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Incidental Capture of Rarely Diagnosed Pediatric Tumor: An Infant Boy With Clear Cell Sarcoma of the Kidney
Pediatric Case Report Incidental Capture of Rarely Diagnosed Pediatric Tumor: An Infant Boy With Clear Cell Sarcoma of the Kidney Robert J. Hartman, Jr., Daniel R. Welchons, Lisa Teot, Jeanne Chow, and Marc Cendron Clear cell sarcoma of the kidney (CCSK) is an uncommon neoplasm that accounts for less than 5% of all pediatric renal tumors. Compared with Wilms’ tumor, CCSK has a higher rate of relapse, greater propensity for bone metastasis, and poorer overall survival. We present the case of a 19-month-old boy with a large renal mass diagnosed incidentally by ultrasonography during surveillance for vesicoureteral reflux. This report describes the rare occurrence of an incidental radiologic capture of CCSK and provides a brief review of disease pathology. UROLOGY 82: 1416e1418, 2013. 2013 Elsevier Inc.
CASE REPORT
A
19-month-old boy initially presented to the pediatric urology clinic at 8 weeks of age. Born vaginally at 41 weeks gestation, a prenatal ultrasound obtained at 40 weeks for delayed delivery was remarkable for severe bilateral hydronephrosis. A voiding cystourethrogram obtained at 6 days of life was notable for bilateral high-grade (grade V) vesicoureteral reflux. Renal scintigraphy with dimercaptosuccinic acid (DMSA) was normal. Given the lack of urinary tract infections or infection-related renal scarring, the decision was made to defer surgical intervention, administer prophylactic antibiotics, and monitor the child with serial urologic evaluation, cystograms, and renal ultrasounds. The child was re-evaluated at 3, 6, and 12 months and was thriving, without urinary tract symptoms or infections. Serial ultrasound imaging demonstrated improving hydroureteronephrosis, bilaterally, with appropriate interval renal growth. A radionuclide cystogram at 12 months demonstrated grade II vesicoureteral reflux, bilaterally. Six months later, the patient remained clinically stable and without symptoms. An abdominal ultrasound obtained before evaluation demonstrated a 9.6 cm 8.8 cm 7.2 cm mass involving the lower pole of the right kidney. On physical examination, the child had a palpable mass extending from just below the right rib cage to the right lower quadrant. Further evaluation by computed tomography (CT) imaging confirmed the presence of a heterogeneously enhancing mass arising from the right kidney causing mass effect on the right Financial Disclosure: The authors declare that they have no relevant financial interests. From the Department of Urology, Boston Children’s Hospital; and the Division of Urology, Brigham and Women’s Hospital, Harvard Medical School, Boston, MA Reprint requests: Robert J. Hartman, M.D., Division of Urology, Brigham and Women’s Hospital, Harvard Medical School, 45 Francis Street, ASB II-3, Boston, MA 02115. E-mail: [email protected] Submitted: June 10, 2013, accepted (with revisions): July 1, 2013
1416
ª 2013 Elsevier Inc. All Rights Reserved
renal vein and inferior vena cava, although without evidence of vascular invasion. In addition, an enlarged periaortic node was observed, concerning for a metastatic process (Fig. 1). Four days later, an uncomplicated right radical nephrectomy with retroperitoneal lymph node dissection was performed. Intraoperative frozen sections demonstrated a spindle cell neoplasm not consistent with Wilms’ tumor (WT). Final pathology confirmed the diagnosis of clear cell sarcoma of the kidney (CCSK; Fig. 2) with negative vascular, ureteral, and renal sinus margins. There was lymphovascular invasion. The parenchyma of the concerning periaortic lymph node was completely replaced with a nodule of clear cell sarcoma. Three other lymph nodes and also the adrenal gland were negative for evidence of metastasis. The child recovered uneventfully postoperatively. A head CT and bone scan were reflexively obtained for evaluation of metastatic processes and were both negative for evidence of disease. A multidisciplinary solid tumor oncology team evaluated the patient postoperatively. He was diagnosed with stage III CCSK. Local radiotherapy was initiated and completed after 6 treatments (total 1080 cGy). An approximately 7-month course of chemotherapy was initiated, consisting of vincristine, cyclophosphomide, and doxorubicin. He is currently tolerating his chemotherapy course well. He remains without urinary symptoms or evidence of urinary tract infections and resolving vesicoureteral reflux.
COMMENT Pediatric renal tumors’ malignant propensity warrants broad consideration and differential diagnosis for early intervention and therapy. This includes WT, accounting for more than 85% of solid renal masses, mesoblastic nephroma (5%), rhabdoid tumors (2%), and CCSK. CCSK is an uncommon neoplasm that accounts for <5% of all pediatric renal masses and approximately 20 cases per year in North America. Until identified as a distinct 0090-4295/13/$36.00 http://dx.doi.org/10.1016/j.urology.2013.07.002
Figure 1. (A) Renal ultrasound of right kidney at 6 months with evidence of resolving hydronephrosis. (B) Renal ultrasound of right kidney at 18 months demonstrating 9.6 cm 8.8 cm 7.2 cm mass involving lower pole. (C) Computed tomography of large heterogenous enhancing mass with mass effect on renal vein and inferior vena cava with enlarged periaortic node (arrow). (Color version available online.)
Figure 2. (A) Classic pattern of clear cell sarcoma of the kidney with entrapped benign renal tubules (arrows) and delicate, arborizing vessels (H&E, original magnification 200). (B) The tumor is composed of short spindle cells with scant cytoplasm and round to ovoid nuclei with pale chromatin. The cells are separate by pale to clear extracellular matrix. The delicate capillary network is evident. (H&E, original magnification 400). (Color version available online.)
clinicopathologic entity by Kidd, CCSK had previously been described as the “bone-metastasizing renal tumor of childhood,” thought to be a variant of the more ubiquitous WT.1 WT accounts for 7% of all pediatric malignancies and is the most common renal tumor in children between the ages of 6 months and 12 years.2 Compared UROLOGY 82 (6), 2013
with WT, CCSK has greater propensity for bone metastasis, higher rate of relapse, and poorer overall survival. Approximately 5% of the patients with CCSK have metastatic disease at presentation. The most common site of metastasis at presentation is the ipsilateral renal hilar lymph nodes. Approximately 40%-60% of patients with 1417
CCSK have bone metastasis as compared with a 2% incidence of bone metastasis found in patients with WT.3 Other common sites of metastasis include brain, lung, liver, and retroperitoneum. CCSK cannot be distinguished from WT by imaging studies (CT or ultrasonography) alone. On CT imaging, both neoplasms demonstrate heterogenous intrarenal masses with areas of low attenuation owing to necrosis and hemorrhage suggesting vascular compromise secondary to rapid growth.4 Both renal tumors may demonstrate vascular invasion of local organs and local metastasis to lymph nodes. Given its infrequency and nonspecific radiologic morphology, preoperative diagnosis of CCSK is nearly impossible and often misdiagnosed until formal pathologic evaluation. If resectable, radical nephrectomy remains the initial intervention, regardless of pathology. Tissue diagnosis remains the gold standard for CCSK. Classic CCSK consists of nests or cords of cells with intervening, arborizing fibrovascular septa, often in a delicate “chicken-wire” pattern.5,6 Tumor cells are small, oval to spindle with scant, pale cytoplasm, and round to ovoid nuclei with pale chromatin or clearing (“Orphan Annie” eye). The tumor cells are loosely arrayed in pale to clear extracellular matrix. In addition to the classic pattern, 1 or more variant histopathologic patterns are present in most tumors. The most common include myxoid (50%), sclerosing (35%), cellular (26%), epithelioid (13%), and spindle cell (7%),5 Entrapped benign renal tubules are characteristically present. CCSK is consistently positive for vimentin and usually negative for cytokeratin.6
1418
After radical nephrectomy and pathologic diagnosis, chemotherapy is suggested. In the most recent NWTS-5 clinical trial, patients diagnosed with CCSK, irrespective of stage, were treated with radical nephrectomy followed by treatment with vincristine, doxorubicin, and cyclophosphamide, alternating with cyclophosphamide and etoposide for 24 weeks, with postoperative radiation. Our patient is currently participating in a similar protocol. Five-year relapse-free survival for stages I, II, III, and IV were 100%, 87%, 74%, and 36%, respectively.7
References 1. Kidd JK. Exclusion of certain renal neoplasms from the category of Wilms’ tumor. Am J Pathol. 1970;59:16A. 2. Hadley GP, Sheik-Gafoor. Clear cell sarcoma of the kidney in children: experience in developing country. Pediatric Surg Int. 2010; 26:345-348. 3. Beckwith JB, Palmer NF. Histopathology and prognosis of Wilms tumor: results from the first National Wilms Tumor Study. Cancer. 1978;41:1937-1948. 4. Miniati D, Gay AN, Parks KV, et al. Imaging accuracy and incidence of Wilms and non-Wilms renal tumors in children. J Pediatr Surg. 2008;43:1301-1307. 5. Argani P, Perlman EJ, Breslow NE, et al. Clear cell sarcoma of the kidney-a review of 351 cases from the National Wilms Tumor Study Group Pathology Center. Am J Surg Pathol. 2000;24:4-18. 6. Sebrie NJ, Vujanic GM. Paediatric renal tumours: recent developments, new entities and pathological features. Histopathology. 2009; 54:516-528. 7. Seibel N, Sun J, Andersen JR. Outcomes of clear cell sarcoma of the kidney (CCSK) treated on the National Wilms’ Tumor Study-5 (NWTS). 24, 5022006 Ref Type Conf Proc Ref ID 2006:6076.
UROLOGY 82 (6), 2013
CASE REPORT
A
19-month-old boy initially presented to the pediatric urology clinic at 8 weeks of age. Born vaginally at 41 weeks gestation, a prenatal ultrasound obtained at 40 weeks for delayed delivery was remarkable for severe bilateral hydronephrosis. A voiding cystourethrogram obtained at 6 days of life was notable for bilateral high-grade (grade V) vesicoureteral reflux. Renal scintigraphy with dimercaptosuccinic acid (DMSA) was normal. Given the lack of urinary tract infections or infection-related renal scarring, the decision was made to defer surgical intervention, administer prophylactic antibiotics, and monitor the child with serial urologic evaluation, cystograms, and renal ultrasounds. The child was re-evaluated at 3, 6, and 12 months and was thriving, without urinary tract symptoms or infections. Serial ultrasound imaging demonstrated improving hydroureteronephrosis, bilaterally, with appropriate interval renal growth. A radionuclide cystogram at 12 months demonstrated grade II vesicoureteral reflux, bilaterally. Six months later, the patient remained clinically stable and without symptoms. An abdominal ultrasound obtained before evaluation demonstrated a 9.6 cm 8.8 cm 7.2 cm mass involving the lower pole of the right kidney. On physical examination, the child had a palpable mass extending from just below the right rib cage to the right lower quadrant. Further evaluation by computed tomography (CT) imaging confirmed the presence of a heterogeneously enhancing mass arising from the right kidney causing mass effect on the right Financial Disclosure: The authors declare that they have no relevant financial interests. From the Department of Urology, Boston Children’s Hospital; and the Division of Urology, Brigham and Women’s Hospital, Harvard Medical School, Boston, MA Reprint requests: Robert J. Hartman, M.D., Division of Urology, Brigham and Women’s Hospital, Harvard Medical School, 45 Francis Street, ASB II-3, Boston, MA 02115. E-mail: [email protected] Submitted: June 10, 2013, accepted (with revisions): July 1, 2013
1416
ª 2013 Elsevier Inc. All Rights Reserved
renal vein and inferior vena cava, although without evidence of vascular invasion. In addition, an enlarged periaortic node was observed, concerning for a metastatic process (Fig. 1). Four days later, an uncomplicated right radical nephrectomy with retroperitoneal lymph node dissection was performed. Intraoperative frozen sections demonstrated a spindle cell neoplasm not consistent with Wilms’ tumor (WT). Final pathology confirmed the diagnosis of clear cell sarcoma of the kidney (CCSK; Fig. 2) with negative vascular, ureteral, and renal sinus margins. There was lymphovascular invasion. The parenchyma of the concerning periaortic lymph node was completely replaced with a nodule of clear cell sarcoma. Three other lymph nodes and also the adrenal gland were negative for evidence of metastasis. The child recovered uneventfully postoperatively. A head CT and bone scan were reflexively obtained for evaluation of metastatic processes and were both negative for evidence of disease. A multidisciplinary solid tumor oncology team evaluated the patient postoperatively. He was diagnosed with stage III CCSK. Local radiotherapy was initiated and completed after 6 treatments (total 1080 cGy). An approximately 7-month course of chemotherapy was initiated, consisting of vincristine, cyclophosphomide, and doxorubicin. He is currently tolerating his chemotherapy course well. He remains without urinary symptoms or evidence of urinary tract infections and resolving vesicoureteral reflux.
COMMENT Pediatric renal tumors’ malignant propensity warrants broad consideration and differential diagnosis for early intervention and therapy. This includes WT, accounting for more than 85% of solid renal masses, mesoblastic nephroma (5%), rhabdoid tumors (2%), and CCSK. CCSK is an uncommon neoplasm that accounts for <5% of all pediatric renal masses and approximately 20 cases per year in North America. Until identified as a distinct 0090-4295/13/$36.00 http://dx.doi.org/10.1016/j.urology.2013.07.002
Figure 1. (A) Renal ultrasound of right kidney at 6 months with evidence of resolving hydronephrosis. (B) Renal ultrasound of right kidney at 18 months demonstrating 9.6 cm 8.8 cm 7.2 cm mass involving lower pole. (C) Computed tomography of large heterogenous enhancing mass with mass effect on renal vein and inferior vena cava with enlarged periaortic node (arrow). (Color version available online.)
Figure 2. (A) Classic pattern of clear cell sarcoma of the kidney with entrapped benign renal tubules (arrows) and delicate, arborizing vessels (H&E, original magnification 200). (B) The tumor is composed of short spindle cells with scant cytoplasm and round to ovoid nuclei with pale chromatin. The cells are separate by pale to clear extracellular matrix. The delicate capillary network is evident. (H&E, original magnification 400). (Color version available online.)
clinicopathologic entity by Kidd, CCSK had previously been described as the “bone-metastasizing renal tumor of childhood,” thought to be a variant of the more ubiquitous WT.1 WT accounts for 7% of all pediatric malignancies and is the most common renal tumor in children between the ages of 6 months and 12 years.2 Compared UROLOGY 82 (6), 2013
with WT, CCSK has greater propensity for bone metastasis, higher rate of relapse, and poorer overall survival. Approximately 5% of the patients with CCSK have metastatic disease at presentation. The most common site of metastasis at presentation is the ipsilateral renal hilar lymph nodes. Approximately 40%-60% of patients with 1417
CCSK have bone metastasis as compared with a 2% incidence of bone metastasis found in patients with WT.3 Other common sites of metastasis include brain, lung, liver, and retroperitoneum. CCSK cannot be distinguished from WT by imaging studies (CT or ultrasonography) alone. On CT imaging, both neoplasms demonstrate heterogenous intrarenal masses with areas of low attenuation owing to necrosis and hemorrhage suggesting vascular compromise secondary to rapid growth.4 Both renal tumors may demonstrate vascular invasion of local organs and local metastasis to lymph nodes. Given its infrequency and nonspecific radiologic morphology, preoperative diagnosis of CCSK is nearly impossible and often misdiagnosed until formal pathologic evaluation. If resectable, radical nephrectomy remains the initial intervention, regardless of pathology. Tissue diagnosis remains the gold standard for CCSK. Classic CCSK consists of nests or cords of cells with intervening, arborizing fibrovascular septa, often in a delicate “chicken-wire” pattern.5,6 Tumor cells are small, oval to spindle with scant, pale cytoplasm, and round to ovoid nuclei with pale chromatin or clearing (“Orphan Annie” eye). The tumor cells are loosely arrayed in pale to clear extracellular matrix. In addition to the classic pattern, 1 or more variant histopathologic patterns are present in most tumors. The most common include myxoid (50%), sclerosing (35%), cellular (26%), epithelioid (13%), and spindle cell (7%),5 Entrapped benign renal tubules are characteristically present. CCSK is consistently positive for vimentin and usually negative for cytokeratin.6
1418
After radical nephrectomy and pathologic diagnosis, chemotherapy is suggested. In the most recent NWTS-5 clinical trial, patients diagnosed with CCSK, irrespective of stage, were treated with radical nephrectomy followed by treatment with vincristine, doxorubicin, and cyclophosphamide, alternating with cyclophosphamide and etoposide for 24 weeks, with postoperative radiation. Our patient is currently participating in a similar protocol. Five-year relapse-free survival for stages I, II, III, and IV were 100%, 87%, 74%, and 36%, respectively.7
References 1. Kidd JK. Exclusion of certain renal neoplasms from the category of Wilms’ tumor. Am J Pathol. 1970;59:16A. 2. Hadley GP, Sheik-Gafoor. Clear cell sarcoma of the kidney in children: experience in developing country. Pediatric Surg Int. 2010; 26:345-348. 3. Beckwith JB, Palmer NF. Histopathology and prognosis of Wilms tumor: results from the first National Wilms Tumor Study. Cancer. 1978;41:1937-1948. 4. Miniati D, Gay AN, Parks KV, et al. Imaging accuracy and incidence of Wilms and non-Wilms renal tumors in children. J Pediatr Surg. 2008;43:1301-1307. 5. Argani P, Perlman EJ, Breslow NE, et al. Clear cell sarcoma of the kidney-a review of 351 cases from the National Wilms Tumor Study Group Pathology Center. Am J Surg Pathol. 2000;24:4-18. 6. Sebrie NJ, Vujanic GM. Paediatric renal tumours: recent developments, new entities and pathological features. Histopathology. 2009; 54:516-528. 7. Seibel N, Sun J, Andersen JR. Outcomes of clear cell sarcoma of the kidney (CCSK) treated on the National Wilms’ Tumor Study-5 (NWTS). 24, 5022006 Ref Type Conf Proc Ref ID 2006:6076.
UROLOGY 82 (6), 2013