Location
Philadelphia, PA
Start Date
8-5-2019 1:00 PM
End Date
8-5-2019 4:00 PM
Description
Introduction:
Renal angiomyolipoma (AML) is one of the most common benign kidney tumors diagnosed. Epithelioid angiomyolipoma (eAML) is a rare variant of these kind of masses that have been classified by the World Health Organization as a potentially malignant mesenchymal neoplasm that metastasizes in one-third of cases. However, conflicting reports have brought in to question the true malignant potential of eAML. Due to eAMLs overall rarity, few studies have characterized this entity. In this study, we further define eAML by describing its genomic alterations and malignant potential by comparing it to a cohort of AML patients at a large-volume cancer center.
Methods:
After IRB approval, a prospectively maintained kidney cancer database was queried for all patients with eAML and AML who underwent nephrectomy between 1994 and 2008 at the Memorial Sloan Kettering Cancer Center. Patients were separated into two histologic groups, those with eAML and those with AML. Clinicopathologic features and genomic alterations were analyzed and then compared between the two cohorts. Descriptive statistics were performed using Mann-Whitney U test, and Chi-squared test, where appropriate, and reported as either median with interquartile range (IQR) or number with percentage. Genomic data was available in 6 eAML and 10 AML patients with mutational burden described as a proportion. Overall survival (OS) and recurrence-free survival (RFS) data were analyzed using Kaplan-Meier method with significance determined by log-rank tests. All statistical analyses were performed using R 3.5.2 with significance set at <0.05.
Results:
Out of 103 patients, 44 had eAML and 59 had AML. Females in their fifth and sixth decade were more commonly diagnosed than males, Table 1. Patients with eAML had larger tumors (p<0.001) and underwent radical nephrectomy more often (p=0.014). Twelve (27.3%) eAML patients metastasized, while no metastases were observed in AML patients. Median RFS for eAML patients was 131 months, and median RFS was not reached in AML patients (p<0.0001), Figure 1. The most frequently mutated gene across both groups expectedly was TSC2, a mutation commonly found in AMLs. The mutational burden in eAMLs was heterogeneous compared to AMLs, with more mutations observed within TP53(43%), RB1 (14%), APC (14%), TERT (14%), ATRX (14%), TSC1 (14%), PIK3CA (14%), GNA11 (14%), and FGFR3 (14%), Figure 2.
Conclusion:
Patients with eAML were observed to have larger tumors and metastasized at a higher rate than patients with AML. A greater frequency of eAML patients underwent radical nephrectomy. The mutational burden across eAML was notable for a more heterogeneity, with largest mutations in TSC2 and TP53 genes. Further investigation into the impact of mutational burden on metastatic potential is warranted.
Embargo Period
5-24-2019
Renal Epithelioid Angiomyolipoma: Genomic Characterization and Malignant Potential
Philadelphia, PA
Introduction:
Renal angiomyolipoma (AML) is one of the most common benign kidney tumors diagnosed. Epithelioid angiomyolipoma (eAML) is a rare variant of these kind of masses that have been classified by the World Health Organization as a potentially malignant mesenchymal neoplasm that metastasizes in one-third of cases. However, conflicting reports have brought in to question the true malignant potential of eAML. Due to eAMLs overall rarity, few studies have characterized this entity. In this study, we further define eAML by describing its genomic alterations and malignant potential by comparing it to a cohort of AML patients at a large-volume cancer center.
Methods:
After IRB approval, a prospectively maintained kidney cancer database was queried for all patients with eAML and AML who underwent nephrectomy between 1994 and 2008 at the Memorial Sloan Kettering Cancer Center. Patients were separated into two histologic groups, those with eAML and those with AML. Clinicopathologic features and genomic alterations were analyzed and then compared between the two cohorts. Descriptive statistics were performed using Mann-Whitney U test, and Chi-squared test, where appropriate, and reported as either median with interquartile range (IQR) or number with percentage. Genomic data was available in 6 eAML and 10 AML patients with mutational burden described as a proportion. Overall survival (OS) and recurrence-free survival (RFS) data were analyzed using Kaplan-Meier method with significance determined by log-rank tests. All statistical analyses were performed using R 3.5.2 with significance set at <0.05.
Results:
Out of 103 patients, 44 had eAML and 59 had AML. Females in their fifth and sixth decade were more commonly diagnosed than males, Table 1. Patients with eAML had larger tumors (p<0.001) and underwent radical nephrectomy more often (p=0.014). Twelve (27.3%) eAML patients metastasized, while no metastases were observed in AML patients. Median RFS for eAML patients was 131 months, and median RFS was not reached in AML patients (p<0.0001), Figure 1. The most frequently mutated gene across both groups expectedly was TSC2, a mutation commonly found in AMLs. The mutational burden in eAMLs was heterogeneous compared to AMLs, with more mutations observed within TP53(43%), RB1 (14%), APC (14%), TERT (14%), ATRX (14%), TSC1 (14%), PIK3CA (14%), GNA11 (14%), and FGFR3 (14%), Figure 2.
Conclusion:
Patients with eAML were observed to have larger tumors and metastasized at a higher rate than patients with AML. A greater frequency of eAML patients underwent radical nephrectomy. The mutational burden across eAML was notable for a more heterogeneity, with largest mutations in TSC2 and TP53 genes. Further investigation into the impact of mutational burden on metastatic potential is warranted.