BACKGROUND.: Pediatric renal cell carcinoma (RCC) is clinically distinct from adult RCC.1 Characterization of the unique biological and clinical features of pediatric RCC are required.METHODS.: A retrospective review and biological analysis of all RCC cases presenting to Cincinnati Children's Hospital Medical Center (CCHMC) in the last 30 years was undertaken. Cases were classified according to the recent World Heath Organization morphologic classification and according to TFE3/TFEB status. A literature review of pediatric TFE+ cases was performed.RESULTS.: Eleven cases of RCC with clinical data were identified in our institutional review as follows: 6 clear cell, 2 papillary, 2 translocation, and 1 sarcomatoid. Upon reanalysis, 1 papillary and 1 sarcomatoid were confirmed, 1 case was “unclassified”, and 8 of 11 (72.7%) had features consistent with translocation morphology. Of these 8, all demonstrated immunoreactivity for TFE3 (7 patients) or TFEB (1 patient) protein. In 3 cases, cytogenetics was available, each demonstrating confirmatory MiTF/TFE translocations. Seven of 8 TFE+ RCC patients presented with TNM Stage III/IV disease. Literature analysis confirmed a significant increase in advanced stage presentation in pediatric TFE+ RCC compared with TFE− RCC. Fourteen of fifteen (93.3%) patients with TFE+ stage III/IV RCC due to lymph node spread (N+ M₀) remain disease free with a median and mean follow‐up of 4.4 and 6.3 years, respectively (range, 0.3‐15.5).CONCLUSIONS.: Translocation morphology RCC is the predominant form of pediatric RCC, associated with an advanced stage at presentation. Patients with TFE+ N+ M₀ RCC maintain a favorable short‐term prognosis after surgery alone. Young RCC patients should be screened for translocation morphology, and the screening information should be considered when debating adjuvant therapy. Cancer 2008. © 2008 American Cancer Society.

BACKGROUND: The current study was conducted to characterize the epidemiology, histology, and radiographic features of as well as the surgical approach to pediatric and adolescent renal cell carcinoma (pRCC).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, 120 of a total of 3250 patients enrolled on AREN03B2 (3.7%) were found to have unilateral RCC (median age, 12.9 years [range, 1.9‐22.1 years]; 52.5% were female). Central review classified these as translocation morphology (56 patients), papillary (20 patients), renal medullary carcinoma (13 patients), chromophobe (4 patients), oncocytoma (1 patient), conventional clear cell (1 patient), and RCC not otherwise specified (25 patients). Lymph node (LN) involvement (N+) was found in 35 of 73 cases (47.9%) for which LNs were sampled, including 19 of 40 cases with primary tumors measuring <7 cm (47.5%). Using a size cutoff of 1 cm, imaging detection of LN involvement had a sensitivity of 57.14% (20 of 35 cases; 95% CI, 39.35%‐73.68%) and a specificity of 94.59% (35 of 37 cases; 95% CI, 81.81%‐99.34%). Distant metastases were present in 23 cases (19.2%). Initial surgery was radical nephrectomy in 88 patients (73.3%), nephron‐sparing surgery in 18 patients (15.0%), and biopsy in 14 patients (11.7%). Compared with patients undergoing radical nephrectomy, those treated with nephron‐sparing surgery were less likely to have LNs sampled (6 of 18 patients [33.3%] vs 65 of 88 patients [73.9%]; P = .002).CONCLUSIONS: Translocation RCC is the most common form of pediatric and adolescent RCC. Lymph node disease is common and observed among patients with small primary tumors. Imaging has a high specificity but relatively low sensitivity for the detection of such lymph node disease. Failure to sample LNs results in incomplete staging and potentially inadequate disease control for younger patients with RCC. Cancer 2015;121:2457–2464. © 2015 American Cancer Society.

BACKGROUND: Renal cell carcinomas (RCCs) are rare in young patients. Knowledge of their pathologic and molecular spectrum remains limited, and no prospective studies have been performed to date in this population. This study analyzes patients diagnosed with RCC who were prospectively enrolled in the AREN03B2 Children's Oncology Group (COG). The objective was to classify these tumors with the aid of focused genetic testing and to characterize their features. METHODS: All tumors registered as RCC by central review were retrospectively re‐reviewed and underwent additional ancillary studies. Tumors were classified according to the 2016 World Health Organization classification system when possible. RESULTS: In total, 212 tumors were identified, and these were classified as microphthalmia transcription factor (MiT) translocation RCC (MiT‐RCC) (41.5%), papillary RCC (16.5%), renal medullary carcinoma (12.3%), chromophobe RCC (6.6%), clear cell RCC (3.3%), fumarate hydratase‐deficient RCC (1.4%), and succinate dehydrogenase‐deficient RCC (0.5%). Other subtypes included tuberous sclerosis‐associated RCC (4.2%), anaplastic lymphoma kinase ( ALK )‐rearranged RCC (3.8%), thyroid‐like RCC (1.4%), myoepithelial carcinoma (0.9%), and unclassified (7.5%). MiT‐RCCs were classified as either transcription factor E3 ( TFE3 ) (93.2%) or EB ( TFEB ) (6.8%) translocations, and characterization of fusion partners was possible in most tumors. CONCLUSIONS: The current study delineates the frequency of distinct RCC subtypes in a large prospective series of young patients and contributes knowledge to the diagnostic, clinical, and genetic features of MiT‐RCC, the most common subtype among this age group. The identification of rare subtypes expands the spectrum of RCC in young patients, supporting the need for a thorough diagnostic workup. These studies may aid in the introduction of specific therapies for different RCC subtypes in the future. Cancer 2018 . © 2018 American Cancer Society .

In high-income countries, the overall survival of children with Wilms tumors (WT) is ~90%. However, overall, 15% of patients experience tumor recurrence. The adverse prognostic factors currently used for risk stratification (advanced stage, high risk histology, and combined loss of heterozygosity at 1p and 16q in chemotherapy-naïve WTs) are present in only one third of these cases, and the significance of these factors is prone to change with advancing knowledge and improved treatment regimens. Therefore, we present a comprehensive, updated overview of the published prognostic variables for WT recurrence, ranging from patient-, tumor- and treatment-related characteristics to geographic and socioeconomic factors. Improved first-line treatment regimens based on clinicopathological characteristics and advancing knowledge on copy number variations unveil the importance of further investigating the significance of biological markers for WT recurrence in international collaborations.

The most common primary malignant liver tumor of childhood, hepatoblastoma has increased in incidence over the last 30 years, but little is still known about its pathogenesis. Discoveries in molecular biology provide clues but have yet to define targeted therapies. Disease-free survival varies according to stage, but is greater than 90% in favorable risk populations, in part due to improvements in chemotherapeutic regimens, surgical resection, and earlier referral to liver transplant centers. This article aims to highlight the principles of disease that guide current treatment algorithms. Surgical treatment, especially orthotopic liver transplantation, will also be emphasized in the context of the current Children’s Oncology Group international study of pediatric liver cancer (AHEP-1531).