Malignant Rhabdoid Tumor Of The Kidney Research Articles

Extracranial malignant rhabdoid tumors in children: high mortality even with the help of an aggressive clinical approach.

This paper aims to explore the epidemiology, clinical characteristics, and prognosis of extracranial malignant rhabdoid tumors (eMRTs) in children. A systematic review and meta-analysis of studies published in PUBMED, MEDLINE, Web of Science, Embase, Cochrane, and China National Knowledge Infrastructure (CNKI) was conducted. The search was limited to studies published between Jan 1, 1990 to Dec 31, 2022, with the last search done on Jan 31, 2023. We identified 496 papers through the literature search, and 12 retrospective cohort studies with 398 patients were included. The pooled age at diagnosis for malignant rhabdoid tumor of the kidney (MRTK) was 10.009months (95%CI (7.542-12.476)), while extracranial malignant rhabdoid tumor (EERT) was 25.917months (95%CI (17.304-34.530)). Among the 398 patients with eMRTs, chemotherapy treatment rate (86.8% (95%CI (74.4-96.0%))) was more frequently than radiotherapy treatment (45.4% (95%CI (38.1-52.6%))). The rate of metastasis in all patients was 41.4% (95%CI (33.9-48.9%)), in which the lung metastasis was occupied 70.4% (95%CI (58.0-81.6%)). SMARCB1/INI1 mutation was up to 93.2% (95%CI (81.3-99.8%)). The rate of total surgical resection was 50.4% (95%CI (35.2-65.6%)), while pooled proportion of death in all patients was 68.7% (95%CI (56.9-79.5%)). Conclusion: EMRTs are highly malignant tumors associated with high mortality rates. The loss of SMARCB1/INI1 gene and the protein expression is observed in the vast majority of eMRTs patients. Patients that suffered MRTK are younger than patients with extrarenal EERT and are more prone to lung metastasis, but there is no significant difference in overall survival, possibly due to the higher rate of R0 resection of primary tumors in MRTK. Trial registration: The study was registered on PROSPERO with registration number CRD42023400985. What is Known: • Malignant rhabdoid tumor (MRT) is a rare and highly malignant tumor that may originate from embryonic stem cells. The incidence of MRT is exceptionally low, estimated at 0.00006%. • Malignant rhabdoid tumor of the kidney (MRTK) and extrarenal extra-cranial malignant rhabdoid tumor (EERT) tend to manifest between 11 to 18 months of age, with a 5-year survival rate of approximately 17%-36%. What is New: • There is no comprehensive meta-analysis or large-scale case series that reported to systematically introduce the eMRTs clinic outcome and prog-nosis based on largely pooled data. • This study performed a meta-analysis through an extensive literature search and clinical data analysis in order to mainly explore the clinical characteris-tics and prognosis of eMRTs, improving the understanding of eMRTs in children..

FDG PET/CT Findings of Malignant Rhabdoid Tumor Arising From a Renal Allograft.

Malignant rhabdoid tumor of the kidney is a rare aggressive malignancy with poor prognosis. We describe FDG PET/CT findings in a case of malignant rhabdoid tumor of the renal allograft with regional lymph node and pulmonary metastases. The primary renal tumor and lymph node metastases showed intense FDG uptake. The pulmonary metastases showed minimal FDG uptake due to small size. Posttreatment FDG PET/CT showed no evidence of residual disease. This case suggests that FDG PET/CT may be useful in the management of malignant rhabdoid tumor from the transplanted kidney.

Clinical application of indocyanine green fluorescence imaging navigation for pediatric renal cancer.

Indocyanine Green (ICG) fluorescence imaging has been widely used in the surgical treatment of adult renal cancers, but its application in pediatric renal cancers has rarely been reported. This study aims to summarize the experience of ICG fluorescence imaging in pediatric renal cancers and explores its safety and feasibility. The clinical features, surgical information, ICG administration regimen, near infrared radiography data in vivo and ex vivo and pathological results of children with renal cancers using ICG navigation were analyzed and summarized. There were 7 cases of renal cancer, including 4 cases of Wilms tumor (WT), 1 case of malignant rhabdoid tumor of the kidney (MRTK) and 2 cases of renal cell carcinoma (RCC). By intraoperative intravenous injection of ICG from 2.5 to 5 mg (0.05-0.67 mg/kg), the tumors were visualized in 6 cases in vivo or ex vivo, and the tumor visualization failed in 1 case due to renal artery embolization before operation. By injecting 5 mg ICG into the normal renal tissue during the operation, 3 patients achieved fluorescent localization of sentinel lymph nodes. No ICG-related adverse reactions were found in any of the patients during or after operation. ICG fluorescence imaging is safe and feasible for renal cancers in children. Intraoperative administration can achieve tumor and sentinel lymph node visualization which will facilitate the development of nephron sparing surgery (NSS). However, the technique is affected by ICG dose, anatomical conditions around the tumor, and renal blood flow. A proper dose of ICG and the complete removal of perirenal fat are helpful for the fluorescence imaging of the tumor. It has potential in the operation of renal cancer in children.

BKM120 inhibits malignant rhabdoid tumor of the kidney through induction of apoptosis and G0/G1 phase arrest

Malignant rhabdoid tumor of the kidney (MRTK) has an inferior prognosis and is insensitive to radiotherapy and chemotherapy. Search for novel, potent medicinal agents is urgent. Herein, data on the gene expression and clinical characteristics of malignant rhabdoid tumors (MRT) were retrieved from the TARGET database. Prognosis-related genes were identified by differential analysis and one-way cox regression analysis, and prognosis-related signalling pathways were identified by enrichment analysis. The prognosis-related genes were imported into the Connectivity Map database for query, and BKM120 was predicted and screened as a potential therapeutic agent for MRTK. A combination of high-throughput RNA sequencing and Western blot verified that the PI3K/Akt signaling pathway is associated with MRTK prognosis and is overactivated in MRTK. Our results outlined that BKM120 inhibited the proliferation, migration, and invasion ability of G401 cells and induced apoptosis and cell cycle G0/G1 phase arrest. In vivo, BKM120 inhibited tumor growth and had no significant toxic side effects. Western blot and immunofluorescence results confirmed that BKM120 could reduce the expression of PI3K and p-AKT, critical proteins of the PI3K/Akt signaling pathway. BKM120 inhibits MRTK by inhibiting PI3K/Akt signalling pathway to induce apoptosis and cell cycle G0/G1 phase arrest, which is anticipated to give the clinical treatment of MRTK a new direction.

Tumor biology, biomarkers, and liquid biopsy in pediatric renal tumors.

The expansion of knowledge regarding driver mutations for Wilms tumor (WT) and malignant rhabdoid tumor of the kidney (MRT) and various translocations for other pediatric renal tumors opens up new possibilities for diagnosis and treatment. In addition, there are growing data surrounding prognostic factors that can be used to stratify WT treatment to improve outcomes. Here, we review the molecular landscape of WT and other pediatric renal tumors as well as WT prognostic factors. We also review incorporation of circulating tumor DNA/liquid biopsies to leverage this molecular landscape, with potential use in the future for distinguishing renal tumors at the time of diagnosis and elucidating intratumor heterogeneity, which is not well evaluated with standard biopsies. Incorporation of liquid biopsies will require longitudinal collection of multiple biospecimens. Further preclinical research, identification and validation of biomarkers, molecular studies, and data sharing among investigators are crucial to inform therapeutic strategies that improve patient outcomes.

Malignant Rhabdoid Tumor of the Kidney in a Young Adult: A Case Report and Review of the Literature

Malignant rhabdoid tumors of the kidney (MRTs) are extremely rare tumors often found in children under 2 years old and even more are in adults with fewer than 10 cases of MRT of the kidney reported in adults. To date, there is no established standard of care for MRTs due to paucity of cases. The present study reports a case of a 21 year-old African American male with a past medical history of sickle cell trait who was found to have MRTs in bilateral kidneys with characteristic clinicopathological features and early onset metastasis. This case of a 21 year-old presents to be the youngest case of MRT present in adults, expanding the previously reported range of 32 to 79 years in adults and reinforcing the importance of recognizing MRTs in a broad range of the adult population.

Clinical and prognostic analysis of 42 children with malignant rhabdoid tumor of the kidney: a 7-year retrospective multi-center study

ObjectiveTo discuss the clinical and prognostic indicators of pediatric malignant rhabdoid tumor of the kidney (MRTK), and to increase the understanding of the occurrence and development of MRTK.MethodsFrom July 2014 to September 2021, all cases were confirmed by postoperative pathological examination. Among the 42 patients, there were 25 males and 17 females, with a median age of 10 (1–84) months. Abdominal mass or hematuria were the main clinical manifestations. Preoperative chemotherapy was performed in 9 cases (VC). The tumor stages were stage I-IV. Preoperative metastasis was found in 9 cases; the most common site was the lung. Postoperative patients received conventional chemotherapy, including VDACE regimen and UH-1 regimen. Among the 42 children in this group, survival at follow-up in this study was 26.2%(11/42).ResultsPreoperative anemia was found by univariate analysis, hypertension and hypercalcemia had shorter survival time. In addition, tumor-related factors had a significant impact on survival, with incomplete tumor resection, lymph node metastasis, stage III-IV had a lower survival rate. The impact of postoperative factors on survival included postoperative complications had a lower survival rate. The children were younger than 12 months, preoperative metastasis, no chemotherapy was performed after surgery was an independent risk factor for the prognosis of MRTK.ConclusionThe main clinical manifestations about MRTK were abdominal mass and hematuria. Preoperative chemotherapy did not significantly improve the prognosis. Postoperative chemotherapy can significantly improve the survival rate. Diagnosis depends on clinical manifestations, imaging, histopathology, immunohistochemistry and other comprehensive judgment. Age less than 12 months, preoperative metastasis, and no postoperative chemotherapy were independent risk factors for prognosis.

Analysis of 18 cases of malignant rhabdoid tumor in children

Objective: To investigate the clinical characteristics, treatment and prognosis of malignant rhabdoid tumor (MRT) in children. Methods: Clinical data total of 18 children with MRT treated in the Department of Hematology and Oncology, Children's Hospital, the First Affiliated Hospital of Zhengzhou University between June 2015 to June 2021 were analyzed retrospectively. The patients were grouped according to age, gender, tumor type, clinical stage and other factors.Progression free survival (PFS) and overall survival (OS) were calculated by Kaplan-Meier method, survival differences among different groups were compared by Log-rank test, and prognostic factors were analyzed by Cox regression model. Results: Among the 18 patients, there were 5 males and 13 females. The age of disease onset was 30.5 (12.0, 75.0) months, the tumor diameter was (80±29) mm, and no integrase interactor 1 (INI-1) expression was detected by immunohistochemistry. There were 7 cases of malignant rhabdoid tumor of the kidney (MRTK), 6 cases of atypical teratoid rhabdoid tumor (ATRT) and 5 cases of extrarenal extracranial rhabdoid tumor (EERT). At the time of early diagnosis, 12 patients were clinically stage Ⅲ-Ⅳ, 11 patients had local or distant metastasis, and 4 patients had metastasis during treatment. Surgical excision is the preferred treatment. There were 3 cases with preoperative puncture biopsy, 13 cases with complete resection, 4 cases with partial resection, and 1 case without operation. Thirteen patients were treated with the domestic conventional chemotherapy regimen for Wilms' tumor, medulloblastoma and rhabdomyosarcoma, and 5 patients were treated with the international conventional chemotherapy regimen. Nine patients received radiotherapy, including 1 case of MRTK, 4 cases of ATRT and 4 cases of EERT. By the end of follow-up in January 2022, 7 patients survived and 11 patients died. The 3-year PFS and OS rates were (8±8) % and (14±12) %. Log-rank test showed that the 5-year OS of EERT group was higher than ATRT and MRTK groups (χ²=16.31, P<0.001), the tumor diameter <80 mm group was higher than that of the ≥80 mm group (χ²=4.49, P=0.034), and the radiotherapy group was higher than no radiotherapy group (χ²=3.97, P=0.046). The differences were statistically significant. There was no significant difference in the influence of tumor type, age, tumor diameter, radiotherapy and chemotherapy on OS by Cox regression model (all P>0.05). Log-rank test showed that the 3-year PFS of EERT group was higher than ATRT and MRTK groups (χ²=11.14, P=0.004),>3 years group was higher than ≤3 years group (χ²=10.10, P=0.001), the differences were statistically significant. Tumor type, clinical stage, tumor diameter, age, tumor rupture and radiotherapy were included in the Cox regression model, and the results showed that clinical stage (HR=0.49, 95%CI 0.26-0.94, P=0.031), tumor diameter (HR=8.67, 95%CI 1.84-40.89, P=0.006), age (HR=0.01, 95%CI 0.00-0.15, P=0.001) had statistical significance on PFS. Conclusions: MRT is one of the most aggressive and fatal cancers in early childhood and infancy. There is no standard treatment and the prognosis is extremely poor. Clinical stage, tumor size and age are risk factors for disease progression.

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.

Malignant rhabdoid tumor: Cyto-histologic correlation and immunohistochemical characterization of a rare pediatric malignancy and its differential diagnoses

Malignant rhabdoid tumor of the kidney (MRTK) is a rare aggressive pediatric renal tumor which can be diagnosed via fine-needle aspiration (FNA) cytology and core biopsy. The diagnosis of MRTK is challenging, and requires morphologic, immunohistochemical and clinical correlation to distinguish it from other entities. The differential diagnosis includes Wilms tumor, desmoplastic small round cell tumor, rhabdomyosarcoma, synovial sarcoma, renal medullary carcinoma, and epithelioid sarcoma. Here we describe a case of MRTK diagnosed on renal cytology and core biopsy with immunohistochemistry and follow by nephrectomy with gross and morphologic findings.

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.

Abstract 3900: Β3 adrenergic receptor blockade impairs compensatory mechanism to overcome nutrient deprivation in malignant rhabdoid tumor of the kidney

Abstract In this study, the effects of nutrient deprivation in regulating tumor growth and metabolism in Malignant Rhabdoid Tumor of the Kidney (MRTK) was investigated. MRTK is a rare and highly aggressive tumor occurring in infancy and early childhood. Unfortunately, there are not many studies to date that can help us better understand the involvement of metabolism in MRTK growth and progression. However, it is now well known that nutrient deprivation is an environmental stress factor that can influence the behavior of cancer cells leading to reprogramming in metabolism. Here, we first evaluated the effects on cell survival and metabolic adaptation of MRTK G-401 cells after glutamine or tyrosine/phenylalanine deprivation, or both. Then, the involvement of the β3-adrenergic receptor (β3-AR) in regulating the metabolic changes in G-401 cells exposed to limited conditions was investigated. We demonstrated that deprivation of glutamine alone or in combination with tyrosine/phenylalanine enhanced the expression of the glucose transporter GLUT1, associated with increased glucose uptake, ATP production, and oxidative stress, as a compensatory mechanism following amino acid deprivation partially regulated via β3-AR. Indeed, β3-AR antagonism was able to decrease the expression of GLUT1, glucose uptake and survival in G-401 cells. Furthermore, exposure of G-401 cells to limited conditions induced an improved activity of the TCA cycle enzymes leading to a different and enhanced fumarate production. Overall, our results indicate that tyrosine/phenylalanine and glutamine deprivation in MRTK is able to trigger a compensatory mechanism to sustain tumor growth and proliferation. Citation Format: Angela Subbiani, Alessia Boaretto, Daniela Buonvicino, Cecilia Cecchi, Claudio Favre, Maura Calvani. Β3 adrenergic receptor blockade impairs compensatory mechanism to overcome nutrient deprivation in malignant rhabdoid tumor of the kidney [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2022; 2022 Apr 8-13. Philadelphia (PA): AACR; Cancer Res 2022;82(12_Suppl):Abstract nr 3900.

Identification of Prognostic Biomarkers in Patients With Malignant Rhabdoid Tumor of the Kidney Based on mTORC1 Signaling Pathway-Related Genes.

Background: Malignant rhabdoid tumor of the kidney (MRTK) is an infrequent malignant tumor in childhood, accounting for approximately 2% of all childhood kidney tumors. Although the development of current treatments, the overall survival (OS) rate of MRTK patients is only 25%. The aim of this research was to explore the prognostic value of genes associated with the mTORC1 signaling pathway in MRTK. Methods: The transcriptome data of MRTK samples were downloaded from the TARGET database. The 200 genes of HALLMARK_MTORC1_SIGNALING were downloaded from the Molecular Signatures Database (MSigDB). Furthermore, we applied gene set variation analysis (GSVA) to screen differentially expressed gene sets between the MRTK and normal samples. The 200 genes were combined with differentially expressed genes (DEGs) identified from differentially expressed gene sets. Then, a gene signature of mTORC1 pathway-related genes (mTRGs) was constructed in MRTK. The molecular mechanism of prognostic factors in MRTK was further analyzed using gene set enrichment analysis (GSEA). The target drugs based on these prognostic factors were explored from The Comparative Toxicogenomics Database (CTD). Moreover, six paired fresh tumor tissues and paraneoplastic tissues from children with MRTK were collected to validate the expressions of P4HA1, MLLT11, AURKA, and GOT1 in clinical samples via real-time fluorescence quantitative PCR and Western blot. Results: A four-gene signature (P4HA1, MLLT11, AURKA, and GOT1) related to the mTORC1 pathway was developed in MRTK, which divided the MRTK patients into high-risk and low-risk groups. The patients with high-risk scores were strongly associated with reduced OS. Receiver operating characteristic (ROC) analysis indicated a good prediction performance of the four biomarker signatures. GSEA revealed that the mTOR signaling pathway was significantly enriched. The risk score was demonstrated to be an independent predictor for MRTK outcome. According to the correlation of tumor stem cell index and prognostic factors, the target drugs were obtained for the treatment of MRTK patients. Furthermore, the expressions of RT-qPCR and Western blot were consistent with RNA-sequencing data such that their expressions were significantly elevated in tumor tissues. Conclusion: A total of four genes (P4HA1, MLLT11, AURKA, and GOT1) were screened as prognostic markers, further providing a new understanding for the treatment of patients with MRTK.

Analysis on diagnosis and treatments of 16 cases of extracranial malignant rhabdoid tumor in children.

BackgroundTo explore the clinical features, treatment and early prognosis of malignant rhabdoid tumor (MRT) of kidney and extrarenal extracranial soft tissue in children.MethodsFrom January 2011 to July 2021, a total of 16 patients, who were diagnosed with MRTs of the kidney and extrarenal soft tissue were retrospectively analyzed and were divided into MRT of the kidney (MRTK) and extrarenal extracranial MRT (EERT).ResultsSixteen patients were followed up for at least 15 months. The overall average age of onset was (26.6±20.1 months), the 1-year overall survival (OS) of 71.4% at the age of ≥24 months was significantly higher than the 1-year OS (11.1%) <24 months of age [hazard ratio (HR) =0.21 (0.06–0.77), log-rank P=0.019<0.05]. The distant metastasis rate of children in the MRTK group (83.3%) is significantly higher than EERT group (20%) (P=0.017<0.05), and the proportion of children with lung metastasis in the MRTK group was as much as 83.3%, which was significantly higher than that in the EERT group (10%) (P<0.05), but the related metastases and primary tumors did not regress after radiotherapy and chemotherapy in all cases. In the MRTK group, 5 cases were completely excised, but only 1 survived; while 5 cases in the EERT group that were completely excised and all alive. Children with tumor total excision in EERT group had a 1-year OS of 100% as compared to children with tumor total excision in MRTK group had a 1-year OS of 20% [HR =0.07 (0.01–0.57), log-rank P=0.013<0.05]. The average survival time of dead cases in MRTK group and EERT group were 6.60±3.28 months and 1.40±0.65 months respectively (P=0.008<0.05).ConclusionsChildren with MRT under 2 years of age have significantly worse prognosis than children exceeding 2 years of age. MRTK is more prone to lung metastasis but has longer survival time, which is related to the R0 resection of the primary tumor. Children with EERT may have a better prognosis if the tumor can be completely resected with the impact of age. MRTK and EERT are both insensitive to radiotherapy and chemotherapy.

Imaging of renal tumors in children

Renal tumors in children are treated according to the guidelines of the Renal Tumor Study Group of the International Society of Pediatric Oncology (SIOP-RTSG). Nephroblastoma is the most frequent renal tumor in children. After sonography, magnetic resonance imaging (MRI) is the preferred imaging modality. The task of imaging includes differential diagnosis with the help of morphological and epidemiological criteria. Thorax computed tomography (CT) is introduced for initial staging. Current studies of diffusion-weighted imaging (DWI)-MRI with analysis of the apparent diffusion coefficient (ADC) histogram indicate the potential to differentiate blastemal or anaplastic high-risk histology nephroblatoma subtypes. Imaging criteria for nephron-sparing surgery are defined and allow an individual therapy option in unilateral and especially in bilateral renal nephroblastoma. In addition to nephroblastoma, the differential diagnosis includes congenital mesoblastic nephroma, malignant rhabdoid tumor of the kidney, clear cell sarcoma and renal cell carcinoma. The diagnosis of nephrogenic rests and nephroblastomatosis is challenging. Diagnostic standardization improves diagnosis and therapy of renal childhood tumors, and new prognostic markers may be introduced in the near future.

Case Analysis of 14 Children with Malignant Rhabdoid Tumor of the Kidney.

ObjectiveThis study aims to summarize the clinical features and prognoses of the malignant rhabdoid tumor of the kidney (MRTK) in children. It further aims to analyze the high-risk factors affecting MRTK prognosis.MethodsClinical data from 14 children with MRTK treated in Paediatrics of Beijing Tongren Hospital from January 2010 to December 2019, along with the high-risk factors affecting prognosis, were retrospectively analyzed.ResultsThere were 14 children with MRTK included in the study, with a median onset age of 13 (3–46) months. Thirteen patients had distant metastases, the most common site for metastases being inside the lung. A comprehensive treatment protocol combined with chemotherapy was mainly applied during the surgery. A surgical resection of primary tumors was performed on 13 (13/14) patients, and all 14 children received chemotherapy with ifosfamide + carboplatin + etoposide, ifosfamide + etoposide, and vincristine + pirarubicin + cyclophosphamide regimens, alternately. Three patients received radiotherapy and two received oral targeted drugs after partial response. The median follow-up was after 16.5 months (3–53 months) and the four-year overall survival (OS) was 41.8%. In children aged ≤24 months and children aged >24 months, the two-year OS was 67.2% and 100% (χ2 = 108.998, P<0.05), respectively. In children with Ki 67 > 70% and children with Ki 67 < 70%, the two-year OS was 52.6% and 86.9% (χ2 = 8.544, P = 0.003), respectively. In children with distant metastases and children without distant metastasis, the two-year OS was 70% and 100% (χ2 = 14.239, P<0.05), respectively.ConclusionThe most common MRTK distant metastasis site is the lung. Risk factors for poor MRTK prognoses include an age of <24 months, Ki 67 > 70%, and distant metastases.

Clinical and Molecular Differentiation Between Malignant Rhabdoid Tumor of the Kidney and Normal Tissue: A Two-Case Report.

BackgroundMalignant rhabdoid tumor of the kidney (MRTK) is a rare type of tumor that lacks typical clinical manifestations. Herein, we presented clinical data of 2 children with MRTK. In addition, we used a high-throughput RNA-sequencing (RNA-seq), GO analysis, and KEGG signaling pathway analysis to examine gene expression differences at the transcripts level between 2 patients with MRTK and 3 patients with non-tumor diseases without other symptoms.Case reportPreoperative B-scan ultrasonography and computed tomography (CT) examination in 2 cases suggested nephroblastoma. Both patients were treated with radical nephrectomy. After the operation, MRTK was confirmed by pathological examination. Child 1 and Child 2 then received 7 courses and 12 courses of regular chemotherapy, respectively. Child 1 was followed up for 2 years, and Child 2 for 3.1 years without showing symptoms. RNA-seq results showed 2203 differential genes (DEGs) in the kidney tissue of children with MRTK compared to normal tissue (p <0.01). GO analysis suggested that most DEGs participate in protein binding. KEGG results showed that the DEGs were mainly involved in the PI3K-Akt signaling pathway and microRNA-related proteins.ConclusionThe PI3K-Akt signaling pathway and microRNA-related proteins as targets have extremely high potential value for the diagnosis and treatment of MRTK.

Malignant rhabdoid tumor of the kidney in an adult with loss of INI1 expression and mutation in the SMARCB1 gene.

A 57-year-old man with left flank pain was referred to our institute. Computed tomography scans revealed two enhancing masses in the left kidney. The clinical diagnosis was renal cell carcinoma (RCC). He underwent a radical nephrectomy with an adrenalectomy. Two well-circumscribed solid masses in the hilum and the lower pole (4.5 × 3.5 cm and 7.0 × 4.1 cm) were present. Poorly cohesive uniform round to polygonal epithelioid cells making solid sheets accounted for most of the tumor area. The initial diagnosis was RCC, undifferentiated with rhabdoid features. As the tumor showed loss of INI1 expression and a mutation in the SMARCB1 gene on chromosome 22, the revised diagnosis was a malignant rhabdoid tumor (MRT) of the kidney. To date, only a few cases of renal MRT in adults have been reported. To the best of our knowledge, this is the first report of MRT in the native kidney of an adult demonstrating a SMARCB1 gene mutation, a hallmark of MRT.

Identification of prognostic immune-related genes in rhabdoid tumor of kidney based on TARGET database analysis.

Background: Malignant rhabdoid tumor of the kidney (RTK) is a rare and highly aggressive pediatric malignancy. Immune system dysfunction is significantly correlated with tumor initiation and progression.Methods: We integrated and analyzed the expression profiles of immune-related genes (IRGs) in 65 RTK patients based on the Therapeutically Applicable Research to Generate Effective Treatments (TARGET) database. Prognostic related IRGs in RTK patients were analyzed using univariate and multivariate analysis, based on which a prognostic model with IRGs was constructed. Correlation analysis between the risk score of our model and tumor-infiltrating cell were also investigated.Results: Twenty two IRGs were significantly associated with the clinical outcomes of RTK patients. Gene ontology (GO) analysis revealed that inflammatory pathways were most frequently implicated in RTK. A prognostic model was constructed using 7 IRGs (MMP9, SERPINA3, FAM19A5, CCR9, PLAUR, IL1R2, PRKCG), which were independent prognostic indices that could differentiate patients based on their survival outcomes. Furthermore, the risk scores from our prognostic model was positively associated with cancer-associated fibroblasts (CAFs).Conclusions: We screened seven IRGs of clinical significance to distinguish patients with different survival outcomes. This may enhance our understanding of the immune microenvironment of RTK, and could use to design individualized treatments for RTK patients.Background: Malignant rhabdoid tumor of the kidney (RTK) is a rare and highly aggressive pediatric malignancy. Immune system dysfunction is significantly correlated with tumor initiation and progression.Methods: We integrated and analyzed the expression profiles of immune-related genes (IRGs) in 65 RTK patients based on the Therapeutically Applicable Research to Generate Effective Treatments (TARGET) database. Prognostic related IRGs in RTK patients were analyzed using univariate and multivariate analysis, based on which a prognostic model with IRGs was constructed. Correlation analysis between the risk score of our model and tumor-infiltrating cell were also investigated.Results: Twenty two IRGs were significantly associated with the clinical outcomes of RTK patients. Gene ontology (GO) analysis revealed that inflammatory pathways were most frequently implicated in RTK. A prognostic model was constructed using 7 IRGs (MMP9, SERPINA3, FAM19A5, CCR9, PLAUR, IL1R2, PRKCG), which were independent prognostic indices that could differentiate patients based on their survival outcomes. Furthermore, the risk scores from our prognostic model was positively associated with cancer-associated fibroblasts (CAFs).Conclusions: We screened seven IRGs of clinical significance to distinguish patients with different survival outcomes. This may enhance our understanding of the immune microenvironment of RTK and could use to design individualized treatments for RTK patients.

ATRT-21. RHABDOID PREDISPOSITION SYNDROME: REPORT OF MOLECULAR PROFILES AND TREATMENT APPROACH IN THREE CHILDREN WITH SYNCHRONOUS ATYPICAL TERATOID/RHABDOID TUMOR AND MALIGNANT RHABDOID TUMOR

BACKGROUNDRhabdoid predisposition syndrome is characterized by germline alterations in SMARCB1 or SMARCA4, leading to synchronous or metachronous central nervous system (CNS) and extra-CNS rhabdoid tumors. Rare survivors have been reported to date.METHODSWe describe the molecular profiling and treatment regimen of three patients with synchronous atypical teratoid/rhabdoid tumor (ATRT) and malignant rhabdoid tumor of the kidney (MRT-K). All patients underwent radical nephrectomy of the kidney, and gross total resection of the primary CNS tumor was achieved for two patients. An intensive chemotherapy regimen was administered; an induction phase based on the modified Third Intergroup Rhabdomyosarcoma Study (IRS-III) for ATRT followed by a consolidation phase with three cycles of high-dose chemotherapy and autologous hematopoietic progenitor cell rescue, without irradiation. All three patients were enrolled on an institutional comprehensive genomic profiling protocol.RESULTSA germline focal 22q deletion, including SMARCB1, was detected in two patients, while the third patient had a maternally-inherited heterozygous frameshift variant in SMARCB1. Somatic loss of heterozygosity of 22q was identified in all patients, resulting in biallelic inactivation of SMARCB1. Divergent tumor subgroups were described using DNA methylation. The three MRT-K samples were classified as MYC subtype. One ATRT was classified as SHH while the other as TYR. One patient is currently three years off-therapy without evidence of disease, while the other two patients have completed the consolidation phase without recurrent disease.CONCLUSIONMolecular profiling of CNS and extra-CNS rhabdoid tumors revealed different epigenetic subgroups. An intensive multimodal therapeutic approach without irradiation may achieve prolonged survival.