Characterization of adolescent and pediatric renal cell carcinoma: A report from the Children's Oncology Group study AREN03B2

Abstract

PURPOSE To characterize the epidemiology, histology, radiographic features and surgical approach of pediatric and adolescent renal cell carcinoma (pRCC). PATIENTS AND METHODS pRCC cases prospectively enrolled on the Children's Oncology Group study AREN03B2 underwent central pathology, radiology, surgery and oncology review. RESULTS As of June 2012, of 3250 patients enrolled on AREN03B2, 120 (3.7%) had unilateral RCC (median age 12.9 years, range 1.9-22.1; 52.5% female). Central review classified these as translocation morphology (56), papillary (20), renal medullary carcinoma (13), chromophobe (4), oncocytoma (1), conventional clear cell (1), and RCC not otherwise specified (25). Lymph node (LN) involvement (N+) was found in 35/73 (47.9%) cases for which LN were sampled, including 19/40 (47.5%) with primary tumors < 7cm. Using a size cut-off of 1cm, imaging detection of N+ had a sensitivity of 57.14% [(20/35); 95% CI: 39.35%, 73.68%] and specificity of 94.59% [(35/37); 95% CI: 81.81%, 99.34%]. Distant metastases were present in 23 (19.2%). Initial surgery was radical nephrectomy (RN) in 88 (73.3%), nephron-sparing surgery (NSS) in 18 (15.0%), and biopsy in 14 (11.7%). Patients undergoing NSS compared to RN were less likely to have LNs sampled (6/18 (33.3%) vs. 65/88 (73.9%), p-value = 0.002). CONCLUSIONS Translocation RCC is the most common form of pediatric and adolescent RCC. Nodal disease is common and seen with small primary tumors. Imaging has a high specificity but relatively low sensitivity for detection of such lymph node disease. Failure to sample LNs results in incomplete staging and potentially inadequate disease control for younger RCC patients.

The classification of pediatric and young adult renal cell carcinomas registered on the children's oncology group (COG) protocol AREN03B2 after focused genetic testing

“…5–8 Historically, approximately 16–24% of pediatric RCCs remain unclassified, 5,6 preventing clear diagnostic and therapeutic strategies. Prior to the Children’s Oncology Group (COG) AREN03B2 protocol, 3 no prospective studies had been performed on pediatric RCC, and knowledge of their pathological and molecular spectrum, biological features and clinical behavior remains limited. To address this, our goal is to analyze patients diagnosed with RCC enrolled in the AREN03B2 COG protocol and to apply focused genetic testing in order to clarify their classification.…”

TFE3‐positive renal cell carcinoma occurring in three children with dysfunctional kidneys on immunosuppression

“…For instance, in contrast to adult RCC there is a relatively high rate of pediatric RCC occurring as a secondary event to underlying renal dysfunction, cystic kidney disease, or prior exposure to chemotherapy or immunomodulatory therapy . Further, while clear cell morphology predominates in adult RCC, the predominant form in children is translocation morphology RCC (tRCC), accounting for 47% of childhood RCC, and characterized by translocations involving Xp11.2, the TFE3 gene locus . Locoregional and metastatic disease is common, with 62.5% of tRCC presenting with stage III‐IV disease .…”

“…Compared to adults, children are more likely to present with lymph node involvement, even with small primary tumors (<7 cm) . While children with local lymph node involvement (N+), without distant metastases (M0), in general, have a more favorable prognosis than adults, overall survival in pediatric RCC by modified Robson stage remains suboptimal: 92.5% (stage I), 84.6% (stage II), 72.7% (stage III), and 12.7% (stage IV) . The grave prognosis for the majority of children who present with advanced disease highlights the need to identify children at earlier stages of disease to optimize survival.…”

Imaging of renal medullary carcinoma in children and young adults: a report from the Children’s Oncology Group

“…13 of these cases have been included in a prior report on pediatric renal cell carcinoma, but the subset of patients renal medullary carcinoma was not specifically characterized in this publication [11]. In the current cohort of 26 cases, abdominal imaging was performed with CT in 23 cases, both CT and MR in 2 cases and with MR alone in 1 case.…”