- Email: [email protected]
GPOH Study Group
Treatment of Cystic Nephroma and Cystic Partially Differentiated Nephroblastoma—A Report From the SIOP/GPOH Study Group Tobias Luithle,* Philipp Szavay,* Rhoikos Furtwängler, Norbert Graf and Jörg Fuchs From the Department of Pediatric Surgery, University of Tuebingen, Tuebingen (TL, PS, JF), and Department of Pediatric Hematology and Oncology, University of Homburg/Saar, Homburg/Saar (RF, NG), Germany
Purpose: Cystic partially differentiated nephroblastoma is a rare variant of Wilms tumor, and might be confused with cystic nephroma. Definitive diagnosis can only be made by histological examination. Therefore, initiation of therapy, either primary nephrectomy or preoperative chemotherapy, might create a dilemma when radiological diagnosis is doubtful. Materials and Methods: To define treatment strategies for these entities, we reviewed the records of 1,245 patients enrolled in SIOP (International Society of Pediatric Oncology) trials 93-01 and 2001 GPOH (German Society of Pediatric Oncology and Hematology) between July 1993 and August 2004. Data were collected retrospectively. Therapy, outcome and preoperative management were evaluated. To confirm diagnosis of cystic nephroma/partially differentiated nephroblastoma, all patients underwent review by the Reference Pathology Center of SIOP/GPOH. Results: A total of 14 patients with diagnoses of cystic nephroma (7) and cystic partially differentiated nephroblastoma (7) were identified. Median patient age at diagnosis was 1 year (0.46 to 3). Two patients received preoperative chemotherapy. Primary nephrectomy was performed in 12 patients. Two patients underwent partial nephrectomy. In 1 child postoperative chemotherapy was administered. None of the patients had progression of disease or recurrence. Overall survival was 100%. Median followup was 2.41 years (0.3 to 9). Conclusions: In cystic renal tumors radiological findings should always be reviewed by the reference radiologist of the treatment protocol study group. Irrespective of the chosen therapy, outcome of cystic nephroma and cystic partially differentiated nephroblastoma is favorable. Even in large international trials the number of patients with cystic nephroma or cystic partially differentiated nephroblastoma is too small for statistical analysis. Key Words: kidney neoplasms, Wilms tumor, pediatrics, surgery
spectrum of Wilms tumor.1 They assumed that CN in adults is a neoplasm with no known link to Wilms tumor. In the protocol of the SIOP 93-01 and 2001/GPOH studies CPDN and CN are defined as described by Joshi and Beckwith.9 Cystic partially differentiated nephroblastoma is rated as a low risk tumor, whereas CN is only registered as an associated tumor. Therefore, patients are treated according to tumor histology and stage. Normally, preoperative chemotherapy is also administered in the low risk group. However, the SIOP Working Classification of Renal Tumors of Childhood recommends that these tumors be treated with surgery alone.11 The dilemma is that a distinction between CN/CPDN and malignant neoplasms such as cystic Wilms tumor with preoperative imaging studies is not reliable. The aim of our study was to identify children with CPDN and CN within the population enrolled in the SIOP 93-01 and 2001/GPOH studies. Preoperative management, therapy and outcome were evaluated.
ystic partially differentiated nephroblastoma is a rare variant of Wilms tumor and is often confused with CN, and controversy exists regarding the terminology, classification and natural history of these entities. Distinction between CPDN and CN with preoperative imaging studies is impossible.1-3 More important, in some cases they cannot reliably be distinguished from malignant neoplasms such as cystic Wilms tumor.1 Both of these entities are unusual cystic renal neoplasms in young children, and are composed of purely cystic masses. In the past multiple terms such as multilocular cyst, multilocular cystic nephroma, cystic Wilms tumor and others have been used for these neoplasms.4 Cystic nephroma was first described by Edmunds in 1892.5 In 1951 Powell et al6 suggested diagnostic criteria for cystic nephroma, which were modified by Boggs and Kimmelstiel in 1956.7 The term “cystic partially differentiated nephroblastoma” was first used by Brown in 1975.8 In 1989 Joshi and Beckwith9 established criteria with a clear differentiation between CN and CPDN (see Appendix). Kajani et al simplified the criteria and concluded that CN and CPDN are the same.10 In 1998 Eble and Bonsib postulated that cystic nephroma in young children is the same as cystic partially differentiated nephroblastoma and is part of the
C
MATERIALS AND METHODS A total of 1,245 children were enrolled in the SIOP studies 93-01 and 2001/GPOH between July 1993 and August 2004. Patients with final diagnoses of CN and CPDN were reviewed. Diagnosis was confirmed by the German Reference Pathology Centre of the SIOP/GPOH (I. Leuschner, Kiel, Germany) in all patients. A total of 14 patients were iden-
Submitted for publication June 22, 2006. * Equal study contribution.
0022-5347/07/1771-0294/0 THE JOURNAL OF UROLOGY® Copyright © 2007 by AMERICAN UROLOGICAL ASSOCIATION
294
Vol. 177, 294-296, January 2007 Printed in U.S.A. DOI:10.1016/j.juro.2006.09.011
CYSTIC NEPHROMA AND CYSTIC PARTIALLY DIFFERENTIATED NEPHROBLASTOMA tified. For these 14 patients we retrospectively analyzed specific information concerning demographic data, tumor characteristics, chemotherapy, surgical therapy and outcome data, including local and distant recurrence and survival. RESULTS Median patient age at diagnosis was 1 year (range 0.46 to 3). There were 9 boys and 5 girls. Median followup was 2.41 years (range 0.3 to 9). All children had a unilateral tumor, with 8 right-sided and 6 left-sided tumors. In 7 patients tumor was found incidentally by radiological examination or ultrasound for other conditions. Of the remaining patients a palpable mass with pain was present in 1 child with hematuria. Initial tumor volume was 304.4 ml (range 8.1 to 878.6). Among 14 patients detected there were 7 children with CN and 7 with CPDN in the definitive histopathological findings according to study criteria (see Appendix). Two patients with CN received preoperative chemotherapy consisting of vincristine and dactinomycin. A total of 12 patients underwent complete nephrectomy and 2 underwent partial nephrectomy (1 each with CN and CPDN). One child was treated with postoperative vincristine and dactinomycin based on unclear staging. Therapy was discontinued after down-staging the tumor due to a definitive pathology result revealing CPDN. None of the children treated with chemotherapy had significant related side effects. All patients underwent complete tumor resection. A total of 13 patients had stage I disease and 1 had stage III disease due to intraoperative tumor rupture. This patient had a diagnosis of CN and did not receive postoperative chemotherapy. In 7 children preoperative radiological findings were reviewed by the reference radiologist of the SIOP/ GPOH study group. All patients had adequate followup with no recurrence. Overall survival rate was 100% (see table). DISCUSSION Cystic nephroma and cystic partially differentiated nephroblastoma constitute a group of uncommon multilocular tumors of the kidney in children. In our series CPDN and CN each made up about 0.56% of all tumors registered in the SIOP/GPOH studies. This finding corresponds roughly to the 0.5% of children with CPDN enrolled in the National Wilms Tumor Study during a 20-year period.12 As presented in different studies, cystic nephroma seems to occupy the benign end, CPDN a low risk category and
TABLE 1. Patient and tumor characteristics for cystic nephroma and cystic partially differentiated nephroblastoma Characteristics
CN
CPDN
No. pts Mean age at diagnosis (mos) No. males/females Av tumor vol (ml) Stage Median yrs followup (range) Chemotherapy
7 12.9
7 10.8
3/4 270 I/III 3.2 (0.3–9)
6/1 338 I 2 (0.8–5.6)
2 (dactinomycin ⫹ vincristine) 100
1 (dactinomycin ⫹ vincristine)* 100
% Survival rate
* Postoperative chemotherapy.
295
polycystic Wilms tumor the malignant end of the spectrum of cystic renal neoplasms.9,13,14 Eble and Bonsib even postulated that CN and CPDN in young children are the same entity, and that the term “cystic nephroma” should be reserved for the disease occurring in adults as a composite neoplasm of stroma and epithelium with no known link to Wilms tumor.1 Data on age of appearance in the literature are similar to our findings. Eble and Bonsib demonstrated that most patients with CN are younger than 4 years and most with CPDN are younger than 2 years.1 This observation corresponds to our findings. Concerning the gender of patients, our data differ from the literature, where boys predominate at a ratio of 2:1 in CN whereas in CPDN the tumor occurs with equal frequency.1 Our result might be due to the small number of patients in the study. We believe that primary resection of the tumor is the treatment of choice in CN and CPDN. This estimation has been confirmed by several other groups.1,4,9,12,15 The SIOP recommends in the revised Working Classification of Renal Tumors of Childhood that CPDN be treated with surgery alone.11 This suggestion is reflected in recommendations of the latest SIOP 2001/GPOH protocol, since preoperative differentiation between CN and CPDN is not necessary and surgical treatment alone is sufficient. As mentioned previously, the dilemma presented by this approach is that reliable preoperative differentiation between these 2 entities and a Wilms tumor with cystic changes is impossible.1,16 Wilms tumor with cystic changes is rated as an intermediate risk tumor, and, therefore, should be treated with preoperative chemotherapy according to the SIOP protocols. Graf et al showed that preoperative chemotherapy results in a lower rate of tumor ruptures during surgery and a favorable stage distribution.17 However, chemotherapy is not usually administered in patients with benign tumors, who make up 1.5% of all individuals in the SIOP studies. Overall toxicity is restricted to temporary disturbed liver function in less than 8% and low platelet counts in 4% of all patients enrolled in the SIOP trials.17 Conversely, Blakely et al reported that up to 30% of patients with CPDN enrolled in the National Wilms Tumor Study had significant chemotherapy related toxicity.12 The use of needle biopsy for diagnosis is not helpful and is contraindicated in cystic renal tumors because gross histological examination is essential for interpretation of tumor entity and adequate therapy.9,12 Renal sparing surgery is considered safe for resection of CN and CPDN.4,18 –20 However, there is the potential for recurrence in CPDN with incomplete excision.1,9 Because of the uncertain definitive pathology of total cystic renal tumors, we recommend complete nephrectomy. This recommendation is in accordance with several other studies.1,9,12,15 Partial nephrectomy should be limited to special cases as in unilateral kidney or bilateral tumors, and should only be undertaken after consultation with the study group. CONCLUSIONS Cystic nephroma and partially differentiated nephroblastoma, as cystic variants of Wilms tumor, make up approximately 1% of all Wilms tumor cases. Irrespective of the chosen therapy, outcomes of CN and CPDN are favorable. However, numbers of patients in even large international
296
CYSTIC NEPHROMA AND CYSTIC PARTIALLY DIFFERENTIATED NEPHROBLASTOMA
trials are too small for any statistical analysis. We recommend primary resection as the treatment of choice in cystic renal tumors. Preoperative chemotherapy is unnecessary. For patients treated according to the SIOP protocols radiological findings should always be reviewed by the reference radiologist before any therapy is initiated. This approach improves the diagnostic accuracy in those patients with a cystic renal tumor, in whom a Wilms tumor with cystic changes cannot be ruled out reliably.21 APPENDIX
6. 7.
8. 9.
10.
Definition of Cystic Nephroma and Cystic Partially Differentiated Nephroblastoma Cystic Nephroma: ● Tumor composed entirely of cysts and their septa ● Discrete mass well demarcated from noncystic renal parenchyma ● Septa are the only solid components and conform to outlines of cysts without expansile nodules ● Cysts are lined by flattened, cuboidal or hobnail epithelium ● Septa contain fibrous tissue in which well-differentiated tubules may be present Cystic Partially Differentiated Nephroblastoma: ● Criteria 1– 4 listed above but ● Septa contain blastema with/without embryonal stromal or epithelial elements
11.
12.
13.
14.
Abbreviations and Acronyms CN ⫽ cystic nephroma CPDN ⫽ cystic partially differentiated nephroblastoma GPOH ⫽ German Society of Pediatric Oncology and Hematology SIOP ⫽ International Society of Pediatric Surgery
15. 16.
17.
REFERENCES 1.
Eble JN and Bonsib SM: Extensively cystic renal neoplasms: cystic nephroma, cystic partially differentiated nephroblastoma, multilocular cystic renal cell carcinoma, and cystic hamartoma of renal pelvis. Am J Surg Pathol 1998; 15: 2. 2. Wilson TE, Doelle EA, Cohan RH, Wojno K and Jaccard J: Cystic renal masses: a reevaluation of the usefulness of the Bosniak classification system. Acad Radiol 1996; 3: 564. 3. Bosniak MA: The current radiological approach to renal cysts. Radiology 1986; 158: 1. 4. Castillo OA, Boyle ET Jr and Kramer SA: Multilocular cysts of kidney: a study of 29 patients and review of the literature. Urology 1991; 37: 156. 5. Edmunds W: Cystic adenoma of kidney. Trans Pathol Soc (Lond) 1892; 43: 89.
18.
19.
20.
21.
Powell T, Shackman R and Johnson HD: Multilocular cysts of the kidney. Br J Urol 1951; 23: 142. Boggs LK and Kimmelstiel P: Benign multilocular cystic nephroma: report of two cases of so-called multilocular cyst of the kidney. J Urol 1956; 76: 530. Brown JM: Cystic partially differentiated nephroblastoma. J Pathol 1975; 115: 175. Joshi VV and Beckwith JB: Multilocular cyst of the kidney (cystic nephroma) and cystic partially differentiated nephroblastoma: terminology and criteria for diagnosis. Cancer 1989; 64: 466. Kajani N, Rosenberg BF and Bernstein J: Multilocular cystic nephroma. J Urol Pathol 1993; 1: 33. Vujanic GM, Sandstedt B, Harms D, Kelsey A, Leuschner I and de Kraker J: Revised International Society of Paediatric Oncology (SIOP) working classification of renal tumors of childhood. Med Pediatr Oncol 2002; 38: 79. Blakely ML, Shamberger RC, Norkool P, Beckwith JB, Green DM and Ritchey ML: Outcome of children with cystic partially differentiated nephroblastoma treated with or without chemotherapy. J Pediatr Surg 2003; 38: 897. Joshi VV, Banerjee AK, Yadav K and Pathak IC: Cystic partially differentiated nephroblastoma: a clinicopathologic entity in the spectrum of infantile renal neoplasia. Cancer 1977; 40: 789. Madewell JE, Goldman SM, Davis CJ Jr, Hartman DS, Feigin DS and Lichtenstein JE: Multilocular cystic nephroma: a radiographic-pathologic correlation of 58 patients. Radiology 1983; 146: 309. Shamberger RC: Pediatric renal tumors. Semin Surg Oncol 1999; 16: 105. Agrons GA, Wagner BJ, Davidson AJ and Suarez ES: Multilocular cystic renal tumor in children: radiologic-pathologic correlation. Radiographics 1995; 15: 653. Graf N, Tournade MF and de Kraker J: The role of preoperative chemotherapy in the management of Wilms’ tumor. The SIOP studies. International Society of Pediatric Oncology. Urol Clin North Am 2000; 27: 443. Streif W, Gassner I, Janetschek G, Kreczy A, Judmaier W and Fink FM: Partial nephrectomy in a cystic partially differentiated nephroblastoma. Med Pediatr Oncol 1997; 28: 416. Ferrer FA and McKenna PH: Partial nephrectomy in a metachronous multilocular cyst of kidney (cystic nephroma). J Urol 1994; 151: 1358. Okada T, Yoshida H, Matsunaga T, Kouchi K, Ohtsuka Y, Saitou T et al: Nephron-sparing surgery for multilocular cyst of the kidney in a child. J Pediatr Surg 2003; 38: 1689. Schenk JP, Schrader C, Ziegler B, Furtwangler R, Leuschner I, Ley S et al: Reference radiology in nephroblastoma: accuracy and relevance for preoperative chemotherapy. Rofo 2006; 178: 38.
Purpose: Cystic partially differentiated nephroblastoma is a rare variant of Wilms tumor, and might be confused with cystic nephroma. Definitive diagnosis can only be made by histological examination. Therefore, initiation of therapy, either primary nephrectomy or preoperative chemotherapy, might create a dilemma when radiological diagnosis is doubtful. Materials and Methods: To define treatment strategies for these entities, we reviewed the records of 1,245 patients enrolled in SIOP (International Society of Pediatric Oncology) trials 93-01 and 2001 GPOH (German Society of Pediatric Oncology and Hematology) between July 1993 and August 2004. Data were collected retrospectively. Therapy, outcome and preoperative management were evaluated. To confirm diagnosis of cystic nephroma/partially differentiated nephroblastoma, all patients underwent review by the Reference Pathology Center of SIOP/GPOH. Results: A total of 14 patients with diagnoses of cystic nephroma (7) and cystic partially differentiated nephroblastoma (7) were identified. Median patient age at diagnosis was 1 year (0.46 to 3). Two patients received preoperative chemotherapy. Primary nephrectomy was performed in 12 patients. Two patients underwent partial nephrectomy. In 1 child postoperative chemotherapy was administered. None of the patients had progression of disease or recurrence. Overall survival was 100%. Median followup was 2.41 years (0.3 to 9). Conclusions: In cystic renal tumors radiological findings should always be reviewed by the reference radiologist of the treatment protocol study group. Irrespective of the chosen therapy, outcome of cystic nephroma and cystic partially differentiated nephroblastoma is favorable. Even in large international trials the number of patients with cystic nephroma or cystic partially differentiated nephroblastoma is too small for statistical analysis. Key Words: kidney neoplasms, Wilms tumor, pediatrics, surgery
spectrum of Wilms tumor.1 They assumed that CN in adults is a neoplasm with no known link to Wilms tumor. In the protocol of the SIOP 93-01 and 2001/GPOH studies CPDN and CN are defined as described by Joshi and Beckwith.9 Cystic partially differentiated nephroblastoma is rated as a low risk tumor, whereas CN is only registered as an associated tumor. Therefore, patients are treated according to tumor histology and stage. Normally, preoperative chemotherapy is also administered in the low risk group. However, the SIOP Working Classification of Renal Tumors of Childhood recommends that these tumors be treated with surgery alone.11 The dilemma is that a distinction between CN/CPDN and malignant neoplasms such as cystic Wilms tumor with preoperative imaging studies is not reliable. The aim of our study was to identify children with CPDN and CN within the population enrolled in the SIOP 93-01 and 2001/GPOH studies. Preoperative management, therapy and outcome were evaluated.
ystic partially differentiated nephroblastoma is a rare variant of Wilms tumor and is often confused with CN, and controversy exists regarding the terminology, classification and natural history of these entities. Distinction between CPDN and CN with preoperative imaging studies is impossible.1-3 More important, in some cases they cannot reliably be distinguished from malignant neoplasms such as cystic Wilms tumor.1 Both of these entities are unusual cystic renal neoplasms in young children, and are composed of purely cystic masses. In the past multiple terms such as multilocular cyst, multilocular cystic nephroma, cystic Wilms tumor and others have been used for these neoplasms.4 Cystic nephroma was first described by Edmunds in 1892.5 In 1951 Powell et al6 suggested diagnostic criteria for cystic nephroma, which were modified by Boggs and Kimmelstiel in 1956.7 The term “cystic partially differentiated nephroblastoma” was first used by Brown in 1975.8 In 1989 Joshi and Beckwith9 established criteria with a clear differentiation between CN and CPDN (see Appendix). Kajani et al simplified the criteria and concluded that CN and CPDN are the same.10 In 1998 Eble and Bonsib postulated that cystic nephroma in young children is the same as cystic partially differentiated nephroblastoma and is part of the
C
MATERIALS AND METHODS A total of 1,245 children were enrolled in the SIOP studies 93-01 and 2001/GPOH between July 1993 and August 2004. Patients with final diagnoses of CN and CPDN were reviewed. Diagnosis was confirmed by the German Reference Pathology Centre of the SIOP/GPOH (I. Leuschner, Kiel, Germany) in all patients. A total of 14 patients were iden-
Submitted for publication June 22, 2006. * Equal study contribution.
0022-5347/07/1771-0294/0 THE JOURNAL OF UROLOGY® Copyright © 2007 by AMERICAN UROLOGICAL ASSOCIATION
294
Vol. 177, 294-296, January 2007 Printed in U.S.A. DOI:10.1016/j.juro.2006.09.011
CYSTIC NEPHROMA AND CYSTIC PARTIALLY DIFFERENTIATED NEPHROBLASTOMA tified. For these 14 patients we retrospectively analyzed specific information concerning demographic data, tumor characteristics, chemotherapy, surgical therapy and outcome data, including local and distant recurrence and survival. RESULTS Median patient age at diagnosis was 1 year (range 0.46 to 3). There were 9 boys and 5 girls. Median followup was 2.41 years (range 0.3 to 9). All children had a unilateral tumor, with 8 right-sided and 6 left-sided tumors. In 7 patients tumor was found incidentally by radiological examination or ultrasound for other conditions. Of the remaining patients a palpable mass with pain was present in 1 child with hematuria. Initial tumor volume was 304.4 ml (range 8.1 to 878.6). Among 14 patients detected there were 7 children with CN and 7 with CPDN in the definitive histopathological findings according to study criteria (see Appendix). Two patients with CN received preoperative chemotherapy consisting of vincristine and dactinomycin. A total of 12 patients underwent complete nephrectomy and 2 underwent partial nephrectomy (1 each with CN and CPDN). One child was treated with postoperative vincristine and dactinomycin based on unclear staging. Therapy was discontinued after down-staging the tumor due to a definitive pathology result revealing CPDN. None of the children treated with chemotherapy had significant related side effects. All patients underwent complete tumor resection. A total of 13 patients had stage I disease and 1 had stage III disease due to intraoperative tumor rupture. This patient had a diagnosis of CN and did not receive postoperative chemotherapy. In 7 children preoperative radiological findings were reviewed by the reference radiologist of the SIOP/ GPOH study group. All patients had adequate followup with no recurrence. Overall survival rate was 100% (see table). DISCUSSION Cystic nephroma and cystic partially differentiated nephroblastoma constitute a group of uncommon multilocular tumors of the kidney in children. In our series CPDN and CN each made up about 0.56% of all tumors registered in the SIOP/GPOH studies. This finding corresponds roughly to the 0.5% of children with CPDN enrolled in the National Wilms Tumor Study during a 20-year period.12 As presented in different studies, cystic nephroma seems to occupy the benign end, CPDN a low risk category and
TABLE 1. Patient and tumor characteristics for cystic nephroma and cystic partially differentiated nephroblastoma Characteristics
CN
CPDN
No. pts Mean age at diagnosis (mos) No. males/females Av tumor vol (ml) Stage Median yrs followup (range) Chemotherapy
7 12.9
7 10.8
3/4 270 I/III 3.2 (0.3–9)
6/1 338 I 2 (0.8–5.6)
2 (dactinomycin ⫹ vincristine) 100
1 (dactinomycin ⫹ vincristine)* 100
% Survival rate
* Postoperative chemotherapy.
295
polycystic Wilms tumor the malignant end of the spectrum of cystic renal neoplasms.9,13,14 Eble and Bonsib even postulated that CN and CPDN in young children are the same entity, and that the term “cystic nephroma” should be reserved for the disease occurring in adults as a composite neoplasm of stroma and epithelium with no known link to Wilms tumor.1 Data on age of appearance in the literature are similar to our findings. Eble and Bonsib demonstrated that most patients with CN are younger than 4 years and most with CPDN are younger than 2 years.1 This observation corresponds to our findings. Concerning the gender of patients, our data differ from the literature, where boys predominate at a ratio of 2:1 in CN whereas in CPDN the tumor occurs with equal frequency.1 Our result might be due to the small number of patients in the study. We believe that primary resection of the tumor is the treatment of choice in CN and CPDN. This estimation has been confirmed by several other groups.1,4,9,12,15 The SIOP recommends in the revised Working Classification of Renal Tumors of Childhood that CPDN be treated with surgery alone.11 This suggestion is reflected in recommendations of the latest SIOP 2001/GPOH protocol, since preoperative differentiation between CN and CPDN is not necessary and surgical treatment alone is sufficient. As mentioned previously, the dilemma presented by this approach is that reliable preoperative differentiation between these 2 entities and a Wilms tumor with cystic changes is impossible.1,16 Wilms tumor with cystic changes is rated as an intermediate risk tumor, and, therefore, should be treated with preoperative chemotherapy according to the SIOP protocols. Graf et al showed that preoperative chemotherapy results in a lower rate of tumor ruptures during surgery and a favorable stage distribution.17 However, chemotherapy is not usually administered in patients with benign tumors, who make up 1.5% of all individuals in the SIOP studies. Overall toxicity is restricted to temporary disturbed liver function in less than 8% and low platelet counts in 4% of all patients enrolled in the SIOP trials.17 Conversely, Blakely et al reported that up to 30% of patients with CPDN enrolled in the National Wilms Tumor Study had significant chemotherapy related toxicity.12 The use of needle biopsy for diagnosis is not helpful and is contraindicated in cystic renal tumors because gross histological examination is essential for interpretation of tumor entity and adequate therapy.9,12 Renal sparing surgery is considered safe for resection of CN and CPDN.4,18 –20 However, there is the potential for recurrence in CPDN with incomplete excision.1,9 Because of the uncertain definitive pathology of total cystic renal tumors, we recommend complete nephrectomy. This recommendation is in accordance with several other studies.1,9,12,15 Partial nephrectomy should be limited to special cases as in unilateral kidney or bilateral tumors, and should only be undertaken after consultation with the study group. CONCLUSIONS Cystic nephroma and partially differentiated nephroblastoma, as cystic variants of Wilms tumor, make up approximately 1% of all Wilms tumor cases. Irrespective of the chosen therapy, outcomes of CN and CPDN are favorable. However, numbers of patients in even large international
296
CYSTIC NEPHROMA AND CYSTIC PARTIALLY DIFFERENTIATED NEPHROBLASTOMA
trials are too small for any statistical analysis. We recommend primary resection as the treatment of choice in cystic renal tumors. Preoperative chemotherapy is unnecessary. For patients treated according to the SIOP protocols radiological findings should always be reviewed by the reference radiologist before any therapy is initiated. This approach improves the diagnostic accuracy in those patients with a cystic renal tumor, in whom a Wilms tumor with cystic changes cannot be ruled out reliably.21 APPENDIX
6. 7.
8. 9.
10.
Definition of Cystic Nephroma and Cystic Partially Differentiated Nephroblastoma Cystic Nephroma: ● Tumor composed entirely of cysts and their septa ● Discrete mass well demarcated from noncystic renal parenchyma ● Septa are the only solid components and conform to outlines of cysts without expansile nodules ● Cysts are lined by flattened, cuboidal or hobnail epithelium ● Septa contain fibrous tissue in which well-differentiated tubules may be present Cystic Partially Differentiated Nephroblastoma: ● Criteria 1– 4 listed above but ● Septa contain blastema with/without embryonal stromal or epithelial elements
11.
12.
13.
14.
Abbreviations and Acronyms CN ⫽ cystic nephroma CPDN ⫽ cystic partially differentiated nephroblastoma GPOH ⫽ German Society of Pediatric Oncology and Hematology SIOP ⫽ International Society of Pediatric Surgery
15. 16.
17.
REFERENCES 1.
Eble JN and Bonsib SM: Extensively cystic renal neoplasms: cystic nephroma, cystic partially differentiated nephroblastoma, multilocular cystic renal cell carcinoma, and cystic hamartoma of renal pelvis. Am J Surg Pathol 1998; 15: 2. 2. Wilson TE, Doelle EA, Cohan RH, Wojno K and Jaccard J: Cystic renal masses: a reevaluation of the usefulness of the Bosniak classification system. Acad Radiol 1996; 3: 564. 3. Bosniak MA: The current radiological approach to renal cysts. Radiology 1986; 158: 1. 4. Castillo OA, Boyle ET Jr and Kramer SA: Multilocular cysts of kidney: a study of 29 patients and review of the literature. Urology 1991; 37: 156. 5. Edmunds W: Cystic adenoma of kidney. Trans Pathol Soc (Lond) 1892; 43: 89.
18.
19.
20.
21.
Powell T, Shackman R and Johnson HD: Multilocular cysts of the kidney. Br J Urol 1951; 23: 142. Boggs LK and Kimmelstiel P: Benign multilocular cystic nephroma: report of two cases of so-called multilocular cyst of the kidney. J Urol 1956; 76: 530. Brown JM: Cystic partially differentiated nephroblastoma. J Pathol 1975; 115: 175. Joshi VV and Beckwith JB: Multilocular cyst of the kidney (cystic nephroma) and cystic partially differentiated nephroblastoma: terminology and criteria for diagnosis. Cancer 1989; 64: 466. Kajani N, Rosenberg BF and Bernstein J: Multilocular cystic nephroma. J Urol Pathol 1993; 1: 33. Vujanic GM, Sandstedt B, Harms D, Kelsey A, Leuschner I and de Kraker J: Revised International Society of Paediatric Oncology (SIOP) working classification of renal tumors of childhood. Med Pediatr Oncol 2002; 38: 79. Blakely ML, Shamberger RC, Norkool P, Beckwith JB, Green DM and Ritchey ML: Outcome of children with cystic partially differentiated nephroblastoma treated with or without chemotherapy. J Pediatr Surg 2003; 38: 897. Joshi VV, Banerjee AK, Yadav K and Pathak IC: Cystic partially differentiated nephroblastoma: a clinicopathologic entity in the spectrum of infantile renal neoplasia. Cancer 1977; 40: 789. Madewell JE, Goldman SM, Davis CJ Jr, Hartman DS, Feigin DS and Lichtenstein JE: Multilocular cystic nephroma: a radiographic-pathologic correlation of 58 patients. Radiology 1983; 146: 309. Shamberger RC: Pediatric renal tumors. Semin Surg Oncol 1999; 16: 105. Agrons GA, Wagner BJ, Davidson AJ and Suarez ES: Multilocular cystic renal tumor in children: radiologic-pathologic correlation. Radiographics 1995; 15: 653. Graf N, Tournade MF and de Kraker J: The role of preoperative chemotherapy in the management of Wilms’ tumor. The SIOP studies. International Society of Pediatric Oncology. Urol Clin North Am 2000; 27: 443. Streif W, Gassner I, Janetschek G, Kreczy A, Judmaier W and Fink FM: Partial nephrectomy in a cystic partially differentiated nephroblastoma. Med Pediatr Oncol 1997; 28: 416. Ferrer FA and McKenna PH: Partial nephrectomy in a metachronous multilocular cyst of kidney (cystic nephroma). J Urol 1994; 151: 1358. Okada T, Yoshida H, Matsunaga T, Kouchi K, Ohtsuka Y, Saitou T et al: Nephron-sparing surgery for multilocular cyst of the kidney in a child. J Pediatr Surg 2003; 38: 1689. Schenk JP, Schrader C, Ziegler B, Furtwangler R, Leuschner I, Ley S et al: Reference radiology in nephroblastoma: accuracy and relevance for preoperative chemotherapy. Rofo 2006; 178: 38.