- Email: [email protected]
Risk Assessment of Incidentally Detected Complex Renal Cysts in Children: Potential Role for a Modification of the Bosniak Classification
Risk Assessment of Incidentally Detected Complex Renal Cysts in Children: Potential Role for a Modification of the Bosniak Classification M. Chad Wallis,* Armando J. Lorenzo, Walid A. Farhat, Darius J. Bägli, Antoine E. Khoury and Joao L. Pippi Salle From the Division of Pediatric Urology, University of Utah, Salt Lake City, Utah (MCW), and Division of Urology, University of Toronto and Hospital for Sick Children, Toronto, Ontario, Canada
Purpose: Incidentally detected complex renal cysts in children are a rare but worrisome occurrence due to the perceived potential risk of malignancy. We examined the natural history of such cysts in a cohort of children. Materials and Methods: We obtained access to a database containing all radiology reports generated at a single institution from 1996 to 2004. We used key words to limit our search, subsequently reviewing charts and images to confirm the diagnosis of a complex renal cyst and to collect clinical data. Cases were categorized according to a modification of the Bosniak classification, using ultrasound in most patients and computerized tomography or magnetic resonance imaging when available. Results: Complex renal cysts were identified in 39 children. Mean patient age at presentation was 7 years. Mean cyst size was 1.6 cm. A total of 18 cases diagnosed by ultrasound only were observed with serial imaging. Additional contrast enhanced computerized tomography or magnetic resonance imaging was performed in 21 of 39 patients (54%). Surgical resection was performed in 5 patients and pathological evaluation revealed benign cyst in 3 (modified Bosniak class II in 2 patients and class III in 1) and renal cell carcinoma in 2 (III in 1 and IV in 1). All other patients had modified Bosniak class II cysts, which remained essentially unchanged during a mean followup of 26.8 months (range 9 to 70). Conclusions: While not validated in children, our data suggest the modified Bosniak classification appears useful as a guideline to direct the management of complex renal cysts in the pediatric population. Key Words: carcinoma, renal cell; kidney diseases, cystic; diagnostic imaging; pediatrics
tion, there are no clear guidelines for the management of complex renal cysts in children. To evaluate the risk of malignancy and the potential usefulness of the Bosniak classification, we present data on a retrospectively identified cohort of patients with complex renal cysts.
enal cysts are a relatively common finding in the adult population, and increase in incidence with advancing age.1,2 They are commonly detected incidentally due to the increasing number of imaging studies being performed. Simple cysts are considered benign and need no treatment unless they become symptomatic. However, complex cysts present a diagnostic and therapeutic dilemma that has been the subject of numerous published reports and the well accepted Bosniak scoring system.3–5 By comparison, cysts in children are relatively uncommon, and complex cysts are rarely encountered. By extrapolating the concerns raised by such findings in adults, the diagnosis of a complex renal cyst in children is often accompanied by fears of not only malignant components at the time of diagnosis,6 – 8 but also the perceived potential for malignant degeneration with time. Although based on scarce evidence, these concerns have led to recommendations for surgical resection in many cases. The Bosniak classification for renal cysts has yet to be applied to a pediatric population in the literature. In addi-
R
MATERIALS AND METHODS Patients with a known history of complex renal cyst were identified for review. To capture the maximum number of cases, we searched a database of all radiology reports from 1996 to 2004 at the Hospital for Sick Children. Because ICD-9 codes are not used at our radiology department, a previously developed word recognition software program was used to search the database. We initially looked for reports containing the words “cyst” and “renal” or “kidney.” The search was then further limited to reports containing the words “complex,” “septation” or “septated.” Radiology reports were then reviewed individually to exclude patients with conditions other than complex renal cysts. For each patient all abdominal imaging studies were evaluated, and imaging modality, maximum diameter of the cyst, Bosniak classification (based on proposed modification, see Appendix) and presence of septation, calcification, hemorrhage or additional cysts were recorded when available. Electronic patient records were examined to obtain clinical data regarding each patient, including gender, age at diag-
Submitted for publication November 12, 2007. Study received institutional review board approval. * Correspondence: Primary Children’s Medical Center, 100 North Medical Dr., Suite 2200, Salt Lake City, Utah 84113 (e-mail: [email protected]).
For another article on a related topic see page 379.
0022-5347/08/1801-0317/0 THE JOURNAL OF UROLOGY® Copyright © 2008 by AMERICAN UROLOGICAL ASSOCIATION
317
Vol. 180, 317-321, July 2008 Printed in U.S.A. DOI:10.1016/j.juro.2008.03.063
318
RISK ASSESSMENT OF INCIDENTALLY DETECTED COMPLEX RENAL CYSTS
nosis, presentation, length of followup and surgical intervention (with subsequent pathology report) if any. Patients with evidence of cystic kidney disease, prior renal trauma, previous renal surgery/intervention or insufficient data were excluded from further review. A minimum of 6 months of followup was required for inclusion. Statistical analysis was performed using commercially available software (SPSS®, version 14).
TABLE 2. Patients who underwent surgical resection of complex renal cyst
Pt No.—Age—Sex 1—8 —F 2—10 —F 3—3 —F 4—1ь5 —F 5—11ь2—M
Cyst Size at Time From Diagnosis Diagnosis to (mm) Surgery 48 40 18 50 12
2 Wks 3 Mos 2.5 Mos 7.5 Mos 3 Wks
Surgical Pathology Renal cell Ca Benign multilocular cyst Benign cyst Benign cyst Renal cell Ca
RESULTS Our database search identified 452 documents with the aforementioned key words and limitations. After review of these radiology reports clinical data were obtained on 98 patients who fulfilled the criteria for full review. Complex renal cysts were identified in 39 children (21 girls and 18 boys) who met the inclusion criteria. Mean patient age at presentation to our institution was 7 years (range 4 months to 14 years). Mean cyst size was 1.6 cm (range 0.4 to 5). Otherwise normal renal parenchyma was seen in 37 patients. However, 1 patient had more than 2 additional cysts and 1 had radiographic changes suggestive of cystic dysplasia. Indications for imaging were varied, and are outlined in table 1. Initial diagnosis was made based on ultrasound findings in 36 cases, while the remaining 3 cases were discovered on CT. Of these 36 cases 18 diagnosed by US were observed on serial sonographic imaging only. No significant changes were noted in cyst size or character during followup studies. Contrast enhanced imaging by CT or MRI was performed in 21 of the 39 patients (54%), and supported the diagnosis of complex renal cyst in 12. Simple cysts were diagnosed in 7 patients despite clear visualization of septations on sonographic imaging. The diagnosis in the remaining 2 patients was multiple simple cysts in 1 and caliceal diverticulum in 1. Surgical resection was performed in 5 patients, based on surgeon preference and worrisome characteristics (ie en-
TABLE 1. Indications for imaging at time of initial diagnosis Indications
No. Pts
Unknown Screening: Beckwith-Wiedemann Neurofibromatosis type Vesicoureteral reflux Abdominal/flank pain Abnormal prenatal US findings History of transplant: Liver Lung History of cancer: Acute lymphoblastic leukemia Neuroblastoma History of stones and cystinuria Other: Posterior urethral valves VACTERL* Spina bifida Nephrogenic diabetes insipidus Epispadias status post-enterocystoplasty Trauma Sickle cell and history of hepatic abscess Febrile urinary tract infections Anorectal malformation Incontinence
7
Total
3 1 4 3 3 2 1 2 1 2 1 1 1 1 1 1 1 1 1 1 39
* Vertebral, anal, cardiac, tracheal, esophageal, renal and limb abnormalities.
hancing components of the complex cyst, table 2). All patients underwent open partial nephrectomy. Pathological evaluation showed benign cyst in 3 patients (modified Bosniak class II in 2 and class III in 1) and RCC in the remaining 2 patients (III in 1 and IV in 1). One patient with RCC had a close surgical margin (200 microns) on pathological assessment and underwent immediate re-resection of the tumor bed. No residual tumor was found on subsequent pathological evaluation. All remaining patients were observed with serial imaging studies. Cystic lesions in these patients remained essentially unchanged in appearance during a mean followup of 26.8 months (range 9 to 70). DISCUSSION The incidental finding of complex renal cysts in children, although rare, can present a clinical conundrum for pediatric urologists. Questions abound as to the management of such cysts. What is the risk of these cysts harboring a malignancy? What is the risk of malignant degeneration? Is surgical resection required? Can such cysts be followed with serial imaging? If so, how long must they be followed? While our findings by no means provide definitive answers to these questions, we hope they will provide a preliminary framework for analyzing individual patients, and serve as a basis for prospective studies validating our initial findings. Some general conclusions can be extracted from these data. First, it appears that children who have cysts with enhancing soft tissue densities (detected after intravenous contrast administration) benefit from surgical resection. Two patients in our series had cysts with these characteristics and were discovered to have renal cell carcinoma (fig. 1). This approach is consistent with recommendations based on the Bosniak classification, where class III and class IV complex cysts are usually surgically resected due to the high incidence of malignancy observed in these lesions. While the Bosniak classification has been well studied in adults, to our knowledge it has not previously been applied to a series of pediatric patients. Our main purpose in modifying the Bosniak classification was to provide guidance for categorizing cysts based on ultrasound findings. The original Bosniak classification system is based on contrast enhanced CT imaging. However, in children ultrasound is generally preferred for routine evaluation of the urinary tract. Because our series was retrospective, almost half of the patients had no contrast enhanced axial imaging studies available for application of the original Bosniak classification scheme. In creating the modified system we have remained true to
RISK ASSESSMENT OF INCIDENTALLY DETECTED COMPLEX RENAL CYSTS
319
FIG. 1. Preoperative imaging in 8-year-old girl presenting with hematuria and proteinuria. A, US demonstrates complex cyst with heterogeneous echogenicity. B, Doppler reveals no flow within cyst. C, unenhanced CT shows calcified rim with area of increased density. D, contrast image demonstrates enhancement of cyst wall. Patient underwent right partial nephrectomy and pathological evaluation revealed renal cell carcinoma.
the elements found in each category based on CT imaging, and have simply added US findings, which would be consistent with axial imaging. In addition, we found no evidence of so-called malignant degeneration in our patients with complex renal cysts. While 2 patients had RCC on pathological evaluation, both were recognized as having worrisome characteristics early, and treated with surgical resection. Those patients in our series with modified Bosniak class II cysts who were followed with serial imaging studies did not demonstrate worrisome changes with time. However, without longer followup and greater numbers of patients it would be premature to suggest that children with a modified Bosniak class II cyst on axial contrast enhanced imaging require no further followup, as is the recommendation in adults. This statement is obviously limited by the lack of pathological evaluation in all patients and the incomplete characterization in those who only underwent renal ultrasonography. The most recent reports on the Bosniak classification divide category II cysts into those that can be ignored (category II) and those that require followup imaging (category II,F). We have not made this distinction in our modified Bosniak classification, because we are more comfortable following all children with category II cysts. From our series it is apparent that ultrasound imaging is more sensitive than CT at detecting septations. Seven patients in our series had clear evidence of septations on US, although CT and MRI revealed only simple cysts. In some cases Doppler flow can be detected within these septations. The presence of flow (by Doppler ultrasound) should raise the level of suspicion and trigger further imaging studies.
Thus far, this finding has not resulted in subsequent diagnosis of malignancy (fig. 2). It is unclear if there is a benefit to generating such distinction by ordering both imaging studies, especially if we consider that in children the risk of malignancy for modified Bosniak I and II cysts may be small. Unfortunately, ultrasound currently suffers from an important limitation, since contrast administration is required to detect enhancement. To evaluate a renal mass with the Bosniak classification optimally, the imaging studies should include CT or MRI. The latter exhibits great promise for showing exquisite anatomical detail while avoiding radiation exposure. However, as appealing as that may be, sedation or general anesthesia is typically required, particularly in younger children. While CT is currently the modality of choice for imaging complex renal cysts in adults, legitimate concerns have recently been raised with regard to the long-term implications of radiation exposure in children. Computerized tomography is now one of the most significant sources of radiation exposure for children.9 The risk in an individual is small but the public health implications are significant when the individual personal risk is multiplied by the 2.7 million such procedures that are performed annually in the United States.10 Children are 10 times more sensitive to radiation induced cancer than adults, with their lifetime cancer mortality risk being inversely proportional to their age.11 At the ALARA (as low as reasonably achievable) conference in 2001 it was concluded that the highest priority should be given to reducing the radiation dose while still maintaining acceptable diagnostic image quality.12 In addition, the American Academy of Pediatrics recently released
320
RISK ASSESSMENT OF INCIDENTALLY DETECTED COMPLEX RENAL CYSTS
FIG. 2. Ten-year-old girl presenting with abdominal pain. A, US shows multiseptated right renal cyst. B, Doppler image suggests flow within septation. C, CT with contrast enhancement demonstrates multilocular cyst. D, delayed images reveal distortion of collecting system but no enhancement. Patient underwent right partial nephrectomy and pathological evaluation showed benign multilocular cyst.
a report regarding the risks of radiation exposure in children from CT.13 The report recommended that health care professionals find ways to decrease radiation exposure in children by using the ALARA principle and by performing CT only when necessary. We propose that this goal can be accomplished in children with complex renal cysts by judicious use of CT on initial diagnosis, with most of the followup studies relying on ultrasonography. Magnetic resonance imaging may also be considered, particularly in older children who may not require anesthesia. Our modification of the Bosniak classification may aid in the decision making process and, with prospective validation, better allow clinicians to select patients who require axial imaging studies with intravenous contrast material. There are certainly important limitations to our study beyond the short followup. Our patients were in large part gleaned from a radiological database and, therefore, some were never evaluated by a pediatric urologist. Even when patients were seen by a pediatric urologist at our institution followup protocols varied from physician to physician, and from patient to patient. As a result, a large number of children did not undergo axial imaging evaluation with contrast administration, making assessment with the proposed modification somewhat heterogeneous and limited. Finally, without pathological specimens to examine there is no way of definitively confirming whether benign appearing lesions are harboring small foci of malignant cells. Because of these limitations, it is difficult to construct specific guidelines for followup, particularly in the case of class II cysts. We believe that contrast enhanced axial imaging is warranted in all children with US findings consistent with a class III or class IV cyst. If these findings are confirmed on CT or MRI, surgical resection should be advo-
cated. As a rough guideline, we suggest that followup sonographic imaging be performed in children with class II cysts at 3 to 6-month intervals for the first year, and then annually once the cyst is deemed to be stable. We have no recommendations as to when the decision to discontinue imaging of a stable lesion should be made, hence the lack of a modified Bosniak class II,F lesion in our proposed classification. However, it is our hope that longitudinal study of these patients and those at other institutions will improve our understanding of the natural history of these lesions. Refinement of this modification of the Bosniak classification may be required to address fully the issues of perceived increased risk of radiation exposure in children and the relative lower overall incidence of renal malignancies (in comparison to adults). Furthermore, the issue of balancing the risks of malignancy, radiation exposure with CT and anesthesia or sedation with MRI remains open to further analysis. Future prospective studies on the subject are needed to define the best diagnostic strategy for these patients.
CONCLUSIONS While not validated in children, our data suggest the proposed modified Bosniak classification may be used as a guideline to direct the need for surgical intervention in the pediatric population. In the absence of change or symptoms Bosniak class II cysts may be safely followed with periodic ultrasound imaging. Patients with Bosniak class III and class IV cysts have a significant chance of harboring malignancy, and surgical resection should be considered.
RISK ASSESSMENT OF INCIDENTALLY DETECTED COMPLEX RENAL CYSTS
321
APPENDIX Proposed Modification of Bosniak Classification Applied to Renal Cysts in Children Category
Description
I
Round, smooth thin walled cyst. No echogenic foci and enhanced throughout transmission on US. Homogeneous content consistent with water density and absence of enhancement after intravenous contrast on CT scan. Cyst with thin septa with or without minimal/smooth thickening of the cyst wall or septation(s). Calcifications and/or high attenuation detected on CT scan. No evidence of enhancement after contrast administration. No detectable flow by Doppler ultrasound in septations or cyst wall. Presence of thick or irregular septations. Thick/irregular calcifications detected on CT scan. Enhancement of septa or wall may be present after intravenous contrast administration. Detectable flow by Doppler ultrasound may be present inseptations or cyst wall. If category III by ultrasound, contrast axial imaging study should be strongly considered. Cystic mass with thick wall, solid internal components or nodular areas. Enhancement and marked heterogeneity after contrast administration. Detectable flow detected by Doppler ultrasound in cyst wall, septations, nodular component. If category IV by ultrasound, contrast axial imaging study should be strongly considered.
II* III IV
If both US and CT scan or MRI obtained, in case of discrepancy the findings on the contrast enhanced axial imaging study should be favored for classification purposes. Children found to have renal cysts should be considered for evaluation for hereditary cystic renal diseases. * Children with category II cysts should be periodically followed with serial imaging studies until further experience is gained with this classification scheme.
Abbreviations and Acronyms CT MRI RCC US
⫽ ⫽ ⫽ ⫽
computerized tomography magnetic resonance imaging renal cell carcinoma ultrasound
REFERENCES 1. 2.
3. 4. 5. 6.
Laucks SP Jr and McLachlan MS: Aging and simple cysts of the kidney. Br J Radiol 1981; 54: 12. Terada N, Ichioka K, Matsuta Y, Okubo K, Yoshimura K and Arai Y: The natural history of simple renal cysts. J Urol 2002; 167: 21. Bosniak MA: The current radiological approach to renal cysts. Radiology 1986; 158: 1. Israel GM and Bosniak MA: An update of the Bosniak renal cyst classification system. Urology 2005; 66: 484. Warren KS and McFarlane J: The Bosniak classification of renal cystic masses. BJU Int 2005; 95: 939. Luithle T, Szavay P, Furtwangler R, Graf N and Fuchs J: Treatment of cystic nephroma and cystic partially differen-
7.
8.
9. 10.
11.
12.
13.
tiated nephroblastoma—a report from the SIOP/GPOH study group. J Urol 2007; 177: 294. Menon P, Rao KL, Kakkar N, Saxena AK and Singh M: Multilocular cystic renal cell carcinoma in a child. J Pediatr Surg 2004; 39: e14. 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. Semin Diagn Pathol 1998; 15: 2. Donnelly LF: Lessons from history. Pediatr Radiol 2002; 32: 287. Hall EJ: Lessons we have learned from our children: cancer risks from diagnostic radiology. Pediatr Radiol 2002; 32: 700. Brenner DJ: Estimating cancer risks from pediatric CT: going from the qualitative to the quantitative. Pediatr Radiol 2002; 32: 228. The ALARA (as low as reasonably achievable) concept in pediatric CT intelligent dose reduction. Multidisciplinary conference organized by the Society of Pediatric Radiology. August 18 –19, 2001. Pediatr Radiol 2002; 32: 217. Brody AS, Frush DP, Huda W and Brent RL: Radiation risk to children from computed tomography. Pediatrics 2007; 120: 677.
Purpose: Incidentally detected complex renal cysts in children are a rare but worrisome occurrence due to the perceived potential risk of malignancy. We examined the natural history of such cysts in a cohort of children. Materials and Methods: We obtained access to a database containing all radiology reports generated at a single institution from 1996 to 2004. We used key words to limit our search, subsequently reviewing charts and images to confirm the diagnosis of a complex renal cyst and to collect clinical data. Cases were categorized according to a modification of the Bosniak classification, using ultrasound in most patients and computerized tomography or magnetic resonance imaging when available. Results: Complex renal cysts were identified in 39 children. Mean patient age at presentation was 7 years. Mean cyst size was 1.6 cm. A total of 18 cases diagnosed by ultrasound only were observed with serial imaging. Additional contrast enhanced computerized tomography or magnetic resonance imaging was performed in 21 of 39 patients (54%). Surgical resection was performed in 5 patients and pathological evaluation revealed benign cyst in 3 (modified Bosniak class II in 2 patients and class III in 1) and renal cell carcinoma in 2 (III in 1 and IV in 1). All other patients had modified Bosniak class II cysts, which remained essentially unchanged during a mean followup of 26.8 months (range 9 to 70). Conclusions: While not validated in children, our data suggest the modified Bosniak classification appears useful as a guideline to direct the management of complex renal cysts in the pediatric population. Key Words: carcinoma, renal cell; kidney diseases, cystic; diagnostic imaging; pediatrics
tion, there are no clear guidelines for the management of complex renal cysts in children. To evaluate the risk of malignancy and the potential usefulness of the Bosniak classification, we present data on a retrospectively identified cohort of patients with complex renal cysts.
enal cysts are a relatively common finding in the adult population, and increase in incidence with advancing age.1,2 They are commonly detected incidentally due to the increasing number of imaging studies being performed. Simple cysts are considered benign and need no treatment unless they become symptomatic. However, complex cysts present a diagnostic and therapeutic dilemma that has been the subject of numerous published reports and the well accepted Bosniak scoring system.3–5 By comparison, cysts in children are relatively uncommon, and complex cysts are rarely encountered. By extrapolating the concerns raised by such findings in adults, the diagnosis of a complex renal cyst in children is often accompanied by fears of not only malignant components at the time of diagnosis,6 – 8 but also the perceived potential for malignant degeneration with time. Although based on scarce evidence, these concerns have led to recommendations for surgical resection in many cases. The Bosniak classification for renal cysts has yet to be applied to a pediatric population in the literature. In addi-
R
MATERIALS AND METHODS Patients with a known history of complex renal cyst were identified for review. To capture the maximum number of cases, we searched a database of all radiology reports from 1996 to 2004 at the Hospital for Sick Children. Because ICD-9 codes are not used at our radiology department, a previously developed word recognition software program was used to search the database. We initially looked for reports containing the words “cyst” and “renal” or “kidney.” The search was then further limited to reports containing the words “complex,” “septation” or “septated.” Radiology reports were then reviewed individually to exclude patients with conditions other than complex renal cysts. For each patient all abdominal imaging studies were evaluated, and imaging modality, maximum diameter of the cyst, Bosniak classification (based on proposed modification, see Appendix) and presence of septation, calcification, hemorrhage or additional cysts were recorded when available. Electronic patient records were examined to obtain clinical data regarding each patient, including gender, age at diag-
Submitted for publication November 12, 2007. Study received institutional review board approval. * Correspondence: Primary Children’s Medical Center, 100 North Medical Dr., Suite 2200, Salt Lake City, Utah 84113 (e-mail: [email protected]).
For another article on a related topic see page 379.
0022-5347/08/1801-0317/0 THE JOURNAL OF UROLOGY® Copyright © 2008 by AMERICAN UROLOGICAL ASSOCIATION
317
Vol. 180, 317-321, July 2008 Printed in U.S.A. DOI:10.1016/j.juro.2008.03.063
318
RISK ASSESSMENT OF INCIDENTALLY DETECTED COMPLEX RENAL CYSTS
nosis, presentation, length of followup and surgical intervention (with subsequent pathology report) if any. Patients with evidence of cystic kidney disease, prior renal trauma, previous renal surgery/intervention or insufficient data were excluded from further review. A minimum of 6 months of followup was required for inclusion. Statistical analysis was performed using commercially available software (SPSS®, version 14).
TABLE 2. Patients who underwent surgical resection of complex renal cyst
Pt No.—Age—Sex 1—8 —F 2—10 —F 3—3 —F 4—1ь5 —F 5—11ь2—M
Cyst Size at Time From Diagnosis Diagnosis to (mm) Surgery 48 40 18 50 12
2 Wks 3 Mos 2.5 Mos 7.5 Mos 3 Wks
Surgical Pathology Renal cell Ca Benign multilocular cyst Benign cyst Benign cyst Renal cell Ca
RESULTS Our database search identified 452 documents with the aforementioned key words and limitations. After review of these radiology reports clinical data were obtained on 98 patients who fulfilled the criteria for full review. Complex renal cysts were identified in 39 children (21 girls and 18 boys) who met the inclusion criteria. Mean patient age at presentation to our institution was 7 years (range 4 months to 14 years). Mean cyst size was 1.6 cm (range 0.4 to 5). Otherwise normal renal parenchyma was seen in 37 patients. However, 1 patient had more than 2 additional cysts and 1 had radiographic changes suggestive of cystic dysplasia. Indications for imaging were varied, and are outlined in table 1. Initial diagnosis was made based on ultrasound findings in 36 cases, while the remaining 3 cases were discovered on CT. Of these 36 cases 18 diagnosed by US were observed on serial sonographic imaging only. No significant changes were noted in cyst size or character during followup studies. Contrast enhanced imaging by CT or MRI was performed in 21 of the 39 patients (54%), and supported the diagnosis of complex renal cyst in 12. Simple cysts were diagnosed in 7 patients despite clear visualization of septations on sonographic imaging. The diagnosis in the remaining 2 patients was multiple simple cysts in 1 and caliceal diverticulum in 1. Surgical resection was performed in 5 patients, based on surgeon preference and worrisome characteristics (ie en-
TABLE 1. Indications for imaging at time of initial diagnosis Indications
No. Pts
Unknown Screening: Beckwith-Wiedemann Neurofibromatosis type Vesicoureteral reflux Abdominal/flank pain Abnormal prenatal US findings History of transplant: Liver Lung History of cancer: Acute lymphoblastic leukemia Neuroblastoma History of stones and cystinuria Other: Posterior urethral valves VACTERL* Spina bifida Nephrogenic diabetes insipidus Epispadias status post-enterocystoplasty Trauma Sickle cell and history of hepatic abscess Febrile urinary tract infections Anorectal malformation Incontinence
7
Total
3 1 4 3 3 2 1 2 1 2 1 1 1 1 1 1 1 1 1 1 39
* Vertebral, anal, cardiac, tracheal, esophageal, renal and limb abnormalities.
hancing components of the complex cyst, table 2). All patients underwent open partial nephrectomy. Pathological evaluation showed benign cyst in 3 patients (modified Bosniak class II in 2 and class III in 1) and RCC in the remaining 2 patients (III in 1 and IV in 1). One patient with RCC had a close surgical margin (200 microns) on pathological assessment and underwent immediate re-resection of the tumor bed. No residual tumor was found on subsequent pathological evaluation. All remaining patients were observed with serial imaging studies. Cystic lesions in these patients remained essentially unchanged in appearance during a mean followup of 26.8 months (range 9 to 70). DISCUSSION The incidental finding of complex renal cysts in children, although rare, can present a clinical conundrum for pediatric urologists. Questions abound as to the management of such cysts. What is the risk of these cysts harboring a malignancy? What is the risk of malignant degeneration? Is surgical resection required? Can such cysts be followed with serial imaging? If so, how long must they be followed? While our findings by no means provide definitive answers to these questions, we hope they will provide a preliminary framework for analyzing individual patients, and serve as a basis for prospective studies validating our initial findings. Some general conclusions can be extracted from these data. First, it appears that children who have cysts with enhancing soft tissue densities (detected after intravenous contrast administration) benefit from surgical resection. Two patients in our series had cysts with these characteristics and were discovered to have renal cell carcinoma (fig. 1). This approach is consistent with recommendations based on the Bosniak classification, where class III and class IV complex cysts are usually surgically resected due to the high incidence of malignancy observed in these lesions. While the Bosniak classification has been well studied in adults, to our knowledge it has not previously been applied to a series of pediatric patients. Our main purpose in modifying the Bosniak classification was to provide guidance for categorizing cysts based on ultrasound findings. The original Bosniak classification system is based on contrast enhanced CT imaging. However, in children ultrasound is generally preferred for routine evaluation of the urinary tract. Because our series was retrospective, almost half of the patients had no contrast enhanced axial imaging studies available for application of the original Bosniak classification scheme. In creating the modified system we have remained true to
RISK ASSESSMENT OF INCIDENTALLY DETECTED COMPLEX RENAL CYSTS
319
FIG. 1. Preoperative imaging in 8-year-old girl presenting with hematuria and proteinuria. A, US demonstrates complex cyst with heterogeneous echogenicity. B, Doppler reveals no flow within cyst. C, unenhanced CT shows calcified rim with area of increased density. D, contrast image demonstrates enhancement of cyst wall. Patient underwent right partial nephrectomy and pathological evaluation revealed renal cell carcinoma.
the elements found in each category based on CT imaging, and have simply added US findings, which would be consistent with axial imaging. In addition, we found no evidence of so-called malignant degeneration in our patients with complex renal cysts. While 2 patients had RCC on pathological evaluation, both were recognized as having worrisome characteristics early, and treated with surgical resection. Those patients in our series with modified Bosniak class II cysts who were followed with serial imaging studies did not demonstrate worrisome changes with time. However, without longer followup and greater numbers of patients it would be premature to suggest that children with a modified Bosniak class II cyst on axial contrast enhanced imaging require no further followup, as is the recommendation in adults. This statement is obviously limited by the lack of pathological evaluation in all patients and the incomplete characterization in those who only underwent renal ultrasonography. The most recent reports on the Bosniak classification divide category II cysts into those that can be ignored (category II) and those that require followup imaging (category II,F). We have not made this distinction in our modified Bosniak classification, because we are more comfortable following all children with category II cysts. From our series it is apparent that ultrasound imaging is more sensitive than CT at detecting septations. Seven patients in our series had clear evidence of septations on US, although CT and MRI revealed only simple cysts. In some cases Doppler flow can be detected within these septations. The presence of flow (by Doppler ultrasound) should raise the level of suspicion and trigger further imaging studies.
Thus far, this finding has not resulted in subsequent diagnosis of malignancy (fig. 2). It is unclear if there is a benefit to generating such distinction by ordering both imaging studies, especially if we consider that in children the risk of malignancy for modified Bosniak I and II cysts may be small. Unfortunately, ultrasound currently suffers from an important limitation, since contrast administration is required to detect enhancement. To evaluate a renal mass with the Bosniak classification optimally, the imaging studies should include CT or MRI. The latter exhibits great promise for showing exquisite anatomical detail while avoiding radiation exposure. However, as appealing as that may be, sedation or general anesthesia is typically required, particularly in younger children. While CT is currently the modality of choice for imaging complex renal cysts in adults, legitimate concerns have recently been raised with regard to the long-term implications of radiation exposure in children. Computerized tomography is now one of the most significant sources of radiation exposure for children.9 The risk in an individual is small but the public health implications are significant when the individual personal risk is multiplied by the 2.7 million such procedures that are performed annually in the United States.10 Children are 10 times more sensitive to radiation induced cancer than adults, with their lifetime cancer mortality risk being inversely proportional to their age.11 At the ALARA (as low as reasonably achievable) conference in 2001 it was concluded that the highest priority should be given to reducing the radiation dose while still maintaining acceptable diagnostic image quality.12 In addition, the American Academy of Pediatrics recently released
320
RISK ASSESSMENT OF INCIDENTALLY DETECTED COMPLEX RENAL CYSTS
FIG. 2. Ten-year-old girl presenting with abdominal pain. A, US shows multiseptated right renal cyst. B, Doppler image suggests flow within septation. C, CT with contrast enhancement demonstrates multilocular cyst. D, delayed images reveal distortion of collecting system but no enhancement. Patient underwent right partial nephrectomy and pathological evaluation showed benign multilocular cyst.
a report regarding the risks of radiation exposure in children from CT.13 The report recommended that health care professionals find ways to decrease radiation exposure in children by using the ALARA principle and by performing CT only when necessary. We propose that this goal can be accomplished in children with complex renal cysts by judicious use of CT on initial diagnosis, with most of the followup studies relying on ultrasonography. Magnetic resonance imaging may also be considered, particularly in older children who may not require anesthesia. Our modification of the Bosniak classification may aid in the decision making process and, with prospective validation, better allow clinicians to select patients who require axial imaging studies with intravenous contrast material. There are certainly important limitations to our study beyond the short followup. Our patients were in large part gleaned from a radiological database and, therefore, some were never evaluated by a pediatric urologist. Even when patients were seen by a pediatric urologist at our institution followup protocols varied from physician to physician, and from patient to patient. As a result, a large number of children did not undergo axial imaging evaluation with contrast administration, making assessment with the proposed modification somewhat heterogeneous and limited. Finally, without pathological specimens to examine there is no way of definitively confirming whether benign appearing lesions are harboring small foci of malignant cells. Because of these limitations, it is difficult to construct specific guidelines for followup, particularly in the case of class II cysts. We believe that contrast enhanced axial imaging is warranted in all children with US findings consistent with a class III or class IV cyst. If these findings are confirmed on CT or MRI, surgical resection should be advo-
cated. As a rough guideline, we suggest that followup sonographic imaging be performed in children with class II cysts at 3 to 6-month intervals for the first year, and then annually once the cyst is deemed to be stable. We have no recommendations as to when the decision to discontinue imaging of a stable lesion should be made, hence the lack of a modified Bosniak class II,F lesion in our proposed classification. However, it is our hope that longitudinal study of these patients and those at other institutions will improve our understanding of the natural history of these lesions. Refinement of this modification of the Bosniak classification may be required to address fully the issues of perceived increased risk of radiation exposure in children and the relative lower overall incidence of renal malignancies (in comparison to adults). Furthermore, the issue of balancing the risks of malignancy, radiation exposure with CT and anesthesia or sedation with MRI remains open to further analysis. Future prospective studies on the subject are needed to define the best diagnostic strategy for these patients.
CONCLUSIONS While not validated in children, our data suggest the proposed modified Bosniak classification may be used as a guideline to direct the need for surgical intervention in the pediatric population. In the absence of change or symptoms Bosniak class II cysts may be safely followed with periodic ultrasound imaging. Patients with Bosniak class III and class IV cysts have a significant chance of harboring malignancy, and surgical resection should be considered.
RISK ASSESSMENT OF INCIDENTALLY DETECTED COMPLEX RENAL CYSTS
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APPENDIX Proposed Modification of Bosniak Classification Applied to Renal Cysts in Children Category
Description
I
Round, smooth thin walled cyst. No echogenic foci and enhanced throughout transmission on US. Homogeneous content consistent with water density and absence of enhancement after intravenous contrast on CT scan. Cyst with thin septa with or without minimal/smooth thickening of the cyst wall or septation(s). Calcifications and/or high attenuation detected on CT scan. No evidence of enhancement after contrast administration. No detectable flow by Doppler ultrasound in septations or cyst wall. Presence of thick or irregular septations. Thick/irregular calcifications detected on CT scan. Enhancement of septa or wall may be present after intravenous contrast administration. Detectable flow by Doppler ultrasound may be present inseptations or cyst wall. If category III by ultrasound, contrast axial imaging study should be strongly considered. Cystic mass with thick wall, solid internal components or nodular areas. Enhancement and marked heterogeneity after contrast administration. Detectable flow detected by Doppler ultrasound in cyst wall, septations, nodular component. If category IV by ultrasound, contrast axial imaging study should be strongly considered.
II* III IV
If both US and CT scan or MRI obtained, in case of discrepancy the findings on the contrast enhanced axial imaging study should be favored for classification purposes. Children found to have renal cysts should be considered for evaluation for hereditary cystic renal diseases. * Children with category II cysts should be periodically followed with serial imaging studies until further experience is gained with this classification scheme.
Abbreviations and Acronyms CT MRI RCC US
⫽ ⫽ ⫽ ⫽
computerized tomography magnetic resonance imaging renal cell carcinoma ultrasound
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