We were pleased to receive Dr. Renshaw's comments regarding our article on pediatric renal cell carcinoma (RCC).1 Dr. Renshaw speculates that children with RCC and local lymph node involvement had favorable outcomes because many of the tumors we described were translocation-associated RCC rather than clear cell RCC. To evaluate this important point, we asked an experienced pathologist (J.D.K.) to review the tumor histology of the 13 patients presented in our series. It is interesting to note that 10 of 12 patients with available slides, including 3 of 4 patients with local lymph node involvement, had histology consistent with translocation-associated RCC. This observation supports Dr. Renshaw's speculation and bolsters our premise that distinct biology explains the favorable outcomes in children with lymph node-positive RCC.
Although most tumors in our series had the appearance of translocation-associated RCC, other series found that a minority of pediatric RCC cases are translocation-associated. Recently, Bruder et al.2 employed the current World Health Organization classification3 to demonstrate that 20% (8 of 40 cases) of pediatric RCC cases are translocation-associated RCC. This is consistent with the frequency of “voluminous” tumors reported by Dr. Renshaw (4 of 24 cases; 17%).4 Given the infrequency of translocation-associated RCC in these series, we believe that other biologic features contributed to the clinical phenotype described in our article.1
Dr. Renshaw notes that when translocation-associated RCC is accounted for, clear cell RCC becomes increasingly rare in patients without von Hippel-Lindau disease (VHL). However, the series by Bruder et al. included six cases of clear cell RCC, although none of these cases demonstrated loss of heterozygosity at 3p or mutations in the VHL gene.2 As discussed in our article, reports of clear cell RCC in VHL patients are exceedingly and surprisingly rare in individuals age < 21 years.1
An upcoming Children's Oncology Group study of pediatric RCC will use centralized pathology review to further establish the frequency of RCC subtypes in children and adolescents. Histology and translocation status will be correlated prospectively with clinical parameters, including outcome. The study also will test the hypothesis that children with local lymph node-positive RCC in the absence of distant metastases have a favorable prognosis with surgery alone.