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We report a very rare case of clear cell variant of renal cell carcinoma (RCC) in a 3-year-old male child, who presented to us with a left-sided lump in his abdomen. Computed tomography (CT) scan and technetium-99 Dimercapto succinic acid (DMSA) scan revealed a large left renal mass with compromised left renal function. Left-sided nephroureterectomy was done and histopathology demonstrated clear cell carcinoma, possibly translocation-associated RCC (miT family) staged as pT2NxMx. Postoperative CT scans of the thorax and whole abdomen showed secondaries in the lungs and liver. We discussed treatment options in a multidisciplinary tumor board but meanwhile the child succumbed to respiratory failure. [ABSTRACT FROM AUTHOR]

Background: To the authors' knowledge, AREN0321 is the first prospective clinical study of pediatric and adolescent renal cell carcinoma (RCC). Goals of the study included establishing epidemiological, treatment, and outcome data and confirming that patients with completely resected pediatric RCC, including lymph node–positive disease (N1), have a favorable prognosis without adjuvant therapy. Methods: From 2006 to 2012, patients aged <30 years with centrally reviewed pathology of RCC were enrolled prospectively. Results: A total of 68 patients were enrolled (39 of whom were male; median age of 13 years [range, 0.17‐22.1 years]). Stage was classified according to the American Joint Committee on Cancer TNM stage seventh edition as stage I in 26 patients, stage II in 7 patients, stage III in 26 patients, and stage IV in 8 patients, and was not available in 1 patient. Sixty patients underwent resection of all known sites of disease, including 2 patients with stage IV disease. Surgery included radical nephrectomy (53 patients [81.5%]), partial nephrectomy (12 patients [18.5%]), and unknown (3 patients [4.4%]). Histology was TFE‐associated RCC (translocation‐type RCC; tRCC) in 40 patients, RCC not otherwise specified and/or other in 13 patients, papillary RCC in 9 patients, and renal medullary carcinoma (RMC) in 6 patients. Lymph node status was N0 in 21 patients, N1 in 21 patients (tRCC in 15 patients, RMC in 3 patients, papillary RCC in 2 patients, and not otherwise specified and/or other in 1 patient), and Nx in 26 patients. The 4‐year event‐free survival and overall survival rates were 80.2% (95% CI, 69.6%‐90.9%) and 84.8% (95% CI, 75.2%‐94.5%), respectively, overall and 87.5% (95% CI, 68.3%‐100%) and 87.1% (95% CI, 67.6%‐100%), respectively, for the 16 patients with N1M0 disease. Among patients presenting with metastases, 2 of 8 patients (2 of 5 patients with RMC) were alive (1 with disease) at the time of last follow‐up, including 1 patient who was lost to follow‐up (succinate dehydrogenase deficiency). The predominant RCC subtypes associated with mortality were tRCC and RMC. Conclusions: Favorable short‐term outcomes can be achieved without adjuvant therapy in children and adolescents with completely resected RCC, independent of lymph node status. A prospective study of patients with tRCC and RMC with M1 or recurrent disease is needed to optimize treatment. The current prospective clinical trial confirms that favorable outcomes can be achieved without adjuvant therapy in children and adolescents with completely resected renal cell carcinoma, independent of lymph node status. Prospective study of translocation renal cell carcinoma and renal medullary carcinoma with metastatic or recurrent disease is needed to optimize treatment. [ABSTRACT FROM AUTHOR]

To further study the characteristics of renal cell carcinoma (RCC) in young patients and better define their biological features, 46 RCCs of patients younger than 25 years were morphologically and immunohistochemically characterized with follow-up. Loss of heterozygosity (LOH) analysis of the von Hippel—Lindau (VHL) gene region and screening for VHL gene mutations were performed in all tumors. Applying the 2004 WHO classification for RCC, there were 19 Xp11.2 translocation RCCs, 9 clear cell RCCs, 17 papillary RCCs, and 1 unclassified RCC. All 19 Xp11.2 translocation RCCs showed moderate to strong immunoreactivity for TFE3. None had TFEB immunoreactivity. One Xp11.2 translocation RCC had an unreported morphology with empty or ground glass nuclei, occasional nuclear grooves, inconspicuous nucleoli and abundant mucinous material in stroma.VHL gene analysis revealed deletions at 3p25-26 in 1 clear cell RCC and 1 papillary type 2 RCC. The papillary type 2 RCC was also presented with a family history of VHL disease and found a germline mutation G → C on a splicing site at position 553+5. The present case widens the spectrum of microscopic features to be found in VHL-associated RCC. There were no VHL mutations in the remaining 45 RCCs. Statistical analysis of stage and outcome revealed that TFE+ pediatric RCCs were significantly more frequently associated with a higher pTNM pT3/pT4 stage and a poorer outcome than TFE-RCCs (P < .05). Owing to the already known aggressive behavior of these Xp11.2 translocation RCCs, patients with TFE+ pediatric RCCs should benefit from a stricter follow-up. [ABSTRACT FROM PUBLISHER]

Objectives. Renal cell carcinomas (RCCs) in children and adolescents are much rarer than in adults. In this age group, Xp11.2 translocation RCCs were the most common subtype of pediatric RCCs. Information regarding the clinical behavior of pediatric RCCs remains controversial because of their relatively rare incidence. The authors aimed to perform a systematic review and meta-analysis to better define the biological features of pediatric RCCs. Methods. Eligible studies were identified through multiple search strategies. Studies were assessed for quality using the Jadad Quality Scale. Data were collected comparing overall survival (OS), disease-free survival (DFS), and stage in patients with TFE3 + pediatric RCCs and TFE3 − RCCs. Results. A total of 4 studies were included for meta-analysis, and pooled odds ratios (ORs) with 95% confidence interval (CI) were calculated. The meta-analysis outcomes showed that TFE3 + pediatric RCCs were significantly associated with poorer outcomes (OS and DFS) and a higher stage (III/IV) than TFE3 − RCCs (pooled ORs for each group: 4.59 [95% CI = 1.46-14.42] for OS; 5.79 [95% CI = 1.85-18.16] for DFS; and 5.89 [95% CI = 2.23-15.52] for stage). This result was also confirmed by OS and DFS curves (P = .005 and P = .001). Conclusions. Xp11.2 translocation carcinomas appear to have a poorer prognosis than non-Xp11.2 translocation carcinomas in children and young adults. [ABSTRACT FROM PUBLISHER]

Background: Xp11 translocation renal cell carcinoma (RCC) is an RCC subtype affecting 15% of RCC patients <45 years. We analyzed the benefit of targeted therapy [vascular endothelial growth factor receptor (VEGFR)-targeted agents and/or mammalian target of rapamycin (mTOR) inhibitors] in these patients. Patients and methods: Patients with Xp11 translocation/TFE3 fusion gene metastatic RCC who had received targeted therapy were identified. Nuclear TFE3 positivity was confirmed by reviewing pathology slides. Responses according to RECIST criteria, progression-free survival (PFS), and overall survival (OS) were analyzed. Results: Overall, 53 patients were identified; 23 had metastatic disease, and of these 21 had received targeted therapy (median age 34 years). Seven patients achieved an objective response. In first line, median PFS was 8.2 months [95% confidence interval (CI) 2.6-14.7 months] for sunitinib (n = 11) versus 2 months (95% CI 0.8-3.3 months) for cytokines (n = 9) (log-rank P = 0.003). Results for further treatment (second, third, or fourth line) were as follows: all three patients receiving sunitinib had a partial response (median PFS 11 months). Seven of eight patients receiving sorafenib had stable disease (median PFS 6 months). One patient receiving mTOR inhibitors had a partial response and six patients had stable disease. Median OS was 27 months with a 19 months median follow-up. Conclusion: In Xp11 translocation RCC, targeted therapy achieved objective responses and prolonged PFS similar to those reported for clear-cell RCC. [ABSTRACT FROM AUTHOR]

Abstract: Renal cell carcinoma (RCC) comprises about 5% of pediatric renal neoplasms. It has been recognized as a second malignancy in multiple reports. It is generally symptomatic at diagnosis, and most children with RCC present with more locally advanced disease than do adults. Contemporary investigation of pediatric RCC has demonstrated that a large percentage of these tumors bear cytogenetic translocations involving the MiT family of transcription factors. Surgical therapy for these children resembles operative intervention for adult RCC, though debate continues about the precise role of lymph node dissection. There are no adequately powered studies to support conclusions about adjuvant or neoadjuvant chemotherapy for children with RCC. This may be ameliorated by a multi-institutional protocol which is enrolling patients. [Copyright &y& Elsevier]

Alveolar soft part sarcoma and pediatric renal cell carcinoma share a similar chromosomal abnormality, t(X;17)(p11.2;q25). Recently, it has been suggested that the inactivation of DNA mismatch repair genes hMLH1 and hMSH2 may play an additional role in the pathogenesis of alveolar soft part sarcoma. Immunohistochemical expression of the proteins hMLH1 and hMSH2 is indicative of the activation status of the corresponding genes. We performed immunohistochemistry for hMLH1 and hMSH2 in 4 cases of pediatric renal cell carcinomas with Xp11.2 rearrangements. All cases showed nuclear immunoreactivity for both proteins, although the staining was patchy. Our study demonstrates that inactivation of the DNA mismatch repair genes hMLH1 and hMSH2 does not appear to play a role in the tumorigenesis of pediatric renal cell carcinomas with Xp11.2 rearrangements. [ABSTRACT FROM AUTHOR]

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