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primitive neuroectodermal tumor of the ureter: A case report and review of the literature
Ewing’s Sarcoma/Primitive Neuroectodermal Tumor of the Ureter: A Case Report and Review of the Literature By Caleb K. Charny, Richard D. Glick, Elizabeth M. Genega, Paul A. Meyers, Victor E. Reuter, and Michael P. La Quaglia New York, New York
Extraosseous Ewing’s sarcoma/primitive neuroectodermal tumor (ES/PNET) is a rare soft tissue tumor of childhood usually found in the extremities. The authors present the case of a 17-year-old girl who presented with right flank pain and hematuria and during operation was found to have a right ureteral mass. The histopathologic, immunohistochemical, ultrastructural, and cytogenetic characteristics of the excised mass were consistent with extraosseous ES/PNET. This is the first known reported case of extraosseous ES/
PNET of the ureter. The pathologic features and clinical management of this case, as well as a review of the literature, are presented. J Pediatr Surg 35:1356-1358. Copyright © 2000 by W.B. Saunders Company.
T
spread. The patient was then referred to Memorial Sloan-Kettering Cancer Center. The submitted right ureteral cytologic findings were interpreted as positive for malignant cells of a nonlymphomatous small cell nature. Laboratory findings showed normal liver function tests, electrolytes, and no urinary gonadotropins. She underwent cystoscopy and right ureteroscopy, followed by a right retroperitoneal exploration. Ureteroscopic findings showed the presence of an extrinsically compressing mass with heaped up but otherwise normal-appearing mucosa. A mass was found within the wall of the right ureter and was resected with grossly negative margins. The ureter was anastomosed primarily over a new ureteral stent. Finally, right periureteral lymphadenectomy and obturator lymph node sampling were performed. The patient had an uneventful postoperative recovery and was discharged from the hospital on the fourth postoperative day. Histopathology, immunohistochemistry, electron microscopy, and cytogenetic studies were done on the resected specimen. Histologic sections showed a tumor within the wall of the ureter; the surface urothelium was not involved. The tumor was composed of a monotonous population of small cells with indistinct cell borders, scanty cytoplasm, and hyperchromatic nuclei, suggetive of an ES/PNET (Fig 2). Electron microscopic examination showed small round tumor cells with multiple clusters of cytoplasmic glycogen particles and scattered neurosecretory-type granules. Occasional long cytoplasmic processes also were noted. An immunohistochemical stain for O13 (HBA 71) showed diffuse staining of the cell membranes, supporting the above diagnosis (Fig 3). The t(11; 22) chromosomal translocation specific to ES/PNET was identified by reverse transcriptase polymerase chain reaction (RT-PCR), and the diagnosis of ES/ PNET of the right ureter was made (Fig 4). One obturator and 7 periureteral lymph nodes were negative for metastatic disease. Proximal and distal margins were negative for tumor. Postoperatively, she underwent a Gallium-67 scan, which showed no evidence of gallium-avid disease. Magnetic resonance imaging (MRI) of the spine was negative. Chest CT scan was negative for metastatic disease. Bone marrow biopsy results were unremarkable. She currently is being treated with a cytotoxic chemotherapeutic regimen including vincristine, doxorubicin, and cyclophosphamide.
HE EXTRAOSSEOUS FORM of Ewing’s sarcoma/ primitive neuroectodermal tumor (ES/PNET) mainly occurs in childhood and has a predilection for the soft tissues of the paraspinal region and lower extremity. There have been multiple case reports as well as retrospective multi-institutional reviews of patients with extraosseous Ewing’s sarcoma.1-11 Retroperitoneal extraosseous Ewing’s sarcoma is especially rare. A review by Hara et al12 in 1991 found 11 such cases reported worldwide at that time. In the current study, we describe the case of a 17-year-old girl who presented with flank pain and hematuria. During operation, a mass was found within the wall of the right ureter. Excision of the mass, followed by a primary anastomosis of the ureter, was performed. The final pathology finding was ES/PNET. Clinical details of the case are described below. The pathologic features of extraosseous ES/PNET as well as treatment and prognosis are discussed. CASE REPORT A previously healthy 17-year-old girl presented to her primary physician with right flank pain, vomiting, and hematuria. Cystoscopy was performed, and a contrast study of the right ureter showed an intraluminal filling defect in the right ureter at approximately the level of the pelvic brim (Fig 1). There was only a thin stream of contrast distal to this obstruction, and a stent was placed in the right ureter. Computed tomography (CT) scan showed a soft tissue fullness adjacent to the stent without any evidence of lymphadenopathy or metastatic
From the Departments of Surgery, Pathology, and Pediatrics, Memorial Sloan-Kettering Cancer Center, New York, NY. Address reprint requests to Michael P. La Quaglia, MD, Chief, Division of Pediatric Surgery, Memorial Sloan-Kettering Cancer Center, 1275 York Ave, New York, NY 10021. Copyright © 2000 by W.B. Saunders Company 0022-3468/00/3509-0021$03.00/0 doi:10.1053/jpsu.2000.9333 1356
INDEX WORDS: Extraosseous Ewing’s sarcoma, primitive neuroectodermal tumor, ureter.
DISCUSSION
A review of 84 patients with extraosseous ES/PNET by the Intergroup Rhabdomyosarcoma Study (IRS) ex-
Journal of Pediatric Surgery, Vol 35, No 9 (September), 2000: pp 1356-1358
ES/PNET OF THE URETER
1357
Fig 1. Retrograde contrast study of the right ureter shows ureteral narrowing at the level of the pelvic brim.
amined these tumors with immunohistochemical, as well as electron microscopic techniques.11 This review found that extraosseous ES/PNET could be distinguished from primitive rhabdomyosarcoma with the aid of ultrastructural techniques. Neurosecretory granules were seen on electron microscopy. In addition, the extraosseous ES/ PNET was positive for neuron-specific enolase and S-100 stains. Therapeutic outcome after multimodality therapy, however, was the same in both the rhabdomyosarcoma and extraosseous ES/PNET groups. The most recent review of extraosseous ES/PNET was published in 1997 by the IRS.13 One hundred thirty patients with extraosseous ES/PNET initially were registered in the IRS along with 2,792 patients with rhabdomyosarcoma. The patients with extraosseous ES/ PNET received the same treatment as those with rhabdomyosarcoma, including surgical excision, multiagent chemotherapy, and, in most cases, radiation. The response to treatment was similar in both groups, with an 80% response rate and a 5-year survival rate of 70% to 75%. The investigators conclude that extraosseous ES/ PNET can be treated with the same multimodality therapy as rhabdomyosarcoma. No cases of ureteral ES/ PNET were reported. Cytogenetics have been used to characterize ES/ PNET. The translocation t(11;22)(q24;q12) has been
Fig 2. (A) Tumor within the wall of the ureter (thick arrow). The surface urothelium is unremarkable (thin arrow; H&E, original magnification ⴛ 10). (B) Proliferation of monomorphic small cells with indistinct cell borders and round to oval hyperchromatic nuclei (H&E, original magnification ⴛ100).
Fig 3. Tumor cells exhibit strong cell membrane staining for O13 (original magnification ⴛ50).
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Fig 4. RT-PCR shows EWS-FLI1 fusion in lane 3. Lane 1, patient sample tested for RNA quality; lane 2, negative control; lane 3, patient sample tested with EWS-FLI1 primers; lane 4, positive control; lane 5, negative control; M, size marker.
found in 85% to 90% of patients with osseous ES/ PNET.14 The same translocation also has been reported in several patients with extraosseous ES/PNET.13 This does not imply, however, that patients with extraosseous ES/PNET should be treated with the same chemotherapeutic agents as those with osseous ES/PNET.13 To date, there has been no randomized, prospective study comparing outcomes of treatment in these 2 diseases. Further evaluation is needed. ES/PNET of the kidney and bladder have been decribed previously in the literature.15-17 Our description of ES/PNET of the ureter represents the first such case in the literature to our knowledge. Although 25 cases of retroperitoneal tumors identified as extraosseous ES/PNET have been reported to date, there are no descriptions of a primary ureteral mass with this pathology. The patient currently is being treated with the P6 protocol.18
REFERENCES 1. Newton WA, Soule EH, Hamoudi AB, et al: Histopathology of childhood sarcomas, Intergroup Rhabdomyosarcoma Studies I and II: Clinicopathologic correlation. J Clin Oncol 6:67-75, 1988 2. Bjerklund Johansen TE, Huseby A, Stenwig JT: Extraskeletal Ewing’s sarcoma contiguous with the seminal vesicle. Scan J Urol Nephrol 22:237-239, 1988 3. Dickman PS, Triche TJ: Extraosseous Ewing’s sarcoma versus primitive rhabdomyosarcoma: Diagnostic criteria and clinical correlation. Hum Pathol 17:881-893, 1986 4. Chen KT, Padmanabhan A: Extraskeletal Ewings sarcoma. J Surg Oncol 23:70-72, 1983 5. Sailer SL, Harmon DC, Mankin HJ, et al: Ewing’s sarcoma: Surgical resection as a prognostic factor. Int J Radiat Oncol Biol Phys 15:43-52, 1988 6. Rud NP, Reiman HM, Pritchard DJ, et al: Extraosseous Ewing’s sarcoma. A study of 42 cases. Cancer 64:1548-1553, 1989 7. Thebert A, Francis IR, Bowerman RA: Retroperitoneal extraosseous Ewing’s sarcoma with renal involvement: US and MRI findings. Clin Imaging 17:149-152, 1993 8. Inedjian JM, Thomassin JM, Danoy MC, et al: Extraskeletal pharyngolaryngeal Ewing’s sarcoma. Apropos of a case. Ann Otolaryngol Chir Cervicofac 108:63-66, 1991 9. Brehaut LE, Anderson LH, Taylor DA: Extraskeletal Ewing’s sarcoma. Diagnosis of a case by fine needle aspiration cytology. Acta Cytol 30:683-687, 1986
10. Oya M, Nakashima J, Ishii T, et al: Retroperitoneal Ewing’s sarcoma. Urol Int 54:104-106, 1995 11. Shimada H, Newton WA, Soule EH, et al: Pathologic features of extraosseous Ewing’s sarcoma: A report from the Intergroup Rhabdomyosarcoma Study. Hum Pathol 19:442-453, 1988 12. Hara H, Iwasawa T, Matsuhashi M, et al: Ewing’s sarcoma in the retroperitoneum. Nippon Hinyokika Gakkai Zasshi 82:1504-1507, 1991 13. Raney RB, Asmar L, Newton WA, et al: Ewing’s sarcoma of soft tissues in childhood: A report from the Intergroup Rhabdomyosarcoma Study, 1972 to 1991. J Clin Oncol 15:574-582, 1997 14. Dehner LP: Primitive neuroectodermal tumor and Ewing’s sarcoma. Am J Surg Pathol 17:1-13, 1993 15. Marley EF, Liapis H, Humphrey PA, et al: Primitive neuroectodermal tumor of the kidney—Another enigma: A pathologic, immunohistochemical, and molecular diagnostic study. Am J Surg Pathol 21:354-359, 1997 16. Ranadive NU, Chakravarty U, Kumar M: Primary primitive neuroectodermal tumor (PNET) of the kidney: A case report. Arch Esp Urol 52:190-192, 1999 17. Banerjee SS, Eyden BP, McVey RJ, et al: Primary peripheral primitive neuroectodermal tumour of the urinary bladder. Histopathology 30:486-490, 1997 18. Schwartz RE, Gerald WL, Kushner BH, et al: Desmoplastic small round cell tumors: Prognostic indicators and results of surgical management. Ann Surg Oncol 5:416-422, 1998
Extraosseous Ewing’s sarcoma/primitive neuroectodermal tumor (ES/PNET) is a rare soft tissue tumor of childhood usually found in the extremities. The authors present the case of a 17-year-old girl who presented with right flank pain and hematuria and during operation was found to have a right ureteral mass. The histopathologic, immunohistochemical, ultrastructural, and cytogenetic characteristics of the excised mass were consistent with extraosseous ES/PNET. This is the first known reported case of extraosseous ES/
PNET of the ureter. The pathologic features and clinical management of this case, as well as a review of the literature, are presented. J Pediatr Surg 35:1356-1358. Copyright © 2000 by W.B. Saunders Company.
T
spread. The patient was then referred to Memorial Sloan-Kettering Cancer Center. The submitted right ureteral cytologic findings were interpreted as positive for malignant cells of a nonlymphomatous small cell nature. Laboratory findings showed normal liver function tests, electrolytes, and no urinary gonadotropins. She underwent cystoscopy and right ureteroscopy, followed by a right retroperitoneal exploration. Ureteroscopic findings showed the presence of an extrinsically compressing mass with heaped up but otherwise normal-appearing mucosa. A mass was found within the wall of the right ureter and was resected with grossly negative margins. The ureter was anastomosed primarily over a new ureteral stent. Finally, right periureteral lymphadenectomy and obturator lymph node sampling were performed. The patient had an uneventful postoperative recovery and was discharged from the hospital on the fourth postoperative day. Histopathology, immunohistochemistry, electron microscopy, and cytogenetic studies were done on the resected specimen. Histologic sections showed a tumor within the wall of the ureter; the surface urothelium was not involved. The tumor was composed of a monotonous population of small cells with indistinct cell borders, scanty cytoplasm, and hyperchromatic nuclei, suggetive of an ES/PNET (Fig 2). Electron microscopic examination showed small round tumor cells with multiple clusters of cytoplasmic glycogen particles and scattered neurosecretory-type granules. Occasional long cytoplasmic processes also were noted. An immunohistochemical stain for O13 (HBA 71) showed diffuse staining of the cell membranes, supporting the above diagnosis (Fig 3). The t(11; 22) chromosomal translocation specific to ES/PNET was identified by reverse transcriptase polymerase chain reaction (RT-PCR), and the diagnosis of ES/ PNET of the right ureter was made (Fig 4). One obturator and 7 periureteral lymph nodes were negative for metastatic disease. Proximal and distal margins were negative for tumor. Postoperatively, she underwent a Gallium-67 scan, which showed no evidence of gallium-avid disease. Magnetic resonance imaging (MRI) of the spine was negative. Chest CT scan was negative for metastatic disease. Bone marrow biopsy results were unremarkable. She currently is being treated with a cytotoxic chemotherapeutic regimen including vincristine, doxorubicin, and cyclophosphamide.
HE EXTRAOSSEOUS FORM of Ewing’s sarcoma/ primitive neuroectodermal tumor (ES/PNET) mainly occurs in childhood and has a predilection for the soft tissues of the paraspinal region and lower extremity. There have been multiple case reports as well as retrospective multi-institutional reviews of patients with extraosseous Ewing’s sarcoma.1-11 Retroperitoneal extraosseous Ewing’s sarcoma is especially rare. A review by Hara et al12 in 1991 found 11 such cases reported worldwide at that time. In the current study, we describe the case of a 17-year-old girl who presented with flank pain and hematuria. During operation, a mass was found within the wall of the right ureter. Excision of the mass, followed by a primary anastomosis of the ureter, was performed. The final pathology finding was ES/PNET. Clinical details of the case are described below. The pathologic features of extraosseous ES/PNET as well as treatment and prognosis are discussed. CASE REPORT A previously healthy 17-year-old girl presented to her primary physician with right flank pain, vomiting, and hematuria. Cystoscopy was performed, and a contrast study of the right ureter showed an intraluminal filling defect in the right ureter at approximately the level of the pelvic brim (Fig 1). There was only a thin stream of contrast distal to this obstruction, and a stent was placed in the right ureter. Computed tomography (CT) scan showed a soft tissue fullness adjacent to the stent without any evidence of lymphadenopathy or metastatic
From the Departments of Surgery, Pathology, and Pediatrics, Memorial Sloan-Kettering Cancer Center, New York, NY. Address reprint requests to Michael P. La Quaglia, MD, Chief, Division of Pediatric Surgery, Memorial Sloan-Kettering Cancer Center, 1275 York Ave, New York, NY 10021. Copyright © 2000 by W.B. Saunders Company 0022-3468/00/3509-0021$03.00/0 doi:10.1053/jpsu.2000.9333 1356
INDEX WORDS: Extraosseous Ewing’s sarcoma, primitive neuroectodermal tumor, ureter.
DISCUSSION
A review of 84 patients with extraosseous ES/PNET by the Intergroup Rhabdomyosarcoma Study (IRS) ex-
Journal of Pediatric Surgery, Vol 35, No 9 (September), 2000: pp 1356-1358
ES/PNET OF THE URETER
1357
Fig 1. Retrograde contrast study of the right ureter shows ureteral narrowing at the level of the pelvic brim.
amined these tumors with immunohistochemical, as well as electron microscopic techniques.11 This review found that extraosseous ES/PNET could be distinguished from primitive rhabdomyosarcoma with the aid of ultrastructural techniques. Neurosecretory granules were seen on electron microscopy. In addition, the extraosseous ES/ PNET was positive for neuron-specific enolase and S-100 stains. Therapeutic outcome after multimodality therapy, however, was the same in both the rhabdomyosarcoma and extraosseous ES/PNET groups. The most recent review of extraosseous ES/PNET was published in 1997 by the IRS.13 One hundred thirty patients with extraosseous ES/PNET initially were registered in the IRS along with 2,792 patients with rhabdomyosarcoma. The patients with extraosseous ES/ PNET received the same treatment as those with rhabdomyosarcoma, including surgical excision, multiagent chemotherapy, and, in most cases, radiation. The response to treatment was similar in both groups, with an 80% response rate and a 5-year survival rate of 70% to 75%. The investigators conclude that extraosseous ES/ PNET can be treated with the same multimodality therapy as rhabdomyosarcoma. No cases of ureteral ES/ PNET were reported. Cytogenetics have been used to characterize ES/ PNET. The translocation t(11;22)(q24;q12) has been
Fig 2. (A) Tumor within the wall of the ureter (thick arrow). The surface urothelium is unremarkable (thin arrow; H&E, original magnification ⴛ 10). (B) Proliferation of monomorphic small cells with indistinct cell borders and round to oval hyperchromatic nuclei (H&E, original magnification ⴛ100).
Fig 3. Tumor cells exhibit strong cell membrane staining for O13 (original magnification ⴛ50).
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CHARNY ET AL
Fig 4. RT-PCR shows EWS-FLI1 fusion in lane 3. Lane 1, patient sample tested for RNA quality; lane 2, negative control; lane 3, patient sample tested with EWS-FLI1 primers; lane 4, positive control; lane 5, negative control; M, size marker.
found in 85% to 90% of patients with osseous ES/ PNET.14 The same translocation also has been reported in several patients with extraosseous ES/PNET.13 This does not imply, however, that patients with extraosseous ES/PNET should be treated with the same chemotherapeutic agents as those with osseous ES/PNET.13 To date, there has been no randomized, prospective study comparing outcomes of treatment in these 2 diseases. Further evaluation is needed. ES/PNET of the kidney and bladder have been decribed previously in the literature.15-17 Our description of ES/PNET of the ureter represents the first such case in the literature to our knowledge. Although 25 cases of retroperitoneal tumors identified as extraosseous ES/PNET have been reported to date, there are no descriptions of a primary ureteral mass with this pathology. The patient currently is being treated with the P6 protocol.18
REFERENCES 1. Newton WA, Soule EH, Hamoudi AB, et al: Histopathology of childhood sarcomas, Intergroup Rhabdomyosarcoma Studies I and II: Clinicopathologic correlation. J Clin Oncol 6:67-75, 1988 2. Bjerklund Johansen TE, Huseby A, Stenwig JT: Extraskeletal Ewing’s sarcoma contiguous with the seminal vesicle. Scan J Urol Nephrol 22:237-239, 1988 3. Dickman PS, Triche TJ: Extraosseous Ewing’s sarcoma versus primitive rhabdomyosarcoma: Diagnostic criteria and clinical correlation. Hum Pathol 17:881-893, 1986 4. Chen KT, Padmanabhan A: Extraskeletal Ewings sarcoma. J Surg Oncol 23:70-72, 1983 5. Sailer SL, Harmon DC, Mankin HJ, et al: Ewing’s sarcoma: Surgical resection as a prognostic factor. Int J Radiat Oncol Biol Phys 15:43-52, 1988 6. Rud NP, Reiman HM, Pritchard DJ, et al: Extraosseous Ewing’s sarcoma. A study of 42 cases. Cancer 64:1548-1553, 1989 7. Thebert A, Francis IR, Bowerman RA: Retroperitoneal extraosseous Ewing’s sarcoma with renal involvement: US and MRI findings. Clin Imaging 17:149-152, 1993 8. Inedjian JM, Thomassin JM, Danoy MC, et al: Extraskeletal pharyngolaryngeal Ewing’s sarcoma. Apropos of a case. Ann Otolaryngol Chir Cervicofac 108:63-66, 1991 9. Brehaut LE, Anderson LH, Taylor DA: Extraskeletal Ewing’s sarcoma. Diagnosis of a case by fine needle aspiration cytology. Acta Cytol 30:683-687, 1986
10. Oya M, Nakashima J, Ishii T, et al: Retroperitoneal Ewing’s sarcoma. Urol Int 54:104-106, 1995 11. Shimada H, Newton WA, Soule EH, et al: Pathologic features of extraosseous Ewing’s sarcoma: A report from the Intergroup Rhabdomyosarcoma Study. Hum Pathol 19:442-453, 1988 12. Hara H, Iwasawa T, Matsuhashi M, et al: Ewing’s sarcoma in the retroperitoneum. Nippon Hinyokika Gakkai Zasshi 82:1504-1507, 1991 13. Raney RB, Asmar L, Newton WA, et al: Ewing’s sarcoma of soft tissues in childhood: A report from the Intergroup Rhabdomyosarcoma Study, 1972 to 1991. J Clin Oncol 15:574-582, 1997 14. Dehner LP: Primitive neuroectodermal tumor and Ewing’s sarcoma. Am J Surg Pathol 17:1-13, 1993 15. Marley EF, Liapis H, Humphrey PA, et al: Primitive neuroectodermal tumor of the kidney—Another enigma: A pathologic, immunohistochemical, and molecular diagnostic study. Am J Surg Pathol 21:354-359, 1997 16. Ranadive NU, Chakravarty U, Kumar M: Primary primitive neuroectodermal tumor (PNET) of the kidney: A case report. Arch Esp Urol 52:190-192, 1999 17. Banerjee SS, Eyden BP, McVey RJ, et al: Primary peripheral primitive neuroectodermal tumour of the urinary bladder. Histopathology 30:486-490, 1997 18. Schwartz RE, Gerald WL, Kushner BH, et al: Desmoplastic small round cell tumors: Prognostic indicators and results of surgical management. Ann Surg Oncol 5:416-422, 1998