Clear Cell Sarcoma Of The Kidney Research Articles

Treatment and outcomes of clear cell sarcoma of the kidney: A report from the Children's Oncology Group studies AREN0321 and AREN03B2.

On the fifth National Wilms Tumor Study, treatment for clear cell sarcoma of the kidney (CCSK) included combined vincristine, doxorubicin, cyclophosphamide, and etoposide (regimen I) plus radiation therapy (RT), yielding 5-year event-free survival (EFS) rates of 100%, 88%, 73%, and 29% for patients who had with stage I, II, III, and IV disease, respectively. In the Children's Oncology Group study AREN0321 of risk-adapted therapy, RT was omitted for stage I disease if lymph nodes were sampled, and carboplatin was added for stage IV disease (regimen UH-1). Patients who had stage II/III disease received regimen I with RT. Four-year EFS was analyzed for patients enrolled on AREN0321 and onthose enrolled on AREN03B2 who received AREN0321 stage-appropriate chemotherapy. Eighty-two patients with CCSK enrolled on AREN0321, 50 enrolled on AREN03B2 only. The 4-year EFS rate was 82.7% (95% confidence interval [CI], 74.8%-91.4%) for AREN0321 and 89.6% (95% CI, 81.3%-98.7%) for AREN03B2 only (p=.28). When combining studies, the 4-year EFS rates for patients who had stage I (n=10), II (n=47), III (n=65), and IV (n=10) disease were 90% (95% CI, 73.2%-100.0%), 93.4% (95% CI, 86.4%-100.0%), 82.8% (95% CI, 74.1%-92.6%), and 58.3% (95% CI, 34%-100.0%), respectively. There were no local recurrences among seven patients with stage I disease who were treated without RT. One stage I recurrence occurred in the brain, which was the most common site of relapse overall. Among patients with local stage III tumors, neither initial procedure type, margin status, nor lymph node involvement were prognostic. Patients with stage I CCSK had excellent outcomes without local recurrences when treated without RT. Patients with stage IV disease appeared to benefit from a carboplatin-containing regimen, although their outcomes remained unsatisfactory. Further research is needed to improve outcomes for patients withadvanced-stage disease (ClinicalTrials.gov identifiers NCT00335556 and NCT00898365).

CT radiomics to differentiate between Wilms tumor and clear cell sarcoma of the kidney in children

BackgroundTo investigate the role of CT radiomics in distinguishing Wilms tumor (WT) from clear cell sarcoma of the kidney (CCSK) in pediatric patients.MethodsWe retrospectively enrolled 83 cases of WT and 33 cases of CCSK. These cases were randomly stratified into a training set (n = 81) and a test set (n = 35). Several imaging features from the nephrographic phase were analyzed, including the maximum tumor diameter, the ratio of the maximum CT value of the tumor solid portion to the mean CT value of the contralateral renal vein (CTmax/CT renal vein), and the presence of dilated peritumoral cysts. Radiomics features from corticomedullary phase were extracted, selected, and subsequently integrated into a logistic regression model. We evaluated the model's performance using the area under the curve (AUC), 95% confidence interval (CI), and accuracy.ResultsIn the training set, there were statistically significant differences in the maximum tumor diameter (P = 0.021) and the presence of dilated peritumoral cysts (P = 0.005) between WT and CCSK, whereas in the test set, no statistically significant differences were observed (P > 0.05). The radiomics model, constructed using four radiomics features, demonstrated strong performance in the training set with an AUC of 0.889 (95% CI: 0.811–0.967) and an accuracy of 0.864. Upon evaluation using fivefold cross-validation in the training set, the AUC remained high at 0.863 (95% CI: 0.774–0.952), with an accuracy of 0.852. In the test set, the radiomics model achieved an AUC of 0.792 (95% CI: 0.616–0.968) and an accuracy of 0.857.ConclusionCT radiomics proves to be diagnostically valuable for distinguishing between WT and CCSK in pediatric cases.

Clear Cell Sarcoma of the Kidney Mimicking Wilms Tumor in a Child

Abstract Background: Clear cell sarcoma of the kidney (CCSK) is a rare malignant renal tumor in children, the diagnosis of which is a challenge due to nonspecific clinical and radiological presentation. Clinical Description: A 4-year-old boy presented with a 2-day history of abdominal pain and hematuria, without oliguria, pallor, or hypertension. His renal function was within the normal limits. An initial ultrasound of the abdomen showed an iso- to hyperechoic lesion in the mid pole of the right kidney causing compression of the pelvicalyceal system. A computed tomography scan revealed a relatively heterogenous hypoenhancing mass lesion with a “claw sign” suggestive of solid renal neoplasm with doubtful infiltration of quadratus lumborum and psoas muscle, most probably Wilms tumor. Management and Outcome: The child was started on neoadjuvant chemotherapy with vincristine, actinomycin D, and doxorubicin according to the National Wilms Tumor Study protocol (NWTS) suspecting stage III Wilms tumor. After six cycles, surgical resection of the tumor was done, which on histopathological examination, was consistent with CSSK. The child received postoperative flank irradiation. Chemotherapy was escalated to Regimen I (vincristine, doxorubicin, cyclophosphamide, and etoposide) for 24 weeks. The child improved and was free of metastasis till the last follow-up. Conclusion: Before a renal tumor is labeled as Wilms tumor, all efforts must be made to rule out the more sinister, but similar appearing CCSK, so that an effective and aggressive treatment regimen can be administered timely.

Diagnostic MRI characteristics of pediatric clear cell sarcoma of the kidney and rhabdoid tumor of the kidney: A retrospective multi-center SIOP-RTSG Radiology panel study

IntroductionClear cell sarcoma of the kidney (CCSK) and rhabdoid tumor of the kidney (RTK) are rare malignant pediatric renal tumors, both accounting for 1–5% of diagnoses. Within the International Society of Pediatric Oncology-Renal Tumor Study Group (SIOP-RTSG) protocols diagnostic invasive procedures to determine histology are discouraged. MRI has become the preferred imaging modality, however, non-invasive discrimination of CCSK and RTK remains challenging. Therefore, this study aims to identify diagnostic MRI-characteristics of CCSK and RTK, in the largest series of patients to date. Material and methodsFive SIOP-RTSG national review radiologists identified national diagnostic MRIs of histologically proven CCSKs and RTKs. Scan-protocols were based on MRI-guidelines following SIOP-RTSG protocols. Radiologists assessed their national cases using a validated case report form (CRF). ResultsRetrospectively, 59 patients were identified (n = 38 CCSK, n = 21 RTK). CCSKs showed a high median volume (576 cm3, range 54–4414), which was lower for RTKs (290 cm3, range 20–761) (p = 0.006 *10-3). Fifty-two percent (11/21) of RTK-patients showed disease at other locations, predominantly the lungs and brain, compared to 8% of CCSK-patients (3/38). RTKs showed ill-defined margins (12/21, 57%) and infiltrative growth pattern (13/21, 62%). CCSKs appeared hyper-intense on T2-weighted imaging (27/38, 71%) with a characteristics band-like enhancement (13/38, 34%), whereas RTK cases often showed T2-weighted hypo-intensity (11/21, 52%). The overall mean ADC-value for CCSK was 1.11 * 10-3 mm2/s (range 0.57–2.07 *10-3 mm2/s), and 0.72 * 10-3 mm2/s (range 0.53–0.90 *10-3 mm2/s) for RTK. ConclusionsThis retrospective study suggests a small size, T2-weighted hypo-intensity and an aggressive growth pattern may be characteristic for RTK. CCSK often showed a typical band-like enhancement pattern with relatively high ADC-values. Identified MRI-characteristics may be used in future studies focusing on validation and discrimination from especially WT, aiming for an early non-invasive diagnosis.

Böbreğin Berrak Hücreli Sarkomu: Oldukça Nadir Bir Olgu Sunumu

Clear cell sarcoma of the kidney (CCSK) is one of the most common malignant renal neoplasms in childhood, although it is quite rare. Its incidence peaks around the age of 3 and it is twice as common in males. We present a rare case of CCSK showing a rare histopathological pattern in terms of age and gender. A 7-month-old female patient presented with complaints of vomiting, abdominal swelling, and diarrhea. Imaging analysis revealed a mass in the right kidney, and right radical nephrectomy was performed, considering Wilms tumor (WT). There was a solid gray-white mass that completely filled the kidney, with a maximum dimension of 8.5 cm, macroscopically. The samples obtained showed intratubular structures within the tumor and kidney parenchyma in limited areas at the periphery. The tumor had a normochromic monotonous nucleus with occasional clear cytoplasm and mostly exhibited a palisade-like arrangement pattern. In the differential diagnosis, with blastemal WT and Ewing sarcoma being the primary considerations, the positivity of CyclinD1 markers, negativity of other markers, and morphological characteristics were evaluated in favor of CCSK with a palisaded Schwannian pattern. The patient was put on an intensive chemotherapy process, but was lost after relaps at weet 24. CCSK is seen in a similar age group as WT but is distinguished by its rarity and relatively worse prognosis. Histopathologically, it most commonly presents in a myxoid pattern and least commonly in anaplastic pattern. The palisaded schwannian type seen in our case is recorded at a rate of 11%. No spesific diagnostic marker has been identified immunohistochemically, but the overexpression of markers such as CyclinD1, BCOR, and EZH2 is reported to be helpful in diagnosis. Due to its high metastatic potential and limited treatment options, further research is needed to understand the molecular nature of the disease.

Children's Oncology Group's 2023 blueprint for research: Renal tumors.

Every year, approximately 600 infants, children, and adolescents are diagnosed with renal cancer in the United States. In addition to Wilms tumor (WT), which accounts for about 80% of all pediatric renal cancers, clear cell sarcoma of the kidney, renal cell carcinoma, malignant rhabdoid tumor, as well as more rare cancers (other sarcomas, rare carcinomas, lymphoma) and benign tumors can originate within the kidney. WT itself can be divided into favorable histology (FHWT), with a 5-year overall survival (OS) exceeding 90%, and anaplastic histology, with 4-year OS of 73.7%. Outcomes of the other pediatric renal cancers include clear cell sarcoma (5-year OS: 90%), malignant rhabdoid tumor (5-year OS: 10% for stages 3 and 4), and renal cell carcinoma (4-year OS: 84.8%). Recent clinical trials have identified novel biological prognostic markers for FHWT, and a series of Children's Oncology Group (COG) trials have demonstrated improving outcomes with therapy modification, and opportunities for further care refinement.

Tolerability of ifosfamide-containing regimen in patients with high-risk renal and INI-1-deficient tumors.

Outcomes for children with high-risk renal (HRR) and INI-1-deficient (INI-) tumors are unacceptably poor. Concerns about excessive toxicity-as many are infants and/or undergo nephrectomy-have resulted in decreased chemotherapy dosing and omission of the nephrotoxic drug ifosfamide in collaborative group studies. As cause of death for children with these cancers remains overwhelmingly more from progressive disease rather than treatment toxicity, we examined the tolerability of an intensive ifosfamide-containing regimen. Retrospective review of children with HRR/INI- tumors treated at a single institution with vincristine, doxorubicin, cyclophosphamide alternating with ifosfamide, carboplatin, etoposide (VDC-ICE) from 2006-2016. The primary outcome was regimen tolerability, including kidney injury and grade 3-5 nonhematologic toxicities. Fourteen patients with a median age of 1.7years (range: 0.1-10.5) treated with VDC-ICE were identified. Diagnosis included malignant rhabdoid tumor (n=9) (primary renal [n=2]); diffuse anaplastic Wilms tumor (n=3); clear cell sarcoma of the kidney (n=1); and anaplastic chordoma (n=1). All children with primary renal tumors (43%) underwent complete (n=5) or partial nephrectomy (n=1) before chemotherapy. Nine (64%) completed all intended cycles of chemotherapy; n=5 (36%) did not due to disease progression. Unplanned hospitalizations occurred in 13 (93%) patients, most commonly for febrile neutropenia. No patient experienced severe organ toxicity, diminished renal function, treatment discontinuation due to toxicities, or treatment-related death. In children with HRR/INI- tumors, VDC-ICE chemotherapy was well-tolerated without excessive toxicities, even amongst young patients with solitary kidneys. Concerns about toxicity should not preclude an intensive ifosfamide-containing regimen from use in future trials in this population.

Clinical relevance of BCOR internal tandem duplication and TP53 aberration in clear cell sarcoma of the kidney.

Clear cell sarcoma of the kidney (CCSK) is the second most common pediatric renal malignancy, characterized by BCOR internal tandem duplication (ITD), YWHAE rearrangement, BCOR-CCNB3 fusion, and lack of other consistent structural alteration. We accidentally identified TP53 deletion in CCSK, which was often associated with adverse clinical outcomes. In this study, we assessed the incidence as well as the clinical relevance of these molecules in CCSK patients. BCOR ITD, YWHAE rearrangement, BCOR-CCNB3 fusion and TP53 status were examined by polymerase chain reaction, fluorescence in situ hybridization, or Sanger sequencing in a cohort of 39 patients with CCSK. Among them, 34 cases (87.18%) had BCOR ITD, 1 (2.56%) had YWHAE rearrangement, and 1 (2.56%) had BCOR-CCNB3 gene fusion. The remaining 3 (7.69%) harbored none of these aberrations. BCOR ITD, YWHAE rearrangement and BCOR-CCNB3 were mutually exclusive. Furthermore, 25.64% of the cohort acquired TP53 aberration (10/39, 3 with both copy number deletion and point mutation, 6 with deletion only, and 1 with mutation only), all of which were associated with BCOR ITD. Patients with or without BCOR ITD or TP53 aberration did not differ in demographic characteristics such as sex, onset age, or tumor stage at diagnosis. However, the overall survival rates and progression-free survival rates of BCOR ITD or TP53 deletion groups showed obvious downward trends, albeit not all reaching statistical significance. Patients with both BCOR ITD and TP53 deletion had the poorest prognosis.

Molecular Signature of Biological Aggressiveness in Clear Cell Sarcoma of the Kidney (CCSK)

Clear cell sarcoma of the kidney (CCSK) is a rare pediatric renal tumor with a worse prognosis than Wilms' tumor. Although recently, BCOR internal tandem duplication (ITD) has been found as a driver mutation in more than 80% of cases, a deep molecular characterization of this tumor is still lacking, as well as its correlation with the clinical course. The aim of this study was to investigate the differential molecular signature between metastatic and localized BCOR-ITD-positive CCSK at diagnosis. Whole-exome sequencing (WES) and whole-transcriptome sequencing (WTS) were performed on six localized and three metastatic BCOR-ITD-positive CCSKs, confirming that this tumor carries a low mutational burden. No significant recurrences of somatic or germline mutations other than BCOR-ITD were identified among the evaluated samples. Supervised analysis of gene expression data showed enrichment of hundreds of genes, with a significant overrepresentation of the MAPK signaling pathway in metastatic cases (p < 0.0001). Within the molecular signature of metastatic CCSK, five genes were highly and significantly over-expressed: FGF3, VEGFA, SPP1, ADM, and JUND. The role of FGF3 in the acquisition of a more aggressive phenotype was investigated in a cell model system obtained by introducing the ITD into the last exon of BCOR by Crispr/Cas9 gene editing of the HEK-293 cell line. Treatment with FGF3 of BCOR-ITD HEK-293 cell line induced a significant increase in cell migration versus both untreated and scramble cell clone. The identification of over-expressed genes in metastatic CCSKs, with a particular focus on FGF3, could offer new prognostic and therapeutic targets in more aggressive cases.

Cytoreductive surgery and hyperthermic intraperitoneal chemotherapy for peritoneal malignant tumors in children: Initial experience in a single institution.

Peritoneal malignant tumors in children are rare but commonly associated with disease progression and poor outcome. The successful treatment experience of cytoreductive surgery (CRS) and hyperthermic intraperitoneal chemotherapy (HIPEC) in adult peritoneal carcinoma has been applied to pediatric peritoneal malignancy in recent years. However, patients with desmoplastic small round cell tumor (DSRCT) accounted for the majority of patients treated with CRS and HIPEC in previous studies. The role of CRS and HIPEC remains controversial due to the rarity of the disease and the limited sample size of studies. Additionally, the cases using CRS and HIPEC except DSRCT were mainly small case reports with unclear outcomes. We present our experience in the treatment of pediatric peritoneal malignancies using CRS and HIPEC, with more emphasis on the safety, feasibility, and short-term outcome. A retrospective query from December 2019 to February 2022 identified 19 children with peritoneal malignancies who underwent CRS and HIPEC in our institution. Clinical characteristics, therapies, and outcomes were summarized and analyzed. The median age of the patients was 6.4 years (range, 0.7-13.9 years). The histologic types included rhabdomyosarcoma (7), Wilms tumor (2), clear cell sarcoma of the kidney (2), undifferentiated sarcoma (2), immature teratoma (1), peritoneal serous carcinoma (1), malignant rhabdoid of the kidney (1), malignant germ cell tumor (1), neuroblastoma (1), and epithelioid inflammatory myofibroblast sarcoma (1). Seven patients underwent initial operation, and 12 patients received reoperation for tumor recurrence. The median peritoneal carcinomatosis index was 5 (range, 2-21). There were no perioperative deaths or life-threatening complications of CRS and HIPEC. Two patients had grade 3 complications of wound infection and wound dehiscence. With a median follow-up time of 14 months (range, 1.5-31 months), 14 patients were alive, and 5 died of tumor recurrence. Of the 14 patients who were alive, 2 relapsed after CRS and HIPEC and then received radiotherapy and molecular-targeted therapy or chemotherapy. CRS and HIPEC are safe and feasible in children, without increasing serious complications in the peri- and postoperative periods. The complication is acceptable. The short-term outcome shows possible effectiveness in pediatric peritoneal malignant tumors. The long-term effectiveness needs to be verified by additional cases and long-term follow-ups.

Pediatric BCOR-Altered Tumors From Soft Tissue/Kidney Display Specific DNA Methylation Profiles

In the pediatric population, BCL6-correpresor gene (BCOR)–upregulated tumors include primitive myxoid mesenchymal tumors/undifferentiated sarcomas (PMMTI/UND), clear cell sarcomas of the kidney (CCSK), and high-grade neuroepithelial tumors (HG-NET). We investigated DNA methylation (DNAm) and copy number variation (CNV) profiling in these tumors (N = 34) using an Illumina EPIC BeadChip to better define the potential use of these tools to confirm diagnosis and predict outcomes. Twenty-seven tumors from 25 patients (age range, 0-10 years), showed molecular confirmation of genetic abnormalities as follows: BCOR internal tandem duplication in 14 PMMTI/UND, 8 CCSK, and 3 HG-NET and YWHAE fusions in 2 PMMTI/UND. The remaining 7 cases lacking informative molecular data were analyzed by immunophenotyping and were included in the study as a training cohort, clearly separated from the main study group. These were 4 PMMTI, 1 HG-NET, and 1 CCSK in which poor RNA preservation precluded the confirmation of BCOR rearrangements and 1 CCSK in which no rearrangements were found. DNAm data were compared with those of brain tumor and/or sarcoma classifier. Differentially methylated regions (DMRs) were analyzed in the 3 groups. Twenty-two cases of the 24 molecularly confirmed PMMTI/UND and CCSK and 3 of 6 of those with only immunophenotyping were classified within the methylation class “BCOR-altered sarcoma family” with optimal calibrated scores. PMMTI/UND and CCSK showed similar methylation profiles, whereas thousands of DMRs and significantly enriched pathways were evident between soft tissue/kidney tumors and HG-NET. The CNV analysis showed an overall flat profile in 19 of the 31 evaluable tumors (8/10 CCSK; 9/18 PMMTI/UND; 2/4 HG-NET). The most frequent CNVs were 1q gain and 9p and 10q loss. Follow-up time data were available for 20 patients: ≥2 CNV significantly correlated with a worse overall survival rate. In conclusion, soft tissue and kidney BCOR sarcomas matched with BCOR-altered sarcoma methylation class, whereas those from the brain matched with the central nervous system tumor classifier HG-NET BCOR, supporting the notion that DNAm profiling is an informative diagnostic tool. CNV alterations were associated with a more aggressive clinical behavior.

Hypermethylation of RASSF1A gene in pediatric rhabdoid tumor of the kidney and clear cell sarcoma of the kidney.

Among pediatric renal tumors, rhabdoid tumor of the kidney (RTK) and clear cell sarcoma of the kidney (CCSK) are rare and associated with an unfavorable prognosis, while congenital mesoblastic nephroma (CMN) is associated with a good prognosis. Methylation of the Ras association domain-containing protein 1 isoform A (RASSF1A) promoter has been reported to correlate with a poor prognosis in patients with Wilms tumors, while its methylation status is unclear in other types of pediatric renal tumors. DNA methylation of the RASSF1A promoter in several pediatric renal tumors was analyzed with pyrosequencing. In order to clarify the correlation between expression of RASSF1A and DNA methylation of its promoter, the RTK cell line was treated with 5-Aza-2'-deoxycytidine (5-Aza-dC). RASSF1A was overexpressed in the RTK cell line to evaluate its functional effects. Quantitative methylation analysis demonstrated hypermethylation in the RASSF1A promoter region in RTK and CCSK, but not CMN. The 5-Aza-dC treatment induced demethylation of the RASSF1A promoter as well as increased RASSF1A mRNA expression. The transduction of RASSF1A has an effect on the suppression of viability and proliferation of RTK cells. DNA methylation-mediated deficiency of RASSF1A might be involved in the development and aggressiveness of some pediatric renal tumors and correlated with a poor prognosis.

Incidence and survival of paediatric renal tumours in the Netherlands between 1990 and 2014

BackgroundThis population-based study is the first to provide a detailed analysis of trends in incidence and survival of children and adolescents diagnosed with renal malignancies in the Netherlands. MethodsData on all renal malignancies diagnosed in paediatric patients (0–18 years) between 1990 and 2014 [N = 648, 92% Wilms tumour (WT)] were extracted from the Netherlands Cancer Registry. Five-year overall survival (OS) was estimated using the actuarial method. Time trends in incidence were assessed by calculating average annual percentage change. A parametric survival model was used to compare the multivariable-adjusted risk of dying from WT between two diagnostic periods. ResultsThe incidence was 8 per million person-years and was constant over time (average annual percentage change -0.8%, p = 0.29). Patients with WT had a favourable outcome in both time periods; 5-year OS was 88% in 1990–2001 and 91% in 2002–2014. Multivariable analysis showed that the risk of dying from WT was not significantly decreased in the latest period (hazard ratio, 95% CI: 0.7, 0.4–1.3). Five-year OS decreased with increasing disease stage, ranging from 95 to 100% for stage I-II and about 80% for stage III–IV to 74% for bilateral disease. Five-year OS were 81% for renal cell carcinoma, 77% for clear cell sarcoma of the kidney and 20% for malignant rhabdoid tumour of the kidney. ConclusionsIncidence of paediatric renal malignancies in the Netherlands has been stable since the 1990s. Five-year OS of WT reached 91% and was similar to findings for other developed countries. Contrary to the excellent outcome for WT, the outcome of malignant rhabdoid tumour of the kidney remained inferior.

Overall survival nomogram and relapse-related factors of clear cell sarcoma of the kidney: A study based on published patients.

BackgroundRarity limits the breadth of study on clear cell sarcoma of the kidney (CCSK). There is currently no predictive model that quantifies the overall survival (OS) of CCSK and a few large sample-based analysis of relapse-related factors.MethodsPatients were collected both from the Surveillance, Epidemiology, and End Results (SEER) database and case report articles extracted from the global online document database to form 2 groups. The first was the OS group, which was used to build and verify the nomogram for predicting the OS of CCSK. Independent predictors of OS were screened by Cox regression analysis to develop the nomogram. Nomogram accuracy was assessed by C-index, receiver operating characteristic (ROC), calibration, and decision curve analysis (DCA) curves. In addition, the difference in OS between receiving radiotherapy or not in stage I patients was analyzed by the Chi-square test. The second was the relapse group, which was used to analyze the relapse-related factors by Cox regression analysis and the Kaplan–Meier method with the log-rank test.Result256 patients were included in the OS group. The stage, chemotherapy, and radiotherapy were independent OS-related factors of CCSK, and the nomogram for predicting the OS of CCSK was established based on them. The results of the C-index, ROC, calibration, and DCA curves showed that the nomogram has good discrimination, accuracy, and clinical profitability. The Chi-squared test showed no significant difference in OS with receiving radiotherapy or not in stage I patients. The relapse group included 153 patients, of which 60 relapsed. The univariate Cox regression analysis showed no correlation between radiotherapy and relapse. The multivariate Cox regression analysis showed that stage and surgery/chemotherapy sequence were the independent factors for relapse. The log-rank test of seven chemotherapeutic drugs showed that etoposide (E), cyclophosphamide (C), vincristine (V), and doxorubicin (D) (all P < 0.05) had significant differences in preventing relapse, and then drew the relapse-free survival curves of these four drugs.ConclusionOur nomogram accurately quantified the OS of CCSK. There was no significant difference in OS between receiving radiotherapy or not in stage I patients. Stage, surgery/chemotherapy sequence, and the use of ECVD were relapse-related factors. Radiotherapy had no significant contribution to preventing relapse.

A Nomogram-Based Risk Classification System Predicting the Overall Survival of Childhood with Clear Cell Sarcoma of the Kidney Based on the SEER Database.

Objective Clear cell sarcoma of the kidney (CCSK) is a lethal pediatric renal malignancy with poor prognosis. A prognostic nomogram needs to be established for overall survival (OS) prediction of patients with CCSK. Methods Eligible 2588 CCSK patients (age 0–19) diagnosed between 2000 and 2017 were extracted from the Surveillance, Epidemiology, and End Results (SEER) database. Patients were randomized into training and validation cohorts (7 : 3). Independent prognostic factors were identified by univariate and multifactorial Cox regression analyses and used to construct a nomogram. Receiver operating characteristics (ROC) analysis, calibration curves, and decision curve analysis (DCA) were used to validate the nomogram. Moreover, a risk classification system was established based on the risk scores of the nomogram. Results Cox analyses revealed that age, combined stage, and origin were most significant prognostic factors. Based on these prognostic factors, a nomogram was established for predicting 3- and 5-year OS of patients with CCSK. The area under the ROC curve (AUC) of 3- and 5-year OS was 0.733 and 0.728 in the training cohort, corresponding to 0.69 and 0.674 in the validation cohort. The C-index of calibration curves in the training and validation cohorts was 0.724 and 0.686. DCAs indicated the clinical utility of this nomogram. A risk classification system stratified CCSK patients into three different risk cohorts. The OS time of low-, intermediate-, and high-risk patients was 76, 68, and 65 months in the training cohort, corresponding to 69.5, 66, and 72 months in the validation cohort. Conclusion A nomogram-based risk classification system has high accuracy for the prognostic prediction of CCSK.

Epidemiologic and Clinical Outcomes of Pediatric Renal Tumors in Korea: A Retrospective Analysis of The Korean Pediatric Hematology and Oncology Group (KPHOG) Data.

Renal tumors account for approximately 7% of all childhood cancers. These include Wilms tumor (WT), clear cell sarcoma of the kidney (CCSK), malignant rhabdoid tumor of the kidney (MRTK), renal cell carcinoma (RCC), congenital mesoblastic nephroma (CMN) and other rare tumors. We investigated the epidemiology of pediatric renal tumors in Korea. From January 2001 to December 2015, data of pediatric patients (0-18 years) newly-diagnosed with renal tumors at 26 hospitals were retrospectively analyzed. Among 439 patients (male, 240), the most common tumor was WT (n=342, 77.9%), followed by RCC (n=36, 8.2%), CCSK (n=24, 5.5%), MRTK (n=16, 3.6%), CMN (n=12, 2.7%), and others (n=9, 2.1%). Median age at diagnosis was 27.1 months (range 0-225.5) and median follow-up duration was 88.5 months (range 0-211.6). Overall, 32 patients died, of whom 17, 11, 1, and 3 died of relapse, progressive disease, second malignant neoplasm, and treatment-related mortality. Five-year overall survival and event free survival were 97.2% and 84.8% in WT, 90.6% and 82.1% in RCC, 81.1% and 63.6% in CCSK, 60.3% and 56.2% in MRTK, and 100% and 91.7% in CMN, respectively (p < 0.001). The pediatric renal tumor types in Korea are similar to those previously reported in other countries. WT accounted for a large proportion and survival was excellent. Non-Wilms renal tumors included a variety of tumors and showed inferior outcome, especially MRTK. Further efforts are necessary to optimize the treatment and analyze the genetic characteristics of pediatric renal tumors in Korea.

Clear cell sarcoma of the kidney with inferior vena cava thrombus: a case report

BackgroundClear cell sarcoma of the kidney is an uncommon pediatric renal malignant neoplasm that is typically characterized in 2–3-year-olds by aggressive behavior and late relapses. Our literature review revealed fewer than ten previously reported cases of CCSK with inferior vena cava thrombus, with only five in the pediatric age group.Case presentationWe report the case of a 14-year-old Syrian girl who complained of mild pain in the left lumbar region pain with hematuria. On physical examination, a mass was palpated in the left flank. Abdominal ultrasonography revealed a left renal mass (7 × 5 × 2 cm3), associated with dilatation of the left renal vein. Contrast abdominal computed tomography showed a mass measuring 7 × 5 × 3 cm3 with the presence of thrombus extending into the inferior cavity down to the right atrium that was initially diagnosed as Wilms’ tumor. Radical right nephrectomy with excision of the thrombus was undertaken. Histological immunostaining revealed a diagnosis of the tumor as clear cell sarcoma with vascular tumor thrombus extending to the inferior vena cava.ConclusionClear cell sarcoma and Wilms’ tumor are similar in terms of typical age of appearance, clinical features, and histopathology, but with different methods of treatment and prognosis. The differential diagnosis of such masses is thus very important. We present the case of a patient with clear cell sarcoma with unusual age, with complete removal of the thromboses in the inferior vena cava and the right atrium.

Paediatric BCOR-associated sarcomas with a novel long spliced internal tandem duplication of BCOR exon 15.

Clear cell sarcoma of the kidney (CCSK) and primitive myxoid mesenchymal tumour of infancy (PMMTI) are paediatric sarcomas that most commonly harbour internal tandem duplications (ITDs) of exon 15 of the BCOR gene, in the range of 87–114 base pairs (bp). Some cases, instead, have BCOR‐CCNB3 or YWHAE‐NUTM2 gene fusions. About 10% of cases lack any of these genetic alterations when tested by standard methods. Two cases of CCSK and one PMMTI lacking the aforementioned mutations were analysed using Archer FusionPlex technology. Two related BCOR exon 15 RNA transcripts with ITDs of lengths 388 and 96 bp were detected in each case; only the 388 bp transcript was identified when genomic DNA was sequenced. In silico analysis of this transcript revealed acceptor and donor splice sites indicating that, at the RNA level, the 388‐bp transcript was likely spliced to form the 96‐bp transcript. The results were confirmed by Sanger sequencing using primers targeting the ITD breakpoint. This novel and unusually long ITD segment is difficult to identify by DNA sequencing using typical primer design strategies flanking entire duplicated segments because it exceeds the typical read lengths of most sequencing platforms as well as the usual fragment lengths obtained from formalin‐fixed paraffin‐embedded material. As diagnosis of CCSK and PMMTI may be challenging by morphology and immunohistochemistry alone, it is important to identify mutations in these cases. Knowledge of this novel BCOR ITD is important in relation to primer design for detection by sequencing, and using RNA versus DNA for sequencing.

Non-Wilms' renal tumors in children: experience with 139 cases treated at a single center

BackgroundPediatric non-Wilms renal tumors (NWRTs), which comprise a small proportion of renal tumors, are a heterogeneous group of neoplasms with variable malignant potential, mortality, and response to treatment. We performed this study to determine the clinical characteristics, management and prognosis of children with Pediatric NWRTs.MethodsMedical records of all patients (n = 139) treated for NWRTs over a 12-year period (2008.01–2019.10) at a single center were reviewed retrospectively.ResultsThe histopathological groups of NWRTs included malignant rhabdoid tumor of the kidney (MRTK) (n: 30, 21.6%), renal cell cancer (RCC) (n: 26,18.7%), clear cell sarcoma of the kidney (CCSK) (n: 24,17.3%), congenital mesoblastic nephroma (CMN) (n: 21,15.1%), cystic nephroma (CN) (n: 16,11.5%), metanephric tumors (n: 12, 8.6%), renal angiomyoliporma (RAML) (n: 3, 2.2%), renal primitive neuroectodermal tumor (n: 2, 1.4%), renal hemangioma (n: 2, 1.4%), inflammatory myofibroblastic tumor (n: 2, 1.4%), ossifying renal tumor of infancy (ORTI) (n: 1, 0.7%). The distribution of all malignant NWRTs, including MRTK, CCSK, RCC and PNET, according to stage was as follows: stages I (n = 26), II (n = 16), III (n = 29), and IV (n = 11). The summary table shows the treatment offered to children with NWRTs. A total of 123 children were followed up for an average of 42 months. Sixteen children were lost to follow-up. Tumor-free survival was observed in 94 children. One patient who suffered from RCC is currently receiving targeted therapy and survives with the tumor. Twenty-eight children (22.8%) died.ConclusionsPediatric NWRTs comprise 19.1% of all renal tumors in our single center. Most NWRTs can readily be distinguished using a range of immunohistochemical markers. Molecular genetic profiling has allowed much progress in the understanding of this group of tumors, making diagnosis and classification less difficult. The mainstay treatment of malignant NWRTs, including MRTK, CCSK, RCC and PNET, is comprehensive treatment. The mainstay treatment of benign NWRTs, including RAML, CN, ORTI, CMN, metanephric tumors, and renal hemangioma, is surgical resection alone and when the tumor diameter is smaller than 7 cm and the tumor locates in one pole, NSS can be performed.

The immune landscape of solid pediatric tumors

BackgroundLarge immunogenomic analyses have demonstrated the prognostic role of the functional orientation of the tumor microenvironment in adult solid tumors, this variable has been poorly explored in the pediatric counterpart.MethodsWe performed a systematic analysis of public RNAseq data (TARGET) for five pediatric tumor types (408 patients): Wilms tumor (WLM), neuroblastoma (NBL), osteosarcoma (OS), clear cell sarcoma of the kidney (CCSK) and rhabdoid tumor of the kidney (RT). We assessed the performance of the Immunologic Constant of Rejection (ICR), which captures an active Th1/cytotoxic response. We also performed gene set enrichment analysis (ssGSEA) and clustered more than 100 well characterized immune traits to define immune subtypes and compared their outcome.ResultsA higher ICR score was associated with better survival in OS and high risk NBL without MYCN amplification but with poorer survival in WLM. Clustering of immune traits revealed the same five principal modules previously described in adult tumors (TCGA). These modules divided pediatric patients into six immune subtypes (S1-S6) with distinct survival outcomes. The S2 cluster showed the best overall survival, characterized by low enrichment of the wound healing signature, high Th1, and low Th2 infiltration, while the reverse was observed in S4. Upregulation of the WNT/Beta-catenin pathway was associated with unfavorable outcomes and decreased T-cell infiltration in OS.ConclusionsWe demonstrated that extracranial pediatric tumors could be classified according to their immune disposition, unveiling similarities with adults’ tumors. Immunological parameters might be explored to refine diagnostic and prognostic biomarkers and to identify potential immune-responsive tumors.