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Clear cell sarcoma of the kidney (CCSK) is a rare primary renal tumor in children. It is known for its propensity to metastasize to bones and lungs at initial diagnosis. Distant metastatic relapses occur in about 15-16% of the patients, with the brain being the most frequent site of relapse. Imaging features of brain metastases from CCSK have only been reported in a few cases and most reports lack a detailed description of the imaging findings. We present brain magnetic resonance imaging (MRI) findings in an infant with relapsed CCSK who developed multiple parenchymal metastases with concentric signal alterations and no tumor-associated edema.
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Neoplasias Encefálicas , Neoplasias Renales , Sarcoma de Células Claras , Niño , Lactante , Humanos , Sarcoma de Células Claras/diagnóstico por imagen , Sarcoma de Células Claras/patología , Riñón/patología , Neoplasias Renales/diagnóstico por imagen , Neoplasias Renales/patología , Neoplasias Encefálicas/patología , Imagen por Resonancia MagnéticaRESUMEN
Pediatric renal tumors account for 3%-11% of childhood cancers, the most common of which is Wilms tumor or nephroblastoma. Epidemiology plays a key role in cancer prevention and control by describing the distribution of cancer and discovering risk factors for cancer. Large pediatric research consortium trials have led to a clearer understanding of pediatric renal tumors, identification of risk factors, and development of more risk-adapted therapies. These therapies have improved event-free and overall survival for children. However, several challenges remain and not all children have benefited from the improved outcomes. In this article, we review the global epidemiology of pediatric renal tumors, including key consortium and global studies. We identify current knowledge gaps and challenges facing both high and low middle-incomes countries.
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Neoplasias Renales , Tumor de Wilms , Niño , Humanos , Neoplasias Renales/patología , Tumor de Wilms/patologíaRESUMEN
Pediatric renal tumors account for 3%-11% of childhood cancers, the most common of which is Wilms tumor or nephroblastoma. Epidemiology plays a key role in cancer prevention and control by describing the distribution of cancer and discovering risk factors for cancer. Large pediatric research consortium trials have led to a clearer understanding of pediatric renal tumors, identification of risk factors, and development of more risk-adapted therapies. These therapies have improved event-free and overall survival for children. However, several challenges remain and not all children have benefited from the improved outcomes. In this article, we review the global epidemiology of pediatric renal tumors, including key consortium and global studies. We identify current knowledge gaps and challenges facing both high and low middle-incomes countries.
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Neoplasias Renales , Tumor de Wilms , Niño , Humanos , Neoplasias Renales/epidemiología , Neoplasias Renales/terapia , Tumor de Wilms/epidemiología , Tumor de Wilms/terapia , Tumor de Wilms/patologíaRESUMEN
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.
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Neoplasias Renales , Sarcoma , Niño , Exones/genética , Humanos , Neoplasias Renales/patología , Mutación , Proteínas Proto-Oncogénicas/genética , ARN , Proteínas Represoras/genética , Sarcoma/genética , Sarcoma/patologíaRESUMEN
Clear cell sarcoma of the kidney is a rare variety of renal tumor accounting for less than 5% of all pediatric renal tumors. Cardiopulmonary bypass along with hypothermic circulatory arrest is frequently used for management of tumor thrombus extending into supra-hepatic inferior vena cava and right atrium. In this paper, we present a strategy of avoiding circulatory arrest and hypothermia and thereby fast-tracking the recovery in managing a case of clear cell sarcoma of the kidney in a 3.5-year-old child with tumor thrombus extending into the right atrium.
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BACKGROUND: The pathology, treatment and prognosis of malignant non-Wilms tumors (NWTs) are different, so it is necessary to differentiate these types of tumors. The purpose of this study was to review the clinical and imaging features of malignant NWTs and features of tumor metastasis. METHODS: We retrospectively analyzed the CT images of 65 pediatric patients with NWTs from March 2008 to July 2020, mainly including clear cell sarcoma of the kidney (CCSK), malignant rhabdomyoma tumor of the kidney (MRTK) and renal cell carcinoma (RCC). Available pretreatment contrast-enhanced abdominal CT examinations were reviewed. The clinical features of the patients, imaging findings of the primary mass, and locoregional metastasis patterns were evaluated in correlation with pathological and surgical findings. RESULTS: The study included CCSK (22 cases), MRTK (27 cases) and RCC (16 cases). There were no significant differences observed among the sex ratios of CCSK, MRTK and RCC (all P > 0.05). Among the three tumors, the onset age of MRTK patients was the smallest, while that of RCC patients was the largest (all P < 0.05). The tumor diameter of CCSK was larger than that of MRTK and RCC (all P < 0.001). For hemorrhage and necrosis, the proportion of MRTK patients was larger than that of the other two tumors (P = 0.017). For calcification in tumors, the proportion of calcification in RCC was highest (P = 0.009). Only MRTK showed subcapsular fluid (P < 0.001). In the arterial phase, the proportion of slight enhancement in RCC was lower than that in the other two tumors (P = 0.007), and the proportion of marked enhancement was the highest (P = 0.002). In the venous phase, the proportion of slight enhancement in RCC was lower than that in the other two tumors (P < 0.001). Only CCSK had bone metastasis. There was no liver and lung metastasis in RCC. CONCLUSIONS: NWTs have their own imaging and clinical manifestations. CCSK can cause vertebral metastasis, MRTK can cause subcapsular effusion, and RCC tumor density is usually high and calcification. These diagnostic points can play a role in clinical diagnosis.
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Neoplasias Renales/diagnóstico por imagen , Tomografía Computarizada por Rayos X/métodos , Adolescente , Estudios de Casos y Controles , Niño , Preescolar , Medios de Contraste , Diagnóstico Diferencial , Femenino , Humanos , Lactante , Masculino , Pronóstico , Estudios RetrospectivosRESUMEN
Molecular characterization has led to advances in the understanding of pediatric renal tumors, including the association of pediatric cystic nephromas with DICER1 tumor syndrome, the metanephric family of tumors with somatic BRAF mutations, the characterization of ETV6-NTRK3-negative congenital mesoblastic nephromas, the expanded spectrum of gene fusions in translocation renal cell carcinoma, the relationship of clear cell sarcoma of the kidney with other BCOR-altered tumors, and the pathways affected by SMARCB1 alterations in rhabdoid tumors of the kidney. These advances have implications for diagnosis, classification, and treatment of pediatric renal tumors.
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Neoplasias Renales/patología , Carcinoma de Células Renales/diagnóstico , Carcinoma de Células Renales/genética , Carcinoma de Células Renales/patología , Niño , Diagnóstico Diferencial , Humanos , Neoplasias Renales/diagnóstico , Neoplasias Renales/genética , Mutación , Nefroma Mesoblástico/diagnóstico , Nefroma Mesoblástico/genética , Nefroma Mesoblástico/patología , Tumor Rabdoide/diagnóstico , Tumor Rabdoide/genética , Tumor Rabdoide/patología , Sarcoma de Células Claras/diagnóstico , Sarcoma de Células Claras/genética , Sarcoma de Células Claras/patologíaRESUMEN
INTRODUCTION: Non-Wilms renal tumors represent a compelling subset of childhood renal tumors. However, their relative rarity renders accurate diagnosis, and therapy challenging which in some instance is inferred from their adult counterparts. OBJECTIVE: To describe the incidence and analyze the diagnostic challenges, therapies and, outcomes of non-Wilms renal tumors at the largest tertiary cancer centre in India. METHODS: All patients with histologically confirmed non-Wilms renal tumours diagnosed in the paediatric oncology unit of Tata Memorial Hospital between 2006 and 2019 were included. Data regarding clinical and radiological features and treatment outcomes were retrieved from the prospectively maintained institutional database. At the outset, histological types were categorised into a high and low-risk group depending on anticipated survival. Survival analysis was performed utilising the Kaplan-Meier method on SPSS software version 24.0. RESULTS: Of the 569 patients with renal tumors, 109 (19%) patients with primary (n = 97) or recurrent (n = 12) non-Wilms renal tumors were included. Histological high-risk group included clear cell sarcoma (CCSK) (39.4%), renal cell carcinoma (RCC) (19.3%), malignant rhabdoid tumor (MRTK) (12.8%), Ewing's sarcoma (rES) (15.6%), synovial sarcoma (2%), and undifferentiated sarcoma (2%). The low-risk group comprised of congenital mesoblastic nephroma (CMN) (4.6%), cystic partially differentiated nephroblastoma (2%), and other rare tumors (3%). Diagnostic error occurred in 2 patients in the high-risk group. All low-risk tumours were treated with surgery alone and most (97%) high-risk tumors were operated either upfront (61.5%) or after preoperative chemotherapy (38.4%). Adjuvant therapy based on histology was offered to 70%. The recurrent tumors received various salvage treatments including chemotherapy; radiotherapy; surgery and immunotherapy, however, only 2 patients could be salvaged. The 3-year overall survival for the entire cohort with primary tumors was 59%, and the survival rates were 76.7%, 77.9%, 0.0%, and 52% for CCSK, RCC, MRTK, and rES (summary figure). Low-risk tumors had 100% survival while the recurrent tumors had a median survival of 10.5 months. CONCLUSIONS: Non-Wilms renal tumors constitute a heterogeneous group of tumors, accounting for less than 20% of all renal tumors. Low-risk tumors are associated with excellent outcomes following surgery alone while the high-risk tumours have a variable outcome. MRTK and recurrent non-Wilms tumour have the worst survival. Favourable outcomes for CCSK and RCC and worst outcomes for MRTK were observed in this study. Renal ES have higher incidence of treatment failure and unsatisfactory outcomes. Recurrent non-Wilms tumours have an extremely poor outcome and more alternative or innovative approaches are needed for their treatment.
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Neoplasias Renales , Nefroma Mesoblástico , Tumor de Wilms , Niño , Humanos , Incidencia , India , Lactante , Neoplasias Renales/diagnóstico , Neoplasias Renales/epidemiología , Neoplasias Renales/terapia , Tumor de Wilms/diagnóstico , Tumor de Wilms/epidemiología , Tumor de Wilms/terapiaRESUMEN
INTRODUCTION: The purpose of this study was to establish a reliable panel of antibodies for immunohistochemical corroboration of a diagnosis of clear cell sarcoma of kidney (CCSK), taking into consideration the various genotypic subsets of CCSK. METHODS: We conducted full genotypic analysis for evidence of YWHAE-NUTM2, BCOR internal tandem duplication (ITD), and BCOR-CCNB3 in 68 archival cases of CCSK and then immunostained all cases for CCND1, TLE1, and BCOR along with 63 control samples representing tumor types that may enter into the differential diagnosis of CCSK, including 7 congenital mesoblastic nephromas, 2 desmoplastic small round cell tumors, 13 malignant rhabdoid tumors, 9 Ewing sarcomas/primitive neuroectodermal tumor, 5 synovial sarcomas, and 27 Wilms' tumors. RESULTS: Molecular assays showed that 54 CCSKs harbored a BCOR-ITD, 1 case expressed a YWHAE-NUTM2 fusion transcript while none expressed the BCOR-CCNB3 fusion. The remaining 13 CCSKs were designated "triple-negative" based on the molecular findings. CCND1 showed positive immunoreactivity across all subgroups. TLE1 was positive in 94% of cases, including 1 YWHAE-NUTM2 fusion-positive case. Three BCOR-ITD-positive tumors were TLE1-negative. BCOR immunostaining was most variable among subgroups, with triple-negative tumors showing the weakest staining. In all, 10/68 (15%) tumors did not stain for BCOR, of which 4 were triple-negative (4/13 = 31%) and 6 were BCOR-ITD-positive (6/54 = 11%). The single YWHAE-NUTM2-positive tumor showed strong staining for all 3 markers. No single case was negative for all 3 stains; however, 3 cases showed no reactivity for either BCOR or TLE1 of which 1 was triple-negative and 2 BCOR-ITD-positive. CONCLUSION: Having completed the first comprehensive evaluation of immunostaining of 68 fully genotyped CCSK tumors, we show herein that there is a rationale for the use of a small panel of antibodies to assist in the diagnosis of CCSK regardless of genotype, and we demonstrate that in combination CCND1, TLE1, and BCOR are compelling markers in aiding CCSK diagnosis.
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Biomarcadores de Tumor/genética , Estudios de Asociación Genética , Neoplasias Renales/diagnóstico , Sarcoma de Células Claras/diagnóstico , Biomarcadores de Tumor/inmunología , Biomarcadores de Tumor/metabolismo , Fusión Génica , Técnicas de Genotipaje , Humanos , Inmunohistoquímica , Inmunofenotipificación , Neoplasias Renales/genética , Neoplasias Renales/inmunología , Neoplasias Renales/metabolismo , Sarcoma de Células Claras/genética , Sarcoma de Células Claras/inmunología , Sarcoma de Células Claras/metabolismo , Secuencias Repetidas en TándemRESUMEN
Purpose. Clear cell sarcoma of the kidney (CCSK) is an uncommon malignant renal tumor. It is the second most common renal pediatric renal malignancy after Wilms tumor. It exhibits a heterogeneous morphology, with overlapping features with its close differentials, which results in diagnostic challenges. There was no specific immunohistochemical marker in the past, to help in this regard. BCOR antibody has recently been suggested to be helpful in the differential diagnosis. We aim to study the utility of the BCOR antibody in the diagnosis of CCSK. Methods. We selected a total of 27 cases of CCSK (n = 12), Wilms tumor (n = 12), and congenital mesoblastic nephroma (n = 3). All cases were evaluated for the extent and intensity of nuclear labeling for BCOR antibody by immunohistochemistry (IHC). Results. We found that BCOR IHC was positive in 11 out of 12 cases with diffuse and strong staining in 8 of the cases. None of the cases of Wilms tumor and congenital mesoblastic nephroma were positive. Only 2 cases of Wilms tumor showed minimal and weak staining in <5% of cells. Conclusion. Diffuse and strong nuclear staining for the BCOR antibody is highly specific for CCSK among common pediatric renal malignancies. Our study confirms that BCOR IHC is a good IHC marker for the diagnosis of CCSK.
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Biomarcadores de Tumor/análisis , Neoplasias Renales/diagnóstico , Proteínas Proto-Oncogénicas/biosíntesis , Proteínas Represoras/biosíntesis , Sarcoma de Células Claras/diagnóstico , Anticuerpos , Preescolar , Femenino , Humanos , Inmunohistoquímica/métodos , Lactante , Masculino , Proteínas Proto-Oncogénicas/análisis , Proteínas Represoras/análisisRESUMEN
BACKGROUND: Clear cell sarcoma of the kidney (CCSK) is a rare malignant pediatric renal neoplasm with a heterogeneous histological appearance which often results in misdiagnosis. There are no specific immunohistochemical markers which can help in differentiating CCSK from other pediatric renal neoplasms. Recently Cyclin D1 has been investigated as a possible marker in this regard. In this study, we aim to determine the usefulness of Cyclin D1 in differentiating between CCSK and other pediatric renal neoplasms and to compare our results with those of recently published studies. METHODS: A total of 48 cases of CCSK, Wilms tumor (WT), renal rhabdoid tumor, mesoblastic nephroma, renal Ewing sarcoma and neuroblastoma were included in the study. All cases were stained with cyclin D1. Extent of Cyclin D1 staining was graded according to percentage of positive tumor cells as diffuse (> 70%), focal (5 to 70%), and negative (< 5%). Intensity of Cyclin D1 staining was graded as strong or 3+, moderate or 2+ and weak or 1 + . RESULTS: Most or all cases of CCSK, neuroblastoma and renal Ewing sarcoma demonstrated diffuse and strong positivity for Cyclin D1. Most cases of Wilms tumor (epithelial component) also demonstrated diffuse and often strong positivity for Cyclin D1. In most cases of WT, blastemal component was negative. CONCLUSIONS: Cyclin D1 is a sensitive but not specific immunohistochemical marker for CCSK and many other pediatric renal malignant neoplasms as well as for neuroblastoma. Hence, careful examination of histological features is important in reaching an accurate diagnosis in CCSKs. However, Cyclin D1 is very helpful in distinguishing between blastema-rich WT and CCSK.
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Biomarcadores de Tumor/análisis , Ciclina D1/análisis , Ciclina D1/biosíntesis , Neoplasias Renales/diagnóstico , Sarcoma de Células Claras/diagnóstico , Adulto , Preescolar , Femenino , Humanos , Lactante , Neoplasias Renales/patología , Masculino , Sarcoma de Células Claras/patología , Adulto JovenRESUMEN
INTRODUCTION: Clear cell sarcoma of the kidney (CCSK) is childhood neoplasm with its own distinctive pattern of metastasis and may appear after a disease free interval of 5 years or more. MATERIALS AND METHODS: Histopathology and immunohistochemistry were available from the radical nephrectomy and the later partial cystectomy, which was performed after a seven disease-free interval. RESULTS: The pathologic features of the primary tumor were those of a classic CCSK with a monotypic pattern of uniform rounded to ovoid tumor cells with a background network of delicate blood vessels. By contrast, the bladder recurrence had a myxoid hypocellular appearance (one of the known variant patterns of CCSK). Both tumors displayed immunopositivity for Cyclin-D1 and CD117 with a less intense reaction in the bladder metastasis. CONCLUSIONS: This case demonstrates that CCSK has the potential to metastasize after a prolonged disease-free interval and may have deceptively bland histopathologic features.
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Neoplasias Renales/patología , Sarcoma de Células Claras/secundario , Neoplasias de la Vejiga Urinaria/secundario , Niño , Preescolar , Humanos , MasculinoRESUMEN
The oncogenic mechanisms and tumour biology underpinning clear cell sarcoma of the kidney (CCSK), the second commonest paediatric renal malignancy, are poorly understood and currently, therapy depends heavily on doxorubicin with cardiotoxic side-effects. Previously, we characterized the balanced t(10;17)(q22;p13) chromosomal translocation, identified at that time as the only recurrent genetic aberration in CCSK. This translocation results in an in-frame fusion of the genes YWHAE (encoding 14-3-3ϵ) and NUTM2, with a somatic incidence of 12%. Clinico-pathological features of that cohort suggested that this aberration might be associated with higher stage and grade disease. Since no primary CCSK cell line exists, we generated various stably transfected cell lines containing doxycycline-inducible HA-tagged YWHAE-NUTM2, in order to study the effect of expressing this transcript. 14-3-3ϵ-NUTM2-expressing cells exhibited significantly greater cell migration compared to isogenic controls. Gene and protein expression studies were indicative of dysregulated MAPK/PI3K-AKT signalling, and by blocking these pathways using neutralizing antibodies, the migratory advantage conferred by the transcript was abrogated. Importantly, CCSK tumour samples similarly show up-regulation/activation of these pathways. These results support the oncogenic role of 14-3-3ϵ-NUTM2 in CCSK and provide avenues for the exploration of novel therapeutic approaches. Copyright © 2017 Pathological Society of Great Britain and Ireland. Published by John Wiley & Sons, Ltd.
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Proteínas 14-3-3/metabolismo , Movimiento Celular , Transformación Celular Neoplásica/metabolismo , Neoplasias Renales/enzimología , Proteínas Quinasas Activadas por Mitógenos/metabolismo , Proteínas de Fusión Oncogénica/metabolismo , Sarcoma de Células Claras/enzimología , Proteínas 14-3-3/genética , Animales , Transformación Celular Neoplásica/genética , Transformación Celular Neoplásica/patología , Regulación Enzimológica de la Expresión Génica , Regulación Neoplásica de la Expresión Génica , Fusión Génica , Células HEK293 , Humanos , Neoplasias Renales/genética , Neoplasias Renales/patología , Ratones , Proteínas Quinasas Activadas por Mitógenos/genética , Células 3T3 NIH , Proteínas de Fusión Oncogénica/genética , Fosfatidilinositol 3-Quinasa/metabolismo , Proteínas Proto-Oncogénicas c-akt/metabolismo , Sarcoma de Células Claras/genética , Sarcoma de Células Claras/patología , Transducción de SeñalRESUMEN
AIMS: Clear cell sarcoma of the kidney (CCSK) is a rare paediatric renal malignant tumour. The majority of CCSKs have internal tandem duplications (ITDs) of the BCOR gene, whereas a minority have the YWHAE-NUTM2 gene fusion. A third 'double-negative' (DN) category comprises CCSKs with neither BCOR ITDs nor YWHAE-NUTM2 fusion. The aim of this study was to characterise 11 histologically diagnosed CCSKs immunohistochemically (with CCND1, BCOR and CCNB3 stains) and genetically. METHODS AND RESULTS: By next-generation sequencing, 10 cases (90.9%) had BCOR exon 15 ITDs, with positive BCOR immunoreactivity being found in four (36%) or eight (72%) cases, depending on the antibody clone. By reverse transcription polymerase chain reaction, none had the YWHAE-NUTM2 fusion. The DN case had a BCOR-CCNB3 fusion and strong nuclear CCNB3 and BCOR immunoreactivity. Quantitative polymerase chain reaction showed markedly elevated BCOR expression in this case, whereas BCOR ITD cases had lower levels of elevated BCOR expression. CONCLUSIONS: The majority of the CCSKs in our cohort had BCOR ITDs, and none had the YWHAE-NUTM2 fusion. We verified the strong, diffuse cyclin D1 (CCND1) immunoreactivity in CCSKs described in recent reports. BCOR immunoreactivity was not consistently positive in all CCSKs with BCOR ITDs, and therefore cannot be used as a diagnostic immunohistochemical stain to identify BCOR ITD cases. The DN case was a BCOR-CCNB3 fusion sarcoma. BCOR-CCNB3 sarcoma is typically a primary bone sarcoma affecting male adolescents, and this is the first report of it presenting in a kidney of a young child as a CCSK. The full spectrum of DN CCSKs awaits more comprehensive characterisation.
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Ciclina B/genética , Neoplasias Renales/genética , Proteínas de Fusión Oncogénica/genética , Proteínas Proto-Oncogénicas/genética , Proteínas Represoras/genética , Sarcoma de Células Claras/genética , Niño , Preescolar , Exones , Femenino , Humanos , MasculinoRESUMEN
Clear cell sarcoma of kidney (CCSK) is a rare aggressive malignant renal neoplasm with a high metastatic potential. Its outcome has however, improved with the advent of doxorubicin based neoadjuvant chemotherapy. Here, we present two cases of CCSK in infants diagnosed on cytology followed by nephrectomy. The first case presented in the neonatal period and had the unusual histological finding of islands of cartilage. The second case presented at the age of eight months. The possibility of CCSK should, therefore, be considered in the differential diagnoses of renal masses in infants as well as neonates. Diagn. Cytopathol. 2017;45:761-765. © 2017 Wiley Periodicals, Inc.
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Neoplasias Renales/diagnóstico , Sarcoma de Células Claras/diagnóstico , Biopsia con Aguja Fina , Citodiagnóstico/métodos , Humanos , Lactante , MasculinoRESUMEN
Objective · To investigate the clinical characteristics and multidisciplinary treatment of children with clear cell sarcoma of kidney (CCSK). Methods · Data of seven children with CCSK treated at Xinhua Hospital, Shanghai Jiao Tong University School of Medicine between Jan 2011 and Jan 2016 were collected. The retrospective analysis of clinical manifestations, features of imaging and pathology, treatment, and follow-up was performed. Results · Of 7 children with CCSK, 6 were male and 1 was female with the median age of 28 months (4-59 months), and 3 were at stageⅠ, 2 at stage Ⅲ, and 2 at stage Ⅳ. All cases were discussed and evaluated by multidisciplinary teams, including pediatric hematology/oncology, pediatric surgery, pathology, radiology and radiotherapy. CCCG-WT-2009 protocol was adopted to treat these patients. The median follow-up period was 22 months (8-56 months). Six children survived and one died. Conclusion · The multidisciplinary treatment mode can effectively improve the prognosis of CCSK. CCCG-WT-2009 protocol has good therapeutic effect and high cure rate for children with early stage CCSK, but the treatment of advanced stage CCSK needs to be further explored and perfected.
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Clear cell sarcoma of the kidney (CCSK) is a rare tumor that is diagnosed most often in children between 2- and 4-years-old of age. Usually, patients with CCSK are treated in international study for intrarenal tumors, preferentially Wilms tumor, according to bad histopronostic group. The purpose of this paper is to review the most important features in 2015 about epidemiology, radiology, anatomopathology and genetic of CCSK, and above all a synthesis about successive treatment strategies with their results. Second most common pediatric renal tumor in children less than 5-years-old, its prognosis has improved dramatically in recent years with the use of anthracyclines.
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Neoplasias Renales , Enfermedades Raras , Sarcoma de Células Claras , Antraciclinas/uso terapéutico , Antineoplásicos/efectos adversos , Antineoplásicos/uso terapéutico , Biopsia/métodos , Preescolar , Humanos , Lactante , Neoplasias Renales/diagnóstico , Neoplasias Renales/epidemiología , Neoplasias Renales/patología , Neoplasias Renales/terapia , Recurrencia Local de Neoplasia/diagnóstico , Nefrectomía/efectos adversos , Traumatismos por Radiación/complicaciones , Dosificación Radioterapéutica , Enfermedades Raras/diagnóstico , Enfermedades Raras/epidemiología , Enfermedades Raras/patología , Enfermedades Raras/terapia , Sarcoma de Células Claras/diagnóstico , Sarcoma de Células Claras/epidemiología , Sarcoma de Células Claras/patología , Sarcoma de Células Claras/terapiaRESUMEN
Internal tandem duplication within the BCOR gene sequence that encodes the PUFD domain, important in the formation of the non-canonical or variant polycomb repressor complex 1 (v-PRC1), was very recently described in 100% of 20 clear cell sarcomas of kidney (CCSKs). None of those 20 cases bore the YWHAE-NUTM2 transcript, previously described by us in CCSK, and which constitutes the only other recurrent genetic aberration observed in CCSK, prompting consideration that these mutations might be mutually exclusive in CCSK. We analysed a cohort of 159 CCSKs and can now not only confirm that there is indeed mutual exclusivity of these BCOR and YWHAE mutations, but also show that a substantial proportion (in this series 11.8%) of CCSKs bear neither mutation when tested by these assays, raising the possibility of distinct aetiologies for subsets of CCSK. Clinical differences observed between the subsets support this notion. As CCSK may show poor chemo-responsiveness, and current treatment protocols mandate the use of doxorubicin with its associated side-effects, advances in understanding the disease biology with a view to more targeted and personalized treatment is a pressing need.
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Biomarcadores de Tumor/genética , Duplicación de Gen , Fusión Génica , Neoplasias Renales/genética , Proteínas Proto-Oncogénicas/genética , Proteínas Represoras/genética , Sarcoma de Células Claras/genética , Secuencias Repetidas en Tándem , Adolescente , Secuencia de Aminoácidos , Niño , Preescolar , Análisis Mutacional de ADN , Femenino , Predisposición Genética a la Enfermedad , Humanos , Lactante , Neoplasias Renales/tratamiento farmacológico , Neoplasias Renales/patología , Masculino , Datos de Secuencia Molecular , Mutación , Fenotipo , Pronóstico , Sarcoma de Células Claras/tratamiento farmacológico , Sarcoma de Células Claras/patologíaRESUMEN
Pathological diagnosis of clear cell sarcoma of the kidney (CCSK) is challenging as it resembles blastemal Wilms tumor (WT) and other pediatric sarcomas, and does not have any distinctive immunophenotype. The YWHAE-FAM22 translocation t(10;17)(q22;p13) has been reported in a subset of CCSK. This translocation also occurs in high-grade endometrial sarcoma, in which it is associated with cyclin D1 overexpression. Hence we seek to determine YWHAE-FAM22 translocation status and cyclin D1 immunoreactivity in a series of local CCSK cases. Of 8 CCSK cases from 7 patients identified, no CCSK had the YWHAE-FAM22 fusion transcript by reverse transcriptase-polymerase chain reaction. Novel karyotypes were identified for 2 cases: 1 had t(2;13)(q13;q22) and the other t(3:17)(q29;p11.2). Excluding a case with poor tissue section antigenicity, 7 of 7 CCSKs (100%) showed diffuse and strong nuclear cyclin D1 staining. Cyclin D1 immunohistochemistry was also performed on tissue microarrays of other pediatric renal tumors: blastemal areas of 18 WT cases were negative; 6 rhabdoid tumors and 1 metanephric adenoma showed patchy and weak staining; 3 mesoblastic nephromas and 18 of 29 neuroblastomas had positive staining. Cyclin D1 immunohistochemistry helps distinguish CCSK from blastemal WT and metanephric adenoma and rhabdoid tumors, but not from neuroblastomas and mesoblastic nephromas. Cyclin D1 overexpression in CCSK is not contingent on YWHAE-FAM22 translocation, and cyclin D1 inhibition may potentially be explored as a targeted therapeutic strategy in CCSK.
Asunto(s)
Biomarcadores de Tumor/análisis , Biomarcadores de Tumor/genética , Ciclina D1/análisis , Inmunohistoquímica , Neoplasias Renales/química , Neoplasias Renales/genética , Sarcoma de Células Claras/química , Sarcoma de Células Claras/genética , Translocación Genética , Adolescente , Niño , Preescolar , Diagnóstico Diferencial , Femenino , Fusión Génica , Humanos , Cariotipo , Cariotipificación , Neoplasias Renales/patología , Masculino , Proteínas de Fusión Oncogénica/genética , Valor Predictivo de las Pruebas , Sarcoma de Células Claras/patología , Singapur , Análisis de Matrices TisularesRESUMEN
Paired box (PAX) gene antibodies have made it into the mainstream of tumor diagnosis in the recent years. We report the immunoreactivity expression patterns of three PAX genes (PAX2, PAX5 and PAX8) in poorly differentiated small round cell tumors of childhood for possible useful diagnostic applications. We collected and analyzed 123 cases of poorly differentiated small round cell tumors of childhood for their PAX immunoexpression patterns. The results indicated that PAX2 was strongly positive in all alveolar rhabdomyosarcomas and in two-thirds of the kidney clear cell sarcomas, and displayed variable expression in one-half of the embryonal rhabdomyosarcomas. PAX8 immunoexpression was noticed in five and three cases of alveolar rhabdomyosarcomas and embryonal rhabdomyosarcomas, respectively. About one-third of malignant rhabdoid tumors were PAX2-positive and PAX8-positive. All of the Ewing sarcoma and neuroblastoma cases stained negative with all three PAX stains.