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Pediatric Imaging |
1 From the Departments of Radiology (K.A.C., L.F.D.), Pediatrics (K.A.C., L.F.D., B.C., J.J.B.), and Nephrology (J.J.B.), Children’s Hospital Medical Center, 3333 Burnet Ave, Cincinnati, OH 45229-3039. Received September 25, 2001; revision requested October 25; final revision received May 8, 2002; accepted June 4. Address correspondence to L.F.D. (e-mail: lane.donnelly@chmcc.org).
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ABSTRACT |
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 TOP ABSTRACT INTRODUCTIONMATERIALS AND METHODS RESULTSDISCUSSIONREFERENCES |
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MATERIALS AND METHODS: One hundred thirty-nine renal imaging studies (113 ultrasonographic scans, 15 computed tomographic scans, and 11 magnetic resonance images) were identified in 59 patients with TSC (mean age, 11.4 years; age range, 3 days to 36 years). There were 31 male and 28 female patients. Angiomyolipomas and cysts were identified and characterized according to the following features: number, unilateral versus bilateral, largest diameter, and change over time. In patients whose initial examination results were normal, the age at onset of lesions was noted. The 
2 test was used to determine whether cysts and angiomyolipomas occurred in different subpopulations.
RESULTS: Angiomyolipomas were identified in 47 (80%) patients and were too numerous to count in 36 (76%), focal in 38 (81%), and bilateral in 42 (89%). The mean largest diameter was 21 mm. Cysts were identified in 28 (47%) patients, 18 (64%) of whom had fewer than five cysts. Cysts were bilateral in 17 (61%) patients. The mean largest diameter was 20 mm. In patients with initially normal examination results, the mean age at presentation was 9.0 years for those with cysts and 9.2 years for those with angiomyolipomas. In 80 follow-up examinations, size and/or number increased in 32 (40%) angiomyolipomas and 21 (26%) cysts. Cysts and angiomyolipomas did not occur in significantly different subpopulations (P = .13).
CONCLUSION: Both angiomyolipomas and cysts occur commonly in pediatric patients with TSC and tend to increase in size and number with increasing age. Angiomyolipomas are more common than cysts and tend to be numerous.
© RSNA, 2002
Index terms: Angiomyolipoma, 81.3141 • Kidney, CT, 81.12111, 81.12112, 81.12115 • Kidney, MR, 81.121411, 81.121416, 81.12143 • Kidney, US, 81.1298 • Kidney neoplasms, 81.311, 81.3141 • Sclerosis, tuberous, 40.1852, 81.1852
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INTRODUCTION |
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TOPABSTRACTINTRODUCTIONMATERIALS AND METHODS RESULTSDISCUSSIONREFERENCES |
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MATERIALS AND METHODS |
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TOPABSTRACTINTRODUCTIONMATERIALS AND METHODS RESULTSDISCUSSIONREFERENCES |
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Imaging Studies
In all patients who underwent US, multiple, static, longitudinal, and axial images were obtained of each kidney with both anterior and posterior approaches. In all patients who underwent CT, images were obtained after the intravenous administration of contrast material. Single or multisection helical CT techniques were used in all cases. In some cases, unenhanced images were also obtained. The section thickness ranged from 5 to 10 mm, depending on patient age and scanner used. All MR images were obtained with 1.5-T units and included at least T1-weighted coronal images, fast spin-echo axial T2-weighted images with fat saturation, and gadolinium-enhanced axial and coronal T1-weighted images with fat saturation. The section thickness ranged from 3 to 5 mm, with a gap of 0.5–1 mm. For all modalities, lesions were measured with electronic calipers. Each imaging study was evaluated by two reviewers (L.F.D., K.A.C), and conclusions were reached with consensus. During the retrospective review of each imaging study, the report generated during the initial clinical interpretation of the images was also reviewed.
Cyst
On US scans, criteria for a cyst included the presence of an anechoic structure with sharply circumscribed smooth walls and enhanced through-transmission. On CT scans, criteria for a cyst included a round well-defined lesion with water attenuation, sharply circumscribed smooth walls, and the lack of enhancement or fat attenuation. On MR images, a cyst was defined as a lesion that demonstrated fluid signal intensity on T1- and T2-weighted images, was round with well-defined borders and sharply circumscribed smooth walls, and demonstrated no enhancement on gadolinium-enhanced images. The number of cysts was categorized as none, fewer than five, between five and 20, and too numerous to count. It was noted whether cysts were unilateral or bilateral. The diameter of the largest cyst was recorded. To calculate the mean maximal diameter and mean number of cysts in patients with multiple examinations, the greatest size and number seen was used. The number of patients with both cysts and angiomyolipomas was recorded. In patients with more than one imaging study, the follow-up images were evaluated for the number of examinations that demonstrated a change in the number or size of cysts. The number of patients who had initial examination findings that were normal followed by examinations with cysts was recorded. In such cases, the age at which the first cyst was diagnosed, the number of cysts, and the maximum diameter of the largest cyst at diagnosis were recorded. The youngest age at which a cyst was identified was also noted. The frequency of changes in the size or number of cysts on follow-up images was also evaluated.
Angiomyolipoma
An angiomyolipoma was defined as the presence of a mass, at least a portion of which demonstrated imaging characteristics consistent with fat. On US scans, fat was considered present when there was hyperechogenicity equal to that of renal sinus fat. On CT scans, fat was considered present when there was attenuation equal to that of subcutaneous and retroperitoneal fat. On MR images, fat was considered present when there was high signal intensity on T1-weighted images that was similar to that of subcutaneous and retroperitoneal fat and demonstrated saturation of signal on fat-saturation images.
The number of angiomyolipomas was categorized as none, fewer than five, between five and 20, and too numerous to count. Angiomyolipomas were classified as unilateral or bilateral. The diameter of the largest angiomyolipoma was recorded. To calculate the mean maximal diameter and mean number of angiomyolipomas in patients with multiple images, the greatest size and number seen was used. The number of patients with both angiomyolipomas and cysts was recorded. Patients with angiomyolipoma were classified as having a well-defined focal mass, a poorly defined infiltrative mass, or both. The lesions were also defined as pedunculated if they extended off the peripheral aspect of the kidney, with three "free" sides of the lesion. The presence of intralesional hemorrhage (defined as areas of high attenuation within the mass on CT scans), extrarenal hemorrhage (defined as ill-defined areas of tissue in the perirenal space), or perceptible aneurysm (well-defined area of enhancement to a similar degree as the aorta on CT scans or MR images) was also noted. In patients with more than one imaging study, the follow-up imaging studies were evaluated for the number of examinations that demonstrated a change in the number or size of angiomyolipomas. The number of cases that demonstrated a change from focal well-defined lesions to diffuse infiltrating lesions was also recorded. The number of patients who had initial examination findings that were normal followed by examinations showing angiomyolipoma was recorded. In such cases, the age at which the first angiomyolipoma was diagnosed, the number of angiomyolipomas, and the maximum diameter of the largest angiomyolipoma at diagnosis were recorded. The youngest age at which an angiomyolipoma was identified was also noted. Follow-up examinations were also evaluated for frequency of change in the size or number of angiomyolipoma.
Statistical Evaluation
The 2 test was used to determine whether cysts and angiomyolipomas occurred in different subpopulations. A P value of less than .05 was considered to indicate a statistically significant difference.
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RESULTS |
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TOPABSTRACTINTRODUCTIONMATERIALS AND METHODS RESULTSDISCUSSIONREFERENCES |
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Cysts
Cysts were demonstrated in 28 patients. Of these 28 patients, 18 had fewer than five cysts (Fig 1), three had five to 20 cysts (Fig 2), and seven had cysts that were too numerous to count (Fig 3). The cysts were unilateral in 11 patients and bilateral in 17. The mean largest cyst diameter was 20 mm. Of the 28 patients with cysts, 20 also had angiomyolipomas. Of the 31 patients without cysts, 27 had angiomyolipomas. There was no significant difference between the proportion of patients with angiomyolipomas when we compared those with and those without cysts (P = .135).
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There were 80 follow-up images. Of those 80 images, 21 (26%) showed a change in the size or number of cysts (Fig 1). Of those 21 images in which a change was demonstrated, 19 showed an increase in both the size and the number of cysts and two showed an increase in the size alone. None of the images demonstrated an increase in the number of cysts alone. Of the 59 images that showed no interval change, 36 were normal and 23 were unchanged abnormal studies.
Angiomyolipoma
Forty-seven patients had angiomyolipoma. Six patients had fewer than five angiomyolipomas and five had five to 20 angiomyolipomas. In 36 patients, the angiomyolipomas were too numerous to count (Figs 4, 5). Angiomyolipomas were unilateral in five patients and bilateral in 42. The mean largest diameter was 21 mm. Of the 47 patients with angiomyolipoma, 20 also had renal cysts.
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Thirteen patients did not demonstrate angiomyolipoma at initial examinations and then developed angiomyolipoma at later examinations (Fig 4). The mean age at which angiomyolipoma was detected in this group was 9.2 years. The mean number of angiomyolipomas per kidney at detection was 3.8, and the mean largest diameter was 6 mm. The youngest age at which an angiomyolipoma was detected was 4 months.
There were 80 follow-up examinations; a change in the size or number of angiomyolipomas was detected in 32 (40%) (Figs 1, 4). Of the 32 images in which a change was demonstrated, 28 showed an increase in both the size and number of angiomyolipomas, one showed an increase in the size of angiomyolipomas alone, and three showed an increase in the number of angiomyolipomas alone. Of the 48 images that did not show interval change, 18 were normal and 30 were unchanged abnormal studies. In no case did angiomyolipomas change from well-defined lesions to diffuse infiltrative lesions.
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DISCUSSION |
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TOPABSTRACTINTRODUCTIONMATERIALS AND METHODS RESULTSDISCUSSIONREFERENCES |
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Angiomyolipomas are hamartomatous lesions consisting of abnormal blood vessels, smooth muscle, and adipose tissue (13). The two genes associated with TSC (TSC1, chromosome 9q34; and TSC2, chromosome 16q13.3) may act as tumor suppressor genes (17). Disturbance in the function of these genes may help explain the presence and progressive growth pattern of angiomyolipomas described in TSC (1,17). It has been reported that up to 80% of adult patients with TSC will develop angiomyolipoma and that these lesions tend to increase in size over time (1–17). In this series, angiomyolipoma was the most common renal lesion, occurring in 47 (80%) patients. These results are similar to the previously reported 75% incidence seen in a population of children with TSC (1). In this series, angiomyolipomas tended to be numerous when present, with 36 (76%) of the 47 patients having angiomyolipomas that were too numerous to count. The lesions also tended to be bilateral, occurring in both kidneys in 42 patients (89%). Our findings support the contention that angiomyolipomas occur in childhood and progress in size during adulthood (1,4,7,18). Forty percent of follow-up studies demonstrated an interval increase in the size and/or number of angiomyolipomas. Because angiomyolipomas are often diffuse in adults, we hypothesized that lesions may progress from multiple focal lesions in young children to diffuse infiltrative lesions in adults. Our data do not support this pattern of growth, as it was seen in none of our patients with multiple imaging examinations.
Angiomyolipomas are clinically important lesions in patients with TSC. The lesions are reported to distort renal architecture and compromise renal function. Renal failure is a well-known long-term complication of TSC (14) and is the leading cause of death in adults with TSC (15). Therefore, monitoring the size of angiomyolipomas with imaging studies may provide prognostic information. Angiomyolipomas are at risk for spontaneous hemorrhage. The lesions contain dysmorphic blood vessels and micro- or macroaneurysms that may spontaneously rupture and bleed (9,11), at times resulting in death. Currently, transarterial embolization is the treatment of choice for hemorrhage of angiomyolipoma because, in contrast to surgery, there is potential sparing of normal renal parenchyma (19). It has been suggested that lesions larger than 4 cm are at greater risk of spontaneous hemorrhage (20). Because of this, larger angiomyolipomas are often treated with prophylactic embolization. Monitoring the degree of angiomyolipoma growth in patients with TSC is important if prophylactic embolization is to be performed in lesions larger than 4 cm. In this series, the mean largest diameter of angiomyolipomas was 2.1 cm, well below 4 cm.
In contrast to angiomyolipomas, renal cysts are rarely symptomatic in patients with TSC (1) unless the patient exhibits the polycystic kidney variety of TSC. The TSC2 gene is adjacent to the polycystic kidney disease (PKD1) gene on the short arm of chromosome 16 (1,17). Contiguous deletions involving both the TSC2 and PKD1 have been associated with the severe polycystic phenotype (21,22). Although renal cysts have been associated with mutations in both TSC1 and TSC2 (23), results of recent studies have implicated that the TSC2 gene product, called tuberin, is essential for polycystin-1 protein trafficking (24). Renal cysts occurred in 47% of our patients with TSC, more than the 17% seen in a previous series of children with TSC (1). In this series, in contrast to angiomyolipomas, renal cysts tended to be fewer in number, with fewer than five occurring in 64% of patients. This is in contrast to the 77% of patients who had angiomyolipomas that were too numerous to count. Cysts occurred bilaterally in 61% of patients, which is much less than the 89% seen with angiomyolipoma. On follow-up images, there was an increase in the size or number of cysts in 21 (26%) of 80 images. This suggests a tendency for cysts to increase in size and number over time. Although there may be separate chromosomal abnormalities that cause patients with TSC to develop cysts and angiomyolipomas, in this series there was not a statistically significant difference between the presence of cysts and the presence of angiomyolipomas (P = .135) to suggest different subpopulations.
There has been little published about the appropriate age to begin imaging surveillance for renal lesions in patients with TSC. Findings from one previous study (1) showed that the average age at which a renal US scan became abnormal was 7.2 years. In this series, the youngest age at which an angiomyolipoma was diagnosed was 4 months, and the youngest age at which a cyst was diagnosed was 16 days. In patients with an initially normal examination, however, the mean age at which an angiomyolipoma was detected was 9.2 years and the mean age at which a cyst was detected was 9.0 years. Considering that the mean maximal diameter of angiomyolipomas in all patients was 2.1 cm—well below the 4 cm suggested size to consider prophylactic embolization—imaging surveillance most likely does not yield clinically important information until late in the 1st decade of life.
This study has limitations. The number of patients and examinations is small. Our study, however, is one of the larger series in which renal lesions in patients with TSC were evaluated (1–20). Our study is also limited by its retrospective nature. The imaging studies were not obtained at set ages. The imaging studies were obtained for clinical indications and not as a scientifically rigorous investigation. In addition, different imaging modalities were used for different scenarios at different time periods and in different patients. At the time the images were obtained, there were not well-defined clinical pathways defining which modalities should be used and when. Such decisions were the result of the preference of the ordering physician and attending radiologist supervising the case. Differences in sensitivities and specificities of the different imaging modalities for depicting cysts and angiomyolipomas are a limitation. In addition, the quality of the imaging techniques has improved during the time course of the collected data. All of these factors make comparison between data over time more difficult. Most of the studies (81%) were US examinations. The exact counting of cysts and angiomyolipomas is less accurate in a retrospective review of static images than in a prospective study.
Even when these limitations are taken into consideration, we believe that useful information not otherwise available was obtained through review of the imaging history of this series of patients with TSC. A prospective collection of data may provide additional and more accurate information. In addition, the purpose of this study was to review the renal imaging findings and changes over time in a large series of young patients with TSC. We did not contribute to the understanding of whether the follow up of these changes makes substantial contributions to the clinical care of patients with TSC.
In conclusion, both angiomyolipomas and cysts occur commonly in pediatric patients with TSC and tend to increase in size and number with increasing age. Angiomyolipomas are more common and tend to be numerous, whereas cysts are typically few in number. When the age of typical occurrence of angiomyolipoma and size criteria for increased risk of hemorrhage are considered, imaging surveillance most likely does not yield clinically important information until late in the 1st decade of life.
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FOOTNOTES |
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Author contributions: Guarantor of integrity of entire study, L.F.D.; study concepts, all authors; study design, L.F.D.; literature research, L.F.D.; clinical studies, L.F.D., K.A.C.; data acquisition, L.F.D., K.A.C.; data analysis/interpretation, all authors; statistical analysis, B.C.; manuscript preparation and definition of intellectual content, L.F.D.; manuscript editing and revision/review, all authors; manuscript final version approval, L.F.D.
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REFERENCES |
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TOPABSTRACTINTRODUCTIONMATERIALS AND METHODS RESULTSDISCUSSIONREFERENCES |
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