of spermatic cord sarcoma. Cancer 77:1873, 1996 18. Catton CN, Cummings BJ, Fornasier V, et al: Adult paratesticular sarcomas: a review of 21 cases. J Urol 146:342, 1991 19. Russo P, Brady MS, Conlon K, et al: Adult urological sarcoma. J Urol 147:1032, 1992 20. Otani LH, Jayanthi SK, Chiarantano RS, et al: Sonographic diagnosis of a ureteral inguinal hernia in a renal transplant. J Ultrasound Med 27:1759, 2008 21. Ingber MS, Girdler BJ, Moy JF, et al: Inguinal herniation of a transplant ureter: rare cause of obstructive uropathy. Urology 70:1224.e1, 2007 22. Verbeeck N, Niedercorn JB, McIntyre D, et al: Assessment of renal graft obstruction due to ureteral inguinal hernia: US detection and 3D MR confirmation. JBR-BTR 90:132, 2007 23. Furtado CD, Sirlin C, Precht A, et al: Unusual cause of ureteral obstruction in transplant kidney. Abdom Imag 31:379, 2006 24. Sanchez AS, Tebar JC, Martin MS, et al: Obstructive uropathy secondary to ureteral herniation in a pediatric en bloc renal graft. Am J Transplant 5:2074, 2005 25. Coleman J, Brennan MF, Alektiar K, et al: Adult spermatic cord sarcomas: management and results. Ann Surg Oncol 10:669, 2003 26. Pisters PW, Leung DH, Woodruff J, et al: Analysis of prognostic factors in 1,041 patients with localized soft tissue sarcomas of the extremities. J Clin Oncol 14:1679, 1996 27. Monaco AP: The role of mTOR inhibitors in the management of posttransplant malignancy. Transplantation 87:157, 2009
D
CASE REPORT A 52-year-old man underwent renal transplantation in December 2003 because of autosomal dominant polycystic kidney disease. The donor age was 56 years. Kidney cold and warm ischemia time was 420 and 45 minutes, respectively, and operative time was 180 minutes. The kidney was implanted into the left iliac fossa according to standard surgical technique, without intraoperative complications. Immunosuppression therapy included tacrolimus, mycophenolate mofetil, and steroids. No postoperative complications occurred, and the patient was discharged after 7 days, with standard outpatient follow-up. After 4 years, the patient had painless left inguinal swelling that had been growing over 3 months. The mass was in the left groin, and was solid, firm, and painless. It did not touch the testis, and could not be placed into the abdominal cavity. The testis seemed to
be normal and not involved with the mass. The ipsilateral hemiscrotum and contralateral groin and hemiscrotum were normal, as were locoregional lymph nodes. The provisional diagnosis was irreducible inguinal hernia, and surgical exploration was planned. During the operation, a solid 4-mm gray-white mass, harder than a classic lipoma, was found in the spermatic cord. Cordal structures were easily detached, and the mass was sent for histologic analysis. The final histologic report described a well-differentiated sclerosing liposarcoma (Fig 1). At immunohistochemistry, the tumor was vimentin-positive, ␣-actin negative, desmin-negative, CD34-positive, and S100-negative. A computed tomography scan obtained after surgery was negative for any regional lymph node or distant metastasis. Immunosuppression therapy was changed from tacrolimus to sirolimus. After 3-year follow-up, the patient was disease-free with a functioning graft, and has not experienced any adverse effects of sirolimus therapy.
DISCUSSION
Liposarcoma of the spermatic cord is a rare malignant neoplasm that accounts for 3% to 7% of all sarcomas.10 Histologically, it is composed of adipose, fibromatous, and myxomatous cells,10 –12 which suggests the emergence of a single primordial cell clone capable of differentiating into various fibroblastic, lipoblastic, and osteoblastic matrices.13 Clinically, it develops primarily in adults. It may range in size from a few centimeters to 4.5 kg.14 It is generally painless. Liposarcoma of the spermatic cord frequently is confused with other pathologic conditions such as inguinal From the UOC Trapianti d’Organo (T.M.M., L.T., G.I., A.A., R.A., D.S., M.M., G.T.) and Department of Histopathology (S.F.), Sant’ Eugenio Hospital, University “Tor Vergata,” Rome, Italy, and the Department of Hepatobiliary and Pancreatic Surgery, University Hospitals of Leicester, Leicester, England (G.G.). Address reprint requests to Tommaso Maria Manzia, MD, UOC Trapianti d’Organo, Sant’ Eugenio Hospital, Piazzale dell’Umanesimo 10, Rome, Italy. E-mail: [email protected]
© 2010 by Elsevier Inc. All rights reserved. 360 Park Avenue South, New York, NY 10010-1710
0041-1345/–see front matter doi:10.1016/j.transproceed.2010.03.043
Transplantation Proceedings, 42, 1355–1357 (2010)
1355
1356
MANZIA, GRAVANTE, TOTI ET AL
Fig 1. Upper panels, Fibrous lesion with loose and densely mature collagen fibers and spindle fibroblasts with sporadic hyperchromatic atypical nuclei. Lower panels, Occasionally, atypical cells with large vacuolated cytoplasm and hyperchromatic indented nuclei (lipoblasts) are present.
hernia or lipoma, epididymal or funicular cyst, and testicular tumor. Ultrasonography yields little information about paratesticular sarcomas, some of which are visualized as homogeneous and isoechogenic, and others as dyshomogeneous. Their echodensity is quite variable. On computed tomography scans, liposarcomas demonstrate low density. They may be well demarcated but exhibit no pathognomonic features to differentiate benign from malignant masses.15 Local radical excision is the treatment of choice; however, the tumor may recur in as many as 50% of patients.16 –18 Approximately 200 sarcomas of the spermatic cord have been reported in the literature. About 60 were paratesticular19; only 1 was observed in a renal transplant recipient.9 The peculiar therapeutic implications are as follows. First, the preoperative diagnosis was inguinal hernia, and in renal transplant recipients, the presence of a herniated ureter is not uncommon.20,21 Both conditions require immediate repair to avert obstructive uropathy.22–24 Second, at exploratory surgery, the mass appeared to be a preperitoneal lipoma; however, a reactive inflammatory node due to an inflammatory-immunologic reaction to the adjacent graft could not be ruled out. Complete excision was necessary for the definitive diagnosis. Third, entire removal of the spermatic cord and orchiectomy were necessarily avoided because they may be potentially dangerous for graft survival.25,26 This was not the case in the patient of Zavos et al,9 in whom the mass was scrotal, not inguinal, and close to the testis. Fourth, most important in our patient, immu-
nosuppression therapy was changed from a tacrolimusbased regimen to a sirolimus-based regimen. The peculiarity of our case compared with that of Zavos et al9 is that it is the first since the introduction of sirolimus into clinical practice. The choice to change the immunosuppression regimen was supported by the antiproliferative and antitumoral effects of sirolimus, as demonstrated in preclinical and clinical studies, and favorable outcome in transplant recipients with de novo malignant lesions.1,2,27 Similar to the patient of Zavos et al,9 our patient is alive and disease-free at 3-year follow-up. Whether changing the immunosuppression regimen is beneficial for outcome needs to be further investigated in appropriate prospective studies. Local adjuvant radiation therapy, as some authors have recommended,11,17,18 is useful in incidences of local recurrence; however, it has not been administered routinely because of the close proximity of the transplanted kidney to the radiation field.9 Systemic chemotherapy was not considered because of the possibility that its adverse effects could compromise the function of the adjacent graft.9 REFERENCES 1. Wong G, Chapman JR: Cancers after renal transplantation. Transplant Rev (Orlando) 22:141, 2008 2. Kapoor A: Malignancy in kidney transplant recipients. Drugs 68:11, 2008 3. Zafar SY, Howell DN, Gockerman JP: Malignancy after solid organ transplantation: an overview. Oncologist 13:769, 2008
SPERMATIC CORD LIPOSARCOMA 4. Hora M, Hes O, Reischig T, et al: Tumours in end-stage kidney. Transplant Proc 40:3354, 2008 5. Campistol JM, Eris J, Oberbauer R, et al: Sirolimus therapy after early cyclosporine withdrawal reduces the risk for cancer in adult renal transplantation. J Am Soc Nephrol 17:581, 2006 6. Padilla Nieva J, Lecumberri Castaños D, et al: Retroperitoneal liposarcoma in a patient with renal transplantation [in Spanish]. Actas Urol Esp 25:527, 2001 7. Tahara H, Imanishi M, Ishii T, et al: Myxoid liposarcoma surrounding non-functioning transplanted kidney after living renal transplantation: a case report [in Japanese]. Nippon Hinyokika Gakkai Zasshi 89:854, 1998 8. Kunikata S, Akiyama T, Kurita T, et al: Clinical study of pediatric kidney transplantation at Kansai [in Japanese]. Nippon Hinyokika Gakkai Zasshi 87:50, 1996 9. Zavos G, Papadoukakis S, Kiriakou V, et al: Paratesticular liposarcoma in a transplanted patient. Urol Int 67:254, 2001 10. Schwartz SL, Swierzewski SJ III, Sondak VK, et al: Liposarcoma of the spermatic cord: report of 6 cases and review of the literature. J Urol 153:154, 1995 11. Ballo MT, Zagars GK, Pisters PW, et al: Spermatic cord sarcoma: outcome, patterns of failure and management. J Urol 166:1306, 2001 12. Grey LF, Sorial RF, Shaw WH: Spermatic cord sarcoma: leiomyosarcoma and retroperitoneal lymph node dissection. Urology 27:28, 1986 13. Hajdu SI: Soft tissue sarcomas: classification and natural history. CA Cancer J Clin 31:271, 1981 14. Kent J: Giant liposarcoma of the spermatic cord. Med J Australia 148:600, 1988 15. Cardenosa G, Papanicolaou N, Fung CY, et al: Spermatic cord sarcomas: sonographic and CT features. Urol Radiol 12:163, 1990
1357 16. Blitzer PH, Dosoretz DE, Proppe KH, et al: Treatment of malignant tumors of the spermatic cord: a study of 10 cases and a review of the literature. J Urol 126:611, 1981 17. Fagundes MA, Zietman AL, Althausen AF, et al: The management of spermatic cord sarcoma. Cancer 77:1873, 1996 18. Catton CN, Cummings BJ, Fornasier V, et al: Adult paratesticular sarcomas: a review of 21 cases. J Urol 146:342, 1991 19. Russo P, Brady MS, Conlon K, et al: Adult urological sarcoma. J Urol 147:1032, 1992 20. Otani LH, Jayanthi SK, Chiarantano RS, et al: Sonographic diagnosis of a ureteral inguinal hernia in a renal transplant. J Ultrasound Med 27:1759, 2008 21. Ingber MS, Girdler BJ, Moy JF, et al: Inguinal herniation of a transplant ureter: rare cause of obstructive uropathy. Urology 70:1224.e1, 2007 22. Verbeeck N, Niedercorn JB, McIntyre D, et al: Assessment of renal graft obstruction due to ureteral inguinal hernia: US detection and 3D MR confirmation. JBR-BTR 90:132, 2007 23. Furtado CD, Sirlin C, Precht A, et al: Unusual cause of ureteral obstruction in transplant kidney. Abdom Imag 31:379, 2006 24. Sanchez AS, Tebar JC, Martin MS, et al: Obstructive uropathy secondary to ureteral herniation in a pediatric en bloc renal graft. Am J Transplant 5:2074, 2005 25. Coleman J, Brennan MF, Alektiar K, et al: Adult spermatic cord sarcomas: management and results. Ann Surg Oncol 10:669, 2003 26. Pisters PW, Leung DH, Woodruff J, et al: Analysis of prognostic factors in 1,041 patients with localized soft tissue sarcomas of the extremities. J Clin Oncol 14:1679, 1996 27. Monaco AP: The role of mTOR inhibitors in the management of posttransplant malignancy. Transplantation 87:157, 2009